Background: Ehlers–Danlos syndrome (EDS) is a phenotypically and genetically heterogeneous group of connective tissue disorders. Currently, diagnosis of EDS is based on a series of clinical and genetic tools. On the other hand, the hypermobile form has not yet been characterized from a genetic point of view: it is considered a part of a continuous spectrum of phenotypes, ranging from isolated non syndromic joint hypermobility, through to the recently defined hypermobility spectrum disorders (HSD). The aim of this study is to characterize the pain symptom that is not considered among the diagnostic criteria but is relevant to what concerns the quality of life of patients with EDS. (2) Methods: A review of the literature was performed on two medical electronic databases (PubMed and Embase) on 20 December 2022. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: published in the English language and published between 2000 and 2022. (3) Results: There were fifty eligible studies obtained at the end of the search and screen process. Pain is one of the most common symptoms found in Ehlers–Danlos (ED) patients. Different causes seem to be recognized in different phases of the syndrome. (4) Conclusions: Pain is a nonspecific symptom and cannot be considered among the diagnostic criteria, but it is a negative predictive factor in the quality of life of patients with EDS. Therefore, proper evaluation and treatment is mandatory. Ehlers–Danlos syndrome (EDS) is a phenotypically and genetically heterogeneous group of connective tissue disorders with multiorgan involvement. Its prevalence is about 1:5000 with classical (cEDS), vascular (vEDS) and molecularly unsolved hypermobile (hEDS) variants accounting for more than 90% of all ED cases . DiffereMoreover, the symptom of pain also appears to be widespread in the EDS patient population. With the present review, we wanted to focus on pain as a symptom; it is not included in the diagnostic criteria, but it is important to consider the fact that pain represents the main cause of access to medical care in the ED patient, representing a factor of both physical and emotional disability in various age groups.The research question identified for the literature review was first of all to highlight pain, one of the most common symptoms found in ED patients, as an undiagnosed disabling symptom. Secondly, we also intend to investigate the characteristics and the predictors of the pain to identify the most effective forms of treatment.A literature search was conducted in order to find relevant studies on the topic. These ones were identified by means of Pubmed and Embase databases.-PubMed-EmbaseThe following electronic databases were searched, taking into consideration the chronological span between 2000 and 2022:The research strategy was carefully designed in order to retrieve the most relevant results. Due to the specificity of the two databases employed, a different search string was built for each one . In brackets, the number of the results is given.(“ehlers-danlos”[All Fields] AND (“pain”[MeSH Terms] OR “pain”[All Fields])) AND ((humans[Filter]) AND (1/1/2000:20/12/2022pdat]) AND (english[Filter])) [381];‘ehlers danlos’ AND ‘pain’/exp AND [01-01-2000]/sd NOT [20-12-2022]/sd AND [humans]/lim AND [english]/lim [1315].Twenty-four studies were also included, starting from a review excluded from the analysis, since only primary studies were taken into account according to the inclusion criteria. Article details are reported in Starting from the research question, inclusion and exclusion criteria for the objective selection of the studies identified were defined as follows. Only studies published in the English language between 2000 and 2022 were eligible for inclusion.A standardized data extraction sheet was prepared, where the main information of the studies was collected .Titles and abstracts and full texts were screened by the research team—i.e., two authors performed the study selection and the data extraction independently, and all disagreement was discussed between the authors.Via the literature search, fifty studies were included in this literature review, twenty-six of them were identified via database searches and twenty-four via citation searching . Figure Pain, usually assessed by the Beighton score, is one of the most common symptoms found in ED patients and seems to be inversely correlated to generalized joint hypermobility. In fact, approximately 30% of children with diagnosed hEDS reported arthralgias, back pain and myalgias, while this rate became more than 80% if considering patients over the age of 40 years, who often show a “negative” Beighton score but increased pain . SimilarPain may be localized or widespread and may be acute or chronic. It can interfere with daily life and affect sleep quality with physical and emotional functional impairment . It is fIn conclusion, pain seems to have different causes in different phases of the syndrome: initially, it could be due to joint hypermobility complications, and then the persistent nociceptive input may causes central sensitization in the dorsal horn neurons and abnormalities of the endogenous pain inhibitory control  Table 1Table 1.Recently, Kalisch et al. studied 75 HED patients, using different valuation scales, to find out factors that can be considered predictors of pain and mobility impairment. All participants reported pain, according to previous studies, with 42.7% suffering from severe pain. From this study, it emerged that professional status, delayed diagnosis and helplessness were predictors of severe pain, while body mass index, age and fatigue predicted mobility disability. Although physical therapies are one of the most effective tools in getting quality of life better, Bovet et al. reported that 38% of iatrogenic injuries resulted from an inadequate rehabilitative protocol, while another 30% of patients reported always feeling an increased risk of injury during a rehabilitative program. The reason seems to be the strict adherence of physical therapists to standard treatment programs without any adaptations to patient’s need ,40,41. TAs seen so far, pain is not only one of the most frequent symptoms in ED patients but also the most frequent reason why this category of patients tends to go to a specialist in the hope of improving their quality of life. Recognizing the different origins of pain, it will be essential to act on the different components, both neuropathic and nociceptive, both from the point of view of purely pharmacological treatment and from the point of view of physical therapies and emotional/psychological support. Pharmacological treatment, in fact, is part of a much more complex therapeutic scenario, in which different forms of treatment are articulated to deal with a pain that often proves not to be responsive to a “basic” drug therapy. In this regard, unconventional treatments can represent an additional prevention and therapy tool, capable of addressing not only the purely physical aspect, but also giving support to the psychological one and teaching the patient “pain management”. These methods include psychotherapy, cognitive behavioral therapy, meditation, hypnosis and psychomotor techniques. A great help in the treatment of this pathology comes from physical therapies, such as exercises to improve posture and proprioception, muscle strengthening and physical conditioning . FurtherPain may be localized or widespread and may be acute or chronic. Nociceptive pain is related to ligaments, tendons, joints, muscles and connective tissue and is present in the early stages of acute, localized pain. The main neuropathy of the nerves contributing to chronic pain appears to be central sensitization, which was observed in many patients and suggests a correlation with global hyperalgesia.Chronic pain strictly and negatively affects ED patients’ quality of life, causing physical and emotional impairment and subsequent substantial disability. Many authors reported lower health-related quality of life scores in ED patients if compared to the healthy population ,43. PhysIn this review, we tried to classify the principal EDS pain types by reading and looking for data that are currently in the literature to better understand possible causes, the stage of onset and possible treatments . Then, wPhysiotherapy is a well-established approach that provides immediate and long-term results . PhysicaPsychotherapy appears to be useful in all patients. In particular, the best results were obtained in patients in whom pain negatively affects quality of life and is unresponsive to drug therapy and physiotherapy .A new front of development could be that of subjecting ED patients to pain questionnaires, trying to understand in a case-specific way which is the neuropathy component, and which is the nociceptive component of the perceived pain, to propose pharmacological therapies and not aim at specific treatment of the algic component.Chronic pain is the most frequent symptom, affecting 80% of ED patients older than 40 years of age. Selected studies have highlighted the negative implications of the pain symptom in EDS patients. The psychological consequences of this symptom can result in severe anxiety states and depressive syndromes.The attention of the multidisciplinary team that takes care of the patient, therefore, must not be aimed only at the treatment of those that are recognized as the most striking and typical symptoms of the syndrome, but must be aimed at the treatment and prevention of those symptoms often considered “minor”, because they are extremely unspecific. Pain represents, among these, the most disabling symptom and its treatment requires the involvement of an experienced multidisciplinary team of experts.The research and the evaluation of the articles has not been easy because there is not much material in the literature published in the last 10 years. We are aware that this represents a limitation of the study and consequently further research will be needed. Moreover, we used the databases most commonly accessed by clinicians to explore the research question. The choice of literature from two sources could represent a limitation of sample constitution.


Background: The authors conducted a 2-year retrospective follow-up to investigate the efficiency of an extraforaminal full-endoscopic approach with foraminoplasty used to treat lateral compressive diseases of the lumbar spine in 247 patients. Methods: The visual analogue scale (VAS), Oswestry disability index (ODI), and MacNab scale were used to analyze the results collected during the preoperative and postoperative periods. Results: The most common diagnosis was disk herniation with lateral recess stenosis, and the most common surgical level among patients was between L4 and L5 on the left side. Pain decreased over time, as determined during sessions held to evaluate pain in the lumbar, gluteal, led, and foot regions. The ODI demonstrated significant enhancement over the evaluation period and the MacNab scale classified the surgery as good or excellent. The most common complication was dysesthesia. Conclusions: An extraforaminal full-endoscopic approach with foraminoplasty can be recommended in cases of lateral herniation or stenosis for patients with symptoms of radiculopathy, and for those who have not responded to conventional rehabilitation treatment or chronic pain management. Few complications arose as a result of this approach, and most of them were treated clinically. The lumbar transforaminal endoscopic approach originates from Erlacher’s posterolateral approach to nucleography . In 1975Mayer et al.  pioneereIn the late 1990s, based on the description of the Yeung Endoscopic Spine System (YESS), the multichannel endoscope with continuous irrigation of saline reduced the rates of intra- and postoperative bleeding and infections, significantly improving the visibility of anatomical structures . Yeung’sThe lower risk of dysesthesia supports the idea of not directly accessing the foramen due to the manipulation of the emerging root in the postoperative period. Based on a study of 33 cases, Ahn et al. suggested that an extraforaminal approach might result in less dysesthesia in the postoperative period . However2 in the area in the axial section); (3) previous surgery on the lumbar spine; (4) cauda equina syndrome; (5) tumor; (6) trauma; or (7) infection.The inclusion criteria for patients participating this retrospective study were: (1) unilateral root pain compatible with the site of compression on magnetic resonance imaging; (2) pain of intensity equal to or greater than five on the visual analog pain scale (VAS); (3) moderate or severe functional disability according to the Oswestry Disability Index (ODI); and (4) failure of conservative treatment after 6 weeks. Patients with at least one of the following criteria were excluded from the study: (1) segmental instability ; (2) severe lumbar stenosis  of the caudal vertebra. The final target point was confirmed using fluoroscopy in the anteroposterior and lateral views. From there, a guidewire, dilator, and beveled working cannula were inserted at 70°; subsequently, the 30° inclination endoscope and 4.2 mm working channel, accompanied by continuous saline irrigation, were introduced . The opePatients were evaluated using the following instruments: VAS, ODI, and MacNab scale, in the preoperative moments (T0) and 2 days (T1), 1 month (T2), 3 months (T3), 6 months (T4), 12 months (T5), and 24 months (T6) postoperatively. The VAS scale is a visual pain scale with values ranging from 0 (no pain) to 10 (maximum pain). This scale comprises four variables corresponding to the areas of pain . The ODI is an instrument used to describe pain or limitations. Ten sections are analyzed, each containing six items that describe an increasing degree of severity, with a score of zero indicating little or no pain or functional limitations. In contrast, a score of five indicates extreme pain or restriction. The ODI is composed of 10 variables corresponding to each of the sessions from I to X.The MacNab scale assessed satisfaction with surgery with values from 1 to 4, with 1 meaning excellent, 2 meaning good, 3 meaning regular, and 4 meaning poor. The surgical procedure was considered unsuccessful when the patient had low back or radicular pain (VAS > 5), associated with a moderate or high physical disability (ODI > 20%) at any time during the 24-month evaluation period. Recurrence of lumbar disk herniation (LDH) was defined by the appearance of symptoms associated with lumbar disk herniation imaging on MRI after an asymptomatic 2-week period after surgery.p-value for each variable’s relationship with a scale over time. Models were then created for each period, accounting for the reference period’s interaction and the relationship with other periods. The mean and standard deviation (SD) were used to describe numerical characterization variables. Absolute and relative frequencies were used for each category. We used R software (version 3.5.0) for statistical analyses, with a significance level of p ≤ 0.05. To check the difference in each scale’s values according to time, the generalized equations estimating (GEE) method  was usedHowever, the difference between the percentages was minimal. The patients’ mean age was 51.50 ± 14.68 years. The most frequent diagnosis was herniated disk with lateral recess stenosis (45.7%). The most frequent surgical level among patients was between L4 and L5 (46.6%) and on the left side (51.4%), as seen in p < 0.001). There was a significant reduction in pain in the lumbar and gluteal regions compared to T0 (p < 0.001), and the perceived pain continued to decrease statistically between all the evaluated times (p < 0.05). On the other hand, for the leg and foot regions, patients reported a significant reduction in pain over time (p < 0.001), despite the improvements in this symptom slowing over several months.There was a significant reduction in pain throughout the evaluated times in the lumbar, gluteal, leg, and foot regions (p < 0.001). Regarding the comparison between times, there was a statistical reduction in the rates of physical disability at T2, T3, T4, T5, and T6 compared to T1 (p < 0.05). There was a significant reduction in the ODI at T4, T5, and T6 compared to T2 (p < 0.05). All the data are shown in The ODI showed a significant improvement throughout the evaluation period  associated with a moderate or high physical disability (ODI > 20%) in the postoperative period, failure of conservative treatment after 4 weeks, and regular or poor welfare according to the MacNab scale were introduced to new interventions. Of the 247 patients who underwent surgery, 18 (7.3%) had complications . The mosFour patients with dysesthesia were clinically treated with analgesics, adjuvants (gabapentinoids and antidepressants), corticosteroids (for seven days), and intensive physical rehabilitation. Of these, one was submitted to a root and ganglion block with an improvement in symptoms. The three recurrence cases were treated according to the patients’ symptoms and functional limitations; one patient underwent only conservative clinical treatment and rehabilitation, one underwent foraminal infiltration, and the third patient with a massive hernia underwent a new endoscopic procedure 12 months after the first surgery. Two patients had insufficient decompression; one was treated clinically, and the other underwent a new endoscopic technique. Two patients had an insufficient diskectomy and underwent a new endoscopic procedure at 1.5 and 6 months after the first procedure. Two patients had refractory axial pain that was difficult to control, with no compressive signs on postoperative examinations, and underwent a facet block. Two patients showed significant worsening of disk degeneration at the approached level and underwent arthrodesis 10 and 14 months after the first procedure. One case of diskitis was submitted to a new endoscopy through the same access for material collection and surgical cleaning. One case of dural injury remained asymptomatic for only 24 h under observation and underwent rehabilitation without complications.p < 0.001). In the lumbar spine region, we observed a significant reduction in VAS at the time of analysis compared to that at T0 (p < 0.001). In addition, the VAS at T4 was significantly lower than that at T1 (p = 0.034). There were no significant differences between the other analyzed times. For the gluteal region, the reported pain was statistically lower in T2, T3, T4, and T5 than at T0 (p < 0.05). Pain analysis at T3 and T5 was lower than that at T1 (p < 0.05). For the analysis of leg pain, there was a significant reduction in relation to T0 (p = 0.002), despite the stabilization of the VAS values at the other times analyzed. The reported foot pain was statistically lower in T2, T3, T4, and T5 than at T0 (p = 0.001). Foot pain analysis at T3 and T4 was lower than that at T2 (p < 0.05). Even patients with complications showed a significant reduction in pain at the moments analyzed in relation to T0 (p < 0.001).Patients with complications showed a significant reduction in ODI at the postoperative time compared to T0  the size of the patient and the point of entry of the instruments into the skin; (2) the location of the herniated disk, its degree of extrusion, and its migration characteristics and fragmentation; and (3) the dimensions of the conjugation foramen .Dura injury is another complication associated with lumbar endoscopy and is usually related to instruments, especially Kerrison. Inadvertent punctures of the dura mater most commonly produce low-output fistulas, and no specific treatment is necessary. When removing the working cannula, the musculature closes around the created path as there are no virtual cavities, and there is no formation of fistulas or hygromas. The fistula closes naturally after pressure equalization inside and outside the dural sac, and no further surgical intervention is necessary. According to the literature, this complication has a low incidence in the transforaminal technique ,31,32.The reoperation rate has been reported to range from 2.3% to 15%. Choi et al.  evaluateSpondylodiscitis after lumbar endoscopic surgery is a relatively uncommon complication of microdiskectomy , which rVascular damage to structures anterior to the intervertebral disk and visceral injury are rare complications. Abdominal vessel injury can occur after inadvertent slipping of instruments, especially when approaching extraforaminal herniated disks when the skin puncture occurs more medially. On the other hand, peritoneal perforation can occur when the point of entry into the skin is in an extreme-lateral position, which is associated with the trajectory of the most verticalized puncture.The complication rate in this study was 7.3%. These complications were mostly transient and mild to moderate in severity, with 11 of the 18 patients receiving clinical treatment or an anesthetic. Seven patients had a surgical outcome, of which five required another operation using the same technique, and two required arthrodesis. All cases in this study had favorable clinical outcomes.In this study, we determined the average VAS between the types of complications over time . It was No vascular injury, injury to visceral organs, and permanent neurological injury were observed. There was one case in which spondylodiscitis reopened via the transforaminal endoscopic technique for cleaning and collecting material for culture, and the patient received subsequent treatment with antibiotics for 4 weeks.Performing endoscopic diskectomy and foraminoplasty is dependent on the surgeons’ experience, which can be acquired for each technique via a learning curve. This requires at least 30 cases per operated level , thorougBased on our results, we conclude that the extra-articular full-endoscopic lumbar technique with foraminoplasty is efficient and less invasive than alternative strategies. The safety of the procedure is very well indicated in cases of centrolateral/lateral herniation or stenosis for patients with symptoms of radiculopathy, and for those who did not respond to conventional rehabilitation treatment or chronic pain management; it resulted in few complications, most of which were treated clinically.


AimThe study compared the anesthetic effectiveness of articaine and lignocaine when premolars are extracted bilaterally for orthodontic purposes.Material and methodsThis prospective split-mouth study was performed on 30 cases selected from orthodontic referral patients reporting to the Oral and Maxillofacial Surgery Department at Maharaja Ganga Singh Dental College and Research Center, Rajasthan, India, for bilateral extraction of premolars under local anesthesia. We used 4% articaine hydrochloride and adrenaline 1:100000 (AH) as group A and 2% lignocaine hydrochloride with adrenaline 1:100000 (LH) on the control side as group B. For premolar anesthetization, 0.6-1.6 ml of AH and 1-2 ml of LH were injected submucosally in the buccal vestibular area. The extraction procedure was then carried out after achieving adequate anesthesia. The pain was assessed with Visual Analog Scale. The average onset time and duration of anesthesia were recorded. Data collected were summarized with descriptive statistics. The SPSS version 23.0  was used for data entry, validation, and analysis. Means of continuous variables were compared using the student t-test. All tests were 2-tailed and significant at equal or less than 0.05. (p≤0.05).ResultsWhen comparing the overall anesthetic efficiency, Group A had a lower overall pain score of 0.43 while Group B had a higher overall pain score of 2.9. The average onset time of anesthesia in Group A was 1.2 minutes and 2.55 minutes in Group B. In Group A, the average duration of anesthesia was 70 minutes, and 46.5 minutes in Group B. These parameters were statistically significant with a p-value of <0.05.ConclusionThe study concluded that as an alternative to lignocaine, articaine could be used effectively for maxillary premolar extractions for orthodontic reasons obviating palatal injection which is very painful to the patient. In dentistry, local anesthesia is crucial for pain management because it is thought to be the safest and most effective medication for pain prevention and management for patients undergoing the procedure of oral surgery. Local anesthesia provides the strength for pain management procedures. These are substances that block nerve conduction in a specific, entirely reversible, non-permanent manner without altering the patient’s consciousness ,2.Teeth are important for functions like speech, mastication, one’s personality, and even in facial esthetics. One of the most frequent procedures in the field of oral surgery is tooth extraction. Extraction of teeth can be done for many reasons like irreversible dental pulpitis, advanced periodontal diseases, and orthodontic purposes. Extraction of teeth is considered one of the most dreaded procedures by many people, due to the unpleasant past experience of previous tooth extraction done for them or for others -8. ThereThe most commonly experienced symptom in dentistry is pain, and palatal injection is among the most unpleasant procedures. Since the injection is rather painful, numerous strategies have been proposed to lessen the patient’s agony. The most frequently used technique is topical anesthesia for atraumatic needle penetration. The palatal injection is painful due to the sensitivity of the palatal soft tissue and its tight attachment to the bone present beneath it ,2.A painful injection given palatally can be refrained by using the palatal diffusion of the local anesthetics with solitary buccal infiltration . The maxArticaine spread out into soft and hard tissues is more effective than other local anesthetics and its buccal infiltration in the maxilla provides soft tissue anesthesia on the palatal side, ruling out the necessity of uncomfortable palatal injection -8.Hassan et al.  performeHence, we studied the efficacy of anesthesia with lignocaine and articaine for the extraction of bilateral premolars in orthodontic patients of Maharaja Ganga Singh Dental College and Research Center, Sriganganagar, Rajasthan, which is in North Western India. We analyzed the time for initiation of anesthesia, duration of anesthesia, and pain measurement with a Visual Analogue Scale (VAS) and also observed if there are any intra or post-administration complications.This prospective split-mouth study was performed at Maharaja Ganga Singh Dental College and Research Center and was approved by the Institutional Ethics Committee .The safest and most efficient way to control discomfort and pain management during dental treatment is with local anesthetics. The study group comprised 30 individuals referred for bilateral extraction of maxillary premolars as a part of orthodontic treatment. The sample size calculation was performed using G-power based on the study by Hassan et al. . The medBlinding was not done. The choice of lignocaine or articaine was taken by the coin toss method. They were anesthetized either using Septodont Septanest: 1:100,000 - 4% articaine with epinephrine  or Octocaine 100 - lidocaine HCl 2% and epinephrine 1:100,000 injection , aspirating dental injection syringe of 1.8 ml capacity , disposable needles, 0.40 x 35mm (27 gauge) , and routine extraction instruments  ranging from 0 (no pain) to 100 (very severe pain). VAS was used to evaluate the amount of felt pain during the entire procedure and following the extraction. A pain VAS score of 30, 70, and 100 indicated the upper boundaries of mild, moderate, and severe pain intensity. The pain scores were divided by 100 and utilized for analysis.Other study parameters were also evaluated by the single operator. The mean injection pain rating was measured using VAS. The average time for onset of anesthesia and average anesthesia duration was subjectively assessed by questioning the patient and confirmed with a clinical assessment with a rounded instrument. The patient was retained in the Oral Surgery department till the anesthesia wore off completely and was re-confirmed by subjective and objective assessment. The complications after injection were recorded and tabulated.Statistical analysis was performed using SPSS version 23.0 . Means of continuous variables were compared with the Student t-test. All tests were 2-tailed in nature and the significance level was set at equal or less than 0.05. (p ≤ 0.05).This prospective split-mouth study was performed to assess the anesthetic efficacy of articaine and lignocaine on 30 individuals. Their age range was 14-26 years. Their mean age was 20 years and 47% of patients were above the mean age. Equal gender distribution was noted with 15 males and 15 females.On the basis of malocclusion, we observed Class II Division 1 (n = 12), Class II Division 2 ( n = 5), Class I Bimaxillary protrusion (n = 9), and Class I with severe crowding (n = 4). All these individuals were referred for bilateral extraction of maxillary premolars. Articaine was administered in the A group and lignocaine was used in the B group.A Visual Analog Scale was used to measure the pain during the procedure. On buccal infiltration, the pain score ranged between 30-50 for Group A and 40-60 for Group B. The mean injection pain rating buccally in Group A was found to be 0.4333 ± .8976, whereas, in Group B, it was noted as 0.5 ± 1.137. But, no statistically significant difference existed between the groups (P > .05). We also measured the VAS scores on the palatal mucosa after administering the anesthetic to the buccal vestibule. Group A had a lower VAS score than Group B after buccal infiltration. The pain score range on the palatal mucosa with only buccal infiltration was 0-10 for Group A and 50-70 for Group B. None of the Group A patients needed palatal infiltration, but all of the Group B patients needed additional palatal infiltration. The VAS score of supplemental palatal injection in Group B ranged between 60-80 and it was zero for Group A.Hence, calculation of individual VAS scores for buccal infiltration, the efficiency of palatal anesthesia after buccal infiltration only, the VAS score for additional palatal infiltration in Group B, and overall anesthetic efficiency during extraction showed that Group A had a lower overall pain score of 0.4333 while Group B had a higher overall pain score of 2.9. The difference was highly significant statistically (P< 0.05).The average time of onset of anesthesia in Group A was seen as 1.2 ± .46 minutes and 2.55 ± .69 in Group B. The difference was highly significant statistically (P < 0.05) between both groups. Group A experienced a quicker onset of anesthesia than Group B  and showed that A group had a longer action duration compared to Group B Table .In Group A, the mean Drug Volume used was 0.833± 0.212 ml, and 1.286 ± 0.293 ml in Group B. We also observed that none of the Group A patients needed a palatal infiltration, but all of the Group B patients underwent palatal infiltration.In either the lignocaine or articaine groups, we did not observe any pain during the extraction procedure, nor were there any associated complications.Dental pain management is widely performed with a local anesthetic agent. Because of its comparative safety and potency, articaine is a newly emerging local anesthetic agent . ArticaiRobertson et al.  reportedStudies have reported that articaine is effective at lower volumes than lignocaine, as it created a concentration of active anesthetic molecules at the injection site that is twice as high as lignocaine -6. SreekHassan et al. stated that the onset period for articaine was 0.975 ± 0.1118 and lignocaine was 2.950 ± 0.5104 min, which showed a statistically significant difference [Cowan A  reportedGroup A had a lower overall pain score of 0.4333 while Group B had a higher overall pain score of 2.9 with a high statistical significance. We also found that articaine had quicker onset and longer duration of anesthesia along with enhanced patient compliance. This improved efficacy of articaine is also reported by other studies -18.In comparison to 2.6ml ± 0.09 of lidocaine, Malamed et al.  found thAdequate pain control has a pivotal role in dental practice . SimilarLimitationsThe limitation of this study is the smaller sample size of 30 patients and the fact that only orthodontic extraction cases were taken into consideration. We also compared only the efficacy of maxillary anesthesia between articaine and lignocaine.Lignocaine is considered to be the industry standard for local anesthesia. Our research draws the conclusion that a replacement of lignocaine is possible with articaine which offered quicker onset, only buccal infiltration, longer duration of anesthesia, and better patient comfort with lower pain scores. Hence, It can be used for maxillary premolar extractions for reasons like in orthodontics which obviates painful palatal injection with additional efficacy and safety than lignocaine.There was no difference in pain perception on the buccal side with both anesthetics. However, to support our findings, additional research is needed to analyze the efficacy of articaine in other local infiltration and nerve block techniques in the maxilla or mandible.


To compare efficacy of oral versus intravenous (IV) methadone on postoperative pain and opioid requirements after spine surgery.This was a retrospective, single-academic center cohort study evaluating 1010 patients who underwent >3 level spine surgery from January 2017 to May 2020 and received a one-time dose of oral or intravenous methadone prior to surgery. The primary outcome measured was postoperative opioid use in oral morphine equivalents (ME) and verbal response scale (VRS) pain scores up to postoperative day (POD) three. Secondary outcomes were time to first bowel movement and adverse effects  up to POD 3.A total of 687 patients received oral and 317 received IV methadone, six patients were excluded. The IV group received a significantly greater methadone morphine equivalent (ME) dose preoperatively  and greater total (methadone and non-methadone) opioid dose , intraoperatively. Although pain scores for the oral group were non-inferior to the IV group for all postoperative days (POD), non-inferiority for postoperative opioid requirements was demonstrated only on POD 3. Based on the joint hypothesis for the co-primary outcomes, oral methadone was non-inferior to IV methadone on POD 3 only. No differences in secondary outcomes, including QTc prolongation and arrhythmias, were noted between the groups.Oral methadone is a feasible alternative to IV methadone for patients undergoing spine surgery regarding both pain scores and postoperative opioid consumption. Finding the optimal analgesic regimen for complex spine surgery remains challenging, especially regarding opioids and opioid-sparing approaches. Intraoperative exposure to opioids like fentanyl, sufentanil, or remifentanil have been shown to result in higher pain scores and opioid consumption in the postoperative period –3. MethaOral pain management prior to surgery can effectively reduce postoperative pain . During Here, we compared the impact of a single preoperative dose of oral versus IV methadone for patients undergoing spine surgery, using a joint hypothesis testing approach for reduction in postoperative pain and opioid consumption. We hypothesized that oral methadone would be non-inferior to IV methadone for both postoperative pain and opioid consumption.This study was approved by the University of Virginia Institutional Review Board for Health Science Research (UVA IRB HSR #22498). The requirement for written consent was waived. This study adheres to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines for reporting of observational data.The study sample was a convenience sample. Adult patients (age ≥ to 18 years and < 90 years of age) who underwent elective, > 3 level posterior spinal fusion between July 3, 2017 and July 23, 2020, and received either oral or IV methadone immediately prior to surgery were identified and the electronic medical records reviewed. We identified a total of 1010 patients; 317 (31.4%) patients received IV methadone and 687 (68.0%) were given oral methadone. Six received both IV and oral methadone and were excluded from subsequent analyses.Each patient received either a single dose (mg) of oral methadone preoperatively or a single dose (mg) of IV methadone in the operating room prior to onset of surgery. Given the retrospective nature of the study, standardization of prescribed opioids was not feasible. The methadone dose administered preoperatively was recorded and subsequently converted to morphine equivalent (mg ME) dose using the CDC morphine milligram equivalents table and a conversion ratio of 1:2 for IV to oral methadone , 13. TheOur institution had no specific protocols regarding methadone dosing. Dosing and formulation of the drug were at the discretion of the attending anesthesiologist. Oral methadone was administered in the preoperative area, at the time of patient evaluation (approximately 30 minutes prior to initiating intraoperative care).Co-primary outcomes included postoperative opioid consumption, reported as a postoperative morphine equivalents (ME) and an 11-point patient-reported verbal rating scale (VRS) pain scores (0–10), measured on postoperative days 1–3. Secondary outcomes included time to first bowel movement (days), reintubation rates, postoperative myocardial infarction, or new onset arrhythmia and new QTc prolongation.Data collected included age, sex, body mass index (BMI), and American Society of Anesthesiologists (ASA) physical status classification, preoperative opioid use, preoperative vital signs, preoperative and intraoperative non-opioid medication use. Patient’s age, sex, BMI, ASA class, preoperative opioid use, and intraoperative medications were included as covariates in the models. An a priori sensitivity analyses was planned to evaluate patients left intubated postoperatively using the critical care postoperative observation tool (CPOT) score.Standard perioperative management included induction of anesthesia with IV lidocaine (1–1.5 mg/kg), propofol (1–2 mg/kg), and rocuronium (0.5–1 mg/kg). Anesthesia was maintained with IV infusions of propofol (50–150 mcg/kg/min), lidocaine (40 mcg/kg/min), and ketamine (0.3–0.5 mg/kg/h) with or without up to one half minimum alveolar concentration of volatile anesthetic. Patients received IV hydromorphone towards the end of the procedure at the discretion of the anesthesiologist. Postoperative analgesia included hydromorphone patient-controlled analgesia and oral analgesics. Patients were transferred to the intensive care unit (ICU) for postoperative monitoring.th-75th quartile]) were analyzed using the Wilcoxon rank sum test or linear regression models , where appropriate. We used linear regression models, controlling for preoperative methadone dose and covariates  to examine the extent to which postoperative pain scores and postoperative opioid consumption were different between those who received IV or oral methadone. Three sets of linear regression models were performed for average pain score, maximum pain score, and postoperative opioid consumption as the dependent variable, separately for POD0 to POD3. An additional set of subgroup linear regression models was performed using postoperative CPOT scores as the dependent variable, separately for POD0 to POD3. In all models, group  was included as an independent variable, with IV methadone group used as the reference group. All models controlled for preoperative methadone dose and covariates listed above. Traditional assumptions of linear regression models, including linearity, homoscedasticity, and independence and normality of residuals are met. Pain scores were square root transformed, whereas opioid consumption was log-transformed due to skewness of the data. Estimated results were back-transformed for ease of interpretation.Categorical data between the oral versus IV methadone group were analyzed using the Chi-square test or Fisher’s exact test. Count data was compared using the generalized linear regression model with the Poisson link. Continuous data (expressed as mean ± standard deviation (SD) or median [25The non-inferiority margin for pain scores was defined a priori as a Δ = 1 point, and the equivalence margin for pain scores was defined as a Δ = 1 point in both directions. The non-inferiority margin for morphine equivalent was defined as not more than 20% greater than IV, and the equivalence margin was defined as no more than 20% greater or less than the IV methadone group.For the two-step joint hypothesis gatekeeping procedure for both pain scores and opioid consumption, we considered oral methadone to be non-inferior to IV methadone if: 1) Oral methadone was non-inferior on pain score (maximum or average) and non-inferior on morphine equivalent consumption; or 2) Oral methadone was non-inferior on pain scores (maximum or average) and equivalent on morphine equivalent consumption; or 3) Oral methadone was equivalent on pain scores (maximum or average) and non-inferior on morphine equivalent consumption.Finally, a subgroup analysis of differences in CPOT scores for patients not extubated after surgery, between the oral and IV methadone group, was performed using a linear regression model controlling for the same covariates as previously described. CPOT was square root transformed in the analyses, and back-transformed results were presented for interpretation.As this was a convenience sample, no a priori power analysis was performed. A p value < 0.05 was considered statistically significant for all analyses. No adjustment for multiple comparisons were used. All statistical analyses were conducted in R (version 4.0.3).Preoperative and intraoperative patient characteristics are shown in Regarding opioid consumption, oral methadone only demonstrated non-inferiority on POD 3. Therefore, based on our a priori two-step joint hypothesis approach, non-inferiority of oral methadone compared to IV methadone was only achieved on POD 3 for opioid consumption .We also examined the extent to which CPOT scores for patients who remained intubated postoperatively were different between IV and oral methadone groups  in a subDescriptive statistics for secondary outcomes including time to first bowel movement, reintubation, postoperative myocardial infarction (MI), postoperative arrhythmia, and QTC prolongation are shown in Based on our a priori joint hypothesis approach of both pain scores and opioid consumption, our study demonstrates that oral methadone was non-inferior to IV methadone on POD 3. The literature has extensively evaluated the perioperative analgesic benefits of IV methadone in various surgeries, such as cardiac and spine, but is limited in describing the impact of oral methadone compared to IV. One randomized controlled-trial studied the effects of oral methadone compared to placebo on postoperative analgesia outcomes for sternotomy pain in patients undergoing coronary artery bypass graft surgery . Twenty-Our study included patients with opioid use history and used linear regression models to account for variability between IV and oral methadone group. This retrospective, observational study found no difference in pain scores between the two groups, but a significant reduction in opioid requirements on POD 3 for the oral methadone group . We alsoTo account for this significant finding, we can consider multiple factors, including pharmacological differences in route of medication. Pharmacokinetic studies have demonstrated that a single dose of 20 mg IV methadone provides long duration of analgesia with minimal risk of respiratory depression . The meaThe findings of our study might be related to different pharmacokinetic profiles for oral vs. IV methadone. Equianalgesic dosing for oral and IV methadone is highly variable due to differences in pharmacokinetics and pharmacogenomics. Compared to oral methadone, the intravenous formulation is much more potent. Methadone binds to alpha-1-glycoprotein and is metabolized by cytochrome P450 enzymes. Liver disease may alter alpha-1-glycoprotein levels, which in turn influences methadone’s unbound serum concentrations. Variability in the cytochrome P450 enzymes impacts methadone plasma concentrations as well. Genetic polymorphisms in CYP2B6, the primary enzyme involved in methadone metabolism and clearance, can result in slow to rapid metabolizers –20. A siWhile this observational study’s primary goal was not focused on cost-effectiveness, the results could influence future directions in research as more hospitals focus on cost-saving and enhanced surgical outcomes. Non-inferiority of the oral formulation could influence preoperative multimodal analgesia choices, especially in Enhanced Recovery After Surgery (ERAS) programs. ERAS protocols are widely accepted as key tools to reduce morbidity and mortality in patients across multiple surgical specialties, including spine surgery. Many of these protocols have successfully utilized multimodal oral medications to reduce surgical stress and limit postoperative opioid consumption –25. The Salajegheh et al. found that during a national opioid-shortage, post-operative patient pain scores were similar when comparing IV to PO perioperative analgesia, while using less opioids overall in the PO group . SimilarERAS protocols vary between institutions with medication and facilities costs not standardized across health-systems. A retrospective, single-center cost-saving analysis of ERAS vs standard care in spine surgery performed by Naik et al, found that standard care was more cost-effective compared to ERAS due to a reduced LOS in the standard treatment group . The finOur study has several limitations. Due to the retrospective study design, perioperative analgesia was not standardized and was at the discretion of the anesthesiologist. We could also not account for metabolism differences in patients with liver disease, which could contribute to the variable effects of oral methadone. Our study cohort included a small sample size of inpatients who were monitored in the intensive care unit postoperatively. Secondary outcomes were evaluated only up to POD 3, when acute postoperative pain usually decreases. Long-term impact of oral compared to IV methadone on pain scores and opioid utilization is unknown. More studies are needed to compare the long-term outcomes of oral methadone compared to IV. While we did not see significant differences in secondary outcomes such as respiratory depression , due to Our study also demonstrates that oral methadone is both non-inferior and equivalent to IV methadone for both average and maximum pain scores on all POD days and was non-inferior for opioid consumption on POD 3. This analysis suggests that oral methadone is a suitable alternative to IV methadone for patients undergoing multi-level spine surgery.


Conclusions: The use of botulinum toxin in the subscapularis and pectoralis major muscles resulted in a reduction in shoulder pain in spastic hemiplegic patients without statistical significance.Objective: The primary objective of this paper is to assess whether the use of 200 units of abobotulinum in the pectoralis major and subscapularis muscles modifies the pain complaint assessed using the visual analog scale in subjects with shoulder pain after the onset of spastic hemiplegia due to cerebrovascular disease when compared to the application of a placebo to the same muscles. Design: A prospective, double-blind, randomized, and placebo-controlled clinical trial study in two different rehabilitation centers. Setting: Two distinct outpatient neurological rehabilitation services. Participants: Patients older than 18 years who were included presented upper limb spasticity resulting from ischemic or hemorrhagic stroke and a diagnosis of Painful Hemiplegic Shoulder Syndrome (PHSS) that was independent of motor dominance. Interventions: Patients were divided into two groups, one of them underwent the application of botulinum toxin (TXB-A) in the pectoralis major and subscapularis muscles, at a total dose of 400 U. Main Outcome Measure: Patients were assessed for a change in pain using the Visual Analog Scale (VAS) for at least 13 mm. Results: An improvement in pain and spasticity levels in both groups, more intense in the toxin group, but without statistical significance. The comparison between the groups showed a reduction in pain by VAS ( Stroke is a disease with a great impact on the global population, not only because of the immediate consequences of the event and risk of death, but also due to the sequelae originating in the survivors, which influences the quality of life after the disease. Stroke is currently the leading cause of disability in developed countries ,2,3.Painful hemiplegic shoulder syndrome (PHSS) is shown in this context as a condition of great relevance due to its high prevalence and impact on quality of life. Thus, PHSS interferes with the function of the upper extremity, impairing daily life activities and appropriate participation in rehabilitation programs ,4,5,6,7.The literature contains few studies to assist therapeutic decision-making by physicians and other professionals involved in rehabilitation programs to justify the use of BTxA as a treatment for PHSS. There is no established guideline on this issue. There are few placebo-controlled studies, none of them using the subscapularis and pectoralis muscles ,15. In aTo assess whether the use of 200 units of abobotulinum in the pectoralis major and subscapularis muscles modifies the pain complaint, evaluated by the visual analog scale, in subjects with shoulder pain after the onset of spastic hemiplegia due to cerebrovascular disease when compared to the application of a placebo to the same muscles, after 4 months. To compare the effect of treating PHSS with BTxA with current standard treatment regarding pain, as assessed using the visual analog scale and McGill pain scale, regarding the articulation range of motion, as assessed using manual goniometry and, regarding functionality, assessed using the Fugl-Meyer upper limb domain test, after 4 months.Thirty-five eligible patients were included, and eleven patients were excluded for not achieving the inclusion criteria, not needing to receive the toxin at other points, pain improvement before randomization, and previous shoulder surgeries. Twenty-four patients were randomized, twelve in the therapy group and twelve in the placebo group. After the beginning of the study, two patients were lost in each group. In the therapy group, one patient abandoned the study due to the difficulties imposed by the pandemic but came to the last follow-up and another patient lost contact after the second evaluation. In the placebo group, one was lost due to the impossibility of returning after the first evaluation, and one patient suffered a new stroke and died 2 months after the intervention (placebo).The randomization and follow-up of the patients are shown in The distribution of biodemographic description: age, gender, type of stroke, time of stroke, dominance, and affected side is shown in The results described in p = 0.012) in the group treated with botulinum toxin. Dividing the groups by the highest pain intensity, we divided patients with mild, moderate, or severe pain in the groups in The results described in The results described in In The results showed that there was a decrease in the means of pain reported by the patients for abduction and external rotation of the shoulder at rest, during maximum passive and active movement with the use of botulinum toxin, but with no statistically significant difference when compared to the group that received placebo. These observations do not confirm the primary hypothesis of this study, which aimed to demonstrate pain relief as being superior to the placebo and lasting for at least 4 months. This result differs from most studies that showed pain relief gain and shoulder range of motion increase that was superior to the placebo ,15,18,19The mean pain scores at rest were, as expected, the lowest due to the absence of local movement. Active movement despite increasing pain perception was not as intense as during maximum passive movement, which is expected to mobilize more structures and painful areas. Thus, it was observed that, especially in the first evaluation, the pain means in passive movement obtained more expressive reductions . The reap = 0.012) in the group treated with botulinum toxin. The results presented are in agreement with the response expected by the other methods described in the literature ,12,26. WThe choice of subscapularis and pectoralis muscles occurred because both are muscles frequently affected by spasticity after stroke and contribute to internal rotation and adduction of the shoulder, which are factors associated with a higher frequency of painful shoulder syndrome in these patients . In the The reason we did not find differences between the spasticity evaluated by the Ashworth scale in the evaluated groups can be explained by the fact that the output spasticity of both groups is low  and the improvement can be attributed by the other treatments applied simultaneously  .Regarding the range of articular motion of abduction and external rotation of the shoulder, there was also no significant change, as seen in As all the patients received toxin application in other areas at the same time in the study, some improvement can also be attributed to functional gain, increased gait, and the therapies performed in association.We also observed, using the Fugl-Meyer scale, functional gain in the first month of follow-up, but also without significant differences between the groups after four months. This improvement, although partial, shows that the toxin group had a much clearer evolution than among the participants who received the placebo . The preThe main limiting factors of the study were that its design was to assess pain primarily, and thus the other outcomes studied may not have been strong enough to demonstrate a difference. When assessing the results, we can observe that another factor that can be justified is the large standard deviation of the sample, which might be better controlled in the future by larger samples.The use of botulinum toxin in the subscapularis and pectoralis major muscles did not result in a reduction in shoulder pain in spastic hemiplegic patients compared with a placebo solution.A prospective, with two parallel arms, double-blind, randomized, and placebo-controlled clinical trial study was conducted in two different rehabilitation centers. The study was logged in the Clinical Trials platform under the number NCT04470401. This study did not receive any modification after its registration. This study was funded by the authors.Participants in this study included patients followed up in two different outpatient rehabilitation services, who, agreed to the study procedures and signed the Informed Consent Form (ICF) accepted by these institutions’ research ethics committee. This study followed the recommendations of the Helsinki Declaration and Resolution 196/96 of the National Health Council. The Ethics Committee approved the research in June 2019 under Opinion 3.271.406 Ethic Research Committee (ERC). The patients were recruited from January 2020 to September 2021.The sample size calculation was based on the published results , where tSpastic motor sequelae in the upper limb resulting from ischemic or hemorrhagic stroke;Older than 18 years;Diagnosis of PHSS independent of motor dominance;Willingness and consent of the patient, family members, and/or responsible caregiver to participate in the study. Thus, everyone was informed about the advantages and disadvantages of the treatment, as well as its risks.In this study, the patients who were included presented:Painful condition prior to stroke in the shoulder affected by hemiplegia;Previous treatment using TXB-A for painful shoulder conditions;Pregnant or nursing women;Cognitive impairment that impeded assessment and collaboration with treatment;Contraindication to the use of botulinum toxin;Joint deformity in the shoulder affected.In this study, the patients who were not included presented:Patients who after inclusion were unable to follow the study for reasons not related to health, such as transport limitations and change of address, among others, or development of clinical situations that prevented attendance at follow-up assessments, such as clinical admissions and states of home restriction, were excluded.The evaluation consisted of obtaining the participants’ biodemographic and clinical information, followed by the evaluation of the outcome variables immediately before the BTxA injection, as well as after one and four months.-Demographic characterization by age, gender, origin, time of stroke, use of medications, and previous therapies.-Visual Analog Scale (VAS): Pain is classified as no pain (0), mild (1–3.9), moderate (4–7.9), and severe (8–10). Pain was assessed with the limb at rest and during active and passive mobilization .-Manual goniometry—consists of evaluating the range of motion of the shoulder in the frontal, vertical, horizontal, external, and internal rotation planes of patients in the sitting position. For the study, the ranges of external rotation and shoulder abduction, both active and passive, were considered .-Modified Asworth Scale (MAS): MAS was applied to the same movements evaluated in the goniometry, in this study in the shoulder internal rotator group and shoulder adductors. Patients scored as 1+ were considered as 1 for calculation and statistical purposes.-Characterization of pain: For this item, the McGill questionnaire will be used. In each subgroup, the first descriptor scores less than the last, and the descriptor of each subgroup is considered the most intense .-Fugl-Meyer Test (FM): Motor assessment includes measurement of movement, coordination and reflex activity of the shoulder, elbow, wrist, hand, hip, knee, and ankle. This scale has a total of 100 points for normal motor function, where the maximum score for upper extremity is 66 .The following assessment tools will be used for this study:www.randomization.com) into 2 groups. The first to undergo BTxA treatment and the second to receive the placebo. The randomization list was drawn up in 6 blocks of 4 subjects to ensure balance of the groups. After, the groups were named A or B by an assistant nurse. The subjects were randomized through a computer program-generated list , with the same coloring and appearance as BTxA. All patients, study evaluators, and physicians who applied the botulinum toxin were totally blind.The muscles selected for this treatment were the pectoralis major and subscapularis muscles, which were each treated with 200 U of abobotulinum at two different points per muscle with the same dosage . The application was guided by electrostimulation.® for Mac version 16.72 spreadsheet and exported to the statistical analysis software IBM SPSS Statistics® version 23.0 for MAC. Comparison between groups of categorical data was performed using Pearson’s chi-square test. Continuous data were tested for their distribution using the Shapiro–Wilk test. When the distribution was normal, Student t-test was performed, when it was different from this assumption, the Mann–Whitney test was performed. Once most data sets did not have a normal distribution, the intra-group comparison was performed using the Friedman test. When a difference was observed between the assessments in the time follow-up, the repeated measures test, Wilcoxon test, was performed and the Bonferroni correction was applied. A value of p ≤ 0.05 was accepted as a statistically significant difference.Data were stored in an ExcelIn the absence of patient follow-up, the value of the last observation was assigned and loaded into the missing analysis.


Most patients with hip fractures are elderly patients with comorbidities, and well-managed pain management is associated with positive postoperative outcomes. In recent years, new indications for regional anesthesia techniques have been defined, and they have found more place in clinical practice. Herein we investigate the effect of US-guided PENG block on positioning pain and compare that effect to intravenous opioid in patients undergoing surgery under spinal anesthesia for hip fractures. Additionally, we sought to investigate the effect of PENG block on pain scores, opioid intake, time to first analgesic requirement, and quality of recovery within the first 24 h following surgery.In this study, patients were divided into the PENG (n = 42) and control group (n = 42) one hour prior to surgery. A team who was blinded to the assigned groups, collected and evaluated all data such as spinal anesthesia positioning pain, postoperative pain, opioid requirement.Patients that underwent PENG had statistically significantly lower NRS scores after interventions, immediately before positioning, at positioning and at end of spinal anesthesia. Pain scores during positioning for spinal anesthesia were statistically significantly lower in the PENG group than in the control group (p < 0.001). Total morphine use over the first 24 h was extremely statistically significantly lower in the PENG group (p < 0.001).Positive outcomes of PENG block in patient positioning pain before spinal anesthesia, postoperative pain scores, and morphine consumption are consistent with similar studies. High patient satisfaction in patients who underwent PENG block contributes to the literature.ClinicalTrials.gov Identifier: NCT04871061 Hip fracture surgery is a common orthopedic procedure, especially in elderly patients . These fUntreated/poorly managed perioperative pain is directly linked to delirium, bad prognosis, and secondary chronic pain in hip fracture patients . TherefoUltrasonography-guided (US-guided) regional anesthesia techniques are frequently used as part of a multimodal plan in the management of perioperative pain in patients with hip fractures. One of the most recently described blocks used in hip fracture surgery, US-guided pericapsular nerve group (PENG) block aims to directly block the articular branch of the femoral nerve, the articular branch of the obturator nerve and the accessory obturator nerve that selectively innervate the anterior aspect of the hip capsule . Case reHerein we investigate the effect of US-guided PENG block on positioning pain and compare that effect to intravenous opioid (fentanyl) in patients undergoing surgery under spinal anesthesia for a fractured hip. Additionally, we sought to investigate the effect of PENG block on pain scores, opioid intake, time to first analgesic requirement, and quality of recovery within the first 24 h following surgery.Local Ethics Committee  and Ministry of Health approval as well as clinicaltrials.org registration  was obtained for this prospective, randomized, controlled, assessored study. The study was conducted in the Anesthesiology Department at Çiğli Training and Research Hospital from May 2021 to May 2022. The CONSORT checklist for the study can be found in Fig. Patients aged between 35 and 90 years that were scheduled to undergo hip fracture surgery under spinal anesthesia were recruited for the study. Those with contraindications for spinal anesthesia or PENG block , dementia or similar cognitive function impairments that made participation in some components of the study inadequate, analgesia use within the last 12 h and those with another fracture or problem leading to chronic pain were excluded from the study. In addition, patients who were scheduled for urgent surgery due to hip fracture were excluded. Again, patients who could not obtain written informed consent to participate in the study were excluded from the study.Patients were separated into the PENG and control groups using the closed envelope method, one hour prior to surgery. Each patient was assigned a random ID that was used during all follow up and data collection. The same anesthesiologist performed randomisation and block in the PENG group (HA). However, this anesthesiologist was not involved in the evaluation of spinal anesthesia positioning pain evaluation or subsequent follow up.All patients were taken into the block room before surgery and transferred to the operating room thereafter. Evaluators who were blinded about the interventions and groups were taken to the room ‘just before the spinal anesthesia positioning’. This blinded assesor team  collected and evaluated all data such as spinal anesthesia positioning pain, postoperative pain, and opioid requirement.2 was administered via nasal cannula. Vascular access was obtained via the non-dominant hand. After appropriate skin antisepsis, all blocks were conducted with the in-plane technique, utilizing a 10 cm, 21G block needle using a convex USG transducer on the side of the hip fracture. The USG transducer was placed on the anterior superior spina iliaca in the transverse plane. Thereafter, the transducer was slowly shifted caudally to identify the spina iliaca anterior inferior, with the transducer positioned slightly obliquely, superolaterally and inferomedially. The transducer was positioned so that the femoral artery, femoral nerve, iliacus muscle, psoas tendon, iliopubic eminence and spina iliaca anterior inferior structures were all visible within the field of view. Particular attention was paid to avoid having the hip joint and femoral head within the field of view. The needle was advanced in-plane from lateral to medial until the needle tip was placed between the iliopsoas tendon (IPT) and periosteum, lateral to iliopubic eminence (IPE). First; 1–2mL of saline solution was injected to observe the spread under the iliopsoas muscle (IPM) with the IPT lifted up, then 20 mL of 0.25% bupivacaine was administered  was utilized to assess pain intensity. NRS, a unidimensional measurement of adult pain severity, is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (ranging from 0 to 10) that best depicts the degree of his/her pain. The 11-point numeric scale spans from ‘0’ for one pain extreme  to ‘10’ for the opposite pain extreme (e.g. “pain as bad as you can imagine” or “worst pain imaginable”).Time frames were defined as follows:Preoperatif NRS: NRS at rest before intervention (PENG or iv fentanyl).Prepositioning NRS: NRS score at rest immediately before positioning.Positioning NRS: NRS at positioning, 5 m after intervention in control group or 20 m after intervention in PENG group.Post-positioning NRS: NRS at rest following spinal anesthesia in the supine position.NRS was also measured, at rest, at the 3rd, 6th, 12th, 18th and 24th hours after the end of surgery.All patients received 1 g of iv paracetamol immediately following the end of surgery in the recovery room and every 6 h thereafter in the first 24 h, postoperatively. The patient-controlled analgesia (PCA) device was commenced intravenously in all patients in the recovery room. Patients were instructed to self-administer pain relief by pressing the PCA device when NRS ≥ 4/10. The PCA consisted of 0.5 mg/mL of morphine that was delivered without a basal infusion, followed by boluses of 1 mg each and a 20-minute lockout after each administration. Patient follow-up lasted for 24 h, PCA device was removed after 24 h.Primary outcomes were positioning pain scores - the maximum reported NRS score at 5 min after intervention in the control group and 20 min after intervention in the PENG group. Secondary outcomes were:Duration of spinal anesthesia performance: measured in minutes, from the start of positioning maneuvers to removal of spinal needle.Quality of patient’s position: evaluation of patient position by anesthesiologist that performed spinal anesthesia as “unsatisfactory”, “satisfactory”, “good” or “very good” .Analgesic consumption: Daily morphine consumption from PCA.In addition, parameters such as NRS scores, first analgesia requirement time, etc. were also evaluated in the above-mentioned time frames. At the postoperative 24th hour, the Quality of Recovery-15 (QoR-15) questionnaire was completed to determine the quality of recovery.A previously performed pilot study of 10 patients revealed the maximum NRS score when positioning for spinal anesthesia to be 4.2 ± 1.30 vs. 3 ± 1.22 in the control and PENG groups, respectively. This data was utilized using an alpha 5%, beta 10% and power of 95% to calculate a minimum sample size of 29 patients per group. Taking into consideration possible drop outs, loss to follow up and secondary outcomes, the decision was taken to have each group include 42 patients.Statistical evaluation of data was conducted with SPSS for Windows, Version 16.0. . Normal distribution was evaluated through the Kolmogorov-Smirnov test. Continuous variables were expressed as mean ± standard deviation, and median (25th–75th percentiles). Continuous variables of equal variance were analyzed using the t-test and non-normally distributed data with the Mann Whitney U test. Chi-square was used for comparison of ratios and categorical data was compared using Fisher’s exact test. Finally, Kaplan-Meier analysis and Wilcoxon test was used when comparing time to first analgesia requirement. p < 0.05 was accepted as being statistically significant in all data except for postoperative NRS scores, where after Bonferroni correction statistical significance was considered when p < 0.01.One hundred and sixty two patients were assessed for eligibility. Following the exclusion of 78 patients, a total of 84 patients were randomized into two groups. The CONSORT Flow diagram is shown in Fig. The demographic characteristics of participants are demonstrated in Table Preoperative NRS scores were similar between two groups (p = 0.0885). As the primary outcome of the study; patients that underwent PENG had statistically significantly lower NRS scores after interventions, immediately before positioning, at positioning and at end of spinal anesthesia . Additionally, the anesthesiologist evaluated the quality of the patient’s position, and it was statistically significantly higher in the PENG group when compared to the control group (p < 0.0001) Table .Table Requirement of first analgesia was later in the PENG group . NRS scores were significantly lower at 3rd, 6th and 12th hours in the PENG group, but similar at other times. According to the QoR 15 scores, which is a questionnaire used to measure the quality of recovery in patients, the PENG group demonstrated significantly better recovery quality compared to the control group .There were no complications that we detected or reported afterwards, either in the application of PENG block or in the application of spinal anesthesia.Herein we have demonstrated that application of a PENG block prior to spinal anesthesia in patients undergoing surgery for hip fracture not only reduces pain associated with spinal anesthesia positioning, but also increases practitioner satisfaction and decreases postoperative analgesic consumption compared to a control group. In addition, QoR 15 scores were found to be greater for patients that underwent PENG block.Current guidelines recommend fascia iliaca block or local anesthetic infiltration in hip fracture surgeries, where pain is highly expected . ControlIn a prospective mini-cohort investigating the effects of PENG block in patients undergoing hip surgery, PENG was applied to 20 consecutive patients undergoing hip surgery with satisfactory results reported with regard to spinal anesthesia positioning . HoweverIn a study where the effect of PENG block in hip fracture surgery was compared to femoral block, the authors aimed to evaluate the postoperative analgesic effects and quadriceps weakness in both blocks . This stOur study is the first to investigate the effects of PENG block on both spinal anesthesia positioning and postoperative analgesic efficiency and QoR 15 score. Undoubtedly, additional comparative research on the use of PENG block in hip surgery is required.Although some publications hypothesize that lumbar plexus-like effects can be seen in PENG block when using 30 mL or more of LA, such an effect is not expected with 20 mL. As a result, it is obvious that PENG block will be insufficient for cutaneous anesthesia. Therefore, better results may be obtained with the combination of PENG block with other blocks in patients undergoing hip fracture surgery. A volunteer study on the cutaneous innervation of hip surgeries reported that subcostal nerve block and transversalis fascia plane block could be effective . In ordeThe majority of patients undergoing surgery for hip fracture have a significant degree of fragility. This places patients at an elevated risk for LAST and compels clinicians to exercise greater caution. Volume and concentration of local anesthetic should be given careful consideration. In this investigation, we utilized 20 cc of local anesthetic for PENG block without experiencing any complications.Our study has some limitations. First of all, we did not assess quadriceps weakness in patients, which is crucial for early recovery. However, we did not observe any long-term consequences linked to quadriceps weakness. Secondly, we could have compared the efficacy of PENG block with a technique such as fascia iliaca block, which has previously been demonstrated to improve positioning in clinical studies. However such a design would mean we would have been unable to determine the long-term effects of PENG block by comparing it to a control group. Another limitation was that some patients in the control group had relatively high NRS scores, although all NRS scores were in the acceptable “bearable pain” category. Spinal anesthesia performance time is one of our outcomes, but it can also be affected by many factors of the patient such as anatomy, obesity, and other factors such as the experience of the practitioner.Our study has shown that preoperative PENG block is effective both in eliminating the pain associated with spinal anesthesia positioning, and in reducing the need for opioids in the postoperative period in patients undergoing hip fracture surgery. In addition, we have demonstrated that PENG block increases Quality of Recovery (QoR 15) score in these patients.PENG block in hip surgeries is associated with positive postoperative results.PENG block reduces the pain scores and morphine consumption postoperatively.PENG block significantly reduces pain scores during positioning for spinal anesthesia in patients with hip fractures.PENG block significantly increases Quality of Recovery 15 (QoR 15) scores during positioning for spinal anesthesia in patients with hip fractures.


Personality characteristics affect the long-term well-being and health-related quality of life (HrQoL) of breast cancer (BC) survivors. Persistent pain significantly affects psychosocial well-being and HrQoL in this patient group. We studied the effects of temperament and character via pain-related and psychological factors on dimensions of HrQoL in BC survivors.We studied 273 patients who had been treated for BC and who reported persistent pain at any site of the body in Brief Pain Inventory. The patients were recruited from a longitudinal cohort of patients 4–9 years after surgery for BC. Short-Form-36 inventory was used to assess physical and mental dimensions of HrQoL and Temperament and Character Inventory to assess dimensions of temperament and character. We used parallel mediation modeling for studying effects of temperament and character on physical and mental HrQoL.total = −0.665, p < 0.001) and character dimensions self-directedness (SD)  and cooperativeness (CO)  on physical and mental HrQoL. Additionally, different combinations of pain-related and psychological variables fully mediated the indirect effects of HA, SD, and CO on physical and mental HrQoL.A significant total effect was found for harm avoidance (HA) temperament (βHA temperament is a potential emotional vulnerability factor for psychological burden and impaired HrQoL in BC survivors. Character dimensions SD and CO may protect from the negative effect of mood on HrQoL. The results provide new insights about the risk-and target-factors for clinical interventions and effective pain management to improve psychosocial well-being and HrQoL in BC survivors. Breast cancer (BC) is the most common cancer among women in Western countries . Since oPersistent pain following BC treatments is often multifactorial  and affenovelty seeking (NS), harm avoidance (HA), reward-dependence (RD), and persistence (P) refer to stable and moderately heritable mechanisms of behavioral activation, inhibition, and maintenance. Character dimensions self-directedness (SD), cooperativeness (CO), and self-transcendence refer to concepts of coping and maturation, psychosocial adaptability, and spirituality that have been learned during a lifespan . All patients provided a written informed consent. Data concerning previous surgery and BC treatments were extracted from patient records.We included patients from a subgroup of 402 women who had a research visit during 2014–2016 regarding perioperative surgical nerve injury and persistent post-surgical neuropathic pain (PPSNP) . That coN = 312), were considered. In the second step, only patients who had a complete dataset on an independent variable  and on the main outcome variables  were included. The final study cohort consisted of 273 patients , where 0 indicates no pain and 10 worst pain imaginable, at any site of the body  questionnaire , which hFor SF-36 dimensions of physical and mental HrQoL were formed as composite scores of the first four subscales  and the last four subscales , respectively. Both dimensions ranged from 0 to 100 and higher scores indicate better performance in the dimension.novelty seeking, NS (range 0–40) (Cronbach α = 0.82); harm avoidance, HA (range 0–35) (Cronbach α = 0.89); reward dependence, RD (range 0–24) (Cronbach α = 0.71); and persistence, P (range 0–8) (Cronbach α = 0.56) and three character dimensions  (Cronbach α = 0.79); cooperativeness, CO (range 0–42) (Cronbach α = 0.79); and self-transcendence, ST (range 0–33) (Cronbach α = 0.86), based on a psychobiological model of temperament and character (We used the Finnish translation of the 240-item self-administered Temperament and Character Inventory (TCI)  with a tharacter .NS describes the activation or initiation of behaviors in response to novelty, HA the inhibition or cessation of behaviors, RD the maintenance or continuation of ongoing behaviors, and P perseverance of behavior despite of frustration and fatigue . SD refeHospital Anxiety and Depression Scale (HADS) was used to assess both anxiety (Cronbach α = 0.82) and depressive (Cronbach α = 0.88) symptoms . Pain CaWe used Brief Pain Inventory (BPI) to assess severity and interference of self-reported pains during the past week . Patientp ≤ 0.05 were considered statistically significant.Statistical analyses were performed using SPSS 25.0 for Windows . Descriptive statistics are presented as mean , median , or number (percentage). Pearson’s correlation was used to assess associations between the continuous variables. Results with For all statistical analyses, included variables were standardized by using the mean and S.D. of each variable . Cronbach’s alpha (α) was used for reliability assessment for all psychological variables. For an exploratory statistical approach, we used parallel mediation modeling with multiple mediators. Mediation analyses were done by running a separate mediation analysis for each independent and dependent variable. The personality dimensions and the mediators were selected based on significant correlations between the independent variables and the main outcome variables to fulfill the criteria for mediation analysis . The othmodel 4  and the effect of exposure of an independent variable on the outcome variable with  and without (direct effect) the mediators were reported. The lower limit (LL) and the upper limit (UL) of the confidence interval (CI) were used to test statistical significance of the IE .Demographics, surgery, and treatment related factors of the 273 included patients are presented in Of the 273 patients, 22 (8.0%) used neuropathic pain medications, such as tricyclic antidepressants, gabapentinoids , or serotonin and norepinephrine reuptake inhibitors. Further, 63 (23.1%) used mild opioids, non-steroidal anti-inflammatory drugs, or paracetamol.Descriptive statistics of the assessed pain-related and psychological instruments, including temperament and character dimensions and HrQoL, are presented in p = 0.016) and HA (p < 0.001), and with character dimensions SD (p = 0.013) and CO (p = 0.046). Mental HrQoL correlated significantly with HA (p < 0.001), SD (p < 0.001), and CO (p = 0.005) (p = 0.385), SD (p = 0.607), and CO (p = 0.633), and for pain interference with SD (p = 0.303) and CO (p = 0.402). According to the criteria for mediation analysis, non-significant correlations were excluded from the mediation analyses. All of the potential mediator variables correlated significantly with dimensions of physical and mental HrQoL  . Of the al HrQoL . Intercoharm avoidance (HA) on physical HrQoL  and mental HrQoL  was significant, while the direct effects was not. Depressive symptoms , pain catastrophizing , and pain interference , fully mediate the relationship between HA and physical HrQoL and contribute to the overall IE  and anxiety  fully mediate the effect of HA and contributed to the overall IE  on physical HrQoL  and mental HrQoL  was significant, while the direct effects was not. Depressive symptoms , and pain catastrophizing  fully mediate the relationship between SD and physical HrQoL  and anxiety  fully mediated the effect of SD  on physical HrQoL  and mental HrQoL  was significant, while the direct effects was not. Depressive symptoms , and pain catastrophizing  fully mediate the relationship between CO and physical HrQoL  and anxiety  fully mediated the effect of CO . These might be a target for therapeutic interventions in patients with pain and high HA-related features . CognitiAfter BC treatments, persistent postsurgical pain  and uppeThere are limitations of the study. First, our data consisted only of women who had been treated for BC. Thus, the results cannot be directly generalized to healthy participants, other chronic diseases, or males. Additionally, as the patients with ongoing cancer treatments might suffer from acute side effects of the adjuvant therapies and pronounced psychosocial burden of disease, the results may not be generalized to the patients with active disease. However, a strength of this study is the homogenous and well characterized cohort of patients treated for BC.Secondly, the limited sample size may limit making prominent conclusions. However, to the best of our knowledge, this is one of the largest patient sample related with temperament and character in BC survivors.Thirdly, the study design was observational and cross-sectional. Therefore, despite of the mediation models, conclusions about the causality between studied variables cannot be drawn . In the Fourthly, most measurements were based on self-reports, which may differ from clinical assessment and therefore affect the results. It is possible that the measurement of personality dimensions can be affected by the presence of persistent pain .harm avoidance temperament is a potential vulnerability factor for greater psychological burden of disease and impaired HrQoL in BC survivors. High self-directedness and cooperativeness character may protect from the negative effects of anxiety and depressive symptoms on HrQoL. From a multidisciplinary point of view, our results may provide new insights about the risk-and target-factors for clinical interventions and emphasize the importance of effective pain management to improve psychological health and HrQoL in BC survivors.High The 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 Ethics Committee of the Helsinki and Uusimaa Hospital District (reference number: 149/13/03/00/14). The patients/participants provided their written informed consent to participate in this study.EK, HH, and RS designed the study. HH and RS collected the data. TA analyzed the data supervised by JL and prepared figures and tables. TA wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.This study was funded by the European Union FP7 , NeuroPain.EK has provided consultancy to Orion Pharma and Pfizer and HH to TEVA, Allergan, and Lilly, unrelated to this work.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.