Excisional hemorrhoidectomy (EH) is the major surgical option for high-grade symptomatic hemorrhoids, but it has some shortcomings, especially postoperative pain. This study was performed to assess the effect of lateral internal sphincterotomy (LIS) in patients undergoing excisional hemorrhoidectomy.A systematic literature search  was performed to identify all eligible articles. Randomized controlled trials (RCTs) published until July 7, 2017 comparing EH combined with LIS  with EH only (control group) were eligible for inclusion. The primary outcome of interest was postoperative pain.P = .0002] and resting anal pressure , and lower incidence of anal stricture . However, the differences of urinary retention, bleeding and length of hospital stay were similar between the 2 methods.Ten RCTs involving 1560 patients were identified for inclusion. The pooled analysis revealed that patients undergoing EH and LIS were associated with lower pain score [standardized mean difference (SMD), −0.75; 95% confidence interval (CI), −1.14 to −0.36; z = 3.76; Our meta-analysis suggests that LIS effectively relieves postoperative pain and reduces patient's postoperative analgesic requirements. LIS also reduces the incidence of anal stenosis but increases the incidence of fecal incontinence. And excisional hemorrhoidectomy (EH) is the most effective treatment for high-grade symptomatic hemorrhoids with a 2% medium-term recurrence rate and a 10% long-term recurrence rate.A high prevalence of hemorrhoids (up to 40%) is found during screening colonoscopy in the general population,,4 Therefore, different methods and techniques have been employed to overcome this inevitable problem.However, EH has some shortcomings, especially postoperative pain. The cause of this postoperative pain is multifactorial. One contributory factor may be spasm of the internal anal sphincter (IAS), which is exposed and impinged after EH.Lateral internal sphincterotomy (LIS) is a widely used adjunct treatment following EH. Its advocators have stated that LIS can abolish spasm of the IAS and subsequently relieve postoperative pain. However, this view has not been consistently supported by recent clinical trials. Some researchers have reported limited ability of LIS to relieve postoperative pain and increased incidence of other complications, such as bleeding and fecal incontinence. Few large-sample prospective clinical trials involving this problem have been performed to date, and the precise role of LIS following EH remains controversial.The primary objective of this systematic review was to analyze existing randomized controlled trials (RCTs) regarding the effect of LIS on postoperative pain in patients undergoing EH and perform a meta-analysis of postoperative pain, other complications, and length of hospital stay.22.1A systematic literature search  was performed to identify all eligible articles. RCTs published until 7 July 2017 comparing hemorrhoidectomy combined with LIS  with hemorrhoidectomy only (control group) were eligible for inclusion. The following Medical Subject Headings were used: “hemorrhoids,” “pain, postoperative,” “sphincterotomy,” and “hemorrhoidectomy.” Their combinations or similar headings were also searched, including “hemorrhoid,” “postoperative pain,” “internal sphincterotomy,” “lateral sphincterotomy,” and “Milligan-Morgan.” A personal search was also performed using the reference lists of the retrieved relevant articles and reviews to identify additional trials and ensure that all potential studies were included.2.2All included trials were required to fulfill the following criteria: designed as an RCT, involved humans and were published in English, provided clear documentation of “LIS and EH” as the treatment in the experimental group, reported the treatment as “EH” in the control group, and when 2 or multiple studies were published by the same institution and/or authors, either the higher-quality study or the most recent trial was included in the meta-analysis. Studies were excluded if it was impossible to extract the appropriate data, such as abstracts, case reports, letters, reviews, and commentaries; there was no control group; the number of cases was <20; and the follow-up duration was <2 weeks.2.3Two authors (W-GW and W-ZL) independently scanned the title and abstract of each publication to identify potentially eligible studies. The full articles were then obtained for detailed evaluation. Any disagreement in the selection process was resolved through consensus. If this failed, a third author (H-BH) adjudicated.2.4The following outcomes were compared among the included studies: postoperative pain, postoperative analgesic requirement, fecal incontinence, anal stricture, urinary retention, bleeding, and duration of hospital stay.The primary outcome of interest was postoperative pain. For the purpose of comparing pain scores, the highest pain intensity during the first 24 hours after the operation was compared among the included trials. All pain scores or numeric rating scale scores were converted to a scale of 0 to 10.2.5Two authors (C-MY and K-QY) independently extracted data from all eligible studies using standardized forms. The following data were extracted from each study: first author, country, study period, study design, participant characteristics, technical results, definition of clinical results, and outcomes during the follow-up period. Any disagreements were resolved using the same method mentioned above. We also attempted to contact the authors of all eligible RCTs if any missing data or inaccurate information was encountered.2.6 Any disagreement was resolved through consensus.The Cochrane Risk of Bias tool was used to assess the quality of the RCTs.2.7In this study, the extracted data was collected from published studies. Based on this, it did not require ethical approval. The results of this study will eventually be published in a peer-reviewed journal.2.8,7 Statistical analysis of dichotomous variables was carried out using the odds ratio (OR) as the summary statistic, while continuous variables were analyzed using the standardized mean difference (SMD); both were reported with the 95% confidence interval (CI). The OR represented the odds of an adverse event occurring in the LIS + EH group versus the EH-only group, and it was considered statistically significant at P < .05 if the 95% CI did not include the value 1. The SMD summarized the differences in continuous variables between the 2 groups, and it was considered statistically significant at P < .05 if the 95% CI did not cross the value 0. Heterogeneity between studies was measured using χ2 and I2, and I2 > 50% was considered statistically significant. Either a fixed-effects model or random-effects model was applied to calculate the pooled effect based on the heterogeneity. However, a random-effects model was used first to assess the heterogeneity. A sensitivity analysis, with 1 study removed from the meta-analysis at a time, was performed to assess the stability of the results. All statistical analyses were conducted using the statistical software Review Manager (version 5.3).The meta-analysis was performed in line with the recommendations of the Cochrane Collaboration and the Quality of Reporting of Meta-analyses guidelines.33.1,8–16 The quality of the RCTs is shown in Figure In total, 167 articles were obtained using the above-described search strategy. After the screening process, however, 103 articles were excluded. Of the remaining 64 articles, 54 were excluded and 10 RCTs were finally included in the review . In the random-effects model , the pain score was significantly lower in the experimental group of patients undergoing EH and LIS than in the control group of patients undergoing EH only     of patients in the experimental group but in only 1.8% (13/711) of patients in the control group. The meta-analysis showed a significant difference between the 2 groups  . In the random-effects model, the incidence of urinary retention was similar between the 2 groups  , but the other 2 studies did not find a significant difference between the 2 groups.,13 Furthermore, the meta-analysis did not show a significant difference in bleeding  , I2 = 93%], the hospital stay showed no significant difference between the 2 groups in the random-effects model   Fig. E.3.8Because of the insignificant results in the sensitivity analysis, the stability of the meta-analysis was proved when each study was deleted from the pooled analysis.3.9A funnel plot of the incidence of postoperative pain is shown in Figure 4To the best of our knowledge, this is the first systematic review and meta-analysis of RCTs evaluating the effect of LIS in patients undergoing EH. As one of the most important complaints after EH is postoperative pain that may be associated with several secondary complications such as difficult defecation, urinary retention, and a prolonged hospital stay. An accurate and comprehensive assessment is essential to effectively monitor the severity and duration of postoperative pain and ensure proper management of postoperative pain. Patient self-reporting, which is based on trust, cartoons, or imaginary data and reveals the subjectivity of postoperative pain, is currently a popular observational measurement for researchers.Postoperative pain is an unpleasant physiological and emotional experience following surgical damage.P < .00001, I2 = 83%). The heterogeneity presented the current research status of all included RCTs. Currently, more than 25 types of pain scales were applicable to target population with different characteristics: neonates, infants, children, adolescents, adults, older person, and persons whose communication is impaired. So inherent subjectivity and interindividual variation are basic characteristics of the postoperative pain scale scores among include RCTs. Furthermore, the technical characteristics of pain management . For severe anal stricture, however, a formal anoplasty is more efficient than LIS to treat the loss of anal tissue.Furthermore, due to decrease in anal pressure, LIS is believed to prevent anal stricture, a rare but serious complication after EH. Anal stricture develops in only 5% of patients after EH but always results in serious outcomes such as anal pain, constipation, obstipation, and bleeding. This is one of the most frequent complaints following EH (6.6% of patients). But postoperative anorectal manometry is not the routine test after EH. Only 3 RCTs performed postoperative anorectal manometry and reported a significant decrease in the resting anal pressure in patients undergoing EH and LIS. The drawback of existing RCTs is the short of long-term manometric study. LIS is also performed to resolve anal fissure. The change of anal pressure had been evaluated following LIS in patients with anal fissure. In 2005, Edward et al performed a prospective study that included 50 patients with anal fissure and 12 healthy volunteers. In their studies, the resting anal pressure was significantly decreased after LIS and gradually increased within 1 year after surgery but still remained significantly lower than before surgery. Other similar results were also reported. Lewis et al reported the incidence of fecal incontinence is 17% in their patients after LIS and 2/3 of fecal incontinence were only temporary. Khubchandani et al reported the incidence of fecal incontinence is 22% in their patients and 35.1% of these patients was classified grade 1. These results reported the long-term, dynamic, minor, temporary, and acceptable change of anal pressure after LIS. Some studies have assessed the efficacy of several drugs, such as nitroglycerin and botulin toxin, for temporary relaxation of the IAS to help wound healing while avoiding permanent damage to the IAS. The long-term advantage of these drugs is limited. But in general, the changes of IAS and anal pressure regarding the effect of LIS in patients undergoing EH needed to be proved in further long-term manometric study.Nevertheless, our results show that decrease in anal pressure causes another complication after EH, namely fecal incontinence, which always occurs with an anal pressure of <40 mm Hg. In the present meta-analysis, the incidence of urinary retention was 14.0%. However, the difference was not significant between patients who did and did not undergo LIS following EH. The exact mechanism of urinary retention remains unclear; it might be caused by dysfunction of the detrusor muscle and the detrusor of the anal canal. Furthermore, many risk factors for urinary retention have been documented in previous studies: advanced age, sex, anesthesia methods, severity of hemorrhoids, perioperative fluid administration, hospital stay duration, and others.,37 Therefore, sufficient evidence with which to prove the effect of LIS on urinary retention is lacking.Urinary retention is another common complication after EH.The incidence of postoperative bleeding was also similar between patients who did and did not undergo LIS following EH. Most patients develop mild early postoperative bleeding after EH, especially during defecation. However, such bleeding is always temporary and resolves without intervention. The similar incidence of postoperative bleeding between the 2 groups proves that LIS is a safe additional intervention in patients undergoing EH.Because of the effective decrease in postoperative pain, performing LIS within EH may also shorten patients’ hospital stay and allow them to return to their normal activities of daily life. However, only 3 studies assessed the hospital stay, and the decrease in the hospital stay was not significant in our meta-analysis. Different centers usually apply different hospital discharge criteria, which may have contributed to the heterogeneity of the hospital stay among the studies in this meta-analysis.Several limitations of this meta-analysis should be taken into account. First, only English-language articles and no unpublished trials were included in this meta-analysis. Second, various pain assessment scales were used, and a unified definition of postoperative pain  was lacking. Finally, the sample size of most included studies was relatively small.5LIS, an additional intervention to EH, effectively relieves postoperative pain and reduces patients’ postoperative analgesic requirements. LIS reduces the incidence of anal stenosis but increases the incidence of fecal incontinence. The effect of LIS in patients undergoing excisional EH should be assessed with well-designed, high-quality, large-sample RCTs in the future.W-GW and H-BH designed the study, W-GW and W-ZL collected related data, W-GW performed most of the research, W-GW wrote the manuscript, H-BH offered valuable suggestions, and C-MY and K-QY edited the manuscript.Data curation: Wen-Zhu Lu.Formal analysis: Wei-Guo Wang.Investigation: Chun-Mei Yang.Methodology: Wen-Zhu Lu.Project administration: Ke-Qiang Yu.Validation: Ke-Qiang Yu.Visualization: Chun-Mei Yang.Writing – original draft: Wei-Guo Wang.Writing – review & editing: Hong-Bo He.


Using a 50% reduction on the NRS as a full response criterion, we could identify 57.1% of responders on phenytoin 10% cream and only 9.5% responders on placebo cream. Conclusions: The SIBRET helps patients and clinicians to quickly identify the appropriate treatment and can thus be seen as an important contributor to the domain of personalized medicine in pain. These results can also be regarded as a proof of principle for the analgesic activity of 10% phenytoin cream.Background: Phenytoin cream applied topically has been explored in neuropathic pain conditions. In several case series, phenytoin 5% and 10% cream could reduce pain in a clinically relevant way with a fast onset of action within 30 min, and with positive effects on sleep. Objective: To evaluate a single-blind placebo-controlled response test (SIBRET) for use in clinical practice. Materials and Methods: Patients with localized neuropathic pain, having an equal pain intensity in at least 2 areas , and a pain intensity of at least 4 on the 11-point numerical rating scale (NRS), were selected to perform the SIBRET. In one area, placebo cream consisting of the base cream was applied, and on the other area, phenytoin 10% cream was applied with separate hands to avoid contamination. Responders were defined as patients who experienced within 30 min at least 2-points difference as scored on the NRS, between the phenytoin 10% and the placebo cream applied areas, in favor of the former. Responders were subsequently prescribed phenytoin 10% cream. Results: Of the 21 patients, 15 patients (71.45%) were classified as responders. The mean pain reduction after 30 min as measured with the NRS in the phenytoin 10% cream area was 3.3 (SD: 1.3) and in the placebo cream area 1.2 (SD: 1.1). The difference of the mean percentage pain reduction between phenytoin 10% cream and placebo cream was 33.2% (SD: 17.6,  Localized neuropathic pain is difficult to treat, with existing treatments requiring high numbers (between 3.7 and 9.0), and therefore, new treatment modalities are needed . TopicalSince 2010 we have prescribed many compounded creams, including phenytoin in a dose-range of 5% up to 30% at our Institute for Neuropathic Pain. So far, after treating more than 100 patients with phenytoin cream, there have not been reported any dose-limiting side-effects or major tolerability problems. In two cases, mild transient irritation of the skin was reported.The effects of topical phenytoin cream in neuropathic pain has been described as a reduction of overall pain, a reduction of allodynia, and an improvement in quality of life due to positive effects on sleep ,4,5,6,7.The fast onset of action induced by phenytoin cream led us to develop a single-blind placebo-controlled response test (SIBRET) to allow for assessment of which part of the perceived analgesic effect can be attributed to the active compound in the cream, and which part to the placebo. Furthermore, the test helped us to identify the responders during their first clinic visit and reduce the chances that patients would, after an initial placebo response of some weeks, end up as non-responders to the cream. This SIBRET helps the patients and clinicians to rapidly identify the appropriate treatment and can be seen as one aspect in the domain of personalized medicine. Recently, in a cohort of 70 patients, SIBRET was performed in 12 patients .The described single-blind test paradigm is simple and takes only a few minutes to conduct. Patients are entered in the test if they qualify as patients suffering from neuropathic pain with at least an NRS of 4. The pain has to be in two different areas and has to be preferably symmetrical, usually manifesting in both feet. The SIBRET can also be performed when one area is large enough to divide the area in 2 places .One-point difference in baseline NRS between both pain areas should be the limit of accepting the patient to enter the SIBRET. If, after the SIBRET, phenytoin was clearly superior to the placebo cream, we prescribed phenytoin cream 10%. In the case of phenytoin non-responders, we would prescribe a different compounded cream, such as amitriptyline 10% cream. All creams, phenytoin, placebo and amitriptyline cream were compounded with the same base cream, and creams could not be distinguished from each other.Our responder definition of at least 2-points difference on the NRS in pain reduction between the phenytoin and placebo cream is in line with the recommendation that a clinical relevant cut-off point for the absolute reduction on the NRS should be at least 2 . Such reThis SIBRET is a prelude to a subsequent treatment phase in responders and can therefore be seen as a way to enrich the population we treat. The term enrichment is defined by an U.S. Food & Drug Administration Guidance for Industry document as the prospective use of any patient characteristic to select a study population in which detection of a drug effect (if one is in fact present) is more likely to occur, than it would be in an unselected population . The useRecently, enrichment designs have been developed for patients who are screened and selected by their biomarker status in such a way that only biomarker-positive patients enter the trial . The advThe question whether such SIBRET, used as a diagnostic tool to identify responders, is ethically acceptable without agreement from an institutional review board, is addressed by the American Medical Association Council on Ethical and Judicial Affairs . PhysiciFrom February 2017 to October 2017, data was collected from patients who underwent a SIBRET in our center. Pain intensity before and after test application was measured on the NRS. One-point difference in baseline NRS between both pain areas was the limit of accepting the patient to enter the SIBRET. Furthermore, we included patients with a pain intensity of at least 4 on the NRS. Patients then received an equal amount  of placebo cream and phenytoin cream for application on the 2 different areas, rubbing the creams in where it hurts with separate hands to avoid contamination. Responders were defined as patients who experienced within 30 min at least 2-points difference as scored on the NRS between the phenytoin 10% and placebo cream applied areas in favor of the former. The instruction given by the physician before applying the creams was: “I would like to offer you to test one cream on one pain area, which I believe can help to lessen your suffering without knowing how it exactly works. The other cream I would like to offer you to test for the other area, the working mechanism is clearer, though side effects can occur. After 30 min, you will tell us whether there is a difference in pain scoring on the NRS, and based on your evaluation we know what best to prescribe you.” This way of informing the patient has been presented in the bioethical literature as optimal for such situations .Descriptive statistics were used. To compare means of pain reduction after the application of phenytoin 10% and placebo cream on different areas in the same patient, the Wilcoxon signed-rank test was performed (matched pairs). We calculated the number of patients achieving minimum pain relief (MPR) from baseline of 30% (moderate benefit: MPR30) and 50% (considerable benefit: MPR50) measured on the NRS. The McNemar’s test was used for the dichotomous variables MPR30 and MPR50 to determine statistically significant differences between the areas on which phenytoin 10% and the placebo were applied. As described earlier, the standard phenytoin plasma determination was measured with high-performance liquid chromatography of the plasma protein bound phenytoin concentration, which is approximately 90% of the total phenytoin in plasma ,19. The In total, 21 patients were entered into the SIBRET. Nine patients were female (42.9%) and 12 patients were male (57.1%). The age of the patients ranged between 49 years and 89 years, with a mean age of 64.4 years (SD: 9.2). The diagnoses are summarized in p < 0.001) between scores. In total, 15 patients (71.45%) experienced at least 2-points pain reduction difference on the NRS, in favor of the phenytoin 10% cream. An exact McNemar’s test determined that there was a statistically significant difference in the proportion of MPR50 after application of phenytoin 10% cream and placebo cream, p = 0.002 (p < 0.001 (The mean reduction on the NRS in the phenytoin 10% area was 3.3 (SD: 1.3) and in the placebo area 1.2 (SD: 1.1) within 30 min. The difference of the mean percentage pain reduction between phenytoin 10% cream and placebo cream was 33.2% . In 10 other patients, no plasma levels were detected even after the application of 6.7 g of phenytoin 10% cream in one case .In our clinic, we see many patients suffering from localized neuropathic pain. Most patients suffer from pain due to polyneuropathy, which is a symmetrical pain, often burning, that keeps them awake during the night. The fact that in localized neuropathic pain, sensations are often symmetrical, provoked us to develop blind intra-patient test paradigm (SIBRET and DOBRET), in essence these are pharmacological challenge paradigms. All patients suffering from localized neuropathic pain, and with a pain score at least 4 on the NRS, were entered in this test.Patients had a mean base-line pain score of around 6 on the NRS. The placebo cream resulted in a mean reduction of 1.2 on the NRS. The phenytoin 10% cream resulted in a mean reduction of pain of 3.3 on the NRS, which was more than 50% mean reduction compared to baseline. Placebo cream reduced pain in a much lesser way, and the magnitude of the effect is not considered to be clinically meaningful.The strength of our SIBRET paradigm is that we can monitor the response of the patient within a short period of time, and the patient is his/her own control. Because no phenytoin plasma levels were found and the pain reduction in responders occurred within 30 min, local pain reducing mechanisms are very likely . The judicious use of the placebo in a therapeutic context needs not automatically entail a violation of the doctor’s obligation to heal, depending on the means by which the placebo is presented to the patient . In the Phenytoin is a broad acting sodium channel blocker , and useWe have noticed that patients are able to distinguish between analgesic effects of different creams when applied to both feet. The special situation of being able to compare within the same time frame, both the effects of active medication and of placebo makes this pharmacological challenge paradigm unique and quite well adapted for testing topical analgesics. This SIBRET in 21 patients serves as a proof of principle supporting the pain reducing effect of 10% phenytoin cream in the treatment of localized neuropathic pain.


Background and objectivesPain is the primary reason that dental patients seek endodontic therapy. The inferior alveolar nerve block (IANB) is the most frequently used mandibular injection technique for achieving local anesthesia for endodontic treatment. However, the IANB does not always result in successful pulpal anesthesia. Therefore, the purpose of this study was to determine the effects of preoperative administration of both ibuprofen and ketorolac on the efficacy of the IANB in patients with irreversible pulpitis.MethodsA total of 60 patients diagnosed with irreversible pulpits of a mandibular posterior tooth randomly received identical capsules of either 400 mg ibuprofen or 20 mg ketorolac or a placebo 1 hour before the administration of a conventional IANB. Access was initiated after profound lip numbness was achieved. Success was defined as no, mild, moderate, or severe pain  on accessing the dentin, pulp, and debridement.ResultsKetorolac was associated with superior efficacy in pain reduction when compared with ibuprofen and placebo in all parameters, namely the dentin, pulp, and canal debridement.Interpretation and conclusionIn conclusion, for mandibular posterior teeth, a preoperative dose of 400 mg of ibuprofen or 20 mg of ketorolac showed a statistically significant increase in the success of the IANB in patients with irreversible pulpitis. For the endodontic treatment to be considered successful and accepted readily by the patient and dentist, it must efficiently relieve pain. Local anesthesia, through inhibition of nociceptive signals, is integral to the management of painful endodontic emergencies . A studyProstaglandin-induced sensitization of peripheral nociceptors has been commonly implicated in the high failure rate of local anesthesia in symptomatic teeth with irreversible pulpitis, which is caused by inflammation -6. Non-sThe aim of this study is to compare the effectiveness of pre-operative oral medication with ibuprofen and ketorolac on anesthetic efficacy in an IANB with 1:80000 epinephrine in patients with irreversible pulpitis.n = 20 per each group. Patients with symptomatic irreversible pulpitis of any molar teeth that responded to cold testing with an ice stick and an electric pulp tester without periapical radiolucency on a radiograph, except for widened periodontal ligament, with good systemic health were included. Patients who had NSAIDs within 12 hours of administration of the study drugs, pregnant and breastfeeding patients, and those with a history of active peptic ulcer or bleeding or anticoagulant use within the last month were excluded. The participants received information regarding the nature of the study. Written consent was obtained from each participant.This was a randomized controlled trial. The study plan was approved by the institutional ethical committee . Using n - Master Sample Size Calculation Software with 88% power and 95% confidence interval, the sample size was found to be 60, that is, Prior to injection, the experimental tooth and the contralateral tooth were tested with a Digitest electric pulp tester  to obtain a baseline score. Subsequently, patients with prolonged response to the cold test were selected. The study patients were grouped into three categories based on oral analgesics as follows:n = 20): without premedicationGroup 1 (n = 20): with premedication of ibuprofen tabletGroup 2 (n = 20): with premedication of ketorolac tabletGroup 3 . The treatment was divided into three phases: access into dentin, access into the pulp chamber, and canal instrumentation. Using a VRS, the extent of pain was recorded within the dentin and pulpal space and during canal instrumentation.The data were subjected to descriptive statistics and, non-parametric tests by using SPSS software, version 23 . Table P < 0.001; Table The frequency distribution and median of dentin pain based on VRS scores among various groups calculated using chi-square test were highly statistically significant , calculated using the chi-square test (Table The frequency distribution and median of debridement pain VRS scores between various groups were highly significant (st Table .P < 0.001) compared with that of ibuprofen (P < 0.012); the efficacy of the placebo was not statistically significant compared with the baseline (P > 0.132). In baseline versus pulp extirpation, the efficacy of ketorolac (P < 0.016) and ibuprofen (P < 0.025) was statistically significant and that of placebo (0.739) was statistically non-significant. In baseline versus canal debridement, all three median pain scores showed high significance; ketorolac: P < 0.001, ibuprofen: P < 0.001, placebo: P < 0.001. In dentin removal versus pulp extirpation, the ketorolac (P < 0.001) group was highly significant compared with the placebo (0.034), and ketorolac and the placebo were statistically significant and statistically nonsignificant, respectively, compared with ibuprofen (0.166). In dentin removal versus canal debridement, all three groups showed high significance; ketorolac: (P < 0.001), ibuprofen: (P < 0.001), and placebo: (P < 0.002). In pulp versus canal debridement, all three groups showed high significance; ketorolac: P < 0.001, ibuprofen: P < 0.001, and placebo: P < 0.001  to assess the significant difference in pain scores at various locations in each group. For individual comparison, Wilcoxon signed-rank test was performed. Median pain scores at baseline versus the dentin group showed statistically significant efficacy of ketorolac  score was done performed using Kruskal-Wallis test , whereas Mann-Whitney U test was performed for individual pairwise comparisons. At every location, the ketorolac group showed low pain scores, whereas the placebo group showed the highest pain scores. Therefore, the ketorolac group presented the highest premedication pain reduction compared with the ibuprofen and placebo groups.P < 0.001) as per Friedman value 54.326 ; in the pulp, the mean rank was 25.25 and median was 3(25%); and in the debridement, the mean rank was 15.58 and median 1(75%), which was highly significant  showed a success rate of 85% and 95% with conventional and Gow-Gates techniques, respectively . LidocaiThe precise level of vasoconstrictor in a local anesthetic solution necessary to provide sufficient pulpal anesthesia is unknown. The clinical application of a vasoconstrictor is to attain hemostasis, decrease absorption into the cardiovascular system, and increase the duration of anesthesia. The present study agrees with the findings by Dagher et al. (1997) where the different concentrations of epinephrine  with 2% lidocaine in the IANB showed no significant difference in the success rates .Patients with irreversible pulpitis presented an eight-fold higher failure of local anesthetic injections than control patients ,12. TherPulpal pain is a type of visceral deep somatic pain; therefore, it has a high threshold and poor localization. Several studies have shown that inflammation increases the interstitial fluid pressure in the dental pulp. The absolute magnitude of the pressure increase in the locally inflamed area varied considerably. Dendritic cells present in the pulp release interleukin-8, which serves as a powerful chemotactic agent for other inflammatory cells, including neutrophils, macrophages, and mast cells. Histamines released from mast cells are potent vasodilators that cause vasodilation of arterioles and leakage of venules, which further increases inflammatory infiltration in the pulp and their chemical mediators. This increase in the infiltrate has two main consequences, both of which are synergetic: increase in tissue pressure and increase in inflammatory infiltration.Prostaglandins upregulate various mechanisms that may decrease the efficacy of local anesthetics. Voltage-gated sodium channels are the target of local anesthetics. More than nine subtypes of sodium channels exist. Nociceptors express a tetrodotoxin-resistant class of voltage-gated sodium channels that are relatively resistant to lidocaine and are sensitized by prostaglandins. The specific isoforms Nav1.8 and Nav1.9 play a key role in the generation and maintenance of inflammatory pain. Prostaglandins alter the kinetics of the channels’ activity resulting in increased depolarization, whereas the actual channels themselves are expressed at higher levels . In a reTherefore, ibuprofen and ketorolac were used in this study as they reduce the inflammatory action and treat mandibular molars with irreversible pulpitis. Before beginning the procedure, baseline scores are noted as per the VRS using an electric pulp tester for each tooth. No pain was scored as 1; mild pain of score 2 was not shown in any group. The ketorolac group showed a moderate pain score 3 (15%) and severe pain score 4 (85%). The ibuprofen group showed 30% with score 3 and 70% with score 4. Placebo showed 25% with score 3 and 75% with score 4. VRS was used in this study as it can be readily assessed, is less time-consuming, can be performed without paper and pen, simple to understand for patients, and provides a correlation that is more definitive than a distance mark in a VAS.To re-confirm the vitality of the pulp, the cold test was performed using spray refrigerant (Endo Ice) on a cotton pellet applied to the facial cervical areas of the teeth to be tested. Response to cold should be relatively consistent among normal teeth in a given area. Typically, a normal response would be immediate, possibly sharp and intense, but brief in duration (below 10 seconds). Duration and relative intensity of response was the key to making a diagnosis. An abnormal response would include one that is severe relative to surrounding teeth, or one that lasts longer than 10 seconds. Subsiding of pulsing or throbbing after the initial response would also be considered abnormal, a sign of irreversible pulp damage.The odds of an accurate positive cold response as an indicator of pulp vitality is 90% versus 83% with the heat test and 84% with the electric test . FurtherIn this study, the ibuprofen group showed 50% pain reduction in canal debridement, 25% in both pulp and dentin, and 0% in the baseline. Ibuprofen is a propionic acid derivative of NSAIDs and an effective analgesic, anti-inflammatory, and antipyretic and inhibits the synthesis of prostaglandins in body tissues through inhibition of cyclooxygenase-1 and -2. Ibuprofen 400 mg was used in this study as the daily recommended dose is 1200 mg/day (14 mg/kg) as per the Food and Drug Administration and Nonprescription Drug Advisory Committee. The over-the-counter dosing regimen of 200-400 mg has been shown to provide effective analgesia and allow flexibility in dosing where necessary.In contrast to the present study, Seymour and Ward compared 200, 400, and 600 mg ibuprofen and noted a trend toward improved relief with 600 mg compared with 400 mg. Nielsen et al. showed that 800 mg ibuprofen was superior to 400 mg in a study of laser-induced pain -18. OlesIn a study by Vivek Aggarwal et.al. on irreversible pulpitis, premedication with IANB showed that ketorolac, ibuprofen, and placebo were associated with 39%, 27%, and 29% success rates, respectively . NeighboWithin the limitations of the study, it can be concluded that ketorolac is effective in the reduction of pre-operative pain in symptomatic teeth with IANB 1 hour prior to treatment.


Herpes zoster (HZ) is a painful dermatomal rash caused by reactivation of latent varicella zoster virus surviving in the patient’s sensory ganglia after a previous episode of varicella. The incidence of HZ increases markedly with age as does the proportion of HZ patients who develop postherpetic neuralgia (PHN) with often severe and debilitating pain persisting for months and even years.This prospective study aimed to assess the impact of HZ and PHN on the quality of life (QoL) of individuals aged ≥ 50 years in Germany.Patients were recruited when consulting primary care physicians for a first HZ episode. PHN was defined as a ‘worst’ pain score ≥ 3 on the Zoster Brief Pain Inventory (ZBPI) scale persisting or appearing 90 days or more after rash onset. PHN-cases were followed for up to nine months after rash onset. The interference of pain with patients’ ability to carry out normal activities was assessed by the ZBPI activities of daily living (ADL) scale and QoL by the EuroQoL five-dimension scale (EQ-5D) utility score.Of 513 patients enrolled, 61 (11.9%) developed PHN. At HZ onset, the mean ZBPI worst pain score of all patients was 5.1, the least square (LS)means estimates of the ZBPI ADL and EQ-5D utility scores were 2.970 and 0.740, respectively. Over three months follow-up, the pain scores decreased and the QoL increased monotonically across all age groups. At Day 90, the mean ZBPI worst pain score of the PHN patients was 4.4, while the LSmeans estimates of the ZBPI ADL and EQ-5D utility scores were 2.899 and 0.826, respectively. For patients with PHN persisting at nine months, the pain scores and QoL remained unchanged over the six months following the development of PHN.HZ and PHN had a substantial impact on the patients’ QoL and ability to function in their normal activities. There was a clear association in time between the evolution of pain and estimated QoL. The impact on ADL and QoL did not vary with age.The online version of this article (10.1186/s12879-018-3395-z) contains supplementary material, which is available to authorized users. Herpes zoster (HZ) is a painful and debilitating condition caused by a reactivation of varicella-zoster virus (VZV), which as a primary infection causes chickenpox , 2. In tAcute HZ is usually characterized by a vesicular rash of the skin of the affected dermatome generally accompanied by acute pain –3. AcuteThe most common sequelae of HZ is postherpetic neuralgia (PHN) involving chronic pain that occurs or persists after the rash has resolved. The cause of PHN is not known  and variWithout varicella vaccination programs virtually all inhabitants of temperate regions of the world will have had wild type VZV infection before the age of 30 years and are consequently at risk of developing HZ possibly followed by PHN . DevelopIt is increasingly recognized that HZ and PHN can lead to considerable impairments of the patients’ health related quality of life (QoL) , 5. In pTo date, data on the impact of HZ and PHN on German patients’ QoL are scarce and limited to retrospective studies –9. A recThis prospective observational study was carried out in primary care practices in three regions of Germany . Primary care physicians  were invited to participate in a study over the period November 2010 to December 2014.Patients meeting certain eligibility criteria were invited to participate in a cohort study aiming to estimate the proportion of HZ patients developing PHN and the economic burden and impact on health related QoL of both HZ and PHN. Patients were eligible if they were at least 50 years old at the time of first outpatient consultation presentation with HZ diagnosis, if they were deemed capable of completing the self-administered questionnaires used for measuring the impact and if they gave their written informed consent to participate.The patient was presented with a booklet and asked to complete the QoL and pain assessment questionnaires during the initial consultation, with the physician providing assistance if required. The booklet contained further sets of questionnaires, which the patient was asked to complete and return to the physician or a central study site at the end of the follow-up period. Questionnaires were to be completed 15, 30, 60 and 90 days after rash onset.Patients assessed as having PHN three months after rash onset (day 90) were asked to complete and return additional questionnaires at 120, 150 and 180 days after rash onset. Patients with persisting PHN at six months were asked to continue in the follow-up and complete and return additional questionnaires 210, 240 and 270 days (nine months) after rash onset. Otherwise, the follow-up of patients was not continued.HZ-related pain was assessed by item 3 of the ZBPI , asking In addition to this measure of the ‘sensory’ dimension of pain, the ZBPI also contains items related to the ‘reactive’ dimension of pain intended to assess the impact of pain on the patient’s ADL. These items aim to assess the interference of pain on general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. Each of these seven items are assessed on an 11-point Likert scale with 0 = ‘does not interfere’ and 10 = ‘interferes completely’. The assessments of each item of function and activity were summarized and presented as a single ADL score by taking the mean of the seven items. If a response was missing for one item, the mean of the remaining six was used. If more than one item had no response, the summary score was coded as missing.QoL was assessed by the standardized, generic EuroQoL five-dimension scale (EQ-5D) questionnaire , 15, whiA case of HZ was defined as new unilateral pain  accompanied by a unilateral rash and no alternative diagnosis. Clinically relevant PHN was defined as the presence of moderate or severe ‘worst’ pain  persisting or appearing 90 days after onset of the HZ rash. The duration of PHN was defined as the time between HZ day 0 and the day of the first ZBPI assessment after day 90 in which the worst pain score was < 3. For PHN patients with no assessment in which the ZBPI worst pain score was < 3, the duration of PHN was censored at the day of their last assessment.Descriptive statistics are presented for demographic characteristics, and for the ZBPI pain severity scores. In addition, a repeated measures ANOVA model including terms for gender, age group and age group by time (window) interaction was fitted. The least squares means (LSmeans) estimates for time by age group was obtained from the ANOVA model. The PROC MIXED procedure in SAS was used to carry out the ANOVA, with all terms fitted as fixed effects –19. An ucompletely at random), i.e., drop-out was random conditional on the previous observed data [This procedure was used (as opposed to just taking the means of the observed data) in recognition that patients stop completing the questionnaires after a period of time, generally due to resolution of pain but possibly also for other reasons. An analysis of drop-outs in clinical trials of a candidate zoster vaccine (data not published) indicated that dropout was probably missing at random  and the method of maximum likelihood to estimate the parameters, the final regression equation was used to identify any statistically significant risk factors.To describe the nature of the relationship between the dependent variable (HZ with and without PHN) and independent variables (risk or predictive factors), both univariate and multivariate logistic regression models were used in an exploratory analysis. In a previous epidemiological analysis of data from this study, the severity of acute HZ-related pain was found to be the only statistically significant predictive factor for PHN in a multivariate analysis including the following potential risk factors identified from previous published studies: age group; gender; pre-existing medical conditions ; diabetes; current immunosuppressive therapy; HZ severity at first visit, based on ZBPI ‘worst pain’ score . SubsequAll analyses were carried out using SAS Version 9.2.The study was conducted in accordance with ethical principles having their origin in the Declaration of Helsinki, the principles of “good clinical practice” and all applicable regulatory requirements. The protocol was reviewed and approved by the ethics committees of the study areas  and all enrolled patients gave written informed consent.The demographics of the 513 HZ patients enrolled in the study are presented in Table N = 252) reported having had symptoms before onset of the rash, mainly prodromal pain  and malaise . The mean delay between rash onset and the first consultation was 3.9 days (range 0–30). Of the 513 enrolled patients, only 381 returned evaluable ZBPI questionnaires on or after 90 days following rash onset and were thus evaluable for PHN assessment. The Kaplan-Meier estimate of the median duration of PHN was 276 days and 54.7% of the PHN patients were estimated as still suffering from PHN at day 270.Approximately half of the patients  assessment was 88.5%. For the 61 PHN patients continuing in follow-up a drop in the completion rate was seen during the second three month period with 37 of the 61 subjects (60.7%) completing the assessment at day 180. Of the 25 PHN patients continuing in follow-up after day 180, 20/25 (80%) completed the assessment at day 270.The acute pain at day 0 was rated as moderate by the majority of the patients and the overall mean ZBPI ‘worst pain’ score was 5.1 Fig. . After oFigure At day 0, the patients had an estimated LSmean (SE) EQ-5D utility index of 0.740 0.012) with little variation across the age groups . A similar pattern was observed for the ZBPI ADL score with an estimated LSmean of 2.90 (0.25) at day 90 and a mean of 2.43 at day 270. Neither the ZBPI ‘worst pain’ score nor the ZBPI ADL score showed any systematic relation with age.p = 0.0064), rash location back/spine (p = 0.0128) and all of the health related quality of life variables . Out of 504 subjects with an EQ-5D assessment at Visit 1, 174 reported having moderate/extreme anxiety and depression. Of those 32 (18.4%) developed PHN (p = 0.0015).51 patients (9.9%) reported having current emotional problems, i.e. stress or depression, as part of their pre-existing medical history. Of these 5 (9.8%) developed PHN  and for HZ patients who did not develop PHN (“HZ patients”). At the day 0 assessment, the mean ZBPI ‘worst pain’ scores were 4.9 for HZ patients and 6.7 for PHN patients, diminishing monotonically over time in both groups Table . For HZ For both groups, the EQ-5D utility score increased monotonically over the three-month period and by almost the same absolute amount but the PHN patients had clearly lower utility scores throughout Table . The relThis is the first prospective study of the impact of HZ and PHN on the QoL of primary care patients in Germany aged 50 or older. For the majority of the HZ patients, the period with pain and a considerable negative impact on QoL and interference with ADL was limited to a period of about one month after rash onset. The Kaplan-Meier estimate indicated that for about 50% of all HZ patients who developed PHN, the pain remained moderate or severe even nine months after rash onset. Neither the pain experienced nor the QoL scores showed any association with increasing age of the PHN patients.Previous studies estimating utilities of HZ patients by means of the EQ-5D instrument have reported values ranging from 0.59 to 0.67 , 22–25, If it is tentatively assumed that the mean EQ-5D utility score and VAS score estimated at day 90 for HZ patients who did not develop PHN corresponds to the normal value for people aged 50 or older (as there was not much age-related variation), an estimate of the impact of HZ and PHN may be obtained. With a normal utility score of 0.960, HZ had an immediate impact, i.e., a utility loss of 0.200 for those who did not develop PHN and of 0.346 for those who did. Relating the impact to the severity of acute pain, the estimated reduction of utility was 0.470 for patients with severe ‘worst pain’ and 0.581 for those with severe ‘average pain’. One estimate of the minimal important difference using the EQ-5D instrument is 0.074 , so the Mean utility values were highly correlated with the mean pain scores over time, as has also been reported in other studies , 28. ThiOne study examining the general health states of people aged 75 or older in six European countries by means of the EQ-5D VAS instrument found a mean value for Germans of 60.6 (and a range across the countries from 60.2 to 72.0) . This isThe logistic regression indicated that the risk of developing PHN was higher in patients with more severe acute pain. Anxiety and depression were also determined to be risk factors for PHN. Previous studies have highlighted this association  and it hPrevious studies , 38 haveAn estimate of the quality-adjusted life years (QALYs) gained by preventing one case of HZ in people aged 50 years or older in this study is approximately 0.03 to 0.04 QALY, depending on assumptions used. This is in the same range as reported by Kawai et al. , who estThe enrolled patients were recruited among patients aged 50 years or older consulting primary care physicians for acute HZ. Out of the 1,551 patients screened (and included in the incidence estimation), only one third were enrolled in the study and one of the limitations of our study is that the patients who declined to enroll were not queried about their reasons for declining. The gender distribution of the enrolled patients was similar to that of all the screened patients but the age distribution was somewhat different as the enrolled patients tended to be younger than all the screened, with a higher proportion in the age group 50–59 years and a lower proportion of patients aged ≥ 80 years. And, according to the physicians’ assessment of the patients’ severity of pain at day 0, higher proportions of the enrolled patients had moderate or severe pain. The different age distribution of the enrolled compared to all the screened patients may have biased the proportion of PHN cases downward. In addition, as this study was carried out in a primary care physician setting the proportion of severe cases may be underestimated, as patients might have presented directly at the hospital instead of an ambulatory healthcare setting. This is supported by the proportion of HZ patients hospitalized which was 1.4% in our study compared with 3.2% in the study by Ultsch et al. . Hence, Another study limitation  is that the patients generally do not complete the questionnaires at the time of rash onset. The mean delay from rash onset to initial consultation was 3.7 days (with a range from 0 to 31 days) and this may lead to an underestimation of the overall pain and loss of QoL experienced during an episode of HZ as the impact seems worst at onset and diminishes gradually thereafter. As the delay between rash onset and the initial visit is greater than 72 h in most cases, the value of prescribing antiviral therapy becomes questionable . It is aOne of the strengths of the study was that the patients were recruited at their first primary care consultation for acute HZ albeit with varying and probably unavoidable delays between rash onset and the visit. The patients were also followed over a relatively long time period so that all cases of HZ and most of the PHNs had resolved at the end of follow-up. Furthermore, we used well-validated measuring instruments, a clear and widely accepted definition of PHN and mixed modeling to diminish the potential bias due to questionnaire data missing not completely at random.A lay language summary contextualizing the results and potential clinical research relevance and impact is displayed in Fig. Our study showed that HZ and PHN had a substantial impact on the patients’ QoL and ability to function in their normal activities and relations. For both groups, there was a close association in time between the development of pain and estimated QoL. The proportion of HZ patients developing PHN increased with rising age but the impact of PHN on ADL and patient QoL did not vary with age. For HZ patients, the absolute improvements in QoL over the three months following rash onset were lower for patients aged 80 years or older than for the other age groups.Additional file 1:Discloses the mean zoster brief pain inventory activities of daily living interference score after herpes zoster onset by activities of daily living individual items and overall scores; the univariate predictive factor analysis and the risk factors for developing postherpetic neuralgia; and pain and EuroQoL five-dimension scale utility scores over time for patients with postherpetic neuralgia continuing at or after Day 180. (DOCX 42 kb)


Purpose: High dose monotherapies or drug combinations are used to achieve sufficient analgesia for the treatment of severe chronic low back pain, before invasive therapy options are considered. In order to demonstrate an alternative for an empirical treatment approach, the authors' primary aim was to present an algorithm for the objective identification of treatment predictors. Additionally, the study identified baseline-characteristics in chronic low back pain patients prior to tapentadol PR treatment, as well as scrutinized those patients, either benefitting from a medium/high dose tapentadol PR monotherapy or a combination therapy .Patients and Methods: The statistical approach included data of a previously published randomized, double blind, phase 3b study which compared the effectiveness and safety of tapentadol PR vs. a combination of tapentadol PR and pregabalin. In total, 46 clinical parameters were included in the statistical prediction models which were applied separately either to 50 patients who already responded well during the titration period  or to 261 patients with in the comparative treatment period .Results: The first statistical model identified three co-variables  with predictive effects on patients responding well  to a medium dose tapentadol PR titration. Those patients presented low baseline pain intensity scores, good sleep quality and high painDETECT scores. The second statistical model identified eight co-variables  with predictive effects on patients responding to high dose tapentadol PR monotherapy vs. a combination therapy . The high dose tapentadol PR responders indicated high painDETECT scores, little numbness and a good mental health status. Whereas, the combination therapy  responders were characterized by severe sleep disturbances and little anxiety.Conclusion: The statistical analysis characterized chronic low back pain patients and identified factors contributing to a treatment response. Thus, this retrospective statistical algorithm represents an elegant method, which may contribute to future strategies toward a more individualized and improved mechanism based pain therapy. The management of patients with chronic low back pain remains challenging –4. Therepost hoc stratification approaches. Depending on the scale of the respective outcome variable , or those patients either requiring a high dose monotherapy (tapentadol PR 500 mg/day) or a combination therapy of the investigated agents, would be a crucial step toward an individualized pain therapy –19. EasyThe primary aim was to present a retrospective algorithm, in order to identify patient characteristics toward treatment response in different treatment phases.Identify baseline characteristics (prior to treatment) of patients responding very well to medium doses of tapentadol PR.Identify patients who benefit from high dose tapentadol PR monotherapy or who respond better to a combination therapy of medium dose tapentadol PR and pregabalin.The secondary aims were to include data of a previously performed study  in orderpost hoc analysis of the previously published randomized, double-blind, phase 3b trial (NCT01352741) (This study performed a 1352741) . The ori1352741)   . For fur1352741) , 16. TheClinical characteristics of the patients available at baseline visit  or at randomization visit (randomization co-variables) were analyzed separately for prediction of treatment response to tapentadol. Beside demographic parameters , the focus was set on patients' self-reported characteristics  and symptoms . The following questionnaires were used to assess these parameters: pain intensity score , Sleep Evaluation Questionnaire (SQ), Short Form 12 Health Survey (SF-12) , the subpost hoc analysis is based on patients of ≥18 years of age, with chronic low back pain lasting ≥3 months with an average pain intensity score of ≥6 on the NRS-3 at baseline. Additionally, an “unclear” or “positive” evaluation for neuropathic pain components in the PDQ questionnaire was necessary. Furthermore, all patients included were classified as suitable to receive strong analgesics (highly potent opioids) according to the guidelines set by the WHO  for step III.The present In a recent study assessing the treatment effect of tapentadol in patients with low back pain, alternative patient-reported outcome measures  were shown to be more appropriate as response criteria in prediction models than pain intensity measures . TherefoFurthermore, “optimal responders” were examined in relation to possible influencing and predicting base-line factors . Due to The statistical prediction analysis was performed according to the TRIPOD statement and to recently published guidelines . In thisp < 0.05) in two out of three selection processes and at least highly significant (p < 0.001) in one] were used for consecutive analyses.In the first step, the influence of a single variable at baseline on the outcome in bivariable models  was evaluated, in order to identify possible predictors. Depending on the scale of the respective outcome variable, continuously/quasi-continuously scaled (QoL response variables) or binary scaled  linear and logistic models were applied, respectively. All possible relationships were mapped for evaluation of the validity of consecutively applied models . In parallel, a factor analysis was performed to identify variables with a high potential for collinearity. Among strongly correlating variables, the most important (largest factor-loading) ones were selected for further analysis. As a result, a set of potential predictors was identified and included in a multivariable regression . Three selection processes  were applied. Predictors that were selected consistently . In other words, the pain intensity score should be low and sleep quality good whereas the PDQ should be high, to predict a high response . The aim was to identify patient characteristics at randomization which predict the response in different treatment regimes. The three models  were used for calculation.The number of patients in each arm was small (127 vs. 134), therefore most of the prediction models did not pass all selection tests and the results have to be interpreted with caution. However, significant models were found for several parameters. Patients receiving TapMono had a better chance to respond in case of a high painDETECT score, little numbness and good mental health status (SF-12 MCS) at randomization. In contrast, patients receiving TapPre had a good chance to respond if they had sleep disturbances, but little anxiety or depression, while the painDETECT score and numbness. In contrast, the painDETECT score and numbness had only little influence in the TapPre group . The staThe model passing all predefined criteria (shaded in hatched gray) indicated that the MCS outcome primarily depends on the MCS value at randomization as well as on HADS D and painDETECT scores. The following equation was calculated:This equation can also be visualized as a nomogram  which caA nomogram visualizes the influence of the different predictive variables on different horizontal lines. Depending on the influence of each predictor, the different lines have different lengths. The longer a horizontal line, the stronger is the influence. The influence of each predictor is determined by projecting the value perpendicularly on the horizontal line at the top resulting in a number of points. By adding the points associated with each predictor resulting in total points, the anticipated magnitude of response can be read on the response horizontal line on the bottom of the nomogram see .Demographic data  are not relevant for response prediction.Patients with a low baseline pain, good sleep quality and high painDETECT score (neuropathic component present) have a good chance to respond very well already to medium doses of tapentadol .Patients with high painDETECT scores (neuropathic component present), little numbness and a good mental health status after a medium dose tapentadol PR therapy (at randomization) have a better chance to respond to high dose tapentadol PR monotherapy.Patients with sleep disturbances and little anxiety or depression after a medium dose tapentadol PR therapy (at randomization) have a good chance to respond to a combination therapy of tapentadol PR and pregabalin.Besides the successful implementation of an objective model for a retrospective identification of predictors for treatment response, several important findings can be summarized:The predictor analysis in the study was performed at two different points in time.First, response criteria were analyzed during the titration period . Predictors for a satisfactory pain relief  after the titration period were low pain intensity, good sleep quality, and a high painDETECT score. These results are in line with those of an earlier study with tapentadol in low back pain showing that the intensity of the neuropathic component (high painDETECT score) predicts a good tapentadol outcome . HoweverIn a second step, the response analysis was performed for the two treatment arms using the co-variables at randomization. This analysis may contribute to a more precise use of the investigated drugs by providing guidance on patients who might benefit from a high-dose monotherapy with tapentadol PR or a combination therapy of a medium dose of tapentadol PR and pregabalin. For the outcome measures “quality-of-life” and “functionality,” the statistical approach identified several significant predictors. In fact, patients with high painDETECT scores, little numbness, and a good mental health status had a better chance to respond to high dose tapentadol PR monotherapy whereas patients with severe sleep disturbances and little anxiety had a good chance to respond to the combination therapy of tapentadol PR and pregabalin. Interestingly, the TapPre group benefitted if a sleep disorder was present which might be due to the well-known positive effect of pregabalin on the sleep architecture.Since this analysis uses data of a randomized, double-blind controlled study , the difOur predictor analysis aims to enhance a better understanding of treatment caveats in pain therapy by presenting an approach which helps to assign patients to specific treatment regimens according to objectively determined treatment predictors. However, independently of the identified predictors, the presented study highlights the importance of an appropriate dosage of mono or combination therapies in general. These treatment decisions should be evidence based rather than empirical driven, to achieve the optimum treatment response, especially in accordance with a good tolerability profile.All available characteristics (co-variables) were used to identify potential associations with the endpoints in order to find predictors. Thus, a huge amount of many correlations were calculated  which will inherently lead to an overestimation of the results. To overcome this bias, several correction steps  were implemented after having performed a univariable analysis  and a factor analysis to identify the most relevant independent co-variables. Since the number of patients in each arm was small, many of the prediction models did not pass all selection tests and therefore the results are not very robust. However, these preliminary results can be used to create hypotheses for future research into this important scientific area.Most of the identified predictors are capable of explaining only 2–10% of the variance of the entire response. Clearly, this is too small to predict the response on a single patient level and the implication to the clinical setting is limited. However, significant predictors that explain only part of the variance might be important to understand new pathophysiological mechanisms that are relevant for prediction. Furthermore, a combination of several independent predictors might be summed up to explain higher levels of the variance and might show relevance even in the clinical setting. Thus, the presented algorithm should be applied to larger numbers of patients in the future. For further improvement of prediction models, the results of the clinical characteristics could be complemented with genetic analysis.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Ethik-Kommission der Medizinischen Fakultät der CAU zu Kiel, Universitäts-Kinderklinik Arnold-Heller-Straße 3 Haus 9 24105 Kiel. The patients/participants provided their written informed consent to participate in this study.JO and JF drafted the manuscript and configured the tables and figures. JS gave critical input to the manuscript and contributed to the statistical and methodological part. PH provided critical suggestions to the discussion of the manuscript. MH performed the statistical analysis. TK performed the statistical analysis. JG conceived and designed the retrospective analysis. RB designed the analysis and provided critical suggestions to the final version.JO reports research support and personal fees from Grünenthal GmbH and travel costs from Pfizer. JF reports grants and personal fees from Grünenthal GmbH, during the conduct of the study; personal fees, and non-financial support from Grünenthal GmbH and Sanofi Genzyme, personal fees from Bayer, non-financial support from Novartis, outside the submitted work. JS reports personal fees from Alnylam Pharamaceuticals and Grünenthal GmbH. PH has received speaking fees from Pfizer and Genzyme and travel reimbursement from Grünenthal. MH is an employee of Statconsult GmbH, Germany. This company reports financial support from Grünenthal GmbH and the University of Kiel. TK has been a contract statistical consultant of Statconsult GmbH, Germany until 12/2018 and reports financial support from Grünenthal GmbH and the University of Kiel. JG has received speaking fees and travel grants from Pfizer, Sanofi Pasteur, and Grünenthal and has been a consultant for Glenmark Pharmaceuticals. RB reports grants/research support from Pfizer, Genzyme GmbH, Grünenthal GmbH, Mundipharma. Member of the EU Project No 633491: DOLORisk. Member of the IMI “Europain” collaboration and industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal GmbH, Eli Lilly, and Boehringer Ingelheim Pharma GmbH&Co.KG. German Federal Ministry of Education and Research (BMBF): Member of the ERA_NET NEURON/IM-PAIN Project (01EW1503). German Research Network on Neuropathic Pain (01EM0903), NoPain system biology (0316177C). German Research Foundation (DFG); speaker fees from Pfizer, Genzyme GmbH, Grünenthal GmbH, Mundipharma, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai Co.Ltd., Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD GmbH, Seqirus, Novartis, TAD Pharma GmbH; he has been a consultant for Pfizer, Genzyme GmbH, Grünenthal GmbH, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Novartis, Bristol-Myers Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo, Glenmark Pharmaceuticals, Seqirus, Teva Pharma, Genentech, Galapagos NV, Kyowa Kirin GmbH, Vertex Pharmaceuticals Inc., Biotest AG, Celgene, Desitin, Theranexus.


The annual number of surgical operations performed is increasing throughout the world. With this rise in the number of surgeries performed, so too, the challenge of effectively managing postoperative pain. In Africa, there are scanty data available that make use of multi-center data to characterize the quality of postoperative pain management. In this study using a longitudinal data, we have attempted to characterize the quality of postoperative pain management; among patients scheduled for major elective orthopedic, gynecologic and general surgery.This prospective longitudinal study evaluated the quality of postoperative pain management in patients undergoing elective general, gynecologic, and orthopedic surgery. We quantified the prevalence of moderate to severe postoperative pain with the International Pain Outcome Questionnaire and the corresponding adequacy of treatment with the pain management index. At four time points after surgery, we estimated pain severity, its physical and emotional interference, and patient satisfaction.Moderate to severe postoperative pain was present in 88.2% of patients, and pain was inadequately treated in 58.4% of these patients. Chronic pain  predicted patients’ worst pain intensity. Gender was not associated with the worst pain intensity or percentage of time spent in severe pain. Patient’s pain intensity did not predicted the level of satisfaction.The prevalence of moderate to severe postoperative pain and its functional interference is high in Ethiopian patients. The treatment provided to patients is inadequate and not in line with international recommendations and standards. In the year 2012 alone, 266.2 to 359.5 million operations were performed, representing a 38% increase over the previous eight years; low-income countries thereby had the most dramatic increase [Untreated postoperative pain has dangerous consequences, ranging from prolonged duration of the hospital stay to more severe complications, such as chronic pain, atelectasis, respiratory infection, myocardial infarction , 5, and Developing countries tend to prioritize the eradication of poverty and hunger and reduction of maternal and child mortality and pay little attention to pain management . Global Therefore, this prospective longitudinal study from three tertiary care hospitals assessed the magnitude of and risk factors for postoperative pain. We also estimated key epidemiological profiles that characterize the quality of postoperative pain therapy in Ethiopia on the basis of data obtained from three large teaching and referral hospitals.th to December 17th 2016, we conducted a longitudinal study of elective surgical patients to determine the quality of postoperative pain management in Ethiopia. The study involved repeated measures of patient-reported postoperative pain outcomes. Three state-owned teaching and referral hospitals were selected. Two of the chosen sites, Zewditu Memorial Hospital (ZMH) and Yekatit 12 Hospital Medical College (YK12HMC), are located in the capital, Addis Ababa. The city has approximately 3,197,000 inhabitants [From September 11The study was approved by the Jimma University Institutional Review Board, ref. no. RPGC/06/2016, and the Medical Ethics Committee of the Ludwig Maximillian University, Munich, Germany, ref. no. 17–224. All participating hospitals also granted permission for the study . The study was carried out in compliance with the Declaration of Helsinki. Patients were given comprehensive oral and written information on the purpose and procedures of the study. Before inclusion, participants provided written informed consent and were informed about their rights to refuse to participate or withdraw from the study at any time. They were also informed about the confidentiality of the information gathered during the study and that any personal information would be anonymized before the final analysis.The night before planned operations, we identified eligible patients on the surgical waiting list and approached them to explain the study objectives and measures. We recruited 356 consecutive patients. The inclusion criteria were as follows: adult surgical inpatients aged 18 years or older scheduled for general, orthopedic, or gynecologic surgery. The exclusion criteria were cognitive and mental disabilities ; direct transfer to an intensive care unit; and emergency surgery, including cesarean section. In addition, those who did not stay in the hospital overnight after their surgical procedure were excluded.Pain outcome variables after surgery were measured by the International Pain Outcome Questionnaire (IPOQ), which was originally developed from the American Pain Society Patient Outcome Questionnaire (APSPOQ) . The IPOAdequacy of pain management was measured with the Pain Management Index (PMI). The index is calculated by first categorizing patients’ worst pain intensity into 0 (no pain), 1 (1–3: mild pain), 2 (4–6: moderate pain), and 3 (7–10: severe pain). The final score is then subtracted from the strength of analgesic prescribed: 0 , 1 (non-opioids), 2 (weak opioids), and 3 (strong opioids). The final score ranges from –3 to +3, and negative scores indicate inadequate treatment. Originally, this index was designed to assess the adequacy of cancer pain management; however, it has also been used in surgical patients –16. PatiAt all three hospitals, outcome variables were measured 6, 12, 24, and 48 hours after surgery. Interviewers administered the IPOQ; such a method of administration is justified when patients are too ill, in too much pain, or—as was the case in our setting—unable to read or write. To avoid measurement bias, the nurses who collected data did not participate in treating the respective study participant at the time of data collection.The study considered the following covariates: time (since surgery), patient’s age and sex, pre-existing chronic pain, and time of the operation. We also retrieved information on demographics, medical history, type of surgery, type of anesthesia, patient’s physical condition, and pain treatment from the medical records.We used generalized estimating equations (GEE) for the analysis because we wanted to model the change in outcome measures over time  and wereit is the observed outcome for the subject i at time t, β0 is the intercept, Xijt is the covariate j for the subject i at time t, β1j is the regression coefficient for covariate j, J is the number of covariates, CORRit is the working correlation structure, and εit is the “error” for subject i at time t. A p value of 5% was considered significant, and all analyses were performed with Stata version 13.0 . Graphs were produced using the ggplot2 package [The linear relationship between outcomes and time was analyzed by adding time squared to the GEE model. In case of a non-linear relationship, time was included in the model as a categorical variable. The GEE equation, which allows one to adjust for the dependency of observations within one subject, is as follows: package  and the  package .All eligible patients agreed to participate in the study. There were slightly more women than men . The majority of participants were Ethiopian Orthodox Tewahedo Christians, and Oromo was the dominant ethnic group. According to the medical records, almost all patients had an American Society of Anesthesiologists Physical Status Classification 1 (ASA PS 1). The median (IQR) duration of the surgery was 1.3 (1–2) hours. Most patients underwent general anesthesia; one third spinal anesthesia; and only five patients, ketamine anesthesia. The predominant type of surgery was cholecystectomy, followed by thyroidectomy and prostatectomy. Details of the social and clinical demographics are provided in When we used the patients’ worst pain intensity as a reference, the time course of the PMI scores indicated that 58.4% of patients were inadequately treated during the first 6 postoperative hours. Moderate to severe postoperative pain was reported by 88% of patients at 6 hours after surgery and by 40% of patients at 48 hours after surgery. When asked whether they needed more analgesics than prescribed, 57% of the patients replied “yes” at 6 hours after surgery  and 55% did so at 12 hours after surgery . This figure dropped to 37%  at 48 hours after surgery. None of the patients in our sample received any information about options for pain treatment. Patient pain was treated predominantly with tramadol (92.9%) and sometimes with diclofenac (7.0%). The most prevalent non-pharmacological method of pain management was talking to friends or relatives; this method was used by 88.3%  of the patients at 6 hours after surgery; by 90.6% , at 12 hours after surgery; by 90.1% , at 24 hours after surgery; and by 94.7% , at 48 hours after surgery.The worst pain intensity ratings had mean (SD) NRS scores of 6.5 (1.63) at 6 hours after surgery, 5.7 (1.6) at 12 hours, 4.9 (1.6) at 24 hours, and 4.2 (1.4) at 48 hours. The patients’ current and least pain intensity also declined over time but did not differ between the sexes. However, it is noteworthy that 88% of the participants had moderate to severe pain during the first 6 hours after surgery. Even at the subsequent assessments, the prevalence of moderate to severe postoperative pain was still high: 77% at 12 hours, 63% at 24 hours, and 40% at 48 hours after surgery. The median value for all pain intensity measures across time are shown in The QIC statistic for GEE model selection suggested age, sex, educational status, type of anesthesia, type of surgery, chronic pain severity, and time since surgery as covariates for the final model. The patient’s worst pain intensity rating was affected by time since surgery, age, chronic pain severity, and educational status. In comparison to the pain at 6 hours after surgery, the worst pain intensity was significantly lower at each subsequent measurement time point: 12 hours , 24 hours , and 48 hours . With increasing age, the worst pain intensity decreased . Larger NRS scores of preoperative chronic pain were associated with a higher worst pain rating after surgery . Illiterate patients had higher worst pain intensity scores  than those with formal education. Sex, type of anesthesia, type of surgery, duration of surgery, and physical status did not affect the patients’ worst pain experience see .The NRS scores for the mean (SD) time spent in severe pain were 4.4 (2.0) at 6 hours, 4.2 (1.98) at 12 hours, 3.7 (1.99) at 24 hours, and 3.1 (2.3) at 48 hours. In addition to the predictors of worst pain, the QIC statistic informed the inclusion of ethnic group, religion, marital status, and duration of surgery. Single participants reported higher percentages of time spent in severe pain than married participants , and Muslim and Protestant patients reported less time spent in pain than Orthodox Christian patients . The longer the duration of surgery in hours, the higher the rating for time spent in severe pain . NRS scores of preoperative chronic pain also predicted how much time patients spent in severe pain . The NRS scores of time spent in severe pain did not differ significantly at 12 hours after the surgery compared with at 6 hours; however, time spent in pain subsequently decreased significantly at 24 hours  and 48 hours . Age, sex, type of surgery, type of anesthesia, educational status, and ASA PS classification were not associated with the time spent in severe pain see .The trend of pain interference with function  and emotions (anxiousness and helplessness) over time is depicted in Pain interference with movement was moderate, with mean (SD) NRS scores of 4.5 (1.9), 4.97 (1.7), 4.54 (1.9), and 3.30 (1.92) at 6, 12, 24, and 48 hours after surgery, respectively. ASA PS 2 patients reported greater interference  than ASA PS 1 patients. Compared with patients who underwent general anesthesia with endotracheal intubation, those who underwent spinal anesthesia had higher scores of pain interference with movement . Patients’ ratings of the worst  and current  pain intensity also affected their mobility. When the score for perceived pain relief increased, pain interference with movement decreased significantly . Interference of pain with movement was also affected by the level of education: illiterate patients reported more interference than literate ones . None of the variables time since surgery, ethnic group, time spent in severe pain, level of education, religion, chronic pain severity, and type of surgery had an effect see .The mean (SD) NRS scores for pain interference with activities in bed were 5.7 (2.1), 5.0 (1.9), 4.1 (1.9), and 3.0 (2.0) at 6, 12, 24, and 48 hours after surgery, respectively. As final covariates of pain interference with activities in bed, the QIC statistic suggested time since surgery, time in pain, pain intensity , and perceived pain relief. The worst pain intensity , current pain intensity , and duration of time patients spent in severe pain  significantly predicted the intensity of interference with activities in bed. As time after the surgery elapsed, the intensity of interference decreased ; this finding was not affected by the amount of relief perceived by the patient see .Pain interfered with breathing and coughing mildly at 6, 12, 24, and 48 hours after surgery, with mean (SD) NRS scores of 3.0 (2.3), 2.7 (2.1), 2.3 (2.0), and 1.6 (1.8), respectively. Less pain interference with coughing and breathing was reported by those who underwent spinal anesthesia and orthopedic procedures . Patients with chronic pain reported greater interference with breathing and coughing ; this interference with breathing decreased with increasing perceived pain relief  and time after surgery . ASA PS 2 patients reported greater interference of pain with breathing and coughing  than ASA PS 1 patients. Sociodemographic variables, such as sex, religion, marital status, and ethnic background, showed no effect see .The mean NRS (SD) scores of pain interference with sleep at 6, 12, 24, and 48 hours after surgery were 3.4 (2.2), 3.0 (2.0), 2.4 (1.9), and 1.6 (1.7), respectively. The worst pain intensity , current pain intensity , time in severe pain , and relief received  were strongly associated with pain interference with sleep, but age, duration of surgery, preoperative pain intensity, and least pain showed no effect see .At 6, 12, 24, and 48 hours after surgery, the mean (SD) NRS scores for feelings of anxiousness as a result of pain were 2.2 (2.1), 1.9 (1.9), 1.5 (1.6), and 1 (1.4) and the mean (SD) scores for pain causing a feeling of helplessness were 1.5 (1.6), 1.3 (1.6), 0.9 (1.3), and 0.7 (1.3), respectively. Single participants had less pain interference with anxiousness  and feelings of helplessness  than married participants. Muslims scored higher on pain causing helplessness than Orthodox Christians . Gynecologic surgery patients had less anxiousness  and helplessness  than general surgery patients. Higher chronic pain NRS scores were associated with increased anxiousness  and helplessness . A similar trend was noted for the worst pain intensity: The more intense the worst pain, the higher the rating of anxiousness  and helplessness . Current pain intensity affected pain causing helplessness , but not anxiousness. Age, sex, level of education, and ethnic background showed no effects see .The mean (SD) patient satisfaction as indicated by the NRS scores was 6.8 (1.6) at 6 hours, 7.2 (1.4) at 12 hours, 7.6 (1.3), and 7.9 (1.4) at 48 hours after surgery. Ethnic background, pain interference, and perception of care were associated with patients’ ratings of satisfaction. The only pain intensity variable found to have any correlation with patients’ ratings of satisfaction was the time spent in severe pain . An increase in pain interference with activities in bed decreased patient satisfaction . Pain interference with sleep was associated positively with satisfaction . The degree to which a patient felt relief from pain was also associated with the level of satisfaction . Time since surgery, sex, marital status, religion, type of anesthesia, preoperative chronic pain, type of surgery, and patients’ worst, least, and current pain intensity were not significantly associated with satisfaction see .To compare the hospitals, we carried out an analysis of a subgroup of 306 patients who underwent general and gynecologic surgery. Orthopedic patients were excluded because one of the participating hospitals (ZMH) do not contribute to the population. Significant differences between the three hospitals were observed in worst pain intensity score at 24 and 48 hours . At 48 hours patients from YK12HMC reported significantly lower satisfaction level  and a higher percentage of time spent in severe pain . Compared with JUMC, patients at ZMH had reported higher perceived pain relief at 12, 24 and 48 hours postoperatively . .We provide substantial evidence that postoperative pain management at the three study centers, which were more or less representative for Ethiopia, was insufficient and that pain impaired patients’ physical functioning and emotional well-being during the postoperative period. Most of the analgesics were prescribed by the surgical residents. This seems to have an important implication for the destiny of pain management in the setting. For instance, in battling the opioid crisis, developed world have already identified that agents of change should be the surgical resident as larger amount of opioid were prescribed by them . In the The observed magnitude of pain could originate from interactions of heterogeneous but interrelated factors. First, the poor knowledge of health care providers (HCPs) about pain and their attitude towards it play a role; established evidence already exists to support this argument . A natioThis study also uncovered a mismatch between patients’ pain intensity and the strength of analgesics prescribed. The calculated PMI indicated that 58.4% of participants received sub-optimal pain treatment at 6 hours after surgery; a study from China reported similar results . HoweverNone of the patients in this study received information about pain treatment options. This result is not surprising because there was no supervision of the HCPs’ pain management practices or acute pain services in the country . In factWe noted a link between pain intensity and interference with physical function. However, pain impaired patients’ activities in bed more than their physical movements when out of bed. This might be because patients will not move around when out of bed unless the pain drops to a tolerable level. Furthermore, mobility is affected by the nature of the surgical procedures: early in the postoperative period, orthopedic patients resumed movement somewhat later than non-orthopedic patients. This finding is similar to previous studies, which reported a positive correlation between pain intensity and interference .In line with other investigations, preoperative pain contributed to higher postoperative pain ratings –43. BecaThe influence of ethnicity , religioAlthough it is puzzling, despite high levels of pain intensity patients in this study reported a higher level of satisfaction. This has been termed the “severe pain-high satisfaction paradox” , and seeAs to the strengths of the study, to our best knowledge, this was the first prospective longitudinal study using data from three tertiary hospitals to evaluate the quality of pain management in elective gynecologic, surgical, and orthopedic patients in Ethiopia. The study also attempted to apply modern and advanced methods of statistical analysis, which are recommended by experts in the field . We studAn inherent limitation of an observational study design is that it does not allow us to draw conclusions about causal inferences or temporality. We cannot entirely rule out the possibility of other confounders or other explanatory models when determining the association between chronic pain and postoperative pain intensity or between age and postoperative pain intensity. In addition, we assessed only a limited set of variables that could explain their relationships. The identified risk factors and predictors are not the only models that could be used to examine the link between clinical and sociodemographic characteristics and postoperative pain intensity, and alternative models  could be used to explore other relationships. Unlike most surveys we had a full response rate which contributes positively to the study by minimizing the nonresponse bias. Since, in most surveys about 60% response rate is reported to be satisfactory the power of this study is sufficient for determining a strong association between the predictors and the outcome measures , 67. HowThis study suggests that postoperative pain is not well managed at hospitals in Ethiopia and that there is an unacceptably high prevalence of moderate to severe postoperative pain. It also provides evidence indicating a severe interference of pain with patients’ functional activities in bed, which could result in several complications. It is important to aim to improve the quality of postoperative pain management. Additionally, this report confirmed that patients are satisfied with the postoperative care provided to them, despite having higher pain intensity scores. In limited resource settings, attention needs to be paid to implementing interventions that reduce the amount of pain and aim to deliver high-quality postoperative pain management.


The authors recently used a combination of minimally invasive oblique lumbar interbody fusion (OLIF) and lateral fixation for the treatment of degenerative spine deformity. The early results were promising. Radiographic and clinical results as well as complications were retrospectively assessed in the current study. Eleven patients with degenerative spine deformity underwent combined OLIF and lateral instrumentation without real-time electromyography (EMG) monitoring. Radiographic measurements including coronal Cobb angle, central sacral vertebral line (CSVL), lumbar lordosis (LL), sagittal vertebral axis (SVA), pelvic tilt (PT), and LL-PI (pelvic incidence) mismatch were taken preoperatively and at last follow-up postoperatively in all patients. Concurrently, the visual analog score (VAS) for back pain and the Oswestry Disability Index (ODI) score were used to assess clinical outcomes. The fusion rate of OLIF cage, total blood loss, operation time, hospital stay, and complications were also evaluated. At last follow-up, all patients who underwent combined OLIF and lateral instrumentation achieved statistically significant improvement in coronal Cobb angle , LL , PT , LL-PI mismatch , CSVL , and SVA . VAS for back pain  and ODI  improved significantly after surgery. A combination of OLIF and lateral instrumentation is an effective and safety means of achieving correction of both coronal and sagittal deformity, resulting in improvement of quality of life in patients with degenerative spine deformity. It is a promising way to treat patients with moderate degenerative spine deformity. Degenerative spine deformity is an acquired and progressive disease process that increases in frequency and severity with age . The patSurgical treatment of degenerative spine deformity is extremely variable and ranges from limited minimally invasive procedures to extensive and lengthy multistaged operations , 4, 8, 9However, LLIF is associated with direct muscle injury and a risk of injury to the lumbar plexus as it courses through the psoas , 20. FurThis is a retrospective study. A total of 11 patients in Xuanwu Hospital between May 2017 and February 2018 were included in this study based on the following inclusion criteria: (1) diagnosis of degenerative scoliosis ; (2) treatment of adult degenerative scoliosis with OLIF and lateral instrumentation through the same approach in one stage; (3) availability of preoperative and postoperative 36-inch films of the scoliosis. Patient demographics are summarized in The general technique of OLIF has been previously described , 23. An Standing anteroposterior and lateral 36-in films were obtained in 11 patients preoperatively and at last follow-up for measurement . The Oswestry Disability Index (ODI) before surgery and at last routine postoperative clinic visits were compared. Surgical characteristics and complications were also recorded .Complications were evaluated at last follow-up and retrospectively reviewed in this study.Statistical analysis was calculated using the paired t-test; a p value ≤ 0.05 was considered statistically significant.A total of 11 patients (1 man and 10 women) were included in the study . The meaCoronal Cobb angle, CSVL, LL, PT, LL-PI mismatch, and SVA were significantly improved at the final follow-up compared with the values before surgery p<0.05, . Fusion Lower back pain evaluated by VAS was significantly improved from 6.9±1.4 before surgery to 2.0±0.9 at last follow-up after surgery (P<0.05). ODI was also significantly improved from 39.5±3.1 to 21.9±3.6 (P<0.05).The OLIF procedures in the lumbar spine are associated with transient or permanent symptoms in the thigh. Due to retrospective direction of observation, these data were not consistently available and thus were not included in the study. However, thigh numbness, pain, dysesthesias, or weakness indicative of a lumbosacral plexopathy was not seen in any of the patients by their last follow-up visit. Cage subsidence at 2 levels was observed in 2 of the patients by their last follow-up. There were no other major or minor intraoperative or perioperative complications. Hardware failure did not occur.Minimally invasive spinal fusion in particular has been associated with decreased blood loss, decreased postoperative pain, and shorter hospital stays compared with traditional open procedures , 29. MinThe interbody cage used in LLIF surgery distracts the anterior and middle columns of the lumbar spine, restoring lost disc space height and achieving indirectly decompression. Besides, LLIF surgery has the capability of improving lordosis , 35–37. However, some author reported complications LLIF. Symptoms included pain, numbness, paresthesias, or weakness due to direct muscle injury and injury to the lumbar plexus as it courses through the psoas , 20. FurIn our study, combined OLIF and lateral instrumentation has shown its advantage in treating degenerative spine deformity. OLIF procedure could restore the lost disc space height and achieve indirectly neural decompression as LLIF . FurtherHowever, the current study has some limitations. First of all, it is a small sized study and the duration of follow-up was also short. Moreover, no severe sagittal imbalance case, such as lumbar kyphosis or flat back, was included in our study. Dakwar found that in one-third of patients sagittal plane correction was not adequate after they had undergone lateral interbody fusion for degenerative spine deformity . TraditiOLIF combining lateral instrumentation seems to be a valuable surgical tool for the minimally invasive correction of coronal and sagittal plane deformities in patients with moderate degenerative spine deformity. It is a less invasive procedure to achieve good radiographic and clinic results without any major complications.