Ott1, M. Stein1, E. Uhl1, M. Kolodziej1F. Schwarm1Universitätsklinikum GießenBackground:PNFS is an effective alternative treatment for patients with chronic low back pain. TENS is known for easy application and frequently used in multimodal pain therapy concepts. The aim of this prospective study was to examine the predictive value of TENS treatment for later successful PNFS.Materials and methods:Between 2014 and 2017 a prospective cohort study of 23 patients with chronic lumbar pain was conducted. All patients were treated with multiple pain medications. Pain intensity (NRS), SF12v2 with Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and Oswestry Disability Index (ODI) were assessed before and after TENS use, pre- and postoperatively as well as 3 and 6 months after PFNS implantation. TENS was applied for 3-5 days. The implantation of a rechargeable PNFS-system with 2 percutaneous leads was performed after 4-7 days of positive testing. Statistical analysis was performed using the Mann-Whitney U and the Wilcoxon rank-sum test.Results:The cohort consisted of 23 patients  with a median age of 60.9 years (IQR25-75 52.6-65.7). After positive PNFS testing a neurostimulator was implanted in 8 patients with positive TENS effect and 10 patients with no TENS effect. 5 patients had no PNFS effect and the test electrode was explanted. After 3 and 6 months median NRS was reduced from 8.5 (IQR25-75 7-9) to 2.5  and 3.0 , ODI from 57.0 (IQR25-75 46.5-66) to 38.0  and 34.0  in the TENS positive cohort, respectively. The TENS negative cohort showed a median NRS reduction from 7.0 (IQR25-75 6-8) to 5.0  and 4.0 , after 3 and 6 months, respectively. There was no improvement from initial ODI 45.0 (IQR25-75 44.0-62.5) neither after 3 nor after 6 months. Generic health survey scores (PCS and MCS domains of the SF-12v2) showed slightly better improvement in the TENS positive cohort. All patients with negative PNFS testing belonged to the TENS negative cohort.Conclusion:TENS positive patients showed a significantly better treatment effect after PNFS implantation, thus TENS can be a predictive tool for patient selection in PNFS. PNFS itself is an effective and safe treatment for chronic low back.(Abstract ID: 157)1, W. Stummer2T. Fortmann1Hamm2Uniklinik MünsterBackground:Patients suffer from pain after surgery due to transsection and suturing of skin and other tissues. The aim of this study was to introduce a suitable pain medication management by improving nurses’ autonomy and thereby reducing patients’ pain.Materials and methods:During three time periods from December 2011 until May 2014 a total of 275 patients  were interviewed using the QUIPS-questionnaire to register pain in different situations during the first 24h after surgery, the dose of pain medication, side effects and patients’ satisfaction. Between the first and the second period all doctors and nurse were introduced to the Targin and Palladon-schemes. We also differentiated between head and spine surgery and analysed the key parameters of the performed surgeries.Results:Although there was no significant difference between the three groups concerning different kinds of pain, patients’ satisfaction after head surgery rose significantly from 11,85 to 12,83 . Unfortunately these patients suffered more from nausea and vomiting .There was a significant difference  between head and spine surgery in minimal pain , pain during mobilization  and the reduction of mobility (40 vs 71%).Especially patients with spine surgery lasting more than 2 hours had more pain during mobilization , more requests for pain medication  and woke up more frequently due to pain .Interestingly those patients, who received opioids in the anesthetic recovery room had far more pain problems , minimum pain 2,36 vs 1,67, pain during mobilization, 4,73 vs 3,87, more request for pain medication 25 vs 10%, waking up due to pain 57 vs 37%, reduced mobility 64 vs 48% and less satisfaction 11,28 vs 12,03 (p<1%)).Conclusion:Using pain medication schemes helps to improve patients’ satisfaction since nurses are able to administer more pain medication in pre-determined ranges. For patients after head surgery it might be necessary to reduce the pain medication in order to reduce side effects such as nausea and vomiting. Patients after spinal procedures of longer than two hours should receive enough pain medication right away to improve their mobility and satisfaction.(Abstract ID: 193)1T. Kinfe1Universitätsklinikum BonnBackground:Total knee arthroplasty (TKA) due to osteoarthritis and especially after revisions of previous TKA have been reported to lead to a refractory chronic post-surgical pain (CPSP). The incidence of CPSP ranges between 10-34% and additionally impact quality of life, mood, sleep, cognition and metabolic state of the affected subjects. Complex regional pain syndrome I - II (CRPS) represent clinical phenotypes of CPSP of the knee region. Complex regional pain syndrome (CRPS) and associated co-morbidities have been linked to a pro-inflammatory state driven by different mediators. Most recently, an approach that appears to have a considerable promise for treating focal neuropathic pain has become available . Anatomically targeted DRGSTIM was found to be superior to conventional SCS in a Class I study as well as several controlled and uncontrolled observational clinical trials for a variety of pain conditions. Briefly, DRGSTIM may have the capability to restore the distorted filter function of the DRG, thus inhibiting hyperexcitability of DRG neurons and deeper layer compartments (laminae II/III) of the spinal cord. The precise mechanism of DRG-evoked effects on spino-nociceptive neural transmission as yet is not fully established. However, clinical trials assessing the impact of DRG stimulation on the neuro-immune communication are lacking.Materials and methods:The goal of this study was to assess concentration changes of neuroinflammatory mediators in serum  and in saliva  relative to selective L4-DRG therapy.This study enrolled 24 subjects  and performed immunoassays of inflammatory mediators in saliva and serum along with score-based assessments of pain, mood and sleep quality at baseline and after 3 months of selective L4-DRGSTIM.Results:After 3 months L4-DRGSTIM CRPS associated pain significantly decreased. In addition, disturbed sleep and mood improved post-DRGSTIM, although statistically not significant. Significantly increased serum values of pro-inflammatory markers were detected pre- and post L4-DRGSTIM for high-mobility group box 1, tumor-necrosis factor α, interleukin (IL) 6 and leptin. IL-1β was significantly elevated pre-L4 DRGSTIM, but not post-treatment. Elevated anti-inflammatory IL-10 significantly decreased after 3 months in serum, while saliva oxytocin concentrations increased in CRPS subjects after L4-DRGSTIM (p=0.65). No severe implantation and stimulation associated adverse events were recorded.Conclusion:Selective L4-DRGSTIM improved neuropathic pain and functional impairment in CRPS as previously reported. CRPS patients displayed a pro-inflammatory molecular pattern in serum. Serum anti-inflammatory IL-10 significantly declined, while saliva oxytocin non-significantly increased after L4-DRGSTIM. An evidence-based relational interpretation of our study is limited due to the uncontrolled study design. However, molecular profiling of biofluids  represents a novel and experimental field in applied neuromodulation, which warrant further investigations to unveil mechanisms of neuro-immune modulation.(Abstract ID: 335)1, H. R. Tinneberg1, E. Uhl1, M. Kolodziej1F. Schwarm1Universitätsklinikum GießenBackground:Endometriosis or surgery for it can result in secondary nerve damage and chronic pelvic pain. The results of conservative, surgical treatment, and spinal cord stimulation show only a poor outcome. We present a new surgical method of retroperitoneal sacral nerve stimulation for the treatment of neuropathic pelvic pain caused by endometriosis.Materials and methods:Between 2012 and 2017 five female patients were retrospectively analyzed. All were complaining of chronic pelvic pain, and bladder and bowel dysfunction following several surgeries for endometriosis. These patients underwent laparoscopic re-exploration or re-laparotomy with retroperitoneal implantation of electrodes directly onto the sacral nerve. The intervention was followed by a test period (3-15 days) before the decision for a permanent implantation of a neurostimulator was made. Pain intensity (NRS), generic health status (EQ-5D-5L), Becks Depressions Inventary (BDI-V) and Pain Catastrophizing Scale (PCS) were assessed for the immediate pre- and postoperative status as well as after 3 and 6 months postoperatively. Statistical analysis was performed using Mann-Whitney U and Wilcoxon rank-sum test.Results:Median age was 40.1 years (IQR25-75 29.4-47.0). Significant improvement of NRS from median 9.0 (IQR25-75 8.5-10.0) preoperatively to 5.0  at 3- and 2.5  at 6-month follow-up was achieved. Median EQ-5D-3L index value before treatment was 0.19 (IQR25-75 0.13-0.31) indicating a low quality of life. After 3- and 6-months a significant improvement to 0.73  and 0.76  was seen. The preoperative median BDI-V score of 46.0 (IQR25-75 40.5-58.0) indicating a major depressive mood increased significantly improved to 26.0  and 12.0  after 3 and 6 months respectively. Preoperative PCS was highly elevated with a median score of 42.0 (IQR25-75 37.5-50.5). After 3 and 6 months a significant reduction to 18.0  and 3.0  was seen, respectively. Furthermore, 4 patients had a complete reduction in demand for analgesics.Conclusion:This unique method is an effective treatment option for chronic, neuropathic pelvic pain after endometriosis treatment. However, this method requires an interdisciplinary surgical team approach.(Abstract ID: 26)1, S. Siller2, C. Brem2, J. Lutz2, S. Zausinger2K. Schöller1Universitätsklinikum Gießen2Uniklinik MünchenBackground:Despite its invasiveness, computed-tomography myelography (CT-M) is still considered to be superior to conventional magnetic-resonance imaging (MRI) for preoperative evaluation of multilevel cervical spondylotic myelopathy (MCSM). We analyzed if diffusion-tensor imaging (DTI) could be a less-invasive alternative for this purposeMaterials and methods:In 20 patients with MCSM and indication for decompression of at least one cervical level, CT-M was carried out preoperatively to determine the extent of spinal canal / CSF space and cord compression (Naganawa score) for decision on the number of levels to be decompressed. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) as the main DTI indices were correlated with these parameters and with MRI-based increased signal-intensity (ISI); ROC-analysis was performed to determine the sensitivity to discriminate levels requiring decompression surgery. European-Myelopathy-Score (EMS) and neck/radicular Visual-Analogue-Scale (VAS-N/-R) were utilized for clinical evaluation.Results:According to preoperative CT-M, 20 levels of maximum and 16 levels of relevant additional stenosis were defined and decompressed. Preoperative FA and particularly ADC showed a significant correlation with the CT-M Nagawana score but also with the ISI grade. Furthermore, both FA and ADC facilitated a good discrimination between stenotic and non-stenotic levels with cut-off-values being < 0.49 for FA and > 1.15x10-9 m2/s for ADC. FA and especially ADC revealed a considerably higher sensitivity (79% / 82%) in discriminating levels requiring decompression surgery compared to ISI (55%). EMS and VAS-N/-R were significantly improved at 14 months compared to preoperative values.Conclusion:In MCSM patients, DTI parameters are highly sensitive to identify levels requiring surgical decompression and might therefore represent a less-invasive alternative to CT-M for surgical planning.(Abstract ID: 66)1, M. Bender1, F. Gronen2, E. Uhl1, K. Schoeller1S. W. Kim1Universitätsklinikum Gießen2Diagnostikzentrum Radiologie+Neurologie, GießenBackground:Ossification of the posterior longitudinal ligament (OPLL) is a relatively rare cause of cervical spinal canal stenosis and myelopathy in Central Europe. In cases of severe or progressive myelopathy symptoms, surgical decompression of the spinal cord might be indicated, usually through a posterior approach. C5 palsy (C5P) is a well-known complication of anterior and posterior cervical decompression, particularly in multilevel surgeries that involve the level C4/5. Most of the palsies occur unilaterally. Bilateral cases, however, are very rare, and only few reports have previously described their outcome. We report about a patient with a severe progressive bilateral C5P after posterior decompression and fusion surgery for OPLL who was closely followed by 3 monthly clinical and neurophysiological examinations. The patient has almost recovered complete strength at 12 months under conservative therapy in adherence to a rigorous physical therapy protocol.Results:CasereportA 58 year old female patient with ossification of the posterior longitudinal ligament and resulting spinal canal stenosis underwent surgery in August 2015. Weakness in her both deltoid and biceps muscles was immediately detected after surgery and gradually deteriorated to severe paresis in the following 2 days. Postoperative magnetic resonance imaging showed sufficient decompression of the spinal cord with posterior shifting. However, residual neuroforaminal bilateral stenosis at levels C4/5 and C5/6 was found on postoperative computed tomography. After discussion of the therapeutic options, we decided to start conservative management including physical therapy and to follow the patient closely including clinical and neurophysiological examinations for the next 12 months. After 3 months, improvement of bilateral paresis was already evident. Muscle strength in the right biceps and the right deltoid muscles recovered completely within a year, but Grade 4 muscle weakness remained in the left deltoid and biceps muscles. Repetitive electromyography also showed continuous improvement of the interference patterns of the deltoid and biceps muscles.Conclusion:Several factors potentially influence the development of a C5P after cervical decompression but, up to know, no surgical strategy offers clear advantages over the other. Posterior shifting of the spinal cord should be avoided, but this is not always possible. Nevertheless, the prognosis of a C5P is good, and in our opinion, physical therapy using a rigorous treatment protocol is also adequate in patients with severe and bilateral palsies.(Abstract ID: 364)1S. Gitter1Nova-Clinic, BiberachBackground:The author conducted a retrospective study to compare the implantation of polyetheretherketone (PEEK) cages stand alone after anterior cervical discectomy for double level cervical degenerative disc disease to the hybrid surgical procedures by implantation of one level peek cage in combination with artificial disc implantation on top.The significant importance of pseudarthrosis and impact pathology in stand alone PEEK cage implantation procedures is well discribed in the literature.Materials and methods:Comparison oft wo gropus: 80 patients double level classical stand aone cage vs 80 patients lower level fusion and artificial disc on to level.Preoperative and postoperative radiological and clinical assessments were typically performed.Results:During the mean follow-up period of 36 months, fusion occurred in 73% of patients in the stand alone group. Subsidence developed in 37% oft he patients in the double level stand alone PEEK cage implantation cohorte, clinical relevant in lower than 8%. Subsidence developed in 25% oft he patients in the cage plus artificial disc group, clinicl relevant lower than 5%.Significant pain relief in the first 24 month, related tot he myelon- and root decompression.In the further follow up we observed significant axial , facet related, pain in the double level fusion group in 45% vs 20% facet related pain in the cage plus artificial disc group.In the follow up period we observed relevant , intermittend adjacent level disc desease in 9% oft he PEEK cage stand alone group and in 2.5% oft he cage plus artificial disc group.The subsidence rate is associated further with cage hight (>6mm).Rate of pseudarthroses: in the cage stand alone group: 15% , in the cage plus artificial disc group: 2%We did not observed any insufficiency or dislocation oft he artificial disc during follow up, no heterotopic ossification in the artificial disc level. The rate of adjacent level pathology is significantly lower in the group of fusion with PEEK cage in combination with artificial disc implantation on top.Conclusion:There is in all parameters a significant advantage of PEEK cage implantation in combination with artificial disc implantation on top vs the group of double level fusion by Peek cages in stand alone technique.Fusion and / or subsidence affect the clinical outcomes. Using of artificial disc on top in combination with a lower level PEEK cage implantation is an effective option (recommendet) in cases of combined doubel level disc degeneration.(Abstract ID: 365)1S. Gitter1Nova-Clinic, BiberachBackground:The author conducted a retrospective study to compare the implantation of polyetheretherketone (PEEK) cages after anterior cervical discectomy for double level cervical degenerative disc disease to the additional dynamic ventral screw and plate fixation in 2 different systems . The significant importance of pseudarthrosis and impact in stand alone PEEK cage is well discribed.Materials and methods:A group including a total of 80 patients with double-level degenerative disc disease was treated with anterior cervical discectomy and implantation of PEEK stand-alone cages. We compare this group to another group of 80 patients: the procedure of peek cage implantation was added by ventral dynamic plate and polyaxial screw fixation. Preoperative and postoperative radiological and clinical assessments were performed.Results:Follow-up period of 36 months: fusion occurred in 73% of patients in the stand alone group and in 96 % of all patients in the "plate added group". Subsidence : 37% of the patients stand alone PEEK cage implantation cohorte. No subsidence in the group of additional platement observed. In the early follow up (up to 24 month) pain decreased in all patients, and the patients' satisfaction rate:79% in the stand alone group vs 92 % in the platement group. Neither fusion or subsidence was related to the clinical outcome in the early time of 12 month. In the further follow up we observed significant axial pain in the subsidence group (56%) vs a facet releated pain (intermittend treatment) in the additional platement group (32%). We observe relevant , intermittend adjacent level disc desease in 9% oft he PEEK cage stand alone group and in 10.5% oft he addional platement cohorte.The history of development of NDI is related tot he rate of axial and facet pain syndromes.The subsidence rate is associated further with cage hight (>6mm).Rate of pseudarthroses in the cage stand alone group: 15%, no pseudarthrosis in the platement group.Conclusion:The clinical and radiological demonstrate significant difference in outcome between the cage stand alone vs the additional platement- groups. There ist in all parameters a significant advantage in PEEK cage implantation in duoble level procedures in combination with addional plate and screw fixation. Fusion and / or subsidence affect the clinical outcomes. Using of additional platement is an effective option (recommendet) especially in cases of delordotic and kyphotic cases.(Abstract ID: 580)1, P. Reid2, J. Osorio2, A. Jödicke1, C. Ames2M. Schomacher1Vivantes Klinikum Neukölln, Berlin2University of California San Francisco - UCSFBackground:The atlanto-axial region is a complex anatomical area. Standard posterior fixation techniques  are used widely. Rare instances  may present challenges in screw placement, achievement of bony fusion and avoidance of vascular injury. Reliable salvage techniques and modifications are helpful if well-established C1-C2 fusion techniques cannot consistently performed.Materials and methods:Three cases of C1-C2 posterior fusion with necessity for technical modifications of stabilization were reevaluated:Case 1:A 76 year-old woman with history of prior C4-C7 ACDF and posterior spinal fusion for cervical myelopathy revealed in MRI a pseudotumor and stenosis of the C1-C2 complex as a result of microinstability. Surgery of the patient was performed over a dorsal cervical midline incision. The prior instrumentation was removed at the upper level at C4. The C3-lamina and C2-pedicles were exposed. On right side a C1-lateral mass screw and C2-pedicle screw were placed. Because of degenerative changes at left side with complexity of C1/C2-articular surface a transarticular C1-C2 screw was placed under navigational assistance. The rods were reattached and decompression of the C1-C2 laminar bone was performed. After decortication from C1 to C5 allograft bone mix with BMP was placed.Case 2:A 19 year-old female patient with recurrent symptoms of cerebellar dysfunction demonstrated signs of cerebellar insults in imaging diagnostics , a C1-assimilation anomaly with instability of the C1/C2-segment and a Klippel-Feil-Syndrome at level C4/5. Angiography demonstrated right sided blood-flow reduction at the V3/4-segment during head rotation. Since simple decompression of the vertebral artery was not feasible, occipital-cervical-fusion was indicated. Because of C1-assimilation and dysplastic changes a right C2 lateral mass screw and C2-lamina screw were inserted under navigational assistance. Lateral mass screws were placed at left C3- and C4-level and right C4- and C5-level. Screws were connected with bended rods and fixed to an occipital plate. For supportive boney fusion, patient’s iliac crest material and ceramic bone graft was additionally placed at C1-C2 region.Case 3:An 84 year-old woman showed signs of C2 non-union (CT scans) and symptomatic instability (neck pain) after 8 weeks conservative treatment of a C2 fracture (Anderson-D'Alonzo type II). Posterior C1-C2 fixation was performed over dorsal midline incision and exposure of the C1 lateral mass and the C2 pars- and pedicle region. Two C1 lateral mass screws were inserted under navigational guidance. At C2-level pars screws were inserted and fixed to C1-screws with rods. For additional fusion and stabilization a single midline iliac autograft was placed after decortication of the C1 and C2 arch between the C1 lamina and the spinous process of C2 and fixed with a single sublaminar cable.Results:After surgery all patients showed no new neurological findings and resolved preoperative complaints. Postoperative images (X-ray/CT-Scans) showed a good cervical alignment, regular placed implants, and bony fusion in all cases.Conclusion:The indicated technical modifications of different C1-C2 posterior stabilization procedures caused by complex degenerative and anatomical reasons appear to be safe and feasible options. Such type of modified procedures should be considered in each spine surgeon’s surgical preparations. However to proof reliability of such alternative techniques further studies with large numbers of patients should be conducted.(Abstract ID: 40)1, J. Lehmberg2S. K. Rosahl1Helios-Klinik Erfurt2Städtisches Klinikum München GmbHBackground:Compared to far-field registration, near-field recording of cochlear and brainstem auditory potentials significantly reduces acquisition time during surgery around the cochlear nerve.We have designed and tested new tympanic and brainstem electrodes to monitor the functional integrity of the lower auditory pathway.Materials and methods:Stainless-steel, ball-shaped electrodes were developed in co-operation with inomed Medizintechnik GmbH . The first of these electrodes was connected to a stainless-steel spring running through an insert earphone. It attaches to the tympanic membrane to record a peripheral auditory evoked potential (ECoG). A second mini ball electrode with a diameter of 1.6 mm was placed either on the cochlear nerve or at the dorsal cochlear nucleus of the brainstem to record a central auditory brainstem response (CABR).Dual near-field recording (DNF) with both electrodes in place was applied in a series of 589 patients with lesions in the CPA and internal auditory canal during microsurgery. Near-field potentials have been compared to the far-field Auditory Brainstem Response . Click stimuli were applied at 13.2 Hz. Data processing was carried out with a commercially available electrophysiological monitoring system . Waveforms were injected into the visual field of the operating microscope.Results:Waves I and II of the BAEP were best identified in recordings at the tympanic membrane, wave III to V were largest in recordings at the brainstem or with electrodes places on the cochlear nerve. Compared to far-field recordings, amplitudes were 3 - 4 times larger for ECoG, and 2 - 20 times larger for CABR in patients with functional hearing. CABR was more variable than the ECoG, depending mostly on electrode location relative to the brainstem generators. In patients with good pre-operative hearing acquisition time for reliable averages were 40 seconds in far-field, and as low as two seconds in near-field recordings.Conclusion:Non-invasive electrodes have rendered near-field recording of electrophysiological responses to auditory stimuli the gold standard in hearing-preserving surgery in lesions around the cochlear nerve.In lesions located intradurally around the petrous bone, dual near-field recording adds safety and significantly shortens feedback time to the surgeon, especially with video microscope injection of waveforms.(Abstract ID: 737)1, K. Schwager1, E. Hofmann1R. Behr1Klinikum FuldaBackground:The treatment of vestibular Schwannomas (VS) changed over the last decades. Initially patients were diagnosed mostly with large tumors. The operation was the only treatment modality. With availability of CT and MRI, diagnosis was made earlier and treatment strategies changed. Nowadays 3 modalities are accepted: wait and scan, microsurgical operation and radiotherapy. We add a forth, the interdisciplinary counseling in a skull base center and operation by an oto-and neurosurgical team. This "forth way" provides an optimum in pretherapeutic management and counseling by a peer group of neuro- and otosurgeons, neuroradiologists, neurologists, oncologistc, radiotherapists and an experienced team of neuro- and oto-surgeons, performing the operation together. This concept was started in 1992 at Würzburg University "Kopfklinik" and continued by the authors at different institutions since now.Materials and methods:125 patients, including 7 recurrencies (5.6%), were retrospectively analyzed. The operative concept is a retrosigmoid approach in semi sitting position. IOM was intensively used by SSEP, MEP, direct facial monitoring, facial MEP and BERA. The extrameatal tumor was removed by the neurosurgeon and the intrameatal by the otosurgeon. All tumor sizes and recurrencies were evaluated, only intrameatal location was excluded. The House-Brackmann (HB) scale was slightly modified as to grade 1 comprises HB 1 and 2, grade 2 HB 3 and grade 3 HB 4-6. For hearing evaluation the Gardner-Robinson (GR) scale was used.Results:Of all tumor sizes, 7 patients (5.6%) had a grade 3 facial paresis, most of them with large tumors and recurrency. 116 patients (92.8%) had grade 1, excellent to good results, HB 1-2, one year after the operation. Only a few patients were in grade 2, equivalent HB 3. In all but 2 recurrent tumors the HB grade remained the same as preoperatively. In 3 grade 1, in 2 grade 2 and in 1 grade 3. Facial outcome was related to extrameatal tumor size. In tumors larger than 3.1 cm diameter facial function was in 23% grade 3. Also the rate of hearing preservation was clearly related to tumor size. In 88 patients, 70.4%, there was a preoperative hearing according to GR of 1-3. Which means not in every case a servicable hearing but an augmentable hearing with appropriate hearing aids. Over all tumor sizes the postoperative hearing was in 42 patients, 47.8%, GR 1-3. An interesting parameter was the feasibility of reproducible BERA recordings. In patients with extrameatal tumors of up to 20mm and a preoperative hearing of GR 1-2 and reliable recordings of BERA, the hearing outcome in the same GR scale of 1-2 was 68% (15/22). Including patients with the same Tumor size and preop hearing but worse BERAs, the result was 53.84% (21/39). There were 5 subctaneous CSF pouches and 2 liquorrhea, 1 superficial wound infection and one transient hemiparesis due to pneumatocephalus.Conclusion:The interdisciplinary treatment of VS provides a safe and effective treatment of this disease. The rates of facial nerve and hearing preservation are in the same range as in large other contemporary studies. If the BERA recordings are technically stable and free from artefact, excellent rates of hearing preservation were obtained. A highly sophisticated intraoperative monitoring is essential for good results. With our setup, the learning effect for both surgeons is maximized and the intraoperative discussion is fruitful for the operative team, the students, nurses as well as for the patients outcome. In addition, it bears an excellent possibility to simultaneously train younger skull base specialists from both fields.(Abstract ID: 758)1, K. Schwager1, E. Hofmann1R. Behr1Klinikum FuldaBackground:ABI is a generally accepted method to restore hearing after destruction of the cochlear nerve mostly in neurofibromatosis type 2 (NF-2) patients. In the early years however speech understanding was not possible especially not without visual cues as lipreading. Newer data in NF-2 showed that despite of large tumors a considerable percentage of patients achieved open set speech recognition and even telefone use. In this retrospective study we tried to find factors associated with higher levels, better than 30% open set sentence recognition, of prosthetic hearing.Materials and methods:All NF-2 patients from 6 ABI centers implanted from 1997-2011 with a Med-El ABI device and with at least 3 months of implant experience were evaluated. Only patients out of this group who scored better than 30% open set sentence recognition were investigated more closely. Surgical factors (the author is the main surgeon), patient and tumor characteristics, intraoperative electrophysiology, electrode placement, number of auditory electrodes and distinct pitches, device factors, stimulation strategy and fitting factors were studied.Results:Of 84 patients 26 scored better than 30% open set sentence recognition (31%). Neither patient age, tumor size or -stage influenced hearing outcome significantly. If deafness before implantation was less 1 year scores were over 65% sentence recognition compared to 45% (p=0.03). Patients operated in semi-sitting position scored significantly better than in lying position (p=0.04). 35.7% of semi-sitting vs 16.7% of lying operated patients scored better than 30%. MCL levels of less than 28nC correlated sign. better , 67.1% correct sentence recognition vs 47.2, p=0.04. Number of audible electrodes had no significant effect on outcome. However patients with average number of distinct pitches of 9.1 had scores over 60% and those with 7.4 had between 30-60% (p=0.01). In patients with high stimulation rates, 1200ppse, scores were 67.1% vs 45.7% in those below 1200ppse (p=0.03).Conclusion:In this selected group of excellent and top performing ABI patients it was possible to distinguish some parameters which are probably responsible for improved outcomes. The message is, that exact probe positioning is mandatory. Intraoperative mapping of the cochlear nucleus area by test electrodes and painstaking electrophysiological measurements will support optimal placement. This will cause low thresholds and MCL levels, high stimulation rates and many distinct pitches. Surgery must be as meticulous and atraumatic to the nervous tissue as possible, which is facilitated by semi-sitting position. If any possible, timing of implantation should not be postponed longer than one year after deafness.(Abstract ID: 761)1, K. Schwager1, E. Hofmann1R. Behr1Klinikum FuldaBackground:Endoscopic techniques took over an important place in surgery of skull base lesions. In the last 10 to 20 years significant steps forward could be achieved in surgical treatment of anterior skull base lesions. Especially pituitary adenomas and, with the extended approaches, meningeomas and craniopharyngeomas are now successfully treated with exclusively endoscopic approaches. In the posterior fossa the use of the endoscope is still limited. It is mostly used for exploration of hidden places, which are difficult to be disclosed by the microscope. The question therefore arises if the endoscope can be used more intensively also in lesions of the posterior fossa.Materials and methods:In a prospective analysis 8 female and 2 male patients (pat), with 2 meningeomas (M) and 8 vestibular schwannomas (VS) were operated only by using the endoscope as visualisation tool. A two dimensional Storz endoscope with 0 and 30 degree optics was used. The tumors should not exceed 20mm in extrameatal diameter. VS grew intra- and extrameatal, the M were located laterally to the IAC. Intensive intraoperative monitoring was used. The pat were positioned laterally with slightly elevated head. Follow up period is meanwhile between 42 and 100 months. All pat were revisited on a regular basis with yearly clinical and MRI investigations.Results:Pat mean age was 61.5 years (mean deviation 8.2), mean tumor diameter was 13.6 mm (3.4) largest area was 150 mm2 (79.3), mean operation time was 255.2 minutes (48.7). In all but one case the facial nerve could be preserved with normal function, in one pat the postop result was HB 3 with improvement to 2. The acoustic nerve was anatomically preserved in 8/10 cases. Hearing was preserved at the same level as preoperatively in 7/10 cases. Tumor resection was complete in 9/10 patients. In one pat a small contrast enhancing area is under control and stable. There were no surgical complications as CSF fistula or infections.Conclusion:Exclusively endoscopic resection of CPA tumors is feasible. Results are comparable to microscopic resections. Visualisation in the posterior fossa is excellent, especially in the rostral area of the lesion and in the IAC. Retractors are not always necessary. The size of the approch may be reduced and tailored to the size of the lesion. It remains open if in larger tumors this technique is also beneficial. Problems may occur with severe bleedings in the operating field.


This study aimed to assess feasibility of performing an RCT to evaluate short‐term postoperative analgesia after laparoscopic surgery in Nigeria using two local anaesthetics for port‐site infiltration This was a placebo‐controlled, patient‐ and outcome assessor‐blinded, external feasibility RCT. Patients undergoing elective laparoscopic cholecystectomy for symptomatic ultrasound‐proven gallstones were randomized into three groups: lidocaine with adrenaline (epinephrine), bupivacaine or saline control. The feasibility of recruitment, compliance with randomized treatment allocation, and completion of pain and nausea outcome measures were evaluated. Pain was assessed at 2, 6, 12 and 24 h after surgery using a 0–10‐point numerical rating scale (NRS) and a four‐point verbal rating scale. Nausea was assessed using NRS at the same time points. Clinical outcomes were assessed only in patients who received the correct randomized treatment allocation.Of 79 patients screened for eligibility, 69 were consented and randomized (23 per group). Overall, compliance with randomized treatment allocation was achieved in 64 patients (93 per cent). All pain and nausea assessments were completed in these 64 patients. On the NRS, most patients had moderate to severe pain at 2 h , which gradually reduced. Only six patients (9 per cent) had moderate to severe pain at 24 h.https://www.isrctn.com).Recruitment, compliance with the randomized allocation, and completion of pain outcome measures were satisfactory. This study demonstrates the feasibility of conducting a surgical RCT in a resource‐limited setting. Registration number: ISRCTN 17667918 ( Around 83 per cent of the world's population live in low‐ and low–middle‐income countries (LMICs)Nigeria is a LMIC in West Africa where laparoscopic cholecystectomy has become established in the treatment of symptomatic gallstonesPain is the most frequent perioperative symptom, with approximately one‐third of patients reporting pain intensity greater than 50 on a 100‐point visual analogue scale following laparoscopic cholecystectomyversus placebo, for early postoperative pain control after laparoscopic cholecystectomy.There is no standardized practice across Nigeria for wound infiltration with local anaesthetic. Given the evidence from high‐income settings that local anaesthetic wound infiltration is safe and effective, there is equipoise to undertake a clinical trial in Nigeria. This randomized external feasibility study aimed to determine the possibility of delivering, in a resource‐limited setting, a full phase III trial of two commonly used local anaesthetics, lidocaine with adrenaline (epinephrine) and bupivacaine, infiltrated at laparoscopic port sites This was a single‐centre, placebo‐controlled, patient‐ and outcome assessor‐blinded, randomized, controlled, external feasibility study. The study protocol was approved by the Ethics and Research Committee of the Obafemi Awolowo University Teaching Hospitals Complex, Ile‐Ife, Nigeria (reference number IRB/IEC/0004553). As the study drugs are fully licensed in Nigeria, further study approval from the medicines competent authority was not required. This study is reported in accordance with the guidance set out in the CONSORT guidelinesThis feasibility study aimed to evaluate: recruitment, to see whether informed consent could be taken and recruitment achieved to target; compliance, to see whether interventions could be delivered to patients as per randomized allocation; and outcome measurement, to see whether data on pain‐ and nausea‐related outcome measures could be collected at prespecified time points.Success was evaluated by means of: recruitment, as the ability to consent and recruit 69 patients (23 per group) over a 24‐month period; compliance, as achieving the randomized treatment allocation for more than 90 per cent of randomized patients; and outcome assessment, as completion of pain and nausea assessments using numerical and verbal rating scales at 2, 6, 12 and 24 h after surgery, by at least 60 patients.Adult patients (aged 18 years or more) undergoing elective laparoscopic cholecystectomy for symptomatic gallstone disease were recruited. Patients were diagnosed as having symptomatic gallstone disease on the basis of a suitable clinical history and gallstones on ultrasound imaging. Only patients with ASA physical status class I or II were eligible. The following exclusion criteria were applied: pregnant women; acute cholecystitis confirmed on ultrasonography ; history of allergy to bupivacaine, lidocaine or related local anaesthetic drugs; known peptic ulcer disease; known opiate addiction; or known contraindications to use of NSAIDs . When an abdominal drain was inserted or the operation was converted to an open procedure, the patient did not receive the allocated intervention and was withdrawn from follow‐up, so pain and nausea scores were not collected.Potentially eligible patients scheduled to undergo laparoscopic cholecystectomy were provided with a written patient information sheet and given the opportunity to ask questions. These information sheets were translated and available in English and Yoruba, the predominant languages in south‐west Nigeria. Once eligibility had been confirmed by the senior surgeon , the patient was asked for written informed consent to participate in the study. Consent was obtained by an attending surgeon or surgical trainee. All investigators were trained by the chief investigator to take informed consent.Elective laparoscopic cholecystectomy was performed under general anaesthesia by a single attending surgeon using two 10‐mm and two 5‐mm ports. This included hook diathermy to identify Calot's triangle and complete dissection of the liver bed. All procedures were carried out with locally adapted equipment, used to perform more than 400 laparoscopic procedures before the start of the studyPatients received premedication with intravenous Minijet® Atropine , 0·01 mg/kg. Intravenous cefuroxime  1·5 g, was administered as a prophylactic antibiotic. Anaesthesia was induced with fentanyl  1–2 µg/kg, and propofol  1–2 mg/kg. Tracheal intubation was facilitated with suxamethonium  1–1·5 mg/kg, and anaesthesia was maintained with isoflurane  0·6–1·5 per cent in an oxygen–air mixture. Muscle relaxation was achieved with pancuronium  0·1 mg/kg, then topped up as appropriate. Gastric decompression was performed with a nasogastric tube that was inserted after intubation and removed at the end of surgery, before extubation. Residual neuromuscular blockade was reversed with Minijet® Atropine 1·2 mg and neostigmine methyl sulphate injection BP  2·5 mg in 1 ml. All patients received maintenance fluid during the operation.Fentanyl boluses of 1–2 µg were given for intraoperative analgesia up to a maximum dose of 200 µg. All patients were given intramuscular diclofenac  75 mg at the start of surgery, with further doses 12 and 24 h after surgery. Tramadol  1·0 mg/kg intravenously or intramuscularly was used as an on‐demand postoperative rescue analgesic. Introduction of this agreed standardized postoperative analgesia protocol ensured that the anaesthetists who performed randomization did not prescribe patients' postoperative analgesia, and the surgical team was able to prescribe this safely while blinded to the patients' treatment allocations.At the end of the procedure, patients had their skin, subcutaneous tissue, fascia and parietal peritoneum infiltrated with: lidocaine  in each 10‐mm port site and 2 ml in each 5‐mm port site ; bupivacaine  in each 10‐mm port site and 2 ml in each 5‐mm trocar site ; or 3 ml 0·9 per cent saline in each 10‐mm port site and 2 ml in each 5‐mm port site (control).Patients were randomized in a 1 : 1 : 1 ratio between the three groups. Twenty‐three labelled cardboard cards were sealed in opaque envelopes for each patient in group 1 (lidocaine), group 2 (bupivacaine), and group 3 (control). These envelopes were shuffled and packed by an independent researcher not involved in the study. Envelopes were kept in a secure drawer in the operating room. Before the operation commenced (but after eligibility had been confirmed and informed consent taken), the anaesthetist opened the next envelope in sequence. Once the operating surgeon was about to extract the gallbladder laparoscopically, the anaesthetist prepared the solution based on the randomized allocation. This was recorded on a case report form and the solution was passed to the operating surgeon before wound closure. The operating surgeon, the assessor on the ward, and the patient were all blinded to the randomized allocation. This was not documented in any of the regular intraoperative or postoperative hospital records. The case report form was stored in a locked office within the operating department that was accessible by consultant anaesthetists if required .Postoperative pain was assessed at 2, 6, 12 and 24 h after surgery. Two pain‐related outcome measures were recorded. Patients were asked to rate their pain on a numerical rating scale (NRS) from 0 (no pain) to 10 (worst pain), and on a four‐step verbal rating scale (VRS) of none, mild, moderate and severe pain. Nausea was assessed alongside the pain outcomes, using the NRS. These outcome measures have been validated previously for the assessment of pain in NigeriaThis feasibility study recorded intraoperative complications, 24‐h postoperative complications, drug‐related allergic reactions and other drug‐related adverse events. All complications within 24 h were captured, including expected and unexpected adverse events.As the purpose of the study was to assess whether recruitment to, and delivery of, a full trial would be feasible, no formal sample size calculations were performed. To assess feasibility of outcome assessment, the study aimed to collect outcome measures for 20 patients per trial arm . To take into account intraoperative exclusions (such as conversion to open surgery) or losses to follow‐up, 23 patients were planned per arm (dropout rate 9 of 69 patients). Approximately three laparoscopic cholecystectomies are performed each month in the hospital, so this feasibility study aimed to recruit a total of 69 patients over 24 months.Data were entered into a password‐protected database, held on a secure computer in a locked office by one of the authors. Numbers of patients recruited and allocations are reported as intention to treat (with a denominator of 69). As the intervention was not applied in patients converted to an open procedure or left with an abdominal drain, pain scores are reported only per‐protocol, from those receiving the correct allocation.Outcomes relating to trial feasibility were described using basic statistics and tables. Data are reported as median (i.q.r.) values. As the main aim of the study was to assess trial feasibility, direct statistical comparison of pain scores was not planned. Mean point scores for NRS and VRS are reported, along with their 95 per cent confidence intervals. Statistical analysis was performed in SPSS® version 22 .Fig. Of 79 patients evaluated for inclusion, seven were excluded owing to previous NSAID‐induced gastritis or peptic ulceration, two because of sickle cell anaemia with opioid addiction, and one due to bronchial asthma. The CONSORT diagram illustrates patient flow through the study, including potentially eligible and excluded patients Fig. .Compliance with randomized treatment allocation was 21 of 23 in the lidocaine group (91 per cent), 20 of 23 in the bupivacaine group (87 per cent) and 23 of 23 in the control group (100 per cent). One patient each in the lidocaine and bupivacaine group was withdrawn before receiving the randomized treatment allocation due to conversion to open surgery. A further patient in the lidocaine group and two in the bupivacaine group were withdrawn from follow‐up because of abdominal drain insertion.2. The median duration of surgery was 85 (i.q.r. 68–105) min. Baseline data were comparable across the three groups  were women, and the median age was 44  years. Median BMI was 26·6 (i.q.r. 22·9–30·9) kg/mTable Fig. NRS and VRS pain outcome measurements were complete for all patients, with outcomes recorded at all four prespecified time points. The overall mean pain score on the NRS at 2 h was 4·6 (95 per cent c.i. 3·9 to 5·2), with mean pain scores in the three groups ranging from 4·1 to 5·2 (Table All patients completed nausea scores. Few patients experienced significant nausea as captured by NRS nausea scores; at 2 h mean nausea scores ranged from 0·7 to 1·5 Table , with onOne patient had intraoperative bile spillage, managed with copious irrigation. No other intraoperative or postoperative complications occurred by 24 h. There were no allergic reactions or drug‐related adverse events.This randomized external feasibility study has shown that this surgical RCT is feasible in a resource‐limited setting. The study was completed on schedule. Compliance with randomized treatment allocation was high. Completion of pain scales at prespecified time points within the first 24 h after surgery demonstrated that measurement of patient‐reported outcome measures is also feasible. These objectives were achieved in spite of numerous resource limitations. It took 24 months to recruit 69 patients undergoing laparoscopic cholecystectomy, reflecting the low volume of these procedures in this setting. Additional challenges included interruptions in hospital services owing to industrial action and cancellation of procedures due to lack of surgical supplies. Lacking dedicated research staff, the surgical and anaesthetic teams oversaw all trial processes, including patient eligibility screening, consent, randomization and outcome assessment. The high recruitment rate was made possible by actively engaging surgical residents in the study, ensuring that there was always an investigator available to consent and randomize the patient. Although the recruitment rate may reflect social and cultural factors, it is likely that the in‐theatre intervention and short follow‐up period presented a low burden for participants.There is no social‐security safety net in Nigeria to compensate patients for time off work. As patients are often the main financial providers for their family, a key priority is to return to work at the earliest opportunity. Compared with open surgery, minimal‐access surgery has been demonstrated to result in shorter hospital stays and earlier return to normal activities in LMICsThis study has a number of limitations reflecting the resources available to support its design and conduct. Randomization was conducted using sealed envelopes, which is less robust than remote randomization, such as by telephoneA future phase III RCT could collect additional data for secondary endpoints. These could include pain over the first postoperative week. As most patients are discharged within the first 48 h, mobile phone technology may have a role in facilitating postdischarge follow‐upEvidence‐based analgesic strategies are needed to reduce very early postoperative pain, as at 12–24 h most patients experienced no pain, or only mild pain. A randomized placebo‐controlled trial


Evaluate patient-reported outcomes (PROs) for postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer treated with first-line ribociclib plus letrozole.In the phase III MONALEESA-2 study (NCT01958021), 668 patients were randomized 1:1 to ribociclib  plus letrozole (2.5 mg/day) or placebo plus letrozole. PROs were assessed using the European Organisation for Research and Treatment of Cancer core quality-of-life (EORTC QLQ-C30) and breast cancer-specific (EORTC QLQ-BR23) questionnaires. Changes from baseline and time to deterioration in health-related quality of life (HRQoL) were analyzed using linear mixed-effect and stratified Cox regression models, respectively. Exploratory analysis of area-under-the-curve for change from baseline in pain score (AUC-pain) was performed.On-treatment HRQoL scores were consistently maintained from baseline and were similar between arms. A clinically meaningful (> 5 points) reduction in pain score was observed as early as Week 8 and was maintained up to Cycle 15 in the ribociclib arm. A statistically significant increase in mean AUC-pain was also observed in the ribociclib arm. Scores for all other EORTC QLQ-C30 and EORTC QLQ-BR23 domains were maintained from baseline and were similar between arms.HRQoL was consistently maintained from baseline in postmenopausal women with HR+, HER2− advanced breast cancer receiving ribociclib plus letrozole and was similar to that observed in the placebo plus letrozole arm. Together with the improved clinical efficacy and manageable safety profile, these PRO results provide additional support for the benefit of ribociclib plus letrozole in this patient population. Although symptom scores were generally higher in the ribociclib plus letrozole arm during treatment and at EOT, the mean changes from baseline were less than the MID. Similar results were observed for additional EORTC QLQ-C30 questionnaire domains, including physical, emotional, cognitive, and social functioning and for breast cancer-specific EORTC QLQ-BR23 questionnaire domains, including future perspective, side effects, and upset by hair loss  reduction from baseline in EORTC QLQ-C30 pain score was observed as early as Week 8 in the ribociclib arm . This cl points rp = 0.0412) and subgroups of patients with measurable disease at baseline  in the ribociclib plus letrozole arm compared with the placebo plus letrozole arm, confirming the improvement from baseline in EORTC QLQ-C30 pain score and indicating reduced pain severity (Fig. As conventional longitudinal analysis of PRO endpoints may not always capture the totality of the benefit throughout the treatment period, an exploratory AUC analysis for change from baseline in EORTC QLQ-C30 pain score was performed to characterize changes in pain during treatment. A reduced numeric score versus baseline represented less pain severity, whereas an increased pain score indicated greater pain severity . AccordiSeveral studies have assessed the QoL of patients diagnosed with breast cancer, yet few have investigated QoL in the setting of recurrent/metastatic disease . EvaluatThe association between HRQoL and PFS in oncology clinical trials has not been well characterized . HoweverIn addition to maintaining overall QoL, ribociclib plus letrozole was associated with a clinically meaningful reduction in pain in the overall population, which was observed as early as Week 8 and maintained for at least 15 cycles. Significant improvements in pain score were also observed in all patients and subgroups of patients with measurable disease at baseline in the ribociclib plus letrozole arm following an exploratory AUC analysis. In a cross-sectional study involving 1072 patients with breast cancer, maintaining QoL and controlling pain were among the top 10 most important issues . In addiIn conclusion, our findings demonstrated that overall HRQoL in the MONALEESA-2 study was consistently maintained from baseline in postmenopausal women with HR+, HER2− advanced breast cancer receiving ribociclib in combination with letrozole compared with placebo plus letrozole. In addition, combined ribociclib plus letrozole was associated with early and clinically meaningful improvements in pain severity compared with placebo plus letrozole. Together with the demonstrated clinical efficacy and tolerability, these PRO results provide further evidence for the benefit of ribociclib plus letrozole in this patient population.


Objective: The purpose of this study was to find applicable clusters for the development of different treatment pathways in an inpatient multimodal pain-therapy setting based on the multifaceted nature of CLBP.Methods: Based on data of questionnaires , Marburg Questionnaire on Habitual Health Findings (MFHW), quality of life assessment using the Short-Form 12 (SF 12)), a retrospective two-step cluster analysis involving a sample of chronic low back pain (CLBP) patients (N=320) was calculated. Subsequently, the clusters were precisely described and compared on the basis of further data collected during the patients’ standard care: pain characteristics, socio-demographic data and the general state of health, psychological variables, therapy intensity, and Diagnosis Related Groups (DRG) data.Results: We found a three-cluster solution: little psychological interference but marginal physical and mental quality of life (Cluster 1); poor well-being, low physical quality of life, and marginal mental quality of life (Cluster 2); and heavy mental strain and marginal physical quality of life (Cluster 3).Conclusions: Similar to previous studies, our results suggest that patients suffering from CLBP differ with regard to the magnitude of mental burden and the presence of physical impairment. These differences ascertain the need for precise targeting of treatment for CLBP. Inpatient pain centers therefore should offer different multimodal therapy pathways and integrate a meaningful triage, taking into account the multifaceted nature of CLBP based on sophisticated knowledge about forms, differences, and relationships among the biopsychosocial components of CLBP. Low back pain (LBP) is one of the leading causes of people living with disability. Thus, LBP – with its associated disability – is responsible for a significant personal burden worldwide . About 7CLBP involves a combination of pathoanatomical, neurophysiological, physical, psychological, and social factors , 6], , . It can,The idea of a classification system for LBP and CLBP is not new. Generally, both physicians and therapists agree that patients should be treated differently according to the heterogeneous conditions of LBP or CLBP , 14]. M. M14]. MThis trial has an empirical and exploratory character. It seeks to identify homogenous subgroups of CLBP patients in an inpatient, multimodal therapy setting; thus, it is a hypothesis-setting study . The retThe study did not need to be referred to the ethics committee, because the data used were anonymized and the patients had already signed a consent that their data may be used for research purposes. Furthermore, it was a retrospective analysis of data which was collected during the patients’ standard care; therefore the patients did not receive placebo interventions or the like.The multimodal pain-therapy setting study in which patients took part was set up as follows:Medical consultations (at least once per week for 30 minutes)Physical therapies such as physiotherapy, ergotherapy and sports for individuals and groups (for 30 minutes)Psychological therapy such as relaxation, and cognitive-behavioral interventions for individuals and groups (for 30 minutes)Pain education for groups (for 30 minutes)Peripheral stimulation such as TENS (as required)The current dataset consists of inpatient standard care data from Algesiologikum – Centers for Pain Medicine  for patients whose initial treatment took place between 2010 and 2012 in the Algesiologikum outpatient pain center and who were subsequently targeted for a multimodal pain therapy in an Algesiologikum inpatient pain center by a specialist pain physician. The targeting resulted from medical examination, the results of the questionnaires and the doctor’s experience. The inclusion criteria were:Initial treatment at Algesiologikum – Centers for Pain Medicine between 2010 and 2012At least one back pain diagnosis (ICD-10 diagnosis: M40–M54)Age between 18 and 64 years, because in Germany, people of this age are usually available for the job marketDuration of pain for at least six monthsInpatient multimodal pain therapy for at least seven days in one of the Algesiologikum – Centers for Pain MedicineNo missing values in the variables identified for cluster-buildingA signed declaration of consent, allowing Algesiologikum to use the data for research purposesBefore patients take part in any pain-therapy setting, they are asked to complete the German Pain Questionnaire 2007 (the current version is the German Pain Questionnaire 2015) , which iMainz Pain Staging System (MPSS): The assessment is based on temporal and spatial aspects, drug-taking behavior, and detailed information about the patient’s utilization of the healthcare system. The three stages of this scale represent different phases in the chronification process. The higher the stage, the more extensive are the required therapeutic interventions, and the less likely is the full recovery from chronic pain , 32], , . The MPSChronic Pain Grade (CPG) , 38]: T: T38]: TCPG 1: low disability and low pain intensityCPG 2: low disability and high pain intensityCPG 3: high disability and moderately limiting pain intensityCPG 4: high disability and severely limiting pain intensityKlasen et al.  determinHospital Anxiety and Depression Scale (HADS): this consists of two subscales – the anxiety subscale (HADS-A) and the depression subscale (HADS-D), both of which have seven items and a range of 0–21 and a cut-off of 11. Anxiety and depression values higher than 10 must be considered to be problematic. Both subscales have been shown to be reliable and have been validated for several subgroups. The internal consistency was between 0.80 and 0.81 for both . The valThe Marburg Questionnaire on Habitual Health Findings (MFHW): The MFHW is a seven-item scale for the assessment of the trait dimensions of well-being . It has Quality of life assessment using the Short-Form 12 (SF 12): SF 12 is the short-form of SF 36 and was developed with a total of 12 items to reproduce the Physical Component Summary  and the Mental Component Summary . Both the PCS and MCS range from 0  to 100 . The cut-off for the PCS is 29, while that of the MCS is 44. PCS values lower than 29 points and MCS values lower than 44 points must be considered to be problematic. In 14 validity tests involving physical criteria, relative validity estimates for the 12-item PCS ranged from 0.43 to 0.93 (median=0.67), compared to the best 36-item short-form scale. Relative validity estimates for the 12-item, MCS in 6 tests involving mental criteria ranged from 0.60 to 107 (median=0.97) in relation to the best 36-item short-form scale , 49]..49].The List of Pain Description  was developed to measure the sensory and affective aspects of pain in a differentiated manner in order to gain indicators of psychological burden. The score has a range of 0–12 and a cut-off of 9. An SBL value of 8 stands for an increased pain experience. Higher values are conspicuous. The internal consistency was confirmed with Cronbach’s alpha between 0.79 and 0.83 .2) . T. T58]. TThe aim was to demonstrate the need for the precise targeting of primary care treatment of CLBP patients, as was done, for example, by Viniol et al.  who idenThe profiles taken into consideration range from very distressed patient groups who were hardly able to take part in daily social activities, over groups consisting of adaptive patients who could cope and hence experienced less pain, were less distressed, and were able to take part in daily social activities, through to groups of patients who were experiencing severe pain and high levels of distress, but still taking part in daily social activities.While the focus of this study was on improving the triage of CLBP patients from different groups, Hill et al. , for exaFehrmann et al.  took a dThese findings encourage the authors to also verify the benefits of stratified care for the “types” of patients with CLBP identified in this study, in further investigation.It was hypothesized that CLBP patients would differ in terms of therapy intensity, due to them probably having different needs, but there were no differences in therapy intensity. A reason for this might be that patients with a higher level of fitness or rather less mental strain participated more frequently. Another reason might be that, in the case of multimodal pain therapy, the DRG system does not provide incentives to provide high-intensity therapy because the payments do not increase for higher performance in terms of therapy intensity. On the contrary, the higher the therapy intensity offered, the lower the pain center’s profit. The integration of more clinical considerations, such as adjusting therapy intensity to individual needs, can be more economical while simultaneously improving the quality of a therapy. Inpatient pain centers should offer different multimodal therapy pathways for effective treatment. Therefore, the development of a suitable algorithm which targets patients early so that they receive optimal care as soon as possible is essential. At least two of the three clusters in this study need highly intensive and expensive pain therapy. The difficulty does not lie in developing and offering such programs, but in convincing health insurance providers that certain patients need such high-intensity pain therapy. This trial should also be a basis for the corresponding arguments about which patients fit which treatment pathway, including the required therapy intensity.This study has shown that it is next to impossible to carry out a meaningful triage of patients with severe CLBP without sophisticated knowledge about its forms as well as differences and relationships between the biopsychosocial components. The benefits of stratified care for patients are tailored treatment, individual therapeutic goals, and a higher quality of life. Care providers might profit from it because they would be able to specialize their infrastructure, become more (cost-)effective, and achieve better therapy outcomes while simultaneously increasing revenues. Employers and colleagues could also benefit from stratified care, because employees suffering from CLBP might need fewer days off from work after the specialized pain therapy. Although highly intensive pain therapy is associated with higher costs, the costs related to these patients might come down in the long term, because a better therapy outcome could lead to less medication being required, fewer doctor’s visits, fewer stays in hospital, fewer days off work, and perhaps even the ability to work again. Moreover, it is assumed that stratified care creates the space needed to develop and conclude individual, special treatment pathways, contracts between health insurance providers, non-state actors in the healthcare system, and care providers. Furthermore, an assumption for the future is that stratified care will lead to fewer days off work which enhances economic efficiency and productivity, as well as possibly avoiding costs relating to early retirements, which would have positive implications for the economy . TherefoThe differences found in the current study not only caused CLBP patients to be targeted into special kinds of pain treatment or care, such as inpatient or outpatient. They caused an individual kind of multimodal pain therapy to be developed for each separate CLBP group by taking into account the heterogeneous and multifactorial nature of CLBP. It is hoped that this study will be understood as a form of support, or rather an incentive, for other providers of multimodal pain therapy, in order to develop individual treatment pathways for their CLBP patients’ different needs.The present study has some limitations that need to be considered. The first point that should be mentioned is that cluster analysis is a useful technique for revealing an inherent structure in a dataset, but it must be recognized that it will impose a structure on any dataset, regardless of whether or not one exists. For this reason, no one cluster solution found is likely to be entirely valid for a given pain population and should always be cross-validated . The absFurthermore, it is a retrospective trial using routine basic medical care data because the study design was not specified before the evaluation and the day-to-day business kept running as usual. In addition, the pain center staff was not trained with regard to monitoring questionnaires. Especially in the case of some non-cluster-building variables, there were a lot of missing values and therefore also exclusions. In spite of missing values in some variables, there was still informative content that could provide a better idea of the patient’s needs.With regard to therapy intensity, a randomized controlled trial would be necessary to detect “dose-response relationships”: Unfortunately, such randomized controlled trials are hardly possible in a standard care setting.The authors declare that they have no competing interests. Conflicts might arise if the results of this study lead to a change in the revenue situation in any particular direction.


PNVA symptom co-occurrence was positively correlated (p < 0.001). Conclusions: Anxiety was the most common and severe symptom for hospitalized children. Patients in oncology demonstrated the least severe pain and nausea with no difference in anxiety between services.Background: The prevalence and severity of pain, nausea/vomiting, and anxiety (PNVA) among hospitalized children is not well established. We describe the prevalence and severity of PNVA among hospitalized patients from oncology, general pediatrics, and cardiology services in a tertiary care center. Methods: Patients were recruited on admission and enrolled if their caregiver consented, spoke English, and were anticipated to stay 2–30 days. Symptoms were measured weekdays using age-validated tools. PNVA symptoms were described and compared. Results: We enrolled 496 (49.4%) patients of 1005 admitted. Patients were predominantly Caucasian (57.9%) on their first admission (53.6%). The average (SD) age was 8.6 years (5.9) in oncology, 4.2 (5.3) in general pediatrics and 2.6 (4.0) in cardiology. 325 (65.6%) patients reported anxiety, 275 (55.4%) reported nausea and 256 (52.0%) reported pain. Mean (SD) severity out of 10 was 3.7 (2.5) for anxiety, 3.2 (2.1) for nausea and 3.0 (1.5) for pain. Prevalence of PNVA was no different between clinical programs, but pain ( Pediatric disease-specific symptom prevalence and severity studies have been widely published, such as pain in musculoskeletal conditions, nausea in functional gastrointestinal disorders, and anxiety in type one diabetes mellitus ,2,3. NegManagement for pain, nausea/vomiting and anxiety (PNVA) likewise has been well researched for specific instances of PNVA in specific illnesses. However, our search of the literature did not yield any manuscripts that describe PNVA prevalence and severity for hospitalized pediatric inpatients. Therefore, we sought to describe pediatric PNVA prevalence and severity among patients admitted to three participating hospital inpatient services, in the hopes that a better understanding of PNVA prevalence and severity will result in improved treatment. Under-recognition of pain is a known barrier to adequate management . This maOur study is a single-center, cross-sectional observational study from February 2013 to January 2016, of patients admitted to oncology, cardiology or general pediatrics and treated with standard hospital practices at the Stollery Children’s Hospital in Edmonton, Canada. The Stollery is a quaternary care children’s hospital that provides a full range of cardiology, cardiac surgery services and oncology services with the exception of bone marrow transplant.Children and caregivers were screened at admission to oncology, general pediatrics or cardiology, which included postoperative cardiac surgery patients. There were no other surgical programs in our study. Patients were included if the caregiver could communicate in English, was available to participate and was willing to provide informed written consent. Assent was obtained from the child, whenever possible. Participants were eligible for inclusion for both elective and non-elective admissions and included if their length of stay was predicted to be between 2 and 30 days and if their age at baseline was less than 17 years, as our symptom measurement tools were validated for patients up to 17 years of age. If a patient was discharged and re-admitted during the study period they were included as a new study participant.Demographic and admission data were extracted from the patient charts retrospectively. A trained research nurse from our study team collected symptom data at baseline and daily until they were discharged, transferred, deceased, or 30 days had elapsed, whichever was soonest. All patient symptom score data were collected daily, on weekdays only. Since we were assessing multiple symptoms, each one was measured separately using age appropriate, validated tools. Patient pain was measured in pre-verbal children by parents using the behavioral observational Faces, Legs, Activity, Cry, Consolability (FLACC)  tool. VeVerbal patients or parent proxies were asked to describe their pain, which was then categorized into types from a predetermined list . Nausea and anxiety scores were collected from verbal children only using the Baxter Retching Faces  (BARF) aDescriptive statistics were reported as numbers and percentages for categorical variables or means and standard deviations for continuous variables. Pain scores (FLACC and FPS-R) were analyzed together as continuous variables that ranged from 0–10, lower scores representing less severe symptoms. Daily PNVA symptom scores were collected each day and averaged to compute a mean score for that admission, both with and without zero (symptom free day) scores. Average symptom severity and prevalence were compared between groups with ANOVA for parametric data and Kruskall–Wallis for non-parametric. Daily medication administration was recorded and medications for PNVA were grouped into four: (1) Non-opioid analgesics: acetaminophen, acetylsalicylic acid, ibuprofen, indomethacin, ketorolac, and naproxen; (2) Opioids: hydromorphone, morphine, and fentanyl; (3) Anti-emetics: aprepitant, dimenhydrinate, granisetron, metoclopramide, nabilone, and ondansetron; and (4) Anxiolytics/sedatives were clonazepam, diazepam, lorazepam, midazolam, and melatonin. TM hosted at the University of Alberta [Study data were collected and managed using Research Electronic Data Capture (REDCap) Alberta . Ethics approval was obtained from the University of Alberta Research Ethics Board .There were 1005 patients admitted to the three participating study services during the observation period. Seventy patients (7.0%) were ineligible due to lack of permission from the care team, lack of ability to communicate in English, or their length of stay was outside of the two- to 30-day range . Of the In total, 256 (52.0%) of the 496 participants reported pain at least once during their admission, 275 (55.4%) reported nausea and 325 (65.6%) reported anxiety. The mean (SD) percentage of days with anxiety was 46.0% (37.4), followed by nausea 32.3% (37.8) and pain 28.2% (35.8). When symptomatic, the mean (SD) symptom severity out of 10 was 3.7 (2.5) for anxiety, 3.2 (2.1) for nausea and 3.0 (1.5) for pain .p = 0.008) and nausea (p = 0.006) compared to patients in general pediatrics and cardiology. However, there was no statistically significant difference between services for severity of anxiety (p = 0.11)  .Medication rates of use and percentage of patient days with symptoms are displayed in While many (32.8%) patients reported acute pain, the majority (48.4%) reported “other” type of pain, of which 27% did not further specify the nature of pain. Of those who did, abdominal pain (19.1%) (often related to being “nil per os”) was the most common source followed by generalized pain or irritability (14.3%) and intravenous catheter site pain (5.8%).n = 185), compared to those who had proxy ratings (n = 311). The mean (SD) self-assessed FPS-R score was 1.3 (1.7) compared to 0.81 (1.4) for those rated by proxy (p < 0.001). Pain-nausea, pain-anxiety and nausea-anxiety correlations were statistically significant (p < 0.001); increased severity of any one symptom was correlated with a more severe co-occurring symptom of the PNVA cluster.Pain was more severe in patients who were rated their own symptoms  showed that pediatric cancer pain and anxiety improved over a treatment course . AnotherOur observational cross-sectional study indicates that PNVA symptoms are common in pediatric inpatient populations. An observational study of inpatient pain in adults suggested a comparatively higher pain prevalence (70.4%), yet similar severity (3.76) . The preWe discovered a single trial that offered child life specialists for anxiety not specifically related to a procedure, though it was in the emergency department, and they found a reduction in state anxiety when compared with hospital clowns and controls . In lighOne of the limitations of our study is that non-English speaking patients were excluded. Another was proxy reporting. Although proxy measures were validated (currently under peer-review), it is possible that caregivers under- or over-estimated symptom severity, as this is a widely encountered issue in the literature . In a reThis study shows that PNVA are commonly experienced symptoms among pediatric inpatients and that anxiety is the most common and severe of these. Anxiety, in particular, needs to be more effectively anticipated, identified and treated. Effective and safe approaches to management approaches should consider integrating both pharmacological and non-pharmacological interventions.


ClinicalTrials.gov identifier: NCT01855919) investigated relationships between pain severity (assessed by the Brief Pain Inventory [BPI]) and disease-specific health-related quality of life (assessed by the 24-item Roland-Morris Disability Questionnaire [RDQ-24]) in duloxetine-treated patients with chronic low back pain (CLBP).This post hoc analysis of a Japanese phase 3 randomized study (Patients with CLBP duration >6 months and BPI average score ≥4 received duloxetine 60 mg/d (N = 230) or placebo (N = 226) for 14 weeks. Spearman rank correlation coefficients were calculated for (1) BPI change from baseline and RDQ item change from baseline and (2) BPI change from baseline and the RDQ item baseline score in duloxetine-treated patients.Duloxetine treatment significantly improved the RDQ-24 total score compared with placebo; the greatest improvements were observed for RDQ02, RDQ17, and RDQ13. The strongest correlations between BPI change from baseline and RDQ item change from baseline were for RDQ13, RDQ23, and RDQ10. The correlation coefficients for the correlations between BPI change from baseline and the RDQ item baseline score were generally small.This post hoc analysis suggested that improvement in pain severity was associated with improvement in the RDQ-24 total score and in some individual RDQ items in duloxetine-treated patients with CLBP. Furthermore, positive responses to duloxetine in terms of the RDQ13, RDQ23, and RDQ10 items may correlate with better pain responses.www.clinicaltrials.gov (NCT01855919).The study described in this manuscript was registered at  Pharmacological treatments for CLBP recommended by international and Japanese treatment guidelines include NSAIDs, acetaminophen, muscle relaxants, antidepressants, and opioids.12 Gabapentin had been reported to be effective for pain relief (for radiculopathy)12; however, the recent literature suggests that there is limited evidence to support the use of gabapentinoids  in the treatment of CLBP.13-15 Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has been shown to have analgesic efficacy in CLBP.16171819 The exact mechanism of action of duloxetine in inhibiting pain is unknown. However, by inhibiting the reuptake of serotonin and norepinephrine in the dorsal horn of the spinal cord, it is thought that duloxetine activates descending pain inhibitory pathways, thereby producing an analgesic effect.20 Preclinical studies have shown duloxetine to exhibit analgesic effects at the peripheral level as well, by modifying sodium channels21 and inhibiting P2X4 receptor function.22 Owing to its predominantly centrally acting analgesic effect, duloxetine may be effective against the central sensitization component of CLBP.23Patients with chronic low back pain 19 Patients in the study had no radiculopathy symptoms, no other specific low back diseases, and no history of low back surgery and were diagnosed with CLBP as defined by Japanese1 and international24 guidelines. Duloxetine treatment significantly improved pain compared with placebo, as assessed by the Brief Pain Inventory (BPI) average pain severity score. In addition, duloxetine treatment significantly improved disease-specific HRQoL compared with placebo, as assessed by the 24-item Roland-Morris Disability Questionnaire (RDQ-24). The RDQ-24 is one of the most widely used functional scales for LBP and has a validated Japanese version.25-27 In this study, duloxetine treatment also significantly improved HRQoL compared with placebo, as assessed by the “General Health” and “Mental Health” subscales of the 36-Item Short-Form Health Survey and the “Work time missed” subscale of the Work Productivity and Activity Impairment Questionnaire, but not the European Quality of Life 5-Dimensions questionnaire.19 Treatment goals for CLBP should include improving HRQoL by reducing pain intensity. However, there is limited literature available evaluating the correlation between improvement in pain severity and HRQoL in patients with CLBP receiving analgesics.The efficacy and safety of duloxetine have been demonstrated in Japanese patients with CLBP responding inadequately to NSAIDs in a randomized phase 3 study.19 Second, we assessed which RDQ item baseline scores correlated with the reduction in pain intensity to investigate which patient cohorts might preferentially respond to duloxetine in the treatment of CLBP.The aim of the current post hoc analysis was first to investigate which RDQ item scores improved in parallel with the reduction in pain intensity, as assessed by the BPI, in duloxetine-treated patients in the previously conducted phase 3 study of duloxetine in Japanese patients with CLBP.19 This was a multicenter, randomized, placebo-controlled, double-blind, phase 3 study conducted at 58 medical institutions in Japan from May 2013 to July 2014. The study protocol was approved by the institutional review board of each medical institution . The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent before participating in the study. The study was registered at www.clinicaltrials.gov (NCT01855919).Full details of the study design have been published elsewhere.1 and international24 guidelines, persisting for at least 6 months. Additional inclusion criteria were age 20 to <80 years; used NSAIDs for ≥14 days per month for an average of 3 months before the start of the study and for ≥14 days during the 1-month period before the start of the study (regardless of the dose of NSAIDs and route of administration); and BPI pain severity (average pain) score29 of ≥4 at visit 1 (week −1 to −2) and visit 2 (week 0). Patients were excluded if they had radiculopathy or radicular syndrome, a specific disease in the lower back , spinal canal stenosis with neural claudication, hernia with radicular syndrome, or radiating pain in the dermatome in the lower limbs. Other exclusion criteria were history of low back surgery; invasive treatment for the relief of LBP within 1 month before visit 1; requiring crutches or a walker; and having major depressive disorders according to the Mini-International Neuropsychiatric Interview30 or suicidal tendencies according to the Columbia-Suicide Severity Rating Scale.31Male and female outpatients were eligible for the study if they had CLBP, as defined by JapaneseThe study period consisted of a 1- to 2-week pretreatment period, a 14-week treatment period, a 1-week taper period, and a 1-week follow-up period. Patients were randomized to receive duloxetine 60 mg once daily  or matching placebo capsules. The use of drugs with an analgesic effect was permitted as rescue medication for up to 3 consecutive days and for up to a cumulative total of 20 days.29 BPI average pain severity scores were rated on a scale ranging from 0 (“no pain”) to 10 (“pain as bad as you can imagine”). LBP-specific quality of life was assessed using the self-administered RDQ-24.25-27 For the baseline RDQ-24 score, each item was rated 1 (yes) or 0 (no); the RDQ-24 total score can therefore vary from 0 (no disability) to 24 (maximum disability). For the change in the RDQ-24 score, each item was designated −1 , 0 , or 1 .Pain was assessed using the self-administered BPI average pain severity score, which measures average pain during the past 24 hours.The efficacy outcomes in this post hoc analysis were the change from baseline to week 14 in the BPI average pain severity score and RDQ-24 total score and individual RDQ item scores.The post hoc analysis was performed on the full analysis set, which consisted of all randomized patients who received at least one dose of study drug and for whom postbaseline BPI average pain severity scores were available. Analysis of covariance was used to compare the change from baseline to week 14 in the RDQ-24 total score and RDQ items for duloxetine versus placebo, at a significance level of 5%. As this was a post hoc exploratory analysis, no multiplicity adjustment was conducted. Last observation carried forward was used when data at week 14 were missing. Spearman rank correlation coefficients (r) were calculated for (1) change in pain severity (as assessed by the BPI) and change in HRQoL (as assessed by the RDQ items) and (2) change in pain severity and the RDQ item baseline score in duloxetine-treated patients. For the relationship between change in pain severity and the RDQ item baseline score, multiple regression analysis (stepwise forward selection method) was also conducted to identify which baseline RDQ items were predictors of BPI change, at a significance level of 20%. Analyses were performed using SAS version 9.4 .In total, 456 patients were enrolled in the study, of whom 230 patients received duloxetine and 226 patients received placebo. Baseline characteristics were generally similar between the two treatment groups Table . The meaP = 0.044} (Table P < 0.05) were RDQ02 , RDQ17 , and RDQ13   mean difference : −0.64 ; P < 0.001), RDQ23 , and RDQ10  , RDQ14 , and RDQ11   correlations between BPI change from baseline and RDQ item change from baseline and (2) correlations between BPI change from baseline and the RDQ item baseline score  found correlations between improvement in the pain score and improvement in HRQoL in duloxetine-treated patients with DPNP.35 In addition, another study of DPNP showed different pain improvement profiles in terms of the Neuropathic Pain Symptom Inventory between duloxetine and pregabalin.36 However, there is limited literature addressing the qualitative assessment of HRQoL as a predictor of treatment outcomes or responder profiles in the treatment of CLBP. In this study of Japanese patients with CLBP in which duloxetine improved both pain severity and HRQoL , the current post hoc analysis created a profile of the 24 individual RDQ items by categorizing them into four subgroups based on the following two types of correlations in duloxetine-treated patients: (1) correlations between BPI change from baseline and RDQ item change from baseline and (2) correlations between BPI change from baseline and the RDQ item baseline score. As far as we know, our study is the first report of such an analysis in patients with CLBP.Treatment goals for patients with CLBP are to improve HRQoL and to reduce pain intensity, while avoiding potential negative effects of treatment. For example, the addictive nature of opioids has led to serious opioid-related epidemics, with opioid use being associated with long-term disability,19 duloxetine treatment significantly improved the RDQ-24 total score compared with placebo in this cohort of patients with CLBP. The current post hoc analysis extends these findings by showing different degrees of improvement in the individual 24 RDQ items by duloxetine treatment in this study cohort. In particular, the RDQ02, RDQ13, and RDQ17 items were statistically significantly improved by duloxetine treatment compared with placebo. As the RDQ02 and RDQ13 items were the two worst-rated items at baseline , this suggests that duloxetine has a clinically relevant treatment effect on HRQoL that had deteriorated because of CLBP.As reported previously,P < 0.05), which implies that pain reduction is clinically important in improving disease-specific HRQoL in CLBP. Correlations between improvement in the pain score and improvement in HRQoL have also been reported for duloxetine-treated patients with DPNP.35 In a post hoc analysis of pooled data from three randomized controlled trials of duloxetine in patients with DPNP (335 duloxetine-treated patients), improvements in 24-hour average pain severity scores were correlated with improvements in HRQoL as assessed by the 36-Item Short-Form Health Survey subscales (Pearson correlation coefficients ranging from 0.114 to 0.401) and the European Quality of Life 5-Dimensions questionnaire (Pearson correlation coefficient of 0.271).Irrespective of treatment differences relative to placebo, correlations between BPI change from baseline and RDQ item change from baseline in this post hoc analysis varied in strength for the 24 RDQ items. The strongest correlations between BPI change from baseline and RDQ item change from baseline were RDQ13, RDQ23, and RDQ10, suggesting that duloxetine-treated patients with CLBP who have improvements in these three RDQ items may have a better pain response. Of note, for 14 of the 24 RDQ items (58.3%), the correlations were statistically significant  and positive (12 items) correlations in this cohort of Japanese patients with CLBP. Although the size of the correlation coefficient was generally small, the RDQ items with negative correlations at baseline might be candidates as predictors of the level of pain reduction occurring after treatment. Of note, similar results were obtained from the correlation and multiple regression analyses: three of the four RDQ items for which higher baseline severity predicted greater pain reduction in the correlation analysis  were also identified in the multiple regression analysis. These analyses imply that these three RDQ items might be used as baseline predictors to estimate the posttreatment reduction in pain. It remains to be seen whether the classification of the 24 RDQ items into four categories based on correlations between BPI change from baseline and (1) RDQ change from baseline and (2) the RDQ baseline score in duloxetine-treated patients would allow physicians to predict a level of response to duloxetine treatment and its possible outcomes in terms of disease-specific HRQoL.Despite its overall efficacy as an analgesic, duloxetine has been reported to be more effective in some patient cohorts than others.37 Exploratory post hoc analyses of neuropathic pain symptoms using the Neuropathic Pain Symptom Inventory in this randomized phase 3 study identified subgroups of patients with distinct pain characteristics at baseline who had responded differently to duloxetine and pregabalin when given alone or in combination.36 The authors of this analysis suggested that taking heterogeneity in the patient cohort into account would allow for a more stratified, or even personalized, treatment approach for patients with chronic pain conditions.36The use of patient-reported outcome measures to predict response to duloxetine has been shown for patients with DPNP in the COmbination vs. Monotherapy of pregaBalin and dulOxetine in Diabetic Neuropathy study, which assessed high-dose duloxetine or pregabalin monotherapy or duloxetine plus pregabalin combination therapy.19 As reported previously, patients receiving duloxetine in the current study reported a higher incidence of somnolence (19.2% versus 7.1%), constipation (10.7% versus 2.2%), nausea (9.0% versus 2.7%), dizziness (6.4% versus 0.9%), and dry mouth (6.0% versus 0%) compared with patients receiving placebo.19 Most of these adverse events were mild or moderate in severity and were resolved or improved.19We note that the safety profile for duloxetine in the current study was similar to that reported in studies of patients receiving duloxetine for other pain indications.This was the first analysis of the relationship between pain and HRQoL in duloxetine-treated patients with CLBP. Strengths of this analysis included analyzing data from a randomized, placebo-controlled, double-blind, phase 3 study and the use of an HRQoL measure specific for back pain. Limitations included the post hoc nature of the analysis and the possible difficulty of applying the results of this analysis to clinical practice. As the study was conducted in Japanese patients alone and the duration of duloxetine treatment in the study was relatively short, it might be difficult to generalize the results of the analysis to other cohorts and to longer periods of treatment. In addition, as each RDQ item in the RDQ-24 has only two categories (yes/no), it might be difficult to detect small changes in HRQoL. However, this may also be a strength as it means that changes in HRQoL would need to be clinically relevant and detectable by the patient as well as the physician and, therefore, less likely to be an artifact. In addition, some RDQ items had low proportions of patients responding “Yes” at baseline, making it difficult to evaluate correlations between RDQ baseline severity and pain reduction.In conclusion, this post hoc analysis suggested that improvement in pain severity was associated with improvement in aspects of disease-specific HRQoL in duloxetine-treated patients with CLBP. In particular, positive responses to duloxetine in terms of the RDQ13, RDQ23, and RDQ10 items may correlate with better pain responses. However, further investigation is required to fully elucidate the relationship between pain and HRQoL in duloxetine-treated patients with CLBP. Nevertheless, given the difficulty in treating CLBP and the ease of administering HRQoL measures such as the RDQ-24 in daily clinical practice, determining which baseline HRQoL characteristics might be predictors of response to duloxetine would provide valuable information for making treatment decisions and anticipating treatment outcomes in terms of HRQoL in patients with CLBP.