Pain relief in the prehospital setting is often insufficient, as the administration of potent intravenous analgesic drugs is mostly reserved to physicians. In Australia, inhaled methoxyflurane has been in routine use by paramedics for decades, but experience in Central European countries is lacking. Thus, we aimed to assess whether user friendliness and effectiveness of inhaled methoxyflurane as sole analgesic match the specific capabilities of local ground and air-based EMS systems in Austria.Observational study in adult trauma patients  with moderate to severe pain . Included patients received a Penthrop® inhaler containing 3 mL of methoxyflurane (maximum use 30 min). When pain relief was considered insufficient (NRS reduction < 3 after 10 min), intravenous analgesics were administered by an emergency physician. The primary endpoint was effectiveness of methoxyflurane as sole analgesic for transport of patients. Secondary endpoints were user friendliness (EMS personell), time to pain relief, vital parameters, side effects, and satisfaction of patients.n = 58, 53%) but mild. User satisfaction was scored as very good when pain relief was sufficient, but fair in patients without benefit. Technical problems were observed in 16 cases (14.7%), mainly related to filling of the inhaler. In every fifth use, the fruity smell of methoxyflurane was experienced as unpleasant. No negative effects on vital signs were observed.Median numeric pain rating was 8.0 (7.0–8.0) in 109 patients. Sufficient analgesia (reduction of NRS ≥3) was achieved by inhaled methoxyflurane alone in 67 patients (61%). The analgesic effect was progressively better with increasing age. Side effects were frequent  with moderate to severe pain. Older patients benefit especially from inhaled methoxyflurane. Side effects are mild and vital parameters unaffected. Thus, inhaled methoxyflurane could be a valuable device for non-physician EMS personnel rescue services also in the central Europe region. The treatment of acute pain is a central task in emergency medicine , 2. HoweIn other words, there is an unmet demand for analgesics that are easy and safe to use, ideally by paramedics, independent of emergency physicians . InhaledMethoxyflurane, a volatile anaesthetic from the group of the di-alkyl esters (2-dichloro-1:1-difluoroethyl-methyl-ester) has been used at low, purely analgesic concentrations by paramedics in Australia (Penthrox®) since 1975, in New Zealand since 2002 and in several eastern European countries since 2010 –22. By nThe goal of our study was therefore to test the effectiveness of Penthrop®  as the sole analgesic in patients with moderate to severe pain following trauma. The study was performed by experienced emergency physicians. However, we wanted to explore whether Penthrop® could be an alternative in situations where an intravenous line cannot be established immediately, for example in alpine mountain rescue and whether methoxyflurane could be recommended for use by paramedics in the context of Central European prehospital emergency care.2) and consciousness level (GCS) each at 5, 10, 15, 20, and 30 min after beginning of treatment. The user friendliness of methoxyflurane in the prehospital setting  was scored on a 5-part Likert scale . Additionally, the time until onset of the drug effect, the number of patients who required an intravenous line or supplemental analgesia, and the patient’s satisfaction with the analgesia and the care in general  were evaluated. Finally, any side effects of the medication were documented by proactively asking the patient, and, in addition, any technical problems were recorded.The primary endpoint was effectiveness of Penthrop® as sole analgesic, measured as the proportion of cases in which sufficient analgesia was achieved by giving methoxyflurane alone. The following secondary endpoints were chosen: reduction of the initial pain level  based on the numeric rating scale (NRS) and the effects of the administered medication on the vital parameters circulation , oxygenation , a prospective, non-randomized  Phase IV study was carried out.The drug was used by emergency physicians in accordance with its approval, mainly for fractures and/or dislocations of the upper or lower limbs at 6 ground-based and 6 air ambulance stations in Austria. over 18 years old who had moderate to severe pain (NRS ≥4), were fully conscious and able to give informed consent, and had no impairment of vital functions. The contraindications and exclusion criteria listed in Table Methoxyflurane  was administered as an alternative to intravenous analgesia to trauma patients Methoxyflurane (3 ml) was given in one dose via inhaler over a period of no more than 30 min. If methoxyflurane did not achieve a reduction of pain by ≥3 NRS points within 10 min, other analgesics were given intravenously, at the discretion of the emergency physician . The study data were recorded by hand or using web-based data entry.The primary endpoint was effectiveness of methoxyflurane as sole analgesic for transport of patients. Secondary endpoints were user friendliness (EMS personell), time to pain relief, vital parameters, side effects, technical problems, and satisfaction of patients. Due to the design of the trial  analysing the rate of patients without additional analgesia, power analysis was waived. The number of patients was set at 200 plus an allowance for a dropout rate of 5%  pandemic, the study essentially came to a halt in March 2020. From that time onwards, concerns about potential transmission of severe SARS-CoV-2 by aerosols from the patients led to avoidance of analgesia by inhalation in favour of intravenous drugs. Inclusion of new patients was finally stopped in November 2020, since the number of patients targeted for the interim analysis had been reached.p < 0.01 was chosen.The normal distribution of the results was evaluated using a Shapiro-Wilk test. The results of quantitative data are shown as median and interquartile range; frequencies are shown as absolute and percentage values. The patients were divided into the following arbitrary age categories: 18–30, > 30–45, > 45–65, > 65–80, > 80 years. Differences between groups were analysed using Mann-Whitney U tests, Kruskal-Wallis tests, or Jonckheere-Terpstra tests, as appropriate. Frequencies were analysed using Chi-squared or Fisher’s exact tests. A two-sided significance level of n = 50) to 54.1% (n = 59); their median age was 51 years (37–64); further population characteristics are listed at Fig. From October 2018 to November 2020, a total of 109 patients were included in the study; two patients were excluded before analysis . The ratio of men to women was 45.9%  was 3.0 (3.0–5.0) minutes; no difference between the sexes was observed in this parameter (women 4.0 min (3.0–5.0 min) versus men (3.0 min (3.0–4.0 min), p = 0.14). There was also no significant difference in the time to reduction of pain between the different indications for the emergency callouts.The median NRS pain score on arrival of the emergency physician was 8 points (7.0–8.0), falling to 4.0 (3.0–5.0) 15 min after beginning of treatment. The median time to Sufficient analgesia (effectiveness) was achieved using methoxyflurane alone in 67 patients (61.5%); 41 (37.6%) patients needed supplementary analgesia. In one patient therapy was recorded as insufficient but the patient received no additional analgesia. With increasing age of the patients, a significantly better analgesic effect was observed. Due to the supplemental intravenous analgesia in younger patients, this did not manifest as a reduction of NRS scores, but in the highly significant (p < 0.0001) decline of the proportion of cases in which methoxyflurane therapy was stopped because of insufficient analgesia. Supplementary analgesia was required in 11/18 (61.1%) of the 18–30 years-old patients, 13/30 (43.3%) of the > 30–45 age group, 13/36 (36.1%) between > 45–65, 3/16 (18.8%) of those > 65–80 and 1/9 (11.1%) of the patients > 80 years old (p = 0.044). Patients who received supplemental analgesia were younger  than patients who did not need supplemental analgesia  (p = 0.01). There were no significant differences by sex , BMI (26.4 (23.4–28.5) versus 24.8 (22.8–27.6) (p = 0.31), by the indications for the emergency callout  or the time to onset of the drug effect . Patients who did not require supplemental analgesia tended to have lower initial pain scores, although the difference, of only one NRS point, was clinically marginal: 7.0 (6.0–8.0) vs. 8.0 .atients 6.5%; 41 , the median pulse rate was 85 bpm (78–94), peripheral oxygen saturation was 97% (96–99%). The median score of 15 (15–15) on the Glasgow Coma Scale was also normal. On application of Penthrop®, with the resulting analgesia, blood pressure and pulse rate dropped slightly, i.e. the cardiovascular parameters normalized, without any clinically relevant effect on oxygen saturation and consciousness.In all cases, the patients’ patients’ satisfaction with the pain treatment and care by the emergency team was very good  of them reported that they had experienced them, but mostly described them as mild (Table p = 0.099). Only in one case (0.9%), therapy was stopped because of nausea and the unpleasant odour. Five patients (8.6%) in total reported an unpleasant taste or smell. No adverse event occurred during the study.When the patients were proactively asked about user friendliness (EMS personell) of the inhaler as very good (median 1.0 (1.0–2.0)). The overall user satisfaction (EMS personell) was good (median 2.0 (1.0–3.0). Nevertheless, technical difficulties were reported in 14.7% (n = 16) of cases: although users followed the device instructions, in some cases liquid leaked from the inhaler. In these cases, the emergency personnel reported unpleasant odours, especially in confined spaces . This affected the scoring: in these cases, the median user satisfaction score was only 3.0 (2.0–4.0).The emergency physicians rated the In this prospective observational study, the inhaled analgesic methoxyflurane (Penthrop®) was found to be effective in 61.5% (67 of 109) patients with with moderate to severe pain due to fractures, dislocations and low back pain due to minor trauma. Side effects were frequent (53%) but mild with just one truncation of therapy (0.9%) due to side effects. The original plan to include 200 patients in the study had to be abandoned because of the SARS-CoV-2 pandemic. The study was stopped because of the risk of aerosol transmission due to the inhalation-based delivery method.However, the number of cases collected corresponds to the planned number for an interim analysis, and the amount of data collected is sufficient to draw some conclusions on the main questions. Almost two-thirds of patients who initially had very severe pain (median NRS 8) experienced a significant reduction in pain of 4 NRS points within 15 min of methoxyflurane. This corresponds to or is even better than reports to date from European emergency departments –30. The Methoxyflurane is certainly easier to handle than nitrous oxide , 20, 33.The side effects of Penthrop® are known; the substance has been proven to be safe and effective over many studies , 25. In The main limitation of this trial is the relatively low number of patients. Unfortunately, the premature end of the study due to the pandemic prevented the collection of further observations, e.g. in alpine air rescue operations. However, since the results obtained up to this point answered our primary questions sufficiently, the study was closed. Further investigations in this field will follow. Due to the absence of information about potential viral spreading via inhaler technique, we can neither recommend nor advise against this device during the current or future pandemics. Methoxyflurane was not tested against a placebo, since its analgesic effects are already sufficiently described . Our stuIn prehospital use, inhaled methoxyflurane as sole analgesic is effective for transport of trauma patients (62%) with moderate to severe pain. During the SARS-CoV-19 pandemic or similar situations, the use of an inhaler can be seen as precarious. Especially older patients benefit from inhaled methoxyflurane. Side effects are mild and vital parameters are unaffected. Thus, inhaled methoxyflurane could be a valuable option for non-physician rescue services in Central Europe.


Chronic pain syndrome (CPS) is a common complication after operative procedures, and only a few studies have focused on the evaluation of CPS in foot-forefoot surgery and specifically on HV percutaneous correction. The objective of this study was to compare postoperative pain levels and incidence of CPS in two groups of patients having undergone femoral-sciatic nerve block or ankle block regional anaesthesia before hallux valgus (HV) percutaneous surgery and the association between postoperative pain levels and risk factors between these patient groups.A consecutive patient series was enrolled and evaluated prospectively at 7 days, 1, 3 and 6 months after surgery. The participants were divided into two groups according to the regional anaesthesia received, femoral-sciatic nerve block or ankle block, and their outcomes were compared. The parameters assessed were postoperative pain at rest and during movement by the numerical rating scale (NRS), patient satisfaction using the Visual Analogue Scale (VAS), quality of life and return to daily activities. Statistical analysis was performed.p < 0.0001) and during movement (p < 0.0001) significantly decreased during the follow-ups; at 6 months, 13 patients suffered from CPS. Over time, satisfaction remained stable (p > 0.05), quality of life significantly increased and patients returned to daily activities and work (p < 0.0001). No significant impact of type of anaesthesia could be detected. ASA 3 (p = 0.043) was associated to higher pain during movement; BMI (p = 0.005) and lumbago (p = 0.004) to lower satisfaction. No operative-anaesthetic complications were recorded. Postoperative pain at rest and during movement improved over time independently of the regional block used, with low incidence of CPS at last follow-up. Among risk factors, only a higher ASA was associated to higher pain during movement, while higher BMI and lumbago to lower satisfaction.One hundred fifty-five patients were assessed, 127 females and 28 males. Pain at rest (Both ultrasound-guided sciatic-femoral and ankle blocks were safe and effective in reducing postoperative pain with low incidence of CPS at last follow-up.NCT02886221. Registered 1 September 2016.Clinical Trial  OverallThis definition was later revised and implemented by the International Association of Pain Study (IAPS) . CurrentDifferent anaesthesiological techniques adopted also seem to have a potential influence on postoperative pain and CPS genesis . In orthfemoral-sciatic nerve block is associated with satisfactory anaesthesia without pre- and postoperative complications, besides providing postoperative pain control for an average of 12 h [Ankle block is an attractive alternative to femoral-sciatic nerve block for primary anaesthesia for forefoot procedures that may reduce potential risks associated with a more proximal nerve block [A recent report has shown that ultrasound-guided  of 12 h . Neverth of 12 h . Ankle bve block . While mve block , 20.femoral-sciatic nerve block or ankle block before HV percutaneous operative procedure performed as outpatient surgery. The secondary aim was to assess the association between postoperative pain levels and the risk factors between these two groups of patients.Hence, the primary aim of this prospective study was to evaluate postoperative pain levels and incidence of CPS in patients who underwent ultrasound-guided At our institution, between May 2018 and July 2020, a consecutive series of adult, Caucasian patients with diagnosis of symptomatic Hallux Valgus (HV), resistant to at least six-month conservative treatment  in outpatient surgery by the same experienced surgeon, the senior author, trained in minimally invasive surgery (MIS).Inclusion criteria for the study population were patients undergoing outpatient, elective, unilateral, only percutaneous surgery as previously indicated  and onlyExclusion criteria were as follows: use of peripheral blocks different from ankle-block or sciatic-femoral block, continuous nerve blocks, history of allergy to local anaesthetic, previous dry needling or local corticosteroid injections, bilateral HV, arthritis and stiffness of metatarsophalangeal joint, previous trauma, foot and ankle surgery, congenital deformities of the foot, hallux valgus and rigidus, hypermobility of first ray, Freiberg infraction, metatarsalgia and Morton’s neuroma, and diagnosis of rheumatic, metabolic (diabetes), neurologic , infective or psychiatric pathologies . These strict selection criteria were used to avoid possible confounding factors, which could have impacted the generalisability of our results. Specifically, we excluded those conditions responsible for chronic pain or altered perception of pain in the foot.Two different types of ultrasound-guided regional anaesthesia were performed: sciatic-femoral block and ankle-block. All regional block procedures were performed by one of the three senior anaesthetists of the same experienced anaesthesiological team of our Orthopaedic Department. Both nerve blocks were performed with ultrasound guidance with or without the use of a neurostimulator for sciatic-femoral block and ankle-block, respectively, and employed after positioning the patient in a supine decubitus position. During the two-year study period, both regional block procedures were chosen without any technique preference by the same anaesthesiological team and alternated every week according to the study protocol. Hence, patients were allocated into 2 groups according to the type of block used: sciatic-femoral block and ankle block.To improve patient cooperation and comfort, standard premedication was administered using intravenous Midazolam (1–2 mg) and Fentanyl (0.1 mg). Intra-operative sedation was obtained using Propofol (Diprivan) 1.5 mg/kg to 2.5 mg/kg for induction and a continuous infusion of 4–8 mg/kg/h for maintenance. Finally, no intraoperative morphine and/or nonsteroidal anti-inflammatory (NSAID) was given during the operative procedure, according to routine practice.Sciatic-femoral nerve block was performed via anterior approach, Fig. .Fig. 1UlFor femoral block (A-B), using an ultrasound-guided technique (A), the needle is advanced through the fascia lata and iliaca until an adequate position with respect to the femoral nerve (FN) is reached. The site of needle insertion (B) is located at the femoral crease, below the inguinal crease and immediately lateral to the pulse of the femoral artery (FA).For sciatic block (C-D), the sciatic nerve (SCN) is seen as a hyperechoic oval structure sandwiched between the adductor magnus muscle and the hamstring muscles, typically visualised at a depth of 6–8 cm, under the femoral artery (FA), the femur and the adductor magnus muscle. The femoral block is performed by inserting a 22-gauge needle connected to a nerve stimulator set at a current intensity of 1 mA (0.1 ms/2 Hz), 1.5–2 cm lateral to the femoral artery and 1–2 cm distal to an inguinal ligament in a cephalic direction at a 30–45° angle. As the quadriceps muscle contractions are obtained, the current is gradually decreased while the needle is advanced. The position of the needle is adequate when patellar twitches are elicited with current output between 0.3 and 0.5 mA. The drug is then injected  was routinely administered intravenously 2 times after surgery before discharge from the hospital starting 2 h after the end of the procedure. No intramuscular injection of morphine sulphate or local anaesthesia was administered in the operating room neither suggested during the postoperative period.According to the indications of our institutional forefoot postoperative protocol , 29, pro2 as cut-off value.Demographic and clinical data such as sex, age at time of procedure, body mass index (BMI), American Society of Anesthesiologists (ASA) scale , 32, whiAll patients were followed up using a questionnaire collected by phone the first day after surgery and during the post-operative scheduled consultation at our out-patient clinic at 7 days, 1 month, 3 and 6 months after surgery by an independent investigator not directly involved in the patients’ operative treatment and blind to the patients’ allocated group.The questionnaire was conceived to assess the postoperative pain referred by the patient by a numerical rating scale  both at rest and during movement (dynamic); to index the overall patient satisfaction using Visual Analogue Scale (VAS), ranging from 0 to 10 points with 0 indicating no satisfaction and 10 denoting complete satisfaction for the performed block procedure; to assess the quality of life compared to preoperative conditions by self-reported global change (better/same/worse) on the basis of VR-12 physical and VR-12 mental quality of life ; to examThe a priori power analysis was conducted using the software G*Power 3.1.9.7 for Windows. The minimum sample size required was computed selecting the following: F tests, family option, opting for between-factors, repeated measures ANOVA. In order to capture a small effect size as defined by Cohen , with anBefore proceeding with data handling, statistical processing and manipulation, all figures were visually inspected to capture any potential outlier. Normality of data distribution was verified carrying out the D’Agostino-Pearson omnibus test. Continuous variables were computed as mean ± standard deviation with median reported when appropriate. Categorical variables were expressed as percentages.A univariate analysis was conducted to identify eventual differences between patients under femoral nerve block and those under ankle block. Categorical variables were compared using the chi-square test, whereas continuous parameters were compared conducting Student’s t-test or its nonparametric version, based on the normality of data distribution.A generalised linear model for repeated measures  was used. The homogeneity of covariance matrices and the independence assumptions were checked. The sphericity assumption was verified carrying out the Mauchly’s W test. In case of sphericity violation (when the ‘F’ test was significant) and with epsilon values  less than 0.75, the Greenhouse-Geisser correction was adopted to properly adjust for the degrees of freedom of the interaction effect between different time points and the sample group. Otherwise (in case of ε greater than 0.75), the Huynh-Feldt correction was carried out. Effect size was estimated by computing the partial eta squared (ηp2) and interpreted using the following rule: small if < 0.06, moderate in the range 0.06–0.14 and large if > 0.14. Post-hoc tests using the Bonferroni correction for pairwise comparisons were conducted. This generalised linear model was applied for investigating changes in pain, movement with pain, satisfaction and quality of life at different time points.To shed light on the determinants of the insurgence of CPS, a multivariate logistic regression analysis (with the “enter” method) was conducted.p-values less than 0.05 were considered statistically significant. All statistical analyses were carried out with the commercial software “Statistical Package for the Social Sciences” . Graphs were generated by means of the commercial software MedCalc .Figures with The recruited population included 155 patients. A femoral nerve block was used for 82 (52.9%) patients, while 73 (47.1%) received an ankle block. Demographic and clinical data of the recruited population are reported in Table p < 0.0001), as well as pain during movement from 2.79 to 1.18 . For both measures, all time-points were significant at the post-hoc pairwise comparison analysis except for the comparison between the measurement at 1 and 5 days after the operation and between 3 and 6 months for pain at rest and between 1 post-operative day and the 1-month point as well as between 3 and 6 months for pain during movement. At 3 and 6 months, 11 (7.1%) and 13 (8.4%) patients suffered from CPS, respectively. Satisfaction remained stable at the different time-points , whereas quality of life significantly increased from 1.40 to 2.74 . All time-points were significant at the post-hoc pairwise comparison analysis except for the comparison between the 1 and the 5 post-operative days as well as between 3 and 6 months after the operation (Table p < 0.0001).Pain at rest significantly decreased from 2.17 at the first post-operative day to 0.52 at 6 months . Perceived quality of life on the fifth day also differed between the two groups, being higher among those with ankle block (p = 0.041). However, when correcting for multiple comparisons, these small differences failed to achieve statistical significance. Further, other variables under study did not impact major outcomes apart from the ASA classification (p = 0.043) with higher movement with pain values reported in the ASA 3 group, and BMI (p = 0.005) and lumbago (p = 0.004), with lower satisfaction values  on the outcomes could be detected Table . Pain atAt the multivariate logistic regression analysis, no statistically significant predictors of CPS could be detected at 3 Table  and 6 moOperative procedures of the forefoot usually cause moderate to severe acute pain that can occasionally progress into CPS . For theWhile several studies have focused on the development of CPS after knee and hip surgeries –38, the sciatic-femoral block or ankle-block. Specifically, the impact of these types of anaesthetic blocks and risk factors on the development of postoperative pain, patient satisfaction and quality of life were evaluated.Hence, the aims of this prospective study were to investigate the postoperative pain and CPS in a cohort of patients having undergone the same percutaneous operative procedure for HV correction, performed under ultrasound-guided The most important findings of the present study, observed from the first day to 6-month follow-up after surgery were as follows: a significant decrease of pain at rest and during movement; a stable level of patient satisfaction; a significant increase of patient quality of life and return to daily activities and work. Importantly, no significant impact of type of anaesthesia could be detected. ASA 3 was associated to higher pain during movement, while BMI and lumbago to lower patient satisfaction. Among risk factors, only a higher ASA was associated to higher pain during movement, while higher BMI and lumbago to lower satisfaction.Both types of pain improved over time (from 1 day to 6 months after surgery) as well as the quality of life, in accordance with the literature , 40. Patfemoral-sciatic versus ankle block) on pain, pain during movement, satisfaction and quality of life was also analysed, finding that the block type does not have any influence on clinical outcomes. Many studies have compared ankle blocks to more proximal blocks [ankle block in addition to general anaesthesia or spinal anaesthesia [ankle block versus sciatic-saphenous nerve block in 42 patients with HV having undergone surgery [The impact of risk factors and the type of anaesthesia  were reported to be common elements in promoting a high-impact chronic pain prevalence on the USA population . For thiAn inadequate perioperative anaesthesia and unsatisfactory postoperative pain control protocol may lead to the development of CPS, inducing the use of opioids in postoperative therapy, and sometimes the consequent development of an opioid use disorder (OUD), which can compromise pain management also in the case of future operations. Parrish JM and colleagues  demonstrThe strengths of our study include: (1) the standardization of anaesthesiology, operative procedures and postoperative pain therapy including aftercare, according to our institutional protocol for the same percutaneous operation – the first performed by the same team of anaesthesiologists, the second by the senior surgeon, the third in use at our institution since 2009; these aspects avoid confounding bias and allow adequate methodology for comparative reasons; (2) the prospective data collection of the case series with the same fixed follow-ups using validated questionnaires; (3) an adequate number of patients in both groups – none was lost at different follow-up points until the last one, and the appropriate power calculations were conducted for the primary outcome measures; (4) the analysis of the clinical outcomes, carried out separately by independent investigators; the person who performed clinical assessment was blinded to the type of procedure used; (5) the multivariable statistical analysis performed by an independent statistician.We are also aware of the study’s weaknesses. (1) It was a single centre case series study with the same team of anaesthesiologists and a single surgeon for all operations; these aspects could have affected the generalisability of the operative procedure. (2) There was a lack of randomisation with potential selection biases, although the patients were operated during the 2-year study period alternating weekly one or the other regional anaesthesia block according to our study protocol and without any regional block preference by the anaesthetists. (3) We lacked a control group, which prevented us from comparing results. (4) The mere inclusion of cases of unilateral HV treated percutaneously prevented us from reporting outcomes of cases operated bilaterally or by more traditional open techniques. (5) Multivariate analysis was performed, but no determinants were found, probably because of the small number of CPS subjects. It would require a larger number of individuals. In our study, we found that only 11 (7.1%) and 13 (8.4%) patients suffered from CPS at 3 and 6 months, respectively.Further larger studies aimed at identifying the determinants underlying the occurrence of CPS are needed.Our data show that postoperative pain at rest and during movement improved from the first day to 6-month follow-up after percutaneous HV correction, independently of the regional blocks performed and without postoperative complications of anaesthesia.Supported by a tested institutional aftercare therapy protocol, both sciatic-femoral and ankle blocks were safe and effective in reducing postoperative pain with low incidence of CPS at last follow-up. The ultrasound-guided peripheral blocks were well suited to forefoot outpatient surgery settings, showed high patient acceptance rates and allowed improvement of quality of life and return to daily activities and work.Finally, in relation to the different risk factors analysed, only a higher ASA was associated with pain during movement, while higher BMI values and the presence of lumbago were associated with lower satisfaction values.


Seventy-two patients were randomly allocated to two groups: the Mg group or the control group. The pain intensity was significantly alleviated in the Mg group at 24 h  and 48 h  after surgery compared to the control group. Total opioid consumption was reduced by 30% in the Mg group during the same period . Patients in the Mg group required less additional doses of rocuronium . Adequate IOM recordings were successfully obtained for all patients, and abnormal IOM results denoting warning criteria (amplitude decrement >50%) were similar. Total intravenous anesthesia with MgSO4 combined with opioid-based conventional pain control enables intraoperative patient immobilization without the need for additional neuromuscular blocking drugs and reduces pain intensity and analgesic requirements for 48 h after spine surgery, which is not achieved with only opioid-based protocol.Spine surgery is painful despite the balanced techniques including intraoperative and postoperative opioids use. We investigated the effect of intraoperative magnesium sulfate (MgSO Patients may experience significant pain after major spine surgery despite the balanced techniques including intraoperative opioids and postoperative patient-controlled analgesia (PCA) . Studies4) as an adjuvant to general anesthesia is related to multiple mechanisms of action, including lessening central excitability via N-methyl-d-aspartate (NMDA) receptor antagonism, delaying the development of opioids tolerance, and effects on balance of neurotransmitters [Magnesium is an abundant cation in the body and essential to numerous physiological activities. Magnesium sulfate MgSO as an adsmitters .4 administration can enhance the potency or duration of neuromuscular blockade, thereby reducing the need for NMB drugs during surgery [4 during IOM could interfere with the precise assessment of significant changes in SSEPs and MEPs [4 when used with opioids, especially under IOM during spine surgery to date.Total intravenous anesthesia (TIVA) is widely used in spine surgery these days, as intraoperative neurophysiological monitoring (IOM) has aided spine surgery with the measured evoked potentials provide much information on the integrity of the sensory and motor neurone pathways during the surgery ,7. Durinand MEPs . Neverth4 could reduce pain intensity and total opioid consumption after spine surgery compared to conventional opioids-based therapy. In addition, we investigated the acceptable safety profile of MgSO4 during IOM with regard to concomitant use of NMB drugs, as well as preventive MgSO4 as an essential element of multimodal analgesia through this prospective, randomized, double-blind study.We hypothesized that the intraoperative administration of MgSOThis study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-1804-462-002), Seong-nam, Korea (Chairperson Prof Jae-Ho Lee) on 2 July 2018 and registered at cris.nih.go.kr (accessed on 9 August 2018 registration number KCT0004173). All patients provided informed consent.−2, were not using postoperative intravenous PCA, presence of renal, hepatic, or cardiovascular dysfunction, neuromuscular disease, admission to the intensive care unit at the end of surgery, under medication with calcium channel blockers or magnesium, refusal to participate in the study, anesthesia time more than 5 h preventing excessive infusion of MgSO4, any other physical or mental illness rendering them not capable of answering the pain score.All patients provided informed consent. A total of 72 patients aged 20–79 years were enrolled in this prospective randomized study if they receive IOM while undergoing major spine surgery; decompression, fusion, laminoplasty, or tumorectomy. Patients were excluded from the study for the following reasons: they had an American Society of Anesthesiologists’ (ASA) physical status classification of IV or greater, body mass index < 15 or >35 kg m®, Fresenius vial, France). Rocuronium 0.6 mg kg−1 was administered to facilitate tracheal intubation. Following intubation, patients received either MgSO4 or saline according to a randomization list: the Mg group  or the control group  by the attending anesthesiologists. The effect-site concentration of propofol (3–6 µg ml−1) was set to ensure a bispectral index (BIS)  between 40 and 55. The target concentration of remifentanil (1–5 ng mL−1) was tuned to maintain arterial pressure and heart rate within 20% of the preoperative values, but not below 1 ng mL−1. Nitrous oxide was not allowed because of its NMDA antagonistic properties. Controlled ventilation was adjusted to an end-tidal CO2 of 4.0–4.7 kPa. The train-of-four (TOF) Watch SX®  was stimulated on the ulnar nerve near the wrist at 15 min intervals. The target was at least ≥ 2-count response of TOF stimulation before starting baseline MEP monitoring.Before surgery, patients were asked to rate their pain using a numeric rating scale (NRS) from 0 (free of pain) to 10 (worst pain imaginable) by a member of the research team. Anesthesia was induced by continuous infusion of propofol with remifentanil through a target-controlled infusion pump .Patients were allowed to receive top-up dose of 10 mg rocuronium whenever spontaneous respiration or movement interfered with the surgery or when the surgeon requested. The muscles recorded for TOF and IOM were kept warm with a warm blanket to maintain optimal body temperature. Anemia, hypotension and hypoxemia were avoided. Partial neuromuscular blockade was not considered. After the main procedure, MgSO3 receptor antagonist —was used prior to starting PCA infusion, and preoperative dexamethasone (10 mg) was administered equally in both groups. Metoclopramide 10 mg, and ramosetron 0.3 mg were used as rescue antiemetics at least 6 h interval postoperatively.Thirty minutes before the end of surgery, to control initial postoperative pain, 1000–2000 µg fentanyl was used in all patients depending on age and weight in intravenous PCA pumps . For postoperative nausea and vomiting (PONV) prevention, prophylactic palonosetron—a second-generation 5-HTAll patients were given the same anesthetics and multimodal pain protocol. Preoperative analgesics were administered as needed on the ward with acetaminophen 650 mg, meperidine 25 mg, or fentanyl 50 mcg. Intraoperatively, remifentanil was infused, and PCA was started. For postoperative acute pain management, if necessary, rescue analgesics  were administered in the recovery room and in the wards. Once the patients resumed oral intake, acetaminophen 1300 mg and oxycodone 5 mg were administered every 6 h.The cumulative fentanyl consumption of PCA solution was recorded at 6, 24, and 48 h after surgery by the blinded investigator. Consumption of rescue analgesics and postoperative pain was also evaluated using an NRS at the same time period. The total amount of rocuronium and PONV, rescue antiemetics, and neurophysiological event logs were recorded. Computer-generated block randomization with blocks of size 4 was used and group assignment was kept in sealed envelopes. The preparation and administration of the parenteral drug as well as the collection and measurement of data were performed by doctors and nurses who were blinded to the study group allocations.After anesthesia induction, IOM was started using a Xltek Protektor IOM . The stimulating and recording electrodes were placed and baseline potential of MEP and SSEP waveforms were obtained, before initiation of the surgical procedures. According to the International 10–20 electroencephalogram system, needle-type electrodes were placed subcutaneously over the motor cortex region at C3 and C4 for left and right hemispheric stimulation ,10. BilaThe sample size was determined based on the result of the previous investigation . The conU test. Incidence data were compared using the X2 test or Fisher’s exact test according to the expected counts. All statistical analyses were performed using SPSS software , and statistical significance was defined as p-value < 0.05 (2-sided).Measured continuous variables are shown as absolute values, means (standard deviation), percentages, or median (interquartile range). Continuous variables were compared with Student’s t-test or the Mann–Whitney −1) during maintenance with TIVA  and 48 h  after surgery than in the control group (p = 0.024) and 32.3% (p = 0.038) less fentanyl via PCA on average during the 24 and 48 h after surgery . Adequate IOM recordings were obtained for all patients. Abnormal IOM results denoting warning criteria  were similar  and most of them recovered later  were higher in the Mg group.All the patients met the PACU discharge criteria within an hour of the surgery, and Aldrete score was similar. None of the patients showed any prolonged sedation, delayed recovery, respiratory depression, or electrocardiographic changes. No compatibility issues related to MgSO4 combined with fentanyl-based multimodal protocol reduces postoperative pain intensity and opioids consumption in patients undergoing major spine surgery with IOM, with maximal effects at 24 and 48 h postoperatively. Intraoperatively, TIVA with MgSO4 administration provided patient immobilization and adequate IOM without the need for additional NMB drugs.We demonstrated that intraoperative preventive MgSOp < 0.05), while the pain in the control group remained almost the same as the preoperative level of 4.4 at 24 h after surgery. As with our results, conventional opioid-based pain protocol in surgical patients often remain in suboptimal pain control [Pain intensity was significantly lower in the Mg group than in the control group at 24 and 48 h after surgery. Although the main component of preoperative pain is essentially different from postoperative pain, the Mg group showed a significant reduction in postoperative pain  [4 has more recently been proposed as one component in different multimodal analgesic concepts in the context of opioid-free anesthesia [4, which opioids alone cannot, to manage intraoperative nociception and postoperative pain. Magnesium, which has been proven for over three decades, can be a good, easy and inexpensive option, although not yet widely used, owing to its opioid-sparing and analgesia-potentiating effects. In a recent review paper, MgSO4 was also capable of reducing anesthetic requirements, which is consistent with many other previous studies [4 was between 30 and 50 mg kg−1, followed by continuous infusion of 8–20 mg kg−1, the meta-analysis yielded a result of −213 mg less for maintenance propofol, −112 mcg for remifentanil, which were favorable for the Mg group.Preventive MgSOde (33%) . In partesthesia . We show studies . Unfortu4; rocuronium is a competitive antagonist to acetylcholine, and magnesium-induced acetylcholine reduction from the presynaptic nerve terminal has the possibility of increasing the neuromuscular potency of rocuronium [4 made it possible to withhold further use of NMB drugs to ensure adequate depth of anesthesia. If the use of rocuronium should be minimized, MgSO4 may help reduce patient movement due to its muscle-relaxing effects. There were no cases where the apparent movement of the patient made the surgeon uncomfortable or jeopardized the patient’s safety during the surgery. MgSO4 has been reported to increase both the duration of intense neuromuscular blockade and the period of no response to nerve stimulation [The reason why the demand for top-up of rocuronium was lower in the Mg group (0 cases vs. 6 in control group) is because there is an advantages in the simultaneous use of rocuronium and MgSOcuronium . The myomulation .4 bolus used in previous studies [4 is safe or feasible during IOM we decided to administer a conservative dose, which is known to be effective (30–50 mg kg−1) in pain control. Unfortunately, the maximal magnesium levels were not measured in this study. Following the administration of the 4 g loading dose (vs. an average of 1.8 g in the current study), the serum magnesium levels rose sharply to double the baseline levels and achieved peak serum concentration (1.48–1.70 mmol L−1) at about 0.5 h; thereafter, the levels remained within a similar range (steady-state level) until 24 h [We administered only 60% of the MgSO studies ,23,24 totil 24 h . Since t4. MEP, SSEP, and EMG monitoring was completed in all patients  between the groups, despite differences in opioid usage. The low incidence in both groups may have benefitted from the appropriate stringent antiemetic strategy used in our institution. The TOF ratio before extubation was greater than 0.9 in all patients. No delayed emergence from anesthesia, hypoxemia, or critical respiratory events were reported. There were no differences in intraoperative hypotension, hypothermia, the use of phenylephrine, ephedrine and atropine.4, reducing the requirements of TIVA—which has often been demonstrated in previous studies [4 was used as essentially one addition to intraoperative opiates. Many multimodal analgesic regimens employ multiple drugs and presents a dizzying number of permutations and combinations to potentially study. Whether or not magnesium interacts with other typically used drugs for multimodal analgesia remains open to question. Lastly, long-term follow-up of pain control was not performed. As the types of surgeries were heterogeneous, a simple comparison of follow-up NRS between the groups would have been futile.The present study has several limitations. First, several types of surgery were included in this study, therefore, different pain-related outcomes may have had an impact on the main results. Especially, in relation with spinal surgical level, lumbar surgery is known to be quite different regarding pain from the cervical surgery. In our subgroup analysis, fentanyl consumption and pain scores were lower in cervical surgeries at postoperative 24 and 48 h than non-cervical surgeries. Second, the infused doses of propofol or remifentanil were not collected. Therefore, we could not observe/prove the anesthetic-sparing benefit of MgSO studies ,19,23. C4 reduces postoperative pain intensity and opioids consumption at 24 and 48 h after surgery. The intraoperative benefit of MgSO4 is the lack of any interference to neurophysiological monitoring without the need for additional NMB drugs while maintaining depth of block. With these reasons, we recommend that anesthesiologists and surgeons consider MgSO4 as an essential part of multimodal analgesic therapy to improve patient safety and outcomes for the patients who are undergoing painful surgery.In conclusion, preventive MgSO


Current pharmacological intervention for the cancer-related pain is still limited. The aim of this study was to explore whether repetitive transcranial magnetic stimulation (rTMS) could be an effective adjuvant therapy to reduce pain in patients with advanced non-small cell lung cancer (NSCLC).This was a randomized, sham–controlled study. A total of 41 advanced NSCLC patients with uncontrolled pain  were randomized to receive active  (n = 20) or sham rTMS (n = 20) for 3 weeks. Pain was the primary outcome and was assessed with the Numeric Rating Scale (NRS). Secondary outcomes were oral morphine equivalent (OME) daily dose, quality of life , and psychological distress . All outcomes were measured at baseline, 3 days, 1 week, 2 weeks, and 3 weeks.p < 0.001, Cohen’s d =1.135) and week 3 . The OME daily dose, physiology and psychology domains of WHOQOL-BREF scores, as well as the HAM-A and HAM-D scores all were significantly improved at week 3 in rTMS group.The pain intensity in both groups decreased gradually from day 3 and decreased to the lowest at the week 3, with a decrease rate of 41.09% in the rTMS group and 23.23% in the sham group. The NRS score of the rTMS group was significantly lower than that of the sham group on the week 2 (Advanced NSCL patients with cancer pain treated with rTMS showed better greater pain relief, lower dosage of opioid, and better mood states and quality of life. rTMS is expected to be a new effective adjuvant therapy for cancer pain in advanced NSCLC patients. Recently, the incidence of cancer in the world is increasing year by year . AccordiThe WHO three-step ladder for cancer pain, which is widely used in clinic, follows the rule that the choice of analgesic drugs were based on the pain intensity: step I-nonsteroidal anti-inflammatory drugs  to mild pain, step II- weak opioids  to moderate pain, and step III- strong opioids (morphine or oxycodone) to severe pain . MeanwhiIn the past two decades, neuromodulation technique has gradually become a new direction of pain treatment. Repetitive transcranial magnetic stimulation (rTMS) is one of the most commonly used non-invasive neuromodulation techniques in clinic . rTMS coIn addition, patients with cancer pain are often complicated with depression, which aggravates the complexity and difficulty of cancer pain treatment, and that is also one of the main reasons for poor analgesic effect . Many stThis trial was a randomized, double-blind, parallel-group, sham-controlled clinical trial, approved by the Ethics Committee of Chongqing Cancer Hospital and was registered (ChiCTR.org.cn identifier: ChiCTR 2000029130). All patients provided written informed consents before enrolling. After completing consent forms, patients were randomly assigned to either the rTMS group or the sham stimulation group using a block randomization scheme. An independent investigator carried out the randomization. Two independent, trained assessors and enrolled patients were blinded to the group assignments.NSCLC patients with cancer pain were enrolled consecutively from January 2020 to March 2021. The inclusion criteria were: 1) confirmed diagnosis of advanced NSCLC by pathology or cytology, 2) accompanied with pain symptoms, and confirmed as cancer pain by oncologist, 3) experienced worst pain score≥4  at the site of pain, 4) age between 18 and 70 years, 5) with clear awareness, and could cooperate to evaluate pain severity, 6) estimated that the survival time is more than 3 months, 7) with completion of signed informed consents, and voluntary participation in this study. The exclusion criteria were: 1) brain tumor patients 2) history of seizure, 3) implanted pacemaker, stent and other metal substances 4) acute pain anywhere in the body due to other diseases, 5) serious psychiatric diagnoses All the participants were treated with medications according to WHO three-step principle. In order to facilitate the statistics of the dosage of opioids in patients with cancer pain, morphine sulfate controlled-release tablets or oxycodone hydrochloride sustained-release tablets were used for analgesia in this study .rTMS was applied with a magnetic stimulator (CCY-I) with a figure-of-eight coil . The rTMS protocols used in this study were in accordance with the safety guidelines for rTMS applications . ParametThe pain intensity was assessed at 1 day before rTMS treatment (T0), 3 days (T1), 1 week (T2), 2 weeks (T3) and 3 weeks (T4) after first rTMS treatment. Mood status and quality of life were evaluated only at T0 and T4 timepoints. 1. NRS. The NRS consists of 11-point scale, of which 0 represents no pain and 10 represents the strongest pain imaginable, which has been recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) guidelines .The secondary outcomes were as follows:1. Oral morphine equivalent (OME). The conversion method of OME refer to the previous literature reports: oral oxycodone hydrochloride is 1:1.5, intravenous morphine is 1:3 converted to oral morphine .2. WHO Quality of Life-BREF (WHOQL-BREF) . Quality3. Hamilton Anxiety Scale (HAM-A) . HAM-A w4. Hamilton Depression Scale (HAM-D) . HAM-D wP<0.05 (two-sided test) and an effect size of r = 0.45, a total minimum sample size of 38 patients was required. Considering an estimated 10% dropout rate, the sample size was inflated to 21 participants per group (N = 42).Sample size was estimated using the G Power v.3.1 statistical tool. To achieve a statistical power of 85% with statistical significance at t tests or chi-squared tests. A repeated-measures analysis of variance (rmANOVA) was used to analyze the data for the efficacy of rTMS, with time as the within-subjects factor and treatment as the between-subjects factor. Post hoc analyses were performed with Bonferroni adjustment for further multiple comparisons. P<0.05 were considered statistically significant. The percentage of change within each individual was calculated as follows: [(post-treatment - pre-treatment score)/(pre-treatment score)] *100.Statistical data analyses were performed using IBM SPSS . Baseline group differences were explored with A total of 63 advanced NSCLC patients with cancer pain were screened and 42 eligible patients were enrolled in the study Figure 2P = 0.04, Cohen’s d =-0.735) and week 3   in the rTMS group and 6.37  in sham group. The pain intensity in both groups decreased gradually from day 3 and decreased to the lowest at the week 3, with a decrease of 41.09% in the rTMS group and 23.23% in the sham group. The NRS score for the rTMS group was significantly lower than that of the sham group on the week 2 (- 0.822) Figure 3P = 0.02, Cohen’s d = 0.796), while the sham group both were significantly higher than that of baseline   Figure 4P = 0.02, Cohen’s d = 0.796 and P = 0.031, Cohen’s d = 0.746, respectively). . Figure 4P = 0.005, Cohen’s d = -0.949 and P = 0.011, Cohen’s d =- 0.869, respectively). However, there were no significant improvements in the sham group  for the publication of any potentially identifiable images or data included in this article.YT and Y-sL conceived and designed the study. YT and HC analyzed the experimental data and drafted the manuscript. YT, M-lT, and YZ collected the experimental data. Y-sL, S-lX, YL and X-hJ revised the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.This study was supported by the National Nature Science Foundation of China (81902302) and Chongqing Natural Science Foundation (cstc2018jcyjAX0772).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.


To summarize the technical points and clinical effects of percutaneous balloon compression (PBC) in the treatment of primary trigeminal neuralgia.The clinical data of 13 patients with trigeminal neuralgia who received PBC from April 2020 to July 2021 were retrospectively analyzed. VAS, VRS-4 and PPI were used to evaluate the postoperative pain relief. Different postoperative complications were analyzed.All patients had a smooth operation, the inflation volume of the balloon was 0.7 ml, the average compression time was 120 s, and there was no balloon rupture during the operation. On the day after operation, 12 patients (92.3%) had complete pain relief, and 1 patient (7.7%) was not satisfied with pain relief, but the pain disappeared 2 weeks after the operation. After operation, there were 12 patients with facial numbness in the affected side (92.3%), 3 patients with masseter muscle weakness (23.0%), 1 patient with herpes around the mouth (7.6%), and 1 patient with diplopia (7.6%).PBC is an effective minimally invasive surgical method for the treatment of primary trigeminal neuralgia. It is suitable for the elderly and infirm people, those who cannot tolerate general anesthesia or are afraid of surgery, and patients who had undergone surgery but relapsed after surgery. However, it is necessary to pay attention to the serious facial numbness and postoperative masticatory weakness. These discomforts are generally relieved after half a year. Trigeminal neuralgia is the most common facial neuralgia in clinic. The clinical onset is mainly unilateral pain. Most of the initial pain is a short-term phenomenon, which only appears for a few seconds or minutes. After the initial pain, it may be accompanied by a period of painless remission, and then it will attack again, with typical paroxysmal pain, severe pain, and discharge-like pain , 2. UndeIn recent years, with the continuous development of imaging technology and nerve intervention, surgical treatment has gradually developed to be more mature. In 1983, Mullan's team first used percutaneous puncture to treat diseases, and achieved certain results. This laid the foundation for the germination of percutaneous balloon compression (PBC) in our country . The priBased on this, we observed 13 patients with primary trigeminal neuralgia in our hospital from April 2020 to July 2021, and discussed the therapeutic effect of PBC. The report was as follows.From April 2020 to July 2021, 13 patients with primary trigeminal neuralgia were treated in our hospital. Diagnosis criteria : (a) PaiTrigeminal cardiac inhibitory reflexes have often occurred during PBC procedures, manifesting as transient but pronounced bradycardia during balloon filling. Before foramen ovale puncture, giving patients an appropriate amount of atropine and remifentanil could alleviate this reaction. Instructed patients to take supine position, and performed routine preoperative disinfection and towel spreading. Heart rate, blood pressure, and blood oxygen saturation were monitored in the whole process, and ambulatory arterial blood pressure was monitored in real time. Tracheal intubation, general anesthesia and breathing control, neck slightly extended, with the patient's nose as the highest point, and semilunar ganglion puncture surgery were carried out under the instructions of cross-line screen. (1) 64-slice CT skull reconstruction was performed before surgery, Hartel's anterior approach to the semilunar ganglion of trigeminal nerve was used, and the foramen ovale was the puncture target . The M-sVAS, VRS-4, and PPI were used to evaluate the postoperative pain relief. Complete pain relief: VAS < 10 points, VRS-4 0 grade or PPI 0 grade; Pain relief: VAS 10-40 points, VRS-4 1 grade, or PPI 1-2 grade: pain relief unsatisfactory: VAS ≥ 40 points, VRS-4 ≥ 2 grade, or PPI ≥ 3 grade. Different postoperative complications were analyzed, including facial numbness, masseter muscle weakness, herpes around the mouth, diplopia and so on.All patients had a smooth operation, the inflation volume of the balloon was 0.7 ml, the average compression time was 120 s, and there was no balloon rupture during the operation. On the day after operation, 12 patients (92.3%) had complete pain relief, and 1 patient (7.7%) was not satisfied with pain relief, but the pain disappeared 2 weeks after the operation. After operation, there were 12 patients with facial numbness in the affected side (92.3%), three patients with masseter muscle weakness (23.0%), one patient with herpes around the mouth (7.6%), and one patient with diplopia (7.6%). Follow-up was conducted 3 months after operation, among which 13 cases were effectively followed up, and 1 patient had delayed effect due to the gradual reduction of oxcarbazepine after operation. The pain of this patient improved 1 month after operation, and the total effective rate was 92.3%. Twelve patients (92.3%) had slight numbness in the side of operation, and one patient had severe numbness in the side of operation with ulcer of the affected side, which was photophobia, which had certain influence on the quality of life of patients.At present, the surgical treatment of trigeminal neuralgia can be roughly divided into four categories: MVD, stereotactic gamma knife, PBC, and radiofrequency thermocoagulation with glycerol injection . After MEarly balloon compression surgery lasts for a long time. Although the pain relief rate is high and the effective duration is long, facial sensory disturbance and myasthenia gravis tend to be severe and last for a long time, and there are many postoperative complications, so it is not recommended that the compression time be too long . The shoPBC is a minimally invasive, safe, effective, and minimally invasive treatment with minor complications. The indications of PBC for trigeminal neuralgia are: (1) Those who are afraid of craniotomy and refuse craniotomy; (2) Elderly and infirm people with more basic diseases; (3) Patients with poor general health; (4) Patients who have side effects on drugs; (5) Patients with ineffective microvascular decompression or postoperative pain recurrence; (6) Patients with secondary trigeminal neuralgia who have poor craniotomy treatment effect or can't tolerate drug , 26. ComThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Pingkuang General Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.HW was the instructor of the study. CC and DC were responsible for the design of the study. FL and SH were responsible for collecting clinical data. WD and JW were responsible for data evaluation and recording. WC was responsible for data statistical analysis and papers of writing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Non-specific chronic low back pain (NSCLBP) is a major public health and global socioeconomic burden associated with a complex interplay of biopsychosocial factors. Despite scientific signs of progress, treatment of NSCLBP often tends to stick to a biomechanical model, without targeting psychological and social factors. To enhance the clinical efficacy of usual physiotherapy for NSCLBP, the development of clinical strategies is to be pursued. This study aims to assess the effectiveness of multidimensional physiotherapy based on a biopsychosocial approach compared to usual care physiotherapy, on clinical findings and electroencephalography spectrum in non-specific chronic low back pain.This study is a triple-blind, two-arm (1:1) randomized controlled trial with a 4 months follow-up. Seventy NSCLBP patients will be randomly allocated to either the experimental  or the active control group ; each group will receive 6 weeks of physiotherapy. The main outcome is pain and secondary outcomes are brain function, quality of life, disability, lumbar flexion range of motion, and psychosocial correlates. Assessment will be performed at baseline, post-treatment, and at 1 and 4 months follow-up.Findings may provide evidence on the effectiveness of multidimensional physiotherapy on clinical findings and brain characteristics and might provide evidence towards showing the role of brain and biopsychosocial factors on chronic pain.NCT04270422, Registered on 17 February 2020, IRCT Identifier: IRCT20140810018754N11ClinicalTrials.gov  Low back pain (LBP) is the most frequent self-reported, costly, and debilitating type of musculoskeletal pain that imposes significant health and economic problems , 2. The The perception of pain is the result of a complex, dynamic system. The relationship between nociceptive information and pain is profoundly impressed by affective and cognitive factors. A specific region of the cortex that is responsible for pain processing has not yet been found; however, a complex network of brain regions known as a pain matrix has been identified. According to the neuromatrix theory of pain, chronic pain is considered a multidimensional experience and needs new forms of multidimensional treatment. The area of the brain involved in pain experience is a large and widespread network of neurons that consists of loops between the thalamus and cortex, as well as between the cortex and limbic system. These loops are not just for pain perception but also are involved in other sensory, motor, and cognitive functions , 16. FunAlthough growing knowledge exists on the peripheral and spinal neuronal mechanism of pain chronification processes, little is known about the accompanying neural mechanisms of chronic pain . Recent Various non-surgical treatments have been suggested for NSCLBP. These include non-steroidal anti-inflammatory drugs, patient education, hydrotherapy, manual therapy, physiotherapy, acupuncture, and cognitive-behavioral therapy , 9. PhysIn the present study, the effect of a multidimensional treatment based on the biopsychosocial approach will be compared with a usual care physiotherapy treatment on pain and function, brain function, and pain psychosocial correlates in chronic nonspecific low back pain.Primary objective: Effect of a multidimensional treatment on pain compared to usual care physiotherapySecondary objectives:Effect of a multidimensional treatment on brain function compared to usual care physiotherapyEffect of a multidimensional treatment on lumbar flexion ROM compared to usual care physiotherapyEffect of a multidimensional treatment on quality of life compared to usual care physiotherapyEffect of a multidimensional treatment on psychological correlates of pain compared to usual care physiotherapyThe overall objective of this study is to demonstrate the impact of multidimensional treatment in the management of CNSLBP. The specific objectives are:The present study is a 4-month, triple-blind, randomized, controlled, parallel trial that will be carried out between December 2020 and November 2022. Patients with NSCLBP will be enrolled in a 6-week physiotherapy program organized in IRAN . More specifically multidimensional physiotherapy will be compared to usual physiotherapy. The outcome will be assessed at baseline, after 6 weeks of treatment, and at 1 and 4 months follow-up. The participant flowchart through the study is shown in Fig. The study population will include approximately 70 CNSLBP patients. Participants will be recruited by the participating research groups from the Iran University of Medical Science’s hospitals and via adverts. This study will be conducted in the physiotherapy clinic in the School of Rehabilitation Sciences at the Iran University of Medical Sciences, Tehran, Iran.Patients will be eligible for this study if they have the following: age between 18 and 50, permanent or intermittent local pain between L1 to gluteal fold without any radicular pain for 3 months or more and between 3 and 7/10 based on the Numeric Rating Scale (NRS), disability based on the Oswestry Disability Index (ODI) between 20 and 60, fear of movement based on the Tampa scale for Kinesiophobia > 37, elementary level of education, and Native Persian speaking. The most important exclusion criteria are as follows: any evidence of specific medical diagnosis include spondylolisthesis, fracture, tumor, or inflammation disease; rheumatoid disease, fibromyalgia, neuropathy, and progressive neurological disease; history of headache, dizziness, nausea, epilepsy, migraines, and mental disorders; history of lumbar surgery in the past 3 years; the Beck Anxiety Inventory > 26; the Beck Depression Inventory II > 29; pregnancy; and having other therapies during the present research. The drop-out criteria are as follows: the presence of any condition that interferes with the intervention or assessment, participate in any other treatment during the interventions, inclusion or exclusion criteria are violated, and a patient requests to be removed from the trial.At an in-person meeting, the investigator who performs the assessments will explain the study details and clarify any questions. Then, the participant will be asked to sign the consent form. It consists of the details, such as the title of the study, names of investigators, registered information, research background, how the study was to be conducted, what the participants should do in the study, treatment plans, and obligations.Not applicable.After obtaining written informed consent, baseline measurements will be performed. Participants will then be randomized to either active control or experimental group (1:1 ratio) using a stratified block allocation with stratification factors being gender  and with a block size of four. Randomization will be done at the Iran University Medical Sciences by an independent investigator using WinPepi (version 11.65). The randomization schedule will be known only to 1 investigator who is not involved in recruiting participants. The randomization will be concealed from patients and the other investigators involved in patient assessments, treatments, and analyses.All interventions are performed by two expert and trained physiotherapists with 6 years of work experience in the treatment of LBP patients. The intervention lasts six weeks and each group will receive 12 sessions of physiotherapy.Psychoeducation on pain based on the book “Explain Pain”  and set Anxiety management: The goal of this session is to identify signs and symptoms of anxiety and to learn coping skills to improve the individual’s functioning in the area of anxiety.Interpersonal conflict management: The goal of this session is to have individuals learn how to manage conflict more effectively and increase effective skill use in relationships.Problem-solving training: The goal of this session is to promote problem-solving strategies in complex situations and with others.Coping strategy training: The goal of this session is to deliver insight and information about coping strategies for chronic pain and to learn coping skills for improving patient functioning in the areas of common defense mechanisms.Pain flare-ups management: This session is run to identify triggering events and typical reactions and promote coping skills with the fear and avoidance conditioning.Medication abuse management: This session is held to learn coping skills to improve the individual’s functioning in accepting reality and learn coping skills to improve the individual’s functioning in chemical abuse.Enhancing one’s ability to cope with labeling and stigma: The goal of this session is to give insight and understanding into the effects of stigma and learn coping skills to improve the individual’s ability to cope effectively with stigma.Empowering one to create a daily sleep routine: The goal of this session is to learn coping skills to improve the individual’s functioning in the areas of building and maintaining healthy sleep patterns.Training relaxation techniques .Patients in the experimental group will receive multidimensional physiotherapy include psychoeducation based on cognitive behavioral therapy (CBT), lifestyle education, graded exposure, postural correction exercise, and electrotherapy. Twelve 30-min psychoeducation sessions consist of the following sessions:2 will be performed using a 5-cm square applicator on the paravertebral muscle where the patient reports the most pain, for 5 min. The treatment in this group is twelve sessions and will be performed twice a week.Patients will also receive recommendations for lifestyle modifications, such as encouraging active living and a gradual increase in activity levels, improving the work environment, and training on how to perform daily and work activities correctly. Other treatments include postural correction and training of the necessary exercises, as well as the gradual initiation of movements and activities that the patient is afraid of, and by asking the patient to perform hierarchical activities that he or she fears. The first step is to identify the movements that the patient is afraid of. The exercise begins with a movement that the patient has the least fear of, and that movement begins with the simplest state and the lowest level with the patient least feared, and gradually becomes more difficult , 35. All2 will be performed using a 5-cm square applicator on the paravertebral muscle where the patient reports the most pain, for 5 min. The treatment in this group is twelve sessions and will be performed twice a week.For patients in the active control group, treatment will include education, trunk general exercises, and electrotherapy. Education in this group includes an explanation of the basic biomechanical anatomy of the spine, common causes of spinal pain, pain processing, ergonomic advice on how to perform daily activities, and postures , and training for postural correction exercises. General trunk exercise will focus on abdominal and paraspinal muscles to improve blood flow, mobility, strength, and endurance in each session, and the patient will be asked to perform exercises in each session . The intNot applicableNot applicableRelevant concomitant care and interventions are prohibited during the trial.No physical or psychological damage has been predicted in this study; however, any possible problem, either physical or mental, which arises during the research, due to the treatment will be reported to the Iran University of Medical Sciences ethics committee. The study team will give priority to unpaid examination and treatment according to the regulations of the Ethics Committee.The pain will be the primary outcome. The secondary outcomes will include quality of life, fear avoidance beliefs, kinesiophobia, pain catastrophizing, disability, forward flexion ROM, and absolute and relative power of the frequency spectrum of EEG.A Numerical Rating Scale (NRS) for pain ranging from 0 “no pain at all” to 10 “worst imaginable pain”  .The pain will be assessed through a self-reported questionnaire. This questionnaire will be used for pain assessment at baseline, post-treatment, and at 1 and 4 months follow-up:Self-reported pain catastrophizing based on the Pain Catastrophizing Scale. The Pain Catastrophizing Scale (PCS) will be included to assess catastrophic thinking about pain. It consists of 13 items describing different thoughts and feelings that individuals may have when experiencing pain. Items are scored on a 5-point scale, 0 “not at all” to 4 “all the time.” A general score and scores on 3 subscales  will be obtained; higher scores indicate more severe catastrophic thoughts about pain , 39.Self-reported kinesiophobia based on the Tampa scale of Kinesiophobia. The Tampa Scale for Kinesiophobia (TSK) is a 17-item questionnaire that will be used to measure the fear of(re) injury due to movement. Scores range from 17 to 68, with scores ≤ 37 suggesting low fear of movement and scores > 37 indicating high fear of movement. The TSK-Persian version that will be used in this study is shown reliable and valid , 41.Self-reported fear avoidance beliefs based on the Fear Avoidance Beliefs questionnaire. The Fear Avoidance Beliefs questionnaire (FABQ) is a 16-item self-reporting questionnaire evaluating patient’s attitudes and beliefs toward the effect of physical activity and work on their pain. The FABQ is divided into two subscales which are designed to assess beliefs about work and physical activity. The agreement of patients with each item will be scored by a 7-point Likert scale, ranging from 0 (completely disagree) to 6 (completely agree). Higher FABQ scores indicate higher fear-avoidance beliefs , 43.Patients will complete some questionnaires at baseline, after 12 treatment sessions, and at 1- and 4-month follow-ups. The following standardized and reliable questionnaires (Persian version) will be used to measure psychological factors that may interfere with pain:The 36 Health Status Survey (SF-36) will be used to assess functional status and well-being or quality of life. The SF-36 contains 8 dimensions . The overall value ranges from 0 to 100, with improvement as scores increase. The psychometric properties of the SF-36 are well-characterized in a wide variety of patient populations –46.Self-reported disability based on the Oswestry Disability Index Questionnaire. The Oswestry Disability Index is currently considered for measuring the degree of disability in patients with low back pain. The questionnaire contains ten topics concerning the intensity of pain, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel. Each question is scored on a scale of 0–5 with the first statement being zero and indicating the least amount of disability and the last statement is scored 5 indicating the most severe disability. The scores for all questions answered are summed and a higher score indicates greater disability , 48.Forward flexion ROM will be measured by the third finger to ground distance by a meter.In this study, EEG will be recorded  with 64 channel amplifiers  according to the international 10/20 system, from 19 Ag/AgCl surface electrodes and a diameter of 8 mm electrode sites distributed throughout the whole head of the participants. The 15 electrodes will be placed in Fp1, Fp2, F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2. TCD will be performed in the above areas in the frequency range of delta, theta, alpha, beta, and gamma, and the relative and absolute power levels of each will be evaluated. A reference electrode is placed on the mastoid process and a ground electrode is placed on the Fpz region. To record vertical and horizontal electrooculogram, a pair of electrodes above and below the right eye and another pair are placed on either side of each eye. With the electrooculogram and the O1 and O2 electrodes, blinking and eye movement artifacts are controlled. EEG will be recorded under two conditions: while subjects rested with their eyes open for 3 min and while they will forward flexed in 20 s.This study will be carried out between December 2020 and November 2022. Figure Sample size calculations were performed with G*Power 3.1.9.4  based on the therapy effects on pain and accounting for a 10% loss to follow-up after 4 months. Calculations were based on one-tailed testing with alpha set in 0.025, partial η2 = 0.04, and the desired power of 0.95. The allocation ratio (N2/N1) was defined as 1, resulting in 35 patients in the intervention group and 35 in the control group.We will recruit participants through practitioners from Iran University of Medical Science’s hospitals and clinics. Also, we will use advertising posters in each center and online advertisements on the media. Then, the participants will be referred to the outpatient orthopedic rehabilitation center at the School of Rehabilitation Sciences. They will be screened for inclusion and exclusion criteria and make the final decision regarding the eligibility of the patients.After eligibility has been confirmed, patients will be informed about the study comparing two physiotherapeutic treatment options. After obtaining written informed consent, baseline measurements will be performed. Participants then will be randomized to either active control or experimental group (1:1 ratio) using a stratified block allocation with stratification factors being gender  and with a block size of four. Randomization will be done at the Iran University Medical Sciences by an independent investigator using WinPepi (version 11.65). The randomization schedule will be known only to 1 investigator who is not involved in recruiting participants.The randomization will be concealed from patients, and the other investigators involved in patient assessments, treatments, and analyses.Allocation sequence, participant enrollment, and participant assignment to interventions will be performed by an independent investigator who is not involved in assessments, interventions, and any other part of research.The present study is a triple-blind randomized controlled trial. The patients, investigator, and outcomes assessor will be blind to the treatment groups. To keep patients unaware of any expected treatment group benefit, patients will be informed that the effect of 2 well-established therapies is to be evaluated. An independent and blinded assessor will perform the baseline and follow-up assessments. The researcher who will perform the statistical analyses will not be involved in taking the measurements. The treating physiotherapists will be blinded to the results of the measurements and questionnaires.Not applicableNot applicableNot applicableNot applicableNot applicableNot applicableD) will be calculated as are effect sizes.Data analysis will be performed using SPSS (version 22) and STATA (version 14.2). Baseline characteristics will be summarized with standard descriptive statistics. Categorical variables will be described with percent and counts. Continuous variables will be described with means and standard deviations. Statistical analysis of the primary and secondary outcomes will be based on the intention-to-treat principle including all randomized patients using an analysis of variance/covariance (ANOVA/ANCOVA). A model including baseline as continuous covariate and group as fixed factors will be used with using Bonferroni post hoc analyses and adjusting for differences in patients’ characteristics at baseline where appropriate will be done. Subgroup analysis of pain catastrophizing variable will be done. For all statistical tests, the significance level will be set at 0.05. Mean difference and standardize Mean difference and their 95% confidence intervals , and we are hopeful that this 4-month prospective trial may contribute towards refining guidelines for good clinical practice and may be used as a basis for health authorities’ recommendations.This trial was using protocol version 1.0  at the time of this submission. Recruitment started on December 1, 2020, and is expected to be completed on November 30, 2022.


Domain-general, patient-reported symptoms can robustly classify current severity of chronic pain and predict future pain levels. Chronic pain conditions present in various forms, yet all feature symptomatic impairments in physical, mental, and social domains. Rather than assessing symptoms as manifestations of illness, we used them to develop a chronic pain classification system. A cohort of real-world treatment-seeking patients completed a multidimensional patient-reported registry as part of a routine initial evaluation in a multidisciplinary academic pain clinic. We applied hierarchical clustering on a training subset of 11,448 patients using nine pain-agnostic symptoms. We then validated a three-cluster solution reflecting a graded scale of severity across all symptoms and eight independent pain-specific measures in additional subsets of 3817 and 1273 patients. Negative affect–related factors were key determinants of cluster assignment. The smallest subset included follow-up assessments that were predicted by baseline cluster assignment. Findings provide a cost-effective classification system that promises to improve clinical care and alleviate suffering by providing putative markers for personalized diagnosis and prognosis. Chronic pain is a global epidemic reflecting a health care crisis for the person suffering from it, their family, and society as a whole   Mechanistically, we aimed to uncover whether the multivariate pattern of symptoms and pain-specific measures characterizing each identified cluster reflects a general graded scale of severity or a differential pattern. Furthermore, given the centrality and comorbidity of mental health related factors with chronic pain, predominantly negative affect–related symptoms such as anxiety, depression, and anger . Similarly, none of the demographic characteristics were significantly associated with any specific cluster (P > 0.12). This supported the reliability and validity of the identified clusters. However, two critical questions arose that we addressed in the following two sections.Although the pattern of severity also manifested in the number of self-reported body segments in pain, with Cluster3 indicative of potential widespread and/or overlapping chronic pain conditions, we found no significant associations between specific body regions (table S2 and fig. S1) and any of the clusters  and had a correlation of r = −0.78 with the PROMIS Global Health Mental subscale . To estimate the degree by which the underlying data structure of the clustering symptoms reflect a mental health–related construct, we calculated the Pearson correlation coefficient between the first three principal components derived by the above mentioned PCA and the PROMIS Global Health Mental subscale. To note, this measure was available for subscale . The corTo further illustrate this point, we split the range of possible PROMIS Global Health Mental scores into tertiles and labeled them in order of severity  to match the clustering symptoms’ cluster solution labeling. We then quantified the level of congruence between these two sets of labels by counting how many patients were assigned by each of the solutions to the same cluster label and how many were mismatched between the clusters . The levn = 879, 69.05%) remained within their same cluster between the two time points, there were movements across clusters  or Cluster1  and from Cluster2 to Cluster1 ; and 214 patients (16.81%) had a worsening in their condition and moved from Cluster1 to Cluster2  or Cluster3  and from Cluster2 to Cluster3 . We compared the total movement of patients across clusters between time points  to a bootstrapped distribution of patients moving across clusters within potential measurement error .To provide an estimate of what entails a change in cluster assignment, we calculated the average of absolute change across the nine clustering symptoms’ scores between the two time points, as well as the average number of symptoms that had an absolute change beyond the estimated measurement error. We compared these values between the group of In our study, we offer a novel biopsychosocial-inspired approach to classify patients with chronic pain, resulting in the identification of three robust idiosyncratic groups of patients and generating putative markers that can classify current and predict future severity of chronic pain in a graded manner, regardless of their formal diagnosis or their underlying etiology. We applied a data-driven clustering algorithm on multidimensional self-reported symptom assessments that are agnostic to pain. These assessments were collected through CHOIR, Stanford’s registry-based learning health care system  to reduce time and patient burdens, and is already in wide usage in many settings, even beyond chronic pain, thus allowing others to take a similar approach as ours or to engage with our freely available cluster classifier (https://git.io/Jn8m1) for additional utilization in clinical and research settings. Moreover, previous findings show associations between various PROMIS measures and potential biomarkers in both pain and nonpain clinical contexts , a registry-based, learning health care system that administers an electronic survey assessing self-reported demographic information, pain characteristics, and multiple domains of health status in real-world clinical settings (Data were collected using Stanford University’s CHOIR (settings  (34). PaData analyzed were from a retrospective review of all collected surveys since CHOIR’s inception in October 2013 through August 2019. Our initial data extraction included 24,389 records, from which we removed records based on the following criteria: noncompleted or test records (6002), missing data in any of the nine measures used for clustering , duplicated records (136), and age below 18 years (62). From the resulting 16,538 surveys belonging to 16,538 different patients, we extracted a longitudinal dataset of 1273 patients with a follow-up survey between 3 and 12 months later and again with a minimal requirement of having complete data for the nine assessments used for clustering at both time points. We chose this time frame since 3 months is considered the minimal threshold for diagnosing primary chronic pain , higher T scores reflected a better condition. Further details regarding measure development and validation are available at www.healthmeasures.net.Ultimately, a standardized Pain-specific measures were used independently of the clustering process to validate the diagnostic-like nature of the data-driven generated clusters in terms of pain-related constructs. A composite score of pain intensity was calculated by averaging three self-reported pain intensity measures. These measures used a common and validated  (81). ThAdditional measures assessed using PROMIS instrumentation included pain interference with daily life activities, pain behavior, and physical function  are fused to form a superordinate cluster until all observations belong to one single cluster. Two parameters important for this process are a distance metric that determines how similar observations are to each other and a linkage method to fuse similar observations. The agglomerative coefficient can then assess how tightly packed each cluster is within a cluster solution. We used the Euclidian distance metric combined with the Ward linkage method as it optimized the agglomerative coefficient compared to four other linkage methods (table S5).k  and subsequent Univariate analyses as described above were used to examine differences in clustering symptoms and in pain-specific measures between clusters as assigned at baseline, using data from the follow-up. To control for time-related effects, we added the number of days between the two assessments as covariate. This provided prognostic-like validation of the clusters.T score drops below a specified level of 3.0 T score metric points (T score for each patient and for each of the clustering symptoms at baseline, within that error threshold, i.e., ± 3.0 T score points. The nearest centroid classifier was implemented on each patient’s simulated data to assign a cluster. We then assessed movement across clusters between the simulated dataset and the follow-up dataset and calculated the number and subsequently the percent of patients moving across clusters. This procedure was repeated 1000 times to generate a bootstrapped distribution of the percent of patients moving across clusters within measurement error. This distribution allowed us to calculate the probability of the actual percent of patients moving across clusters between the baseline and follow-up time points being attributed to measurement error.Next, the nearest centroid classifier was implemented on the follow-up dataset to assess patient movement across clusters between the baseline and follow-up time points. Also, we used a bootstrap procedure (


Introduction: Acute abdominal pain can be the first manifestation of a hernial pathology. The estimated risk of incarcerated hernia is 1%-3% over a person's lifetime. Therefore, hernial orifice examination should be conducted routinely, especially in cases of abdominal pain. We hypothesized that physical examination of hernial orifices is not routinely performed and documented in patients presenting with acute abdominal pain.Methods: A retrospective chart review of 100 patients who were evaluated for abdominal pain over a three-month time frame at our institution.Results: From the 100 reviewed cases, the hernial orifice examination was performed in two cases by an Internal Medicine or Emergency Medicine physician (2%). Out of the eight cases with General Surgery consultation, only one case had hernial orifices examination (12.5%). In the 10 cases with Gastroenterology consultation, not a single case had hernial orifice examination.Conclusion: We demonstrate that hernial examination is infrequently performed in clinical practice and suggest that emphasis should be placed on the efficient performance of physical examination and maintain the art of physical diagnosis. The etiology of acute abdominal pain can vary in severity. Abdominal pain can be the first manifestation of the acute abdomen, which requires aggressive management, including surgical interventions to prevent devastating consequences. A well-performed history and physical examination may promote early diagnosis and proper management -4. A hypThe primary approach in acute abdominal pain is to narrow the differential diagnosis using history and physical examination and determine the best next step. A thorough physical examination also helps with avoiding unnecessary paraclinical testing and thereby delays in diagnosis and management. There are four components to an abdominal physical examination  along with some specialized maneuvers which are highly predictive of certain diseases. Something as basic as a visual inspection can provide a wealth of information. A complete physical examination in patients with abdominal pain requires examination of hernial orifices -4.Hernia as a medical condition has been mentioned in history as early as the fifth century. Hippocrates referred to this pathology as "etru rhexis," which means rupture of the abdominal wall . The preWe hypothesized that physical examination of hernial orifices is not routinely performed and documented in patients presenting with acute abdominal pain.This study entails a retrospective chart review of 100 patients presented with abdominal pain at Saint Peter's University Hospital, New Brunswick, NJ, USA, in the period February 24, 2020 to May 31, 2020. The physical examination section of the ED, admission history and physical, and consultant notes were reviewed. The study's protocol was approved by the Committee for the Protection of Human Subjects in Research at Saint Peter's University Hospital. For the sample selection, specific inclusion and exclusion criteria were used. We included patients who presented with abdominal pain as chief complaint during the selected period. Specifically, inpatients, patients under observation, and patients evaluated and discharged in the Emergency Department (ED patients) were included. In addition, documentation of physical examination performed by emergency physicians, Internal Medicine residents/attendings, gastroenterology fellows/attendings, and surgery residents/attendings was reviewed. The documentation was examined carefully for evidence of hernial orifice examination. Specifically, we searched for evidence of ventral, groin hernias, or pelvic hernial examination. We excluded patients <18 years old, patients without abdominal pain as chief complaint, patients presenting for elective outpatient procedures, and those admitted by the study's authors.One hundred patient cases were included in this study. Of the 100 patients, 19 patients were admitted to the medical ward (inpatients) and 81 patients were treated in the ED without being admitted (ED visits). Of the 100 patients, 39 were males and 61 were females. The average age of the patients was 44 years old Figure .From the 100 cases, the hernial orifice examination was documented to have been performed for two cases (2%) Figure . In one Followingly, the duration and location of the pain were estimated in all cases. Seventy patients presented with abdominal pain lasting less than four days, and 30 of them with abdominal pain lasting for weeks. None of the patients had abdominal pain for more than four weeks. The location of the pain varied, as depicted in Figure Abdominal pain is a common complaint, with approximately 5%-10% of the estimated ED visits be due to abdominal pain . The difInguinal hernias are the most common type of hernias and a proper physical examination has a sensitivity of 74.5% and specificity of 96.3% for their detection . The exaAlthough most of the hernias are often asymptomatic, various clinical manifestations can be commonly recognizable. Some common symptoms for hernial strangulation include a painless bulge in the hernia site, and abdominal pain followed by nausea and vomiting . During During a clinical encounter, the physician should act as an investigator and collect clues that will lead to the diagnosis of the disease. Although science provided a tremendous number of imaging and laboratory investigations to diagnose most diseases, the effectiveness of a properly executed history and physical exam is enough to determine most of the common medical conditions . HoweverIn contrast to the common belief, technological evolution continuously provides ever-increasing opportunities to diagnose medical conditions at the bedside. Ultrasound remains the best initial diagnostic modality to diagnosed inguinal hernias in patients with equivocal physical findings . MultiplThe current reality of a devastating pandemic could negatively affect the physical diagnosis, with the addition of necessary regulations that decrease the physical contact between the clinician and the patient ,19. AlthAlthough this study provides evidence that hernial orifice examination is not commonly performed and documented in patients presenting with acute abdominal pain, several limitations applied: (1) This is a retrospective study of a single community medical institution, and therefore studies including other institutions should be performed. (2) The study relies on clinical documentation to determine whether an examination was performed. Ideally, clinical documentation should represent the physical examination maneuvers performed. However, it is possible that a hernial orifice examination was actually performed but not documented in some of the cases included in this study.Overall, our study provides evidence that examining the hernial orifices is infrequently performed and documented in clinical practice at our institution. We suggest that Emergency Medicine physicians, Internal Medicine physicians, and Specialists should perform and document the examination of the hernial orifices in every patient encounter with a chief complaint of abdominal pain, as the literature suggests. We support the power of clinical skills and physical diagnosis as a way to maintain a cost-effective, evidence-based, and patient-centered clinical practice. Finally, we suggest that emphasis should be placed on the efficient performance of physical examination and maintain the art of physical diagnosis.