One of the most difficult symptoms for persons with sickle cell disease (SCD) to manage is chronic pain. Chronic pain impacts approximately one-third of persons with SCD and is associated with increased pain intensity, pain behavior, and frequency and duration of hospital visits. A promising category of nonpharmacological interventions for managing both physical and affective components of pain are mindfulness-based interventions (MBIs).The primary aim of this study is to conduct a randomized controlled study to evaluate the acceptability and feasibility, as well as to determine the preliminary efficacy, of a telephonic MBI for adults with SCD who have chronic pain. We will enroll 60 adult patients with SCD and chronic pain at an outpatient comprehensive SCD center in the southeastern United States. Patients will be randomized to either an MBI or a wait-listed control group. The MBI group will complete a six-session (60 minutes), telephonically delivered, group-based MBI program. The feasibility, acceptability, and efficacy of the MBI regarding pain catastrophizing will be assessed by administering questionnaires at baseline and weeks 1, 3, and 6. In addition, ten randomly selected MBI participants will complete semistructured interviews to help determine intervention acceptability.In this study protocol, we report detailed methods of the randomized controlled trial. Findings of this study will be useful to determine the acceptability, feasibility, and efficacy of an MBI for persons with SCD and chronic pain.NCT02394587. Registered on 9 February 2015.ClinicalTrials.gov identifier: The online version of this article (doi:10.1186/s13063-017-1948-x) contains supplementary material, which is available to authorized users. A VOC is caused by an accumulation of sickled red blood cells in the vasculature, resulting in damage (acute pain) to surrounding tissue areas [Sickle cell disease (SCD) is a genetic hematological disorder that affects more than 7 million people globally , 2. It iue areas . In addiue areas , 7. A prue areas , 9).There is strong evidence to support the use of MBIs for persons with chronic pain , 11. MBIWhereas MBIs have shown positive effects, the generalizability of these results for persons with SCD is unknown . Some MBThe overall goals of this pilot randomized controlled clinical trial (RCT) are to explore the feasibility and acceptability of an abbreviated six-session MBI that is targeted for persons with SCD and chronic pain and to obtain preliminary data on the efficacy of this intervention relative to a wait-listed control condition on pain catastrophizing and other pain-related outcomes. The specific aims are to (1) evaluate the feasibility and acceptability of the telephonic MBI designed to reduce pain-catastrophizing symptoms for adults with SCD and chronic pain and (2) determine preliminary efficacy of the MBI relative to the control condition on pain catastrophizing as well as pain interference and severity, depression, health-related quality of life , and mindfulnessWe are conducting a single-site pilot RCT comparing MBI and a wait-listed control condition with assessments at four time points  in adult patients with SCD and chronic pain. Individuals who provide written informed consent will be enrolled and randomized to an MBI or control condition. The MBI will be conducted as a ten-person group teleconference call led by a certified MBI instructor. A 2:1 treatment allocation will be implemented in this initial pilot study to collect more data on the feasibility and acceptability of the MBI. Feasibility will include measures of enrollment, randomization, attendance, and intervention completion along with assessment completion. Acceptability will be assessed with semistructured interviews conducted with randomly selected MBI participants. The primary efficacy outcome will be pain catastrophizing total score.Patients will be recruited from an outpatient comprehensive SCD center in the southeastern United States. An interdisciplinary team of physicians, nurses, psychologists, and social workers run the center, providing care for approximately 600 adults with SCD. The target sample for this pilot study is 60 patients with SCD and chronic pain, with 40 patients randomly assigned to receive the MBI and 20 patients to the control condition. With a sample size of 60, the study does not have 80% power to detect a significant difference between the MBI and control conditions on the primary outcome of pain catastrophizing with a level of significance set a 0.05 (two-tailed). However, the focus of this pilot study is to estimate treatment effect sizes rather than to conduct statistical significance testing.Patients meeting the following criteria will be eligible for inclusion: (1) self-reported diagnosis of SCD; (2) be age 18 years or older; (3) self-identified as having chronic, noncancer pain that has persisted on most days for more than 6 months and adversely affects function or well-being; (4) possess the ability to speak and read English; (5) have access to a landline or cell phone; and (6) have access to a compact disc (CD) or MP3 player. Patients will be excluded if they (1) previously participated in an MBI study  or (2) regular practitioners of mindfulness, including yoga.Recruitment letters will be mailed in waves of 50 to patients with a scheduled appointment at the outpatient center within 2 weeks of their appointment. This decision was made because there is no rigorous method to determine which patients are experiencing chronic pain. The recruitment letter will explain the study purpose, inclusion criteria (including definition of chronic pain), and participant involvement and provide contact information for the study principal investigator (PI). On the basis of previous research experience in the center, including poor response to recruitment letters, the recruitment letter will use institutional review board-approved opt-out language to notify patients that the PI will contact them via phone to describe the study, unless the patient informs the PI via phone or email that he or she does not want to be contacted. A period of 2 weeks will be provided prior to initiating phone calls after the mailing is sent to allow potential subjects time to contact the PI. Three attempts to contact the patient will be made before determining that the patient is not interested in participating. The same recruitment script used for in-person recruitment will be used to discuss the study with potential subjects by phone. Individuals who meet all inclusion criteria and verbally agree to participate will be mailed a consent form along with the study packet.In-person recruitment will occur immediately before or after a patient’s clinic appointment. Prior to being approached by study personnel, patients will be prescreened by their healthcare provider and a study staff member to assess their general capacity to participate , current involvement in other research studies, and if they have already been mailed a recruitment letter. Patients already enrolled in a cognitive or behavioral intervention study will not be approached for recruitment, owing to the potential of carryover effects between interventions. A recruitment script will be used to discuss the study with potential participants, verify the presence of chronic pain per the study definition, and solicit participation. Individuals who meet all inclusion criteria and verbally agree to participate will then sign a consent form and receive a study packet containing a copy of the consent form, a set of headphones, a mindfulness practice CD, and four copies of assessments. For participants who have an email address, identical digital versions of the questionnaires will be provided through hyperlinks managed with REDCap electronic data capture tools .n = 10) or to a control condition (n = 5). The random number function in Excel 2007 software  will be used to randomize patients to either the MBI (n = 40) or control (n = 20) condition using a permuted block randomization scheme to achieve a 2:1 allocation. Within each block size of 15, 10 patients will be randomized to receive the MBI and 5 will be randomly assigned to the wait-listed control condition.Patients who provide informed written consent and meet the participant selection criteria will be enrolled and randomized using a 2:1 treatment allocation to either the MBI or control condition. Because the MBI condition is group-based, randomization of participants will be divided into 4 cohorts of 15 participants to reduce the amount of idle time between informed consent and intervention delivery. After the first cohort of 15 participants provides informed consent, they will be randomly assigned either to receive the MBI  on the morning of each mindfulness session and again 1 h before each session. In addition, all participants will receive weekly and biweekly contact from study personnel to remind them of their study participation, upcoming due dates for assessments, and when compensation checks have been mailed to their home address.Three monetary payments will be provided to help increase retention and compensate participants for their time: (1) $10.00 after baseline assessments are received and/or participation in MBI session 1 has occurred, (2) $20.00 after receiving measurements at the end of week 3 and/or participation in MBI session 3, and (3) $30.00 at the conclusion of the study upon receiving the final measurements and/or participation in MBI session 6. All subjects in the in MBI and control groups will receive payments upon return of each assessment according to this schedule. In addition to providing monetary compensation, the MBI program will be provided at no cost to subjects, a value of over $400.00.Participants randomized to the MBI condition will receive a telephonically delivered MBI program. The MBI adapts all core elements from John Kabat-Zinn’s original MBSR program  and targOn the basis of needs described, and in line with adapting specific elements of MBSR, the original MBSR content was simplified and compressed into six 60-minute telephonic group sessions that teach (1) breath awareness , (2) body scan , (3) walking meditation , (4) loving-kindness , and (5) choiceless awareness . Each of these practices, all of which are part of the original MBSR program, is focused on cultivation and practice of mindfulness techniques. Breath awareness, body scan, loving-kindness, walking meditation, and choiceless awareness promote and foster “open monitoring” and intentional observation of thoughts, feelings, and bodily sensations . With guCurrently, there is much debate on the mechanisms of how each of these practices may elicit changes for pain-related outcomes , but becTable Our decisions to reduce the number of minutes per session and remotely deliver the MBI are supported by the MBI literature. Prior studies have found time commitment to be a common barrier to recruitment and MBI completion , 30, as The same MBI instructor will deliver all MBI sessions. The instructor is a healthcare professional and graduate of the University of Massachusetts Center for Mindfulness professional training program. In total, the instructor has more than 10 years of instructional experience in mindfulness, 2 years of experience in teaching telephone-based MBSR, and experience in leading groups for research studies.Last, each 60-minute MBI session will require patients to call a toll-free 1-800 telephone number. The toll-free number does not require an access or login code; can accommodate up to 100 callers simultaneously; and can be accessed by telephone, Internet, and mobile app (iOS and Android only). The conference service used will be UberConference .Patients randomized to the control condition will not receive the MBI but will receive treatment as usual. Treatment as usual consists of standard medication management as prescribed by the subject’s hematologist, primary care physician, psychologist, and/or any other medical professionals overseeing treatment.see Additional file Wait-listed patients will be offered the opportunity to cross over to the MBI condition once patients in the intervention arm complete six sessions. Patients who cross over from the wait-list to the MBI will participate in the same protocol as patients originally randomized to the MBI condition. The schedule of enrollment, interventions, and assessments of this study is shown in Fig. Sociodemographic data and clinical characteristics will be self-reported by participants and collected only at study enrollment (baseline). Participants will be asked to report their sex, age, race, genotype, socioeconomic status, educational history, hospital use , and disease-related complications . These items have been used to assess sociodemographic and clinical characteristics of persons with SCD in prior studies , 37.The first aim of this study is to determine feasibility and acceptability. Measures of feasibility are (1) enrollment (number of participants consented and enrolled) and (2) randomization (percentage of patients enrolled who are randomized). Participant-level measures of feasibility include (1) attendance (percentage of sessions attended by each MBI participant), (2) intervention completion , and (3) assessment completion (percentage of completed patient-reported assessments at each time point). Failure to complete measures within 2 weeks of recruitment (baseline) or MBI sessions 1, 3, and 6 results in missing data for that time point.Acceptability will be assessed qualitatively. Semistructured interviews will be performed with ten randomly selected participants from the MBI condition within 2 weeks of the final MBI session by telephone to assess acceptability and help interpret quantitative findings related to the exploratory aim . Each MBBecause we were unable to find any literature on the subjective experiences of persons with SCD and chronic pain who participated in a mindfulness intervention, the guiding questions listed in Table To address aim 2, five valid and reliable patient-reported questionnaires will be administered to determine the effects of MBI relative to the control condition on pain catastrophizing, as well as on pain interference and severity, depression, health-related quality of life , and mindfulness Table . Each quSee Table Participants will have the option of completing each questionnaire on paper or via an online form. Participants who opt for paper forms will be provided with a packet of questionnaire copies with return envelopes and stamps. Participants who opt for online forms will provide an email address and be emailed hyperlinks that contain exact copies of the paper forms managed by a REDCap database . The ordThe Pain Catastrophizing Scale (PCS) will be used to assess pain catastrophizing. The PCS contains 13 items rated on a 5-point scale from 0  to 4 . The total score for the PCS ranges between 0 and 52, with a higher score demonstrating more severe catastrophizing. In addition, the PCS contains three subscales: helplessness (six items), rumination (four items), and magnification (three items) . The PCSThe Brief Pain Inventory (BPI) will be used to assess physical pain. As one of the standard psychometric tools for clinical trials of pain , 44, theThe Patient Health Questionnaire–9 items (PHQ-9) will be used to assess depression. The PHQ-9 is a multipurpose instrument used for screening, diagnosing, monitoring, and measuring the severity of depression . ConsistThe Patient-Reported Outcomes Measurement Information System (PROMIS)  global sMindful Attention Awareness Scale (MAAS) will be used to assess mindfulness. The MAAS measures present moment awareness, interpersonal communication, thoughts, emotions, and physical states. Consisting of 15 items on a Likert scale , the measurement provides a single total score of mindfulness, with a higher score indicating a higher level of mindfulness.Atlas ti 7™ software  will be used to analyze qualitative data, and SAS version 9.3™ software  will be used to conduct statistical procedures for quantitative data and to estimate effect sizes for the efficacy outcomes. When statistical significance testing is conducted, nondirectional tests will be performed, with the level of significance set at 0.05. As noted earlier, the focus of this pilot study is to examine the direction and magnitude of effect of the MBI on primary and secondary outcomes rather than to conduct statistical significance testing.Descriptive statistics will be used to summarize sociodemographic and clinical characteristics. Nonparametric Wilcoxon two-sample tests will be used to test for differences in continuous sociodemographic and clinical variables between conditions. Chi-square tests will be performed to test for differences in categorical sociodemographic and clinical variables between conditions. A sensitivity analysis will be performed to compare sociodemographic and clinical characteristics between randomized participants who complete at least one assessment at any time point with those who do not complete any outcome assessments (observable cases = no or yes).Number and percent will be used to summarize enrollment, randomization, assessment completion, intervention completion, and MBI session attendance. Additionally, the sociodemographic and clinical characteristics of those observable subjects in the MBI condition who complete four or more intervention sessions will be compared with those who complete less than four.Acceptability will be determined by qualitative analysis of semistructured interviews using an inductive data-driven approach. This will allow for extraction of core themes, as recommended by, for example, Hsieh and Shannon , for casDescriptive statistics will be used to summarize the five measures at baseline and weeks 1, 3, and 6 for randomized participants with at least one outcome assessment completed (observable cases). Tables for unadjusted mean scores for each condition by time will be presented. Random coefficients regression models, a type of hierarchical mixed-effects model for longitudinal data, will be used to evaluate the trajectory of change in pain catastrophizing total scores and other pain-related outcomes. Nonlinear temporal patterns will be fitted as needed. The models will be used to examine the pattern of change in each outcome over time and estimate effect sizes.This pilot will provide preliminary evidence regarding the feasibility, acceptability, and efficacy of a telephonic MBI for persons with SCD and chronic pain. Considering how difficult it is to manage SCD, pain in particular, this trial will provide valuable insight into whether a telephonic MBI may help improve the care of persons with chronic pain and SCD. We believe the results of this trial will provide significant new insights for the development of future MBIs for persons with SCD and provide additional information regarding the efficacy of a remote intervention for managing a chronic disease.Participants are no longer being recruited.


The correlation between epidurography contrast patterns and the clinical outcomes of percutaneous epidural neuroplasty (PEN) remains unclear.  To analyze the correlation between postadhesiolysis epidurography contrast patterns and the clinical outcomes of patients who undergo lumbar PEN.  This study is a retrospective analysis of 78 consecutive patients who underwent lumbar PEN between April 2012 and March 2013.  The analysis was done in the university hospital center.  The clinical outcomes of all patients were assessed before and 1, 3, 6, and 12 months after undergoing lumbar PEN. Specifically, the intensity of back and leg pain, quality of life, and procedural outcomes were evaluated using a visual analog scale (VAS), the Oswestry Disability Index (ODI), and the 12-Item Short-Form Health Survey (SF-12). P < 0.01 versus preprocedural scores). At most follow-up time points, patients exhibiting extraforaminal contrast distribution (n=22) on postadhesiolysis epidurograms exhibited a similar improvement in VAS scores and a significantly better improvement in ODI and SF-12 scores compared with patients exhibiting intracanal contrast distribution (n=56).  The VAS scores for back and leg pain, ODI score, and SF-12 score exhibited a significant improvement during the follow-up period ( Extraforaminal contrast distribution during lumbar PEN may be associated with better functional outcomes. Chronic low back pain is a common health problem with widespread socioeconomical reverberations which is experienced by most individuals at some point in their lives –3. SeverThis retrospective analysis of medical and radiographic records included 78 patients who underwent lumbar PEN procedures between April 2012 and March 2013 at a single university hospital. The study protocol was approved by the ethics committee, and informed consent was obtained from all subjects. The inclusion criterion was chronic low back pain with or without leg pain due to lumbar disc herniation and/or lumbar spinal stenosis. All patients reported a history of discogenic or radicular symptoms refractory to conservative treatments for a minimum of 6 weeks. Diagnoses were established using magnetic resonance imaging (MRI) and/or computed tomography (CT) performed before PEN. Patients with a history of spinal surgery and those with cauda equina syndrome, bleeding diathesis, associated somatic or psychiatric disease, vertebral fractures, pregnancy, and tumors or other underlying systemic diseases that could significantly affect the procedural outcomes were excluded. All procedures were performed by one of the authors (DAS) using the same procedural protocol.A standard PEN procedure was used to lyse adhesions and achieve nerve blockades in all patients, as previously described , 14. A 1Postadhesiolysis epidurography contrast patterns were defined and classified into five grades according to the system proposed by Mathis et al. : grade 1All patients were clinically evaluated before and 1, 3, 6, and 12 months after PEN by a nurse specialized in pain management and blinded to the treatment details. The intensity of leg and back pain was assessed using a subjective visual analog scale (VAS) calibrated from 0 to 10 (0 = no pain and 10 = the worst pain imaginable). For functional assessments, the Korean versions of the Oswestry Disability Index (ODI) and 12-Item Short-Form Health Survey (SF-12) were used , 23. ODIt-tests were used to assess differences in VAS, ODI, and SF-12 scores at each time point between the EF and IC groups. Chi-square tests were used to compare clinical outcomes between the two groups. Spearman's rank correlation tests were used to determine the correlation between epidurography contrast patterns and clinical outcomes. All statistical analyses were performed using the Statistical Package for the Social Sciences software . A P value of <0.05 was considered statistically significant.Age, the duration of symptoms and follow-up, and VAS, ODI, and SF-12 scores are expressed as means ± standard deviations. Student's A total of 78 patients (27 men and 51 women) were included in this study. All patients were clinically followed up for more than 11 months. The mean age was 58.1 ± 14.1 years , and the average duration of major symptoms before PEN was 7.1 ± 4.1 months . Before PEN, the VAS score for back pain, VAS score for leg pain, ODI score, and SF-12 score were 5.8 ± 2.6, 5.0 ± 3.1, 19.4 ± 7.0, and 30.0 ± 7.2, respectively .P < 0.01 when compared with preprocedural scores; The clinical outcomes of patients exhibited a significant improvement during the follow-up period. At 1, 3, 6, and 12 months after PEN, the VAS score for back pain was 2.6 ± 2.3, 3.1 ± 2.1, 3.0 ± 2.0, and 3.4 ± 2.4, respectively; the VAS score for leg pain was 1.9 ± 2.0, 2.6 ± 2.1, 2.6 ± 2.2, and 2.7 ± 2.6, respectively; the ODI score was 10.6 ± 8.0, 11.7 ± 7.4, 11.0 ± 7.3, and 11.0 ± 8.0, respectively; and the SF-12 score was 41.8 ± 9.6, 40.5 ± 9.0, 41.2 ± 9.2, and 41.2 ± 10.2, respectively (n=56), there were 19, 25, and 12 patients with grade 1, grade 2, and grade 3 patterns, respectively. In the EF group (n=22), there were 7 and 15 patients with grade 4 and grade 5 patterns, respectively. Before PEN, the VAS score for back pain was 5.7 ± 2.6 and 6.0 ± 2.4 (P=0.639), the VAS score for leg pain was 4.7 ± 3.1 and 6.0 ± 2.8 (P=0.101), the ODI score was 20.0 ± 6.9 and 17.8 ± 7.1 (P=0.222), and the SF-12 score was 29.6 ± 7.0 and 31.0 ± 7.7 (P=0.452) in the IC and EF groups, respectively, with no significant differences between groups. At most follow-up time points, the EF group exhibited a similar improvement in VAS scores and a significantly better improvement in ODI and SF-12 scores compared with the IC group (P < 0.05)). A representative case of a patient with radicular pain in the left leg who exhibited significant pain relief and functional recovery after PEN is depicted in The patients were categorized into IC and EF groups according to the contrast patterns on postadhesiolysis epidurograms. In the IC group (IC group . Thus, eEpidurograms provide anatomical information and help in confirming accurate needle placement. Spinal interventions can be safely performed using a fluoroscope and epidurograms with radiopaque dye. The aim of the present study was to evaluate the correlation between contrast patterns on postadhesiolysis epidurograms and clinical outcomes in patients who underwent lumbar PEN. We observed that PEN ameliorated the pain associated with lumbar disc herniation and/or lumbar spinal stenosis. VAS scores for leg and back pain, ODI scores, and SF-12 scores exhibited a significant improvement over the entire 12-month follow-up period. Racz et al.  reportedIn the present study, we found that the clinical outcomes of lumbar PEN were correlated with the presence of extraforaminal contrast spread on the final epidurogram obtained after adhesiolysis. Extraforaminal contrast spread is believed to be an indicator of successful adhesiolysis. The purpose of PEN is to eliminate the barriers in the epidural space that disturb drug delivery. Extraforaminal contrast spread may be related to the creation of channels around the target site through adhesiolysis, and it facilitates drug delivery to the lesion site. Exposure to the ideal amount of medication can result in better pain reduction. It can also enhance the recovery of the perineural circulation, which can improve neural congestion and decrease the associated pain. The results of our study confirmed that access to the exact position of the lesion site is associated with a better outcome. These findings suggest that mechanical adhesiolysis is meaningful only at the lesion site. Moreover, if the exact lesion site cannot be reached, both adhesiolysis and drug delivery will fail and the target area will remain untreated.In 1991, Kuslich et al.  demonstrIn the present study, there were no direct correlations between cutoff signs or filling defects and the clinical outcomes of PEN. In our practice, we cannot easily resolve cutoff signs and filling defects. Cutoff signs are a result of severe spinal stenosis, while filling defects are frequently associated with disc herniations. Currently, gross adhesions cannot be easily lysed by soft PEN. However, regardless of the presence of cutoff signs or filling defects, better outcomes were achieved with extraforaminal contrast spread. There may be microscopic adhesions that are more relevant and can be lysed by soft PEN. Park et al. also reported that there was no correlation between the degree of pain relief and epidural filling defects in patients with lumbar stenosis .This study has several limitations. These include the small sample size, the unequal groups, the short follow-up duration, and the retrospective design. Future studies should ideally include an appropriate control group. Nevertheless, the strength of our study is the use of clinical outcome measures, namely, ODI and SF-12, for assessment of the quality of life in addition to pain scores. Furthermore, the results of the study are more in line with the prognosis because the patients received a single treatment rather than repetitive treatments. With the use of epidurograms, physicians can design and plan adhesiolysis that aims at a precise target point and creates effective tunnels, which will help in predicting the prognosis.In conclusion, the findings of our study suggest that the contrast patterns on final epidurograms obtained after adhesiolysis during PEN are indicators of clinical outcomes. Specifically, extraforaminal contrast spread during PEN is associated with better functional outcomes.


Objective: Our study aims to evaluate the clinical outcomes of cortical screws in regards to postoperative pain.Background: Pedicle screw fixation is the current mainstay technique for posterior spinal fusion. Over the past decade, a new technique called cortical screw fixation has been developed, which allows for medialized screw placement through stronger cortical bone. There have been several studies that showed either biomechanical equivalence or superiority of cortical screws. However, there is currently only a single study in the literature looking at clinical outcomes of cortical screw fixation in patients who have had no prior spine surgery.Methods: We prospectively looked at the senior author’s patients who underwent cortical versus pedicle lumbar screw fixation surgeries between 2013 and 2015 for lumbar degenerative disease. Eighteen patients underwent cortical screw fixation, and 15 patients underwent traditional pedicle screw fixation. We looked at immediate postoperative pain, changes in short-term pain (six to 12 weeks post-surgery), and changes in long-term pain (six to eight months). All pain outcomes were measured using a visual analog scale ranging from 1 to 10. Mann-Whitney or Kruskal-Wallis tests were used to measure continuous data, and the Fisher Exact test was used to measure categorical data as appropriate.Results: Our results showed that the cortical screw cohort showed a trend towards having less peak postoperative pain (p = 0.09). The average postoperative pain was similar between the two cohorts (p = 0.93). There was also no difference in pain six to 12 weeks after surgery (p = 0.8). However, at six to eight months, the cortical screw cohort had worse pain compared to the pedicle screw cohort (p = 0.02).Conclusions: The cortical screw patients showed a trend towards less peak pain in the short-term (one to three days post-surgery) and more pain in the long-term (six to eight months post-surgery) compared to pedicle screw patients. Both cohorts had a statistically significant reduction in pain levels compared to preoperative pain. More studies are needed to further evaluate postoperative pain, long-term functional outcomes, and fusion rates in patients who undergo cortical screw fixation. Every year, over 120,000 lumbar fusions are performed nationwide for degenerative and traumatic spine conditions [Over the past decade, there have been several studies that showed either biomechanical equivalence or superiority of cortical screws compared to pedicle screws -11. One Due to the promising biochemical studies and the minimally invasive nature of cortical screws, some surgeons are starting to utilize the technique in lumbar fusions. However, there is currently only one study in the literature looking at the clinical efficacy or outcomes of cortical screws in non-redo patients . In thatbefore the institution of lumbar cortical trajectory screws at SCVMC. The only patients who had pedicle screw fixation done after the institution of cortical trajectory screws were the ones with small pedicles (< 7 mm diameter) on preoperative CT scans.We prospectively enrolled patients with lumbar degenerative disease and instability who needed lumbar fusion from 2013 to 2015 at the Santa Clara Valley Medical Center (SCVMC) in San Jose, CA. SCVMC is a level one trauma center and the county hospital wing of Stanford University Medical Center. IRB approval for the prospective data registry was obtained through SCVMC . Informed patient consent was obtained at the time of treatment. All patients underwent pedicle or cortical screw placement by the senior author. Patients who underwent surgery because of trauma or infection, such as osteomyelitis, were excluded. In total, 18 patients underwent cortical screw fixation, and 15 underwent pedicle screw fixation. Most of the patients in the lumbar pedicle screw fixation group had their spinal fixation surgeries All patients received the same pain regimen postoperatively, with a morphine patient-controlled analgesia pump for 24 hours, followed by long-acting OxyContin and IV morphine and/or Percocet thereafter during the hospital stay. Patients were discharged home on oral Percocet.Traditional pedicle screws were placed using the technique described by Weinstein, et al. . A standThe cortical screw starting point is at the lateral aspect of the pars interarticularis and, therefore, requires significantly less lateral muscle dissection. The angulation is medial to lateral, rather than lateral to medial as in the traditional pedicle screw technique. Screws are inserted approximately 10 degrees laterally in the axial plane and 25 degrees cranially in the sagittal plane, although actual angulations are determined by intraoperative fluoroscopy  and changes in long-term pain (six to eight months), when compared to preoperative pain in the two cohorts. All pain outcomes were measured using a visual analog scale ranging from 1 to 10.Mann-Whitney or Kruskal-Wallis tests were used to analyze the difference in pain outcomes between the two groups and over time, respectively. Categorical data was analyzed using Fisher’s exact test. A p - value of less than 0.05 was considered statistically significant. GraphPad Prism v 6.0 was used to conduct all statistical analyses.A total of 36 patients were included in the study. Three were excluded because of trauma and infection being the indications for fusion, with a total of 33 patients remaining. Eighteen patients underwent cortical screw fixation and 15 underwent pedicle screw fixation. Overall, the patient characteristics in the cortical versus the pedicle screw groups were similar  compared to the cortical screw group (38.9%) (p = 0.01). Degenerative disc (DD) disease was the predominant finding on MRI in both cohorts, and presenting pain symptoms were also similar Table .Overall, there was no difference in average p = 0.93) or peak (p = 0.09) immediate postoperative pain between patients who underwent cortical or pedicle screw fixation, as seen in Figure  or peak There was no difference in postoperative pain at the time of short-term follow-up at six to 12 weeks, with an average pain score of 4.97 in the cortical group compared to 4.93 in the pedicle group (p = 0.8)   (p = 0.09). This is consistent with the hypothesis that a smaller incision with less muscle detachment and soft-tissue dissection in cortical screws may lead to less postoperative pain. This is also consistent with the findings in the Lee, et al. study where cortical screws were associated with lower immediate postoperative pain (within one week of surgery) compared to pedicle screws .Although there was no difference in pain between cortical and pedicle screw patients at the six to 12-week follow-up, pedicle screw patients appeared to have less pain at the six to eight-month follow-up  (p = 0.02). This is an interesting finding, as most of the biomechanical studies have shown superior pullout strength and stability in cortical screws compared to pedicle screws [One explanation for these phenomena might be that, even though cortical screws are biomechanically stronger and prevent spinal micromotion and, therefore, pain generation in the short-term, long-term stability of the construct depends on the formation of a stable fusion mass. This might be happening more effectively in the pedicle screw cohort with posterolateral fusion in the lateral gutters, compared to the cortical screw cohort where arthrodesis was performed over the facet joints, but not in the lateral gutters. Although plain radiographs did not show any hardware failure in either group at the six to eight-month follow-up, long-term follow-up is needed to see if cortical screw patients have higher levels of pseudoarthrosis compared to pedicle screw patients and whether the difference in pain outcomes between the two cohorts remains divergent into the future. Notably, Lee, et al. did not find any difference in the pain scores or fusion rates between their two cohorts at one-year follow-up . HoweverThere are some limitations to our study, including the small sample size and the lack of randomization. Although patient characteristics overall were similar between the two groups, the pedicle screw group did have a higher percentage of female patients compared to the cortical group Table . This maOur paper is the first prospective cohort study comparing pain outcomes for 33 patients who underwent cortical versus pedicle screw fixation in lumbar degenerative disease, with or without interbody fusion. Overall, cortical screw fixation results in similar to improved immediate postoperative pain but showed a trend towards worsening low back pain at the six to eight-month follow-up compared to pedicle screw patients. Both cohorts had statistically significant reduction in pain levels compared to preoperative pain after surgery . Our paper is a pilot study, and more prospective randomized clinical studies are needed to further evaluate postoperative pain, long-term functional outcomes, and fusion rates in patients who undergo cortical screw fixation.


To validate the German version of OMPSQ (OMPSQ-G) for patients with chronic neck pain.After translating OMPSQ to German, we assessed the discriminant validity between patients and healthy adults. Convergent validity was assessed using Pearson’s correlation coefficients between domains of OMPSQ-G and the German version of neck disability index (NDI-G) and visual analogue scale (VAS) of neck pain intensity. Floor and ceiling effects, internal consistency, test–retest and relative reliability were assessed. Fifty patients with chronic neck pain  and 24 healthy adults  participated. Mann–Whitney U tests showed significant differences in OMPSQ scores between both groups at the baseline  and second time point . OMPSQ-G scores highly and moderately correlated with NDI-G (ρ = 0.70) and VAS (ρ = 0.41) scores, respectively. There were no floor or ceiling effects. Cronbach’s alpha was 0.94. OMPSQ-G showed high reliability . The Bland–Altman plot indicated no systematic error. OMPSQ-G showed good validity and reliability in patients with neck pain.Trial registration NCT02540343The online version of this article (10.1186/s13104-018-3269-x) contains supplementary material, which is available to authorized users. Neck pain is a common complaint that affects 70% of individuals at least once in their lifetime . Only loSo far the original German version of OMPSQ has not previously been validated in patients with chronic neck pain. This study aimed to evaluate OMPSQ-G in German-speaking patients with chronic neck pain. In addition, discriminant and construct validity and reliability were evaluated.This is a translation and validation study. At the beginning the original OMPSQ was translated and culturally adapted into German and afterwards tested for its validity and reliability in patients with chronic neck pain.This project was authorised by the author of the original OMPSQ. Language translation was based on the original OMPSQ . The croFrom November 2014 until October 2016, 50 patients with chronic neck pain were recruited from the department of chiropractic medicine at Balgrist University Hospital. All patients had chronic neck pain for at least 90 days before enrolling for the study . After 3–7 days, all participants were asked to independently complete all questionnaires a second time at home and to send them back in a prepaid envelope. Therefore, it can be assumed that the conditions were similar when the participants filled out both the questionnaires. If the questionnaires were not returned by day 4, the participant received a reminder telephone call. Participants who did not return the questionnaires by day 7 were excluded from the study. The mean imputation was conducted for values missing from OMPSQ-G . If moreOMPSQ is a self-administered pain screening questionnaire that was developed to identify patients with acute or subacute musculoskeletal pain who are at risk of delayed recovery , 17. A hNDI is a questionnaire used for assessing self-rated disability in patients with neck pain of mechanical origin . It has VAS is an reliable outcome measure used to assess pain intensity . The lefDescriptive statistics were used to describe participant characteristics. Consistency of the patients’ pain was tested using paired t-test of VAS scores.To assess discriminant validity, the ability of OMPSQ-G to differentiate between healthy adults and patients with chronic neck pain was tested using Mann–Whitney U test. All other tests were conducted in the chronic neck pain sample. Criterion validity was established by correlating the total score of OMPSQ-G with those of VAS and NDI-G. Spearman’s coefficient values were interpreted as excellent (> 0.9), good (0.7–0.9), moderate (0.5–0.69), fair (0.2–0.5) or minimal-to-absent (0.0–0.2) . A factoIntraclass correlation coefficients (ICCs) and their associated 95% confidence intervals (CIs) were selected to calculate the test–retest reliability of OMPSQ-G in patients with chronic neck pain . ICC valThe translated OMPSQ-G was pre-tested in 10 patients with complaints of chronic neck pain. The general impression of these patients was that OMPSQ-G was easy to understand. No changes were made to OMPSQ-G after the pre-test  were included in this study. Two healthy adults had more than three missing items and were excluded from the analysis. Thirteen of 1050 total items (1.2%) were missing values ‘not working’ at the baseline, and 14 of 1050 items (1.3%) were missing at the second time point. Furthermore, three different items from three separate patients were missing (0.2%).Patients’ pain levels were considered consistent because VAS scores did not significantly change (p = 0.92). Participant characteristics and results of all questionnaires at the two time points are shown in Table Mann–Whitney U tests showed significant differences in OMPSQ-G scores between the two groups at baseline  and at the second time point . All Spearman’s rho (ρ) coefficients that assessed the correlation between questionnaire scores were significant at baseline  and at the second time point . No floor or ceiling effects were observed. The lowest and highest possible OMPSQ-G scores were only found once. Sub-group analysis revealed the following correlations in healthy participants: OMPSQ-G and NDI-G , OMPSQ-G and VAS , NDI-G and VAS . In chronic neck pain patients the correlations were as follows: OMPSQ-G and NDI-G , OMPSQ-G and VAS  and NDI-G and VAS .OMPSQ-G showed high test–retest reliability . Cronbach’s alpha was 0.94, SEM was 6.9 and SDC was 19.3 points. Bland–Altman plot . Translated and validated German version of the Orebro musculoskeletal pain screening questionnaire.


Difficulties in kneeling, one of the poorest scoring functional outcomes post total knee arthroplasty (TKA),have been attributed to a lack of patient education. This is the first study to investigate specific factors affecting a patient’s perceived ability to kneel post TKA, following exposure to a preoperative kneeling education session.n = 115) and 12 (n = 82) months post TKA. In addition to the 12-month kneeling questionnaire, patients also completed the Oxford knee score (OKS) survey.A cross-sectional study was conducted following TKA with patients who had been educated about kneeling prior to the operation. Patients completed kneeling questionnaires at 6 (R = 0.70), strongly correlated with pain scores (R = 0.45) and weakly correlated with knee stability scores (R = 0.29). When asked about other factors preventing kneeling other than pain or discomfort, 75 % had reasons unrelated to the knee or TKA. The most common reason was ‘problems with the other knee’ (n = 19).Seventy-two percent of patients perceived they could kneel at 12 months post TKA. Overall, pain and discomfort were the most common factors deterring patients from kneeling. Perceived kneeling ability was the poorest scored outcome on the OKS with patients reporting mild to moderate difficulty with this task. Kneeling scores were strongly correlated with overall knee function scores (Patients in this study were provided with education regarding their kneeling ability post TKA, yet still experienced limitations in perceived kneeling ability postoperatively. Contrary to previous research, our study suggests that factors other than patient education affect a patient’s perceived kneeling ability post TKA. Osteoarthritis is a leading cause of pain and disability worldwide and when present in the knee often leads to total knee arthroplasty (TKA) because of poor responses to conservative medical or physical treatments . Over thSatisfaction among TKA patients has increased, with as many as 81–89 % of patients being satisfied with their procedure –12. In MPatients want to be able to kneel after TKA ; howeverOur study investigated factors which prevent kneeling at 6 and 12 months post TKA in patients who received a preoperative education session about kneeling. The aim of this study is to determine if providing patient education prior to surgery and, therefore, provide more realistic expectations about kneeling capability post surgery has any effect on a patient’s perceived kneeling ability post TKA. The change in kneeling capabilities between 6 and 12 months after TKA will also be examined. Finally, we aimed to identify factors other than pain and discomfort, which impair the ability to kneel at 12 months post TKA.Patients attending an outpatient clinic between July 2013 and May 2014, following their elective TKA (from the same surgeon) were invited to participate. Ethical approval was granted by the University of Wollongong Human Research Ethics Committee.The primary indication for TKA of all volunteering patients was end-stage osteoarthritis. A midline incision with a medial parapatellar approach was used for each TKA. The patellar was resurfaced with a cemented polyethylene button and a cemented hydroxyapatite-coated posterior cruciate-retaining prosthesis was used. Circumpatellar electrocautery was performed as part of the TKA in all patients. On enrolment to the study all patients received a 30-min education session by the practice nurse. This was a standardized education session outlining what to expect on the day of TKA, what was to be expected in the recovery post-TKA period and the long-term functional prognosis of TKA. All patients were advised that they may experience pain or discomfort when kneeling and that this would not harm the prosthesis. A safe kneeling technique was also demonstrated. This education was repeated in their postoperative physiotherapy sessions. All patients received daily postoperative physiotherapy until they were deemed safe for discharge.Patients completed two surveys, one at 6 and another at 12 months post TKA. At both 6 and 12 months, a questionnaire including patient demographics and the patient’s ability to kneel was mailed to the volunteers. The 12-month questionnaire also included a validated Oxford knee score (OKS) questionnaire .The questions included in the kneeling survey included (1) Are you able to kneel on your replaced knee? (2) Do you have pain with kneeling? (3) Do you have discomfort or increased pressure within the knee with kneeling? (4) Does pain stop/prevent you from kneeling? These questions were scored as ‘yes’ or ‘no’ answers and each question was analyzed using descriptive statistical analysis. Additionally, the 12-month kneeling survey asked patients to comment on any additional factors that prevent them from kneeling or make kneeling difficult? The answers to this question were grouped into subjects for analysis.The OKS, which was included with the 12-month kneeling survey, is a validated 12-question survey that is commonly used to gauge the functional activity and pain experienced over the past month by the patient following TKA  to 4 (best). From each of the responses to the OKS, we calculated overall patient perceived pain and function scores  patients  with a mean age of 68 years responded to the survey. Questionnaire response rate at 12 months was 83.7 % with 82 patients  with a mean age of 69 years responding to the survey.n = 28). By 12 months post TKA, there was an increase in the percentage of patients who reported they could kneel to 72 % (n = 59). The number of patients reporting pain as the reason for not being able to kneel decreased to 14 (17.1 %), with 15 patients (18.3 %) reporting pain as a deterring factor. The percentage of patients reporting discomfort and pressure as deterring factors at 12 months post TKA increased to 75.6 % (n = 62).At 6 months post TKA, 73 (63.5 %) patients reported that they were able to kneel. Twenty-eight (24.3 %) patients reported that they were unable to kneel due to pain, and a further 10 (8.7 %) reported pain to a deterring factor. Discomfort and pressure in the knee were reported as deterring factors in 38.3 % of patients  were then calculated for kneeling versus knee stability, knee function and knee pain scores. There was a very strong correlation between kneeling scores and knee function scores (R = 0.70), a strong correlation between kneeling and knee pain (R = 0.45), and a weak relationship between kneeling and knee stability (R = 0.29).Pearson’s correlation coefficients  at 6 months with a mean age of 68 and 82 patients  at 12 months with a mean age of 69. These characteristics are comparable to previous studies on kneeling ability, which ranged in age from 66−72.2 years .n = 58) has previously looked at the effect of education on kneeling post partial knee replacement [Patients with osteoarthritis have a poor ability to kneel preoperatively. Although this improves following TKA, patients are still expected to continue to have some difficulty kneeling , 21. Onllacement . This stlacement . Our reslacement , 17, 18,lacement , 15, 18,The percentage of patients reporting pain as the reason for not being able to kneel decreased from 24.3 to 17.1 %. Discomfort and pressure as deterring factors at 12 months post TKA increased from 38.3 to 75.6 %. This indicates that the pain experienced by patients post TKA lessens over time and possibly becomes a residual ‘discomfort’ or ‘pressure’ in the knee. Examining discomfort post TKA would be an important area for further analysis in future studies due to the significant number of patients who are deterred from kneeling due to this experience.There has been a growing recognition in the orthopedic field that patient-centered evaluation tools should be used to evaluate patient outcomes after TKA procedures . We chosR = 0.70), a strong correlation between kneeling and knee pain (R = 0.45), and a weak relationship between kneeling and knee stability (R = 0.29). Importantly, the weak relationship between kneeling and knee stability in combination with the near perfect (3.8/4) knee stability score demonstrates that the inability of the patients to kneel was not related to an unstable knee. When comparing the scores of the patients who could and could not kneel, significant differences were detected for both standardized pain and function . These results are similar to those found in a recent study in Iran for a similar-sized group of patients with osteoarthritis [We analyzed whether the ability of our patients to kneel was related to overall functional scores, pain scores and knee stability scores using the OKS . There wrthritis .Previous studies evaluating kneeling ability post knee replacement have identified various factors preventing patients from being able to perform the task. For perceived inability to kneel, reasons included ‘think it may be painful’, ‘have not tried’, ‘been told not to’, ‘think it would be difficult’, ‘afraid of damaging the prosthesis’, ‘did not think they should’, ‘numbness’ and ‘stiffness’. Sixty-three percent gave reasons that could be addressed by education or rehabilitation . ContrarThere are a number of other factors such as numbness, decreased range of motion, gender , and choThere are limitations to this study that need to be acknowledged. This study did not include preoperative scores of pain and functional abilities including ability to kneel. The study included a small sample size, and included patients operated on by only one surgeon at two hospital sites. The amount of information obtained through the survey was limited and may have been better addressed though an interview format. The implementation of these education sessions was not performed with a control group. Therefore, further randomized controlled trials are needed to provide a higher level evidence for this intervention. Finally not all of the patients completed the survey at 12 months.There are several important conclusions supported by this current study. This is the first study to evaluate the effect of preoperative patient education on kneeling ability post TKA, as recommended in a number of previous studies. Even with appropriate education on kneeling ability, patients identified that pain and discomfort were significant factors preventing them from kneeling post TKA. Patients who had more pain and less overall functional ability were more unlikely to be able to kneel. This study showed an increase in the number of patients able to kneel with little or no difficulty compared to previous studies. Importantly, in contrast to previous studies, only one patient reported their reason for not kneeling as due to a fear of injuring their knee. Therefore, education sessions should be a routine part of the TKA patient journey. Consistent with previous studies, our results show that kneeling continues to be the poorest functional outcome post TKA and therefore an important area for continued research.


Hypericum perforatum is known as a remedy for unbearable, shooting or jabbing pain especially when neural damage is involved. Reduction of pain after application of H. perforatum has been observed in previous studies. This study is aimed to investigate whether homeopathic H. perforatum in a potentisation of C200 leads to the reduction of post-operative pain and a decrease of pain medication compared to placebo.Spinal disc herniation is a frequently occurring degenerative disease of the spine. Many patients undergoing surgery suffer from radicular pain, known as memory pain, beginning from the third post-operative day. This results in the prescription of high-dose opioid medications. In homeopathy, This is a monocentric, double-blind, randomised placebo-controlled trial conducted at the Department of Neurosurgery at the Community Hospital Herdecke, Germany. One hundred study participants are being recruited from inpatients undergoing elective, monosegmental, lumbar microdiscectomy surgery. Patients are randomly allocated to receive homeopathic treatment or placebo in addition to usual pain management after surgery. The primary clinical outcome is pain reduction after 3 days of inpatient care as measured by pain reduction of subjective pain on a 100-mm Visual Analogue Scale (VAS) at the third post-operative day. Statistical analysis will be carried out by means of a covariance model with adjustment for baseline values and patient expectation for all randomised patients.H. perforatum after monosegmental spinal microdiscectomy. We intend to clarify the potential of homoeopathic H. perforatum to reduce surgery-associated pain.This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic DRKS00007913. Registered on 17 October 2014.German Clinical Trials Register, ID: EudraCT – Nr: 2013–001383-31.http://apps.who.int/trialsearch/.Data sets from the German Clinical Trials Register  are updated every 4 weeks automatically to the International Clinical Trials Registry Platform of World Health Organisation: ResponsibilitiesSponsor:Witten/Herdecke UniversityAlfred-Herrhausen-Straße 5058,448 WittenDeputy of the sponsor:Dr. Wolfgang Eglmeier Alfred-Herrhausen-Straße 5058,448 WittenE-mail: wolfgang.eglmeier@uni-wh.dePrincipal investigator:Prof. Dr. med. Wolfram ScharbrodtCommunity Hospital HerdeckeDepartment for NeurosurgeryGerhard-Kienle-Weg 458,313 Herdeckew.scharbrodt@gemeinschaftskrankenhaus.deProject coordination:Christa RaakFaculty for Health (Department for Integrative and Anthroposophic Medicine)University Witten/Herdecke gGmbhGerhard-Kienle-Weg 458,313 Herdeckechrista.raak@uni-wh.deProject manager/data analysis/biometry:Prof. Dr. Thomas OstermannFaculty for Health (Department for Psychology and Psychotherapy)University Witten/Herdecke gGmbhAlfred-Herrhausen-Straße 5058,448 Wittenthomas.ostermann@uni-wh.deThe online version of this article (10.1186/s13063-018-2631-6) contains supplementary material, which is available to authorized users. Disc herniation is one of the most common degenerative diseases of the lumbar spine. The incidence for lumbar disc herniation in Germany is 150/100,000 people per year. Sixty out of those 100,000 patients undergo intervertebral disc surgery, resulting in 50,000 operations a year . MoreoveTreatment options for a lumbar disc herniation are determined by the duration and presence of the symptoms and the severity of the resulting pain. Besides, the nature of the symptoms (such as weakness or numbness), the patient’s age and further progression of pain relief are important decision-making parameters for conservative therapy or surgery . If mediDepending on the main diagnosis, in 2010, patients with lower back problems were subjected to back surgery in 38% of the cases . Since tFor the feasibility and the course of mobilisation and rehabilitation, post-surgical pain management plays a crucial role . The pos-6, while a dilution of C30 denotes a dilution of 100-30 [At the Community Hospital Herdecke, Germany, homeopathic remedies are also offered in addition to the standard treatments mentioned above on patient request . Homeopaf 100-30 . Homeopaf 100-30 . This idf 100-30 .Hypericum perforatum is indicated in order to improve wound healing and reduce repeatedly occurring neural pain [From a homeopathic perspective, the administration of ral pain , 20.H. perforatum (St. John’s wort) is a member of the Guttiferae family with about 400 known species of Hypericum in Europe and is one of the oldest medical plants with a history of more than 2000 years. It grows in sunny locations with well-drained, limey soil and reaches a height of 50 to100 cm. Yellow star-shaped flowers, often clustered in a trio, have five petals and the leaves contain tiny, transparent oil glands resembling perforations [orations .Hypericum can lead to a reduction of symptoms due to spinal disc pathology and associated pain caused by a pinched and irritated nerve [Hypericum could also be observed in a number of studies, amongst others in neuropathic pain [Hypericum have not been resolved so far. The adjuvant administration of Hypericum for the present indication of post-surgical pain after lumbar microdiscectomy surgery has not been investigated within the framework of a scientific clinical setting.Experimental studies have demonstrated that the administration of potentiated ed nerve . In clinhic pain –25, aftehic pain , or aftehic pain . HoweverHypericum C200 in post-operative pain management. The primary aim of the study is to assess the reduction of subjective pain on the 100-mm VAS at the third post-operative day. In consideration of the side effects of conventional pain medication and the potential benefit of Hypericum in wound healing and neural pain reduction, it is reasonable also to investigate the dosage of conventional analgesic intake between the groups as a secondary outcome measure.The aim of the study is to investigate the effect of Finally, the reduction of subjective pain on the VAS at the fifth post-operative day and the development of sensory and affective pain perception ) between the groups, as well as the amount of post-surgical intake of analgesic/anti-inflammatory agents, are also secondary outcomes.The study will be a randomised, placebo-controlled, double-blind trial with a 3–5-day duration.The study will be conducted at the Department of Neurosurgery at the Community Hospital Herdecke, Germany.The Community Hospital Herdecke is a hospital for acute cases requiring supportive care level II with specific responsibility for ambulant and outpatient care. It contains over 471 beds and around 50,000 patients are treated here yearly, ambulant or as outpatients. For a number of years the hospital has offered an established integrative therapy concept with the emphasis on holistic/anthroposophic medicine. It is an academically specialised hospital and has a research centre with methodological competence in the areas of basic research, clinical research and research in supportive care .Over 900 brain and spinal surgeries, or surgeries involving peripheral nerves, are carried out at the department of neurosurgery each year.Participant recruitment precedes allocation, meaning that participants will be recruited from those electively admitted to the Department of Neurosurgery at the Community Hospital Herdecke for monosegmental spinal microdiscectomy surgery due to a lumbar disc herniation. They will be approached by the responsible neurosurgeon and made aware of the ongoing study within the framework of a counselling interview. No further recruiting measures will be taken. After signing the informed consent, patients will be allocated to one study arm. No study participants will be included who are in a direct relationship with, or dependent on, the sponsor or research team .➢ Clinical indication for the described monosegmental spinal microdiscectomy➢ Age between 18 and 85 years➢ Informed consent/declaration of data protection➢ Legal capacityThe suitability of a patient will be verified pre-operatively based on the following inclusion criteria:➢ Neurosurgical intervention requirement➢ Previous diagnosis of a somatic pain condition➢ Ongoing early retirement proceedings due to back problems➢ Other chronic pain conditions not caused by a lumbar spinal stenosis➢ Gravid or breast-feeding women➢ Limited communicative ability➢ Consumption of sedative medications➢ Consumption of other homeopathic remedies➢ Severe comorbidities➢ Acute psychotic conditions➢ Simultaneous participation in other clinical studies or completion of participation in a study less than 6 months prior (patients are explicitly asked about this)➢ Ongoing accommodation in an institution after official or judicial orderIn case one of the following criteria holds for a patient they will be excluded from the study:H. perforatum C200 or placebo twice a day every 12 h. The application of homeopathic remedies will start in the morning of the first post-operative day up to the fifth post-operative day.There will be no restriction in terms of post-operative standard treatment and on-demand pain medication in any way. Homeopathic remedies will be applied as an add-on with a time delay of at least 30 min after food intake or alongside oral hygiene. Regarding dosage, the present study is orientated on the dosage recommendations of the Drug Commission D of the German Medical Associations for homeopathic remedies in high grades of dilution  as well The intake of the study medication will be monitored and is documented using the number of returned empty pharmaceutical vials which contained either placebo or the active treatment.➢ Withdrawal of the patient’s consent➢ Consumption of drugs or, rather, medications which are not permitted during the duration of the clinical study➢ Deficient compliance of patients after the evaluation of the examining physician (regular and specified consumption of study medication)➢ A newly occurring condition which influences the efficacy of the study investigation or is contra-indicative to the intake of study medication or which needs to be treated with a medication which is not permitted as a concurrent medication during the study➢ Retroactive appraisal of either unfulfilled inclusion criteria or fulfilled exclusion criteria after the decision of the examining physician/leader of the clinical study➢ Medically necessary transfer of the patient to a different department/a different hospital during the study phase➢ Unexpected findings which make the continuation of therapy from an ethical or medical point of view unjustifiable. The decision will be made by the clinical examination leaderPatients can be excluded from further participation within the study or withdraw themselves without having to provide any further reasons. Possible reasons for this therapy dropout are expected to be:If the patient withdraws their consent the treating physician will end the patient’s participation in the study.The complete study can be discontinued prematurely if it is perceptible early on that it cannot fulfill the aforementioned inclusion criteria.➢ The necessary recruiting numbers cannot be achieved➢ There are serious violations of the protocol➢ The documentation is incomplete or was deliberately filled out incorrectly and legal or ethical instructions are not metThis includes:Discontinuation due to reasons mentioned above is only possible if an agreement between the study leader, examining physicians and the biometric statistician can be reached.In case of serious occurring AEs or severe side effects, or in case of accumulating AEs, the leader of the clinical investigation can terminate the study. In particular, the study will be stopped in case of undesirable results which question the safety of the homeopathic therapy.Since this clinical examination is subject to formalities of a regulatory phase IV study and will be carried out in accordance to Good Clinical Practice (GCP) guidelines, any adverse event (AE) and serious adverse event (SAE) observed during the trial will be reported.Each AE will be assessed by the examining physician according to its severity and its possible connection to the investigated therapy. SAEs will be documented using the MedDRA® standard of reporting SAEs .SAEs will immediately be reported to the responsible ethics commission, the responsible federal authority, the participating examiners as well as the biometrician and thus a benefit to risk profile will be outlined. Documentation and assessment will be done using the OPEN-CLINICA reporting system .To enhance the validity of the data, participants have to return the unused medical vials with remaining globules after the last intervention day and the final visit. Unused vials with globules will be counted and recorded in the drug accountability log.The primary endpoint of this study is pain reduction as measured by the subjective pain sensation on a straightforward 100-mm Visual Analogue Scale (VAS). The VAS will be handed out to patients for their individual evaluation of their subjective pain perception. For each entry, a VAS scale is designated on a separate sheet, so patients will be able to fill in the scale independently. The pages will then be collected as source data and kept in each patient file. Measurement of pain will occur four times a day and the average will be determined for each day.The secondary endpoint is the amount of post-surgical intake of analgesic / anti-inflammatory agents. The number and dosages (in milligrammes) of the medical application will be collected for standard as well as the individually requested medicine. All occurring AEs will be descriptively recorded in the Case Report Form (CRF). Data regarding medication requested and taken by the patient will be extracted from the medical record folder.In order to be able to describe the post-operative pain more precisely the standardised ‘Pain Experience Scale’ ) will be applied during study visits T− 1, T1, T3 and T5 once a day  as bulk product . Both will be repacked in glass bottles and labelled according to the randomisation list at the pharmacy of the Community Hospital Herdecke and allocated to the particular patient by the associated study nurse. The identification will be carried out according to a uniform, identical sticker according to the GCP ordinance in obligatory labelling of testing compounds according to § 5 where for information only the continuing identification number will be noted (GCP-V § 5).Participants, the principal investigator and the subinvestigator, the study nurse and the statistician will remain blinded to the identity of the two treatment groups until the end of the study.Unblinding of individual participants through the investigator occurs in cases of SAEs if there is a sufficient causal link to the trial medication. In case of emergency, envelopes are deposited in the Investigator Site File (ISF) in order to clarify the random allocation.n = 40 in each group is aimed for the two-sided t test in the analysis of covariance (ANCOVA) model. Assuming a moderate correlation of ρ of between 0.2 and 0.5 [n = 50 patients per group is sufficient.In accordance to the usual standard deviations of the 20-mm VAS, a minimal relevant difference of 15 mm and a power of 0.90, the level of significance for the testing of pain reduction at a significance level of α = 0.05 requires a minimum sample size of  and 0.5  and undeStudy data will be collected from day − 1 until day 5 Fig. . The oriCRFs will be stored in numerical order in a secure place and manner. Patient files will be maintained in storage for a period of 10 years after completion of the study. All forms related to the study data will be kept in locked cabinets. Access to the study data will be restricted.The statistical analysis of the study will be carried out at the Chair of Research Methodology and Statistics in Psychology, Witten/Herdecke University, using SAS as validated software for clinical studies .➢ Who discontinued the clinical trial; they will be evaluated as if they had complied with it➢ Who had their examining therapy modified or changed; they will be analyzed in their original randomised group➢ Who took accompanying medication or received accompanying therapy without permission; they will still be taken into consideration in the analysis➢ Whose planned examinations were not carried out within the planned time frame; they will still be taken into consideration in the analysisAll evaluations, in particular the evaluation of the primary outcome measure, will be made on the basis of all randomised patients (intention-to-treat population), regardless of whether or not they adhered to the treatment protocol or provided complete data sets. These are, in particular, patients:Aside from the analysis of all randomised patients, a per-protocol analysis will also be carried out which is supposed to indicate which effect sizes can be reached under optimal circumstances. In the per-protocol population all patients will be included who fulfill all study requirements.Patients who withdraw their consent to use their personal data for statistical analyses will be excluded from the analysis (dropouts).➢ Missing reports of individual responses on the SES questionnaire will be replaced according to the recommendations of the Test Manual➢ Missing total scores will be replaced numerous times according to the principle of multiple imputations (MI) by using the MCMC method . The MI ➢ The replacement of missing values will be done with a model of regression model. It includes the final score as dependent variable and baseline values, study group membership and attitude of expectation as independent variables. A total of 50 complete data sets will be produced that way. From the 50 individual results point estimates will then be determined for the main objective and its varianceMissing values will be replaced by applying the following measures:A detailed description about patient evolution within each group as well as the handling of non-compliant cases and missing values will be given in a future Statistical Analysis Plan according to  as a frep values will be reported which are based on analogue models like the one for the main objective criterion. Those have a self-explanatory character and do not distinguish between the efficacies of the examined therapies.Merely the criteria of the primary objective will be evaluated inductively. All secondary outcome variables will be analyzed descriptively throughout the distribution across both therapy arms. For criteria that are of side objective, 95% confidence intervals and t test, with a two-sided level of significance of α = 5%, will test whether both intervention groups differ from one another.A univariate analysis of covariance (ANCOVA) will be used to generate results for the criterion of the main objective, which was to test whether there would be changes in pain intensity comparing to the beginning of the study to the fifth post-operative day on a 100-mm VAS. For this analysis the main parameter will be measured as a function of group affiliation (graded as a fixed factor on two levels), the baseline measure , patient expectation , time and duration of surgery (as measured in hours) as well as pain intensity on the day before surgery will be modelled. Within this ANCOVA a p values and confidence intervals will be based on the relevant t test.Additionally, the progress of VAS changes will be modelled with the help of a mixed linear model. For this model aside from group membership (binary), the VAS score at baseline (linear), time of surgery and patient expectation will be entered as fixed factors and the patient code (graded) will be entered as a random factor. The intra-individual correlation will be assumed to be exponentially decreasing with time. The estimated therapy effect, The Center for Clinical Studies at Witten/Herdecke University (ZKS UW/H) will monitor and examine abidance with the study protocol.The relevant regulations of the data protection legislation will be entirely fulfilled. All appropriate and necessary precautionary measures will be met in order to perpetuate the confidentiality of medical data and personal information.The application has been approved to the competent ethics committee (Witten/Herdecke University) and the Federal Institute for Drugs and Medical Devices .This study is in compliance with the Helsinki Declaration and with the International Conference on Harmonisation (ICH) – Good Clinical Practice.In case of necessary protocol amendments the amendment will be submitted to the ethics committee and competent authority and implementation will be done after approval. Due to the study design  and close contact between study team, sponsor and site, a separate communication plan is not necessary.Despite the fact that homeopathy has a long tradition in the complementary treatment of patients and is part of the medical curriculum in many European universities  there isHypericum in a randomised controlled trial compared to placebo for the first time. The prescription of homeopathic Hypericum for pain conditions is historically well established and respective publications can be traced back to the medieval age [Hypericum will be reminded of a class of injuries involving sentient nerves and it is not surprising that this remedy has come into use for the results of such injuries’ [This study evaluates the application of highly diluted eval age . In the njuries’ .Hypericum is a promising additional treatment option in multimodal pain management, even though its effectiveness still has an insufficient evidence base [Neural pain after surgery caused by damage or injuries of the nerves often develops into stabbing and unbearable pain. Management of such post-surgical pain conventionally includes the application of opioids in varying dosage, codeine, dihydrocodeine, tilidine, naloxone or tramadol. If necessary, opioids are combined with peripheral pain-relieving medication or substances like gabapentin or pregabalin. As opioids are associated with a variety of potential side effects, including respiratory depression, homeopathic nce base . Our stunce base , 41. If nce base  and Mathnce base  for modeThis study makes use of a non-individualised classical homeopathic approach. Other researchers decided to make use of a complex homeopathic approach, i.e. in the treatment of low back pain due to osteoarthritis  or an inHypericum is known as a remedy for stabbing pain, especially when nerve root irritation or nerve damage is involved, we decided to apply Hypericum C200 as a sole remedy for this condition.Our decision to apply only one remedy is based on the concept of ‘homeopathically proven indications’ where injuries are treated with typical remedies that were shown to be effective irrespective of the individuality of a given patient . As HypeThis is a monocentric study in an integrative hospital. Although the treatment completely adheres to the respective guidelines, the setting might not be regarded as representative for inpatient treatment of lumbar disc herniation.At the time of initial manuscript submission, recruitment had already started (November 2015) but was not completed. The manuscript reports protocol version 2 (1 December 2016).Additional file 1:SPIRIT 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 122 kb)


Corneal abrasions are one of the most common ocular injuries seen in the emergency department. While most patients with corneal abrasions complain of excruciating pain, permanent sequelae may develop if not managed properly. The use of topical antibiotics and other standards of treatment have greatly reduced the incidence of complications. However, there is still a lack of consensus regarding the proper management of pain in corneal abrasions. Proposed analgesics for the control of corneal abrasion pain include topical nonsteroidal anti-inflammatory drugs (NSAIDs), topical anesthetics, and topical cycloplegics. For this review, ten published randomized controlled trials were identified, focusing on the efficacy and safety of different topical analgesics used in treating corneal abrasions.  Six of the trials focused on topical NSAIDs, three on topical anesthetics, and one on topical cycloplegics. There were mixed results regarding the efficacy of topical analgesics in reducing pain in patients with corneal abrasions. This review of the literature revealed that topical NSAIDs produced reductions in pain symptoms, whereas topical anesthetics and cycloplegics did not demonstrate significant improvements in either healing rates or pain control. Thus, this evidence supports the use of topical NSAIDs in the standard management of corneal abrasions. Unfortunately, the power of these studies is largely limited by small sample sizes. Larger studies must be conducted before topical analgesics can be recommended or discouraged for pain management in corneal abrasions. However, based on this review of the literature, the use of topical NSAIDs does not appear to complicate wound healing, and thus remains a safe option in patients desiring medical treatment.   Corneal abrasions account for a large portion of eye-related injuries seen with an incidence of approximately 3 in 1000 persons presenting to the emergency room .  BecausIn the past, corneal abrasions were traditionally treated with eye patching . It was This review seeks to determine which topical analgesic is best supported by literature to provide pain relief following patients with corneal abrasions. We have separated the review by drug type starting with NSAIDs as demonstrated in Table The study published in 2001 by Goyal et al. sought to determine the efficacy of the topical NSAID ketorolac trometamol 0.5% solution on pain reduction and healing following corneal abrasion [P < .02). Szucs et al. assessed the effectiveness of Diclofenac solution for corneal abrasions in the emergency department  by recruiting 49 patients for a double-blinded study [n = 40 and n = 49, respectively), therefore larger sized studies may be required before this drug is recommended above others for the standard of treatment for corneal abrasions.Diclofenac is another ophthalmic NSAID that has been studied and published with results regarding pain management. In a study of 40 patients with corneal abrasions, participants were asked to provide visual and categorical pain scores over a period of three days . The pared study . Szucs eP = .007) with the NSAID solution compared to the control group receiving gentamicin eye drops without indomethacin. However, the significance of pain reduction after days 1-3 is not clear. No p-value is provided for other reported times. Limitations  for this study include the following: major differences between treatment groups including distribution of iris colors (p = .026), corneal lesion depths (P = .05), conjunctival hyperemia (P = .001) and associated symptom pain scores (P = .03). These statistical differences between groups may limit the strength of association between the indomethacin treatment and reduced pain scores. Patrone et al. further extrapolated on the role of indomethacin 0.1% in a study that assessed for its analgesic properties in traumatic corneal abrasions. In this randomized, blind-unspecified study, 347 patients with traumatic corneal abrasions were provided either indomethacin 0.1% with netilmicin drops 0.3% or the control consisting of just the antibiotic drops [P ≤ .0001). There was no significant difference in delay of corneal healing in either group. This study used linear regression analysis which demonstrated that there is a relationship between the dimension of the abrasion at presentation and the level of pain that was elicited.  At 12 hours after receiving treatment, there was no longer a correlation between  pain and the size of abrasion in the treatment group, whereas in the control group, pain continued to be  worse relative to the size of the abrasion. This relationship suggests that indomethacin provided relief to the patient independent of the size of abrasion.There are two published studies that have assessed the role of indomethacin in corneal abrasions. Alberti et al. evaluated 123 patients in a double-blind, multicenter, randomized controlled trial that assessed whether indomethacin 0.1% and gentamicin given in combination would lead to decreased pain and associated symptoms in patients with traumatic corneal abrasions [ic drops . PatientP < .05). Additionally, the patients that received flurbiprofen took less oral analgesia than the controls (P < .01), had fewer sleep disturbances (P < .05), and took less time off work (P < .01). Brahma et al. asked 21 of the patients in the treatment groups to report significant adverse effects; no complications related to the topical NSAID were reported. Flurbiprofen eye drops were found to be beneficial and significantly improve pain relief in patients with superficial corneal injuries.A 1996 study by Brahma et al. examined the effects of flurbiprofen 0.03%, a topical NSAID, on pain relief in superficial corneal injuries, including corneal foreign bodies and abrasions [Topical anesthetics are another class of ocular intervention that has been used to provide pain relief for corneal abrasions. These results are demonstrated in Table n = 12, M = 404±75 mm) compared to the control group  on VAS pain rating. Pain ratings were scored from 0 mm (no pain) to 100 mm (worst pain imaginable). These scores were taken every 3 hours for 36 hours, creating a cumulative pain score based on 12 pain assessments for each patient. However, the clinical significance of these findings is hindered by the low power secondary to small sample size.In 2009, Ting et al. published an article assessing both the efficacy and safety of topical amethocaine in the management of corneal abrasions . 47 totaP = .007).  The satisfaction of patients was also evaluated using a 10 point VAS; the treatment group had a median satisfaction of 8.0 (IQR = 6.0-9.0) compared to that of the control group median satisfaction of 2.6 (IQR = 1.0-8.0) (P = 0.027). Proparacaine was effective at short-term pain reduction and was perceived by patients to be more efficacious as well.A study released in 2010 by Ball et al. investigated the efficacy of proparacaine in the management of corneal insult . A totalP = .761). However, on VAS ratings, there was no statistically significant difference in pain scores between the two groups. The average difference in reported pain over 48 hours was 0.53 on a 100 mm VAS (P = .149). Despite this, the patients in the treatment group reported that on a scale of 0-10 of effectiveness, tetracaine was rated 7.7. The patients in the control group reported the saline as 3.8 on a scale of 0-10 effectiveness. Thus, patients felt that the tetracaine was more effective (P < .0005).Another study released in 2014 by Waldman et al. examined the use of tetracaine in the management of corneal abrasions . The stuCycloplegics are another class of intervention that can be administered for corneal abrasions; however, the existing literature is limited. Table P > .05). Meek et al. concluded that cycloplegics should not be considered for routine use but may be considered if ciliary muscle spasm or intraocular inflammation is present.A triple-blind, randomized controlled trial conducted by Meek et al. in 2010 investigated the effect of 5% homatropine eye drops compared with 0.5% hypromellose placebo eye drops on pain ratings . Pain waWhile topical ophthalmologic solutions are commonly given to patients presenting to the emergency department for corneal abrasions, there has been limited progress in establishing specific guidelines to stratify the best treatment option. Patients with corneal abrasions are typically treated with a minimum of topical antibiotics to reduce the risk of infection, but the protocol for optimal pharmacological pain management remains a topic of debate. Three main classes of topical medication have been explored: NSAIDs, anesthetics, and cycloplegics. Trials involving the use of NSAIDs for pain management in corneal abrasion have shown a statistically significant decrease in subjective pain experienced by the patient. However, the efficacy of topical anesthetics on pain control in corneal abrasions is unclear and requires more studies. The current literature  involving topical anesthetics suffers from small sample sizes. Because of the limitations of the available studies, it is difficult to recommend or discourage the use of topical anesthetics for pain control. The sole published study on cycloplegics showed no significant pain reduction; therefore, further studies are necessitated before this intervention can be encouraged for use in corneal abrasions. Thus, based on this review of the current literature, NSAIDs and proparacaine, an anesthetic agent, have been shown to be the most effective topical interventions for subjective pain reduction in corneal abrasions. Additionally, NSAIDs have been shown to have no effect on the rate of corneal epithelial growth after an abrasion. Because these studies investigating the efficacy of topical analgesia for corneal abrasions are limited by small sample sizes, the current available data, especially regarding topical anesthetics and cycloplegics, is too limited to draw recommendations for management. As a result, large multi-center randomized controlled trials should be performed in order to properly demonstrate effective pain control.