A subgroup of patients continue to report pain with walking 12 months after total knee arthroplasty (TKA). The association between walking pain and self-rated health (SRH) after TKA is not known. This prospective longitudinal study aimed to investigate the association between a comprehensive list of preoperative factors, postoperative pain with walking, and SRH 12 months after TKA.N = 156) scheduled for TKA completed questionnaires that evaluated demographic and clinical characteristics, symptoms, psychological factors, and SRH. SRH was re-assessed 12 months after TKA. Clinical variables were retrieved from medical records. Pain with walking was assessed before surgery, at 6 weeks, 3, and 12 months after TKA. Subgroups with distinct trajectories of pain with walking over time were identified using growth mixture modeling. Multiple linear regression was used to investigate the relationships between pain with walking and other factors on SRH.Patients (p = 0.005) and explained 56.1% of the variance in SRH 12 months after surgery. SRH improved significantly over time. Higher C-reactive protein levels, higher number of painful sites before surgery, higher fatigue severity, and more illness concern was associated with poorer preoperative SRH.Higher body mass index, a higher number of painful sites at 12 months, recurrent pain with walking group membership, ketamine use, higher depression scores, and poorer preoperative self-rated health were associated with poorer SRH 12 months after TKA. The final model was statistically significant (In patients whose walking ability decreases over time, clinicians need to assess for unreleaved pain and decreases in SRH. Additional research is needed on interventions to improve walking ability and SRH. Osteoarthritis (OA) of the knee is a common disorder that leads to pain and restricted mobility. Total knee arthroplasty (TKA) for OA aims to relieve pain and improve function when conservative treatment is no longer effective. Although the procedure is highly effective in terms of prosthesis-related outcomes  and qualThe mechanisms that underlie this variability in TKA outcomes are likely to be multifactorial and complex . For exaWalking difficulties seem to influence patients’ future health. For example, walking difficulties were associated with higher mortality rates 10 years after TKA . In addiSRH is a global measure of general health status  and is cData collection for this longitudinal study was performed between October 2012 and September 2014 at a high volume surgical clinic in Norway. The clinic serves patients from all regions of Norway. Patients ≥18 years of age were eligible for inclusion if they were scheduled for TKA for OA, agreed to participate, and did not have a diagnosis of dementia. Patients undergoing unicompartmental or revision surgery were excluded. The study was approved by the Regional Medical Research Ethics Committee of Health South East of Norway (# 2011/1755).Written information was distributed to all patients considered for eligibility prior to or on the day of admission. A nurse approached patients who met the inclusion criteria and invited them to participate. Written consent regarding questionnaires and extraction of data from the medical records was obtained from all patients before completing the baseline questionnaire that assessed demographic, clinical, symptom and psychological characteristics, as well as health-related quality of life and pain interference with walking. Follow-up assessments of pain interference with walking were performed at postoperative day (POD) 4, 6 weeks, 3 months, and 12 months after surgery. Health-related quality of life follow-up questionnaires were completed 12 months after surgery. All questionnaires were returned in sealed envelopes. Non-responders received a reminder by mail or phone.The surgical department had a standardized regimen for anesthesia, surgery and postoperative pain management. All patients received the same posterior cruciate-retaining fixed modular-bearing implant for the TKA using an intraoperative tourniquet and with drains that were removed on POD 1. The full regimen for pain management was described in detail elsewhere . PatientSelf-rated health: Patients rated their own perceived overall health status today  on a numeric rating scale from the well validated EuroQol-5D-3 L . The scaData on comorbidities, BMI, American Society of Anesthesiologists (ASA) classification score, blood pressure, type of anesthesia, type of implant, length of surgery, length of stay, C-reactive protein (CRP), and creatinine values were extracted from the medical records. Data on opioid consumption and use of ketamine were obtained through chart review.The Brief Pain Inventory (BPI) was used to measure pain and interference with walking [ walking . The BPI walking .For this study, pain interference with walking was a factor of particular interest and was assessed on the day before surgery, on POD 4, at 6 weeks, 3 months, and 12 months after surgery. This final endpoint was chosen because the largest gains in functional improvement typically occur within 1–3 years after TKA , 20. In Fatigue severity was evaluated using the 5-item Lee Fatigue Scale (LFS). Each item was rated on a 0 to 10 NRS. A mean score using all items was calculated with higher scores indicating higher fatigue severity. The LFS has satisfactory validity and reliability . In thisFatigue interference during the past week was measured using the 7-item Fatigue Severity Scale (FSS-7). Patients used a 7 point Likert scale to rate their agreement with 7 statements. A total mean score using all seven items was calculated. Scores can range from 1 to 7 with higher scores indicating higher levels of interference. Psychometric properties of the Norwegian version of the FSS-7 were good . In thisThe Hospital Anxiety and Depression Scale (HADS)  was usedThe Brief Illness Perception Questionnaire (BIPQ) [e (BIPQ)  was usede (BIPQ) .Data analysis was performed using Statistical Package for Social Science version 22 . Growth mixture modeling (GMM) with full maximum likelihood estimation using Mplus Version 7.3  was perfFor the current analysis, descriptive statistics were generated on sample characteristics, pain, and health related quality of life. A paired t-test was done to evaluate for changes in SRH from prior to until 12 months after TKA. Exploratory analyses using Pearson’s bivariate correlation coefficients were performed to select potential variables for inclusion in the multivariate analyses. Non-significant variables were excluded from further testing. Separate regression analyses were performed for preoperative SRH and SRH at 12 months. For both analyses, age, sex and number of comorbidities were included as covariates since these variables were associated with SRH in various populations –26.p-value) with the dependent variable were excluded one by one and nested models were repeated until the final model was determined.Variables with a statistically significant association with preoperative SRH in the exploratory analysis Table  were entp-value) with the dependent variable were excluded one by one and nested models were repeated until the final model was determined. For both analyses, the blocks were created based on the framework used in our previous studies [Variables with a statistically significant association with SRH at 12 months in the exploratory analysis  from before surgery  until 12 months after surgery .As displayed in Table p = .002) and explained 37.0% of the variance in SRH prior to surgery. Higher levels of CRP, a higher number of painful sites before surgery, higher fatigue severity, and higher illness concern were significantly associated with poorer SRH, after controlling for age, sex, and number of comorbidities.The final model for preoperative SRH is shown in Table p = 0.005) and explained 56.1% of the variance in SRH 12 months after surgery. Higher BMI, higher number of painful sites 12 months after surgery, Recurrent Interference group membership, perioperative use of ketamine, higher preoperative depression score, higher perceived personal control, and poorer preoperative SRH were associated with poorer SRH 12 months after TKA, after controlling for age, sex and number of comorbidities. Among all associated factors, pain interference walking group membership had the strongest association with SRH at 12 months (Beta = −0.33). Patients who had no improvement in pain with walking scored 12.45 points (CI: −17.67 to −7.24) lower on SRH 12 months after TKA, compared to patients whose pain with walking decreased.The final model for SRH 12 months after surgery is shown in Table This study aimed to investigate key predictors associated with poorer SRH 12 months after TKA. Findings from this study suggest that lack of improvement in walking during the first year following TKA was the strongest predictor of poorer SRH scores 12 months after surgery. After controlling for demographic, clinical, and personal factors, membership in the Recurrent Interference group was associated with a 12 point lower SRH score, well above the minimally clinically important difference of 8 points for this scale . In addiThe preoperative SRH scores in our sample were comparable to OA patients awaiting joint replacement and TKA patients , 31. As Consistent with other studies , 32, the2 are at increased risk for poorer knee function, revision surgery within 5 years, superficial infection and deep venous thrombosis [2 had significantly lower implant survivorship and lower function scores. However, this association was not seen in patients with a BMI ≥30 kg/m2 [2 may guide patient selection for TKA. However, Kulkarni and colleagues argued that because all patients are unique, the decision to perform surgery should not rely solely on a patient’s BMI but consider each patient’s potential risks and benefits [2 needs to be informed about the risk of a poorer outcomes including SRH, prior to deciding to undergo TKA.Interestingly, higher preoperative BMI was associated with poor SRH at 12 months after surgery, but not with SRH preoperatively. Obesity is considered a modifiable risk factor for OA  and weigrombosis . In addi30 kg/m2 . Based obenefits . Patientp = .008) but not with number of painful sites after 12 months . It is well known that patients with OA have a large number of painful sites often accompanied by pain sensitization [Patients with a higher number of painful sites before and 12 months after surgery were more likely to report poorer SRH, both prior to surgery and 12 months after TKA. This characteristic was the only factor common to both time points. Interestingly, number of comorbidities correlated with number of painful sites prior to surgery . More specific details on other chronic diseases 12 months after surgery may have provided us with more detailed information about other factors that impact patients’ SRH. Finally, the use of objective measures of walking ability may have provided additional insight.The prospective design and relatively large sample are advantages with our study. In addition, all patients received the same type of implant and a standardized regimen for pain management and mobilization. Finally all of the patients received physical therapy for 4–6 months after TKA.In conclusion, patients with no improvements in terms of pain interference with walking report poorer SRH 12 months after TKA. In addition, poorer SRH after TKA was associated with higher BMI, a higher number of painful sites, higher depression scores and poorer preoperative SRH. Patients whose pain with walking over time does not improve need to be followed closely and may need additional physical therapy to improve their general health status. While a screening tool may enable clinicians to detect patients who need additional follow-up, more research is needed to develop and test such a screening tool. Finally, more research is needed to determine what type and dose of physical therapy is needed to improve TKA patients’ walking ability.


Integrative medicine inpatient treatment has been shown to improve physical and mental health in patients with internal medicine conditions. The aim of this study was to investigate the effectiveness of a 2-week integrative medicine inpatient treatment in patients with chronic pain syndromes and the association of treatment success with patient-related process variables.Inpatients with chronic pain syndromes participating in a 2-week integrative medicine inpatient program were included. Patients’ pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were measured on admission, discharge, and 6 months after discharge. Likewise process variables including ability and will to change, emotional/rational disease acceptance, mindfulness, life and health satisfaction, and easiness of life were assessed.P < 0.05). Ability to change and implementation, disease acceptance, mindfulness, life and health satisfaction, and light heartedness/easiness likewise improved . Improved outcomes were associated with increases in process variables, mainly ability to change and implementation, disease acceptance, life and health satisfaction, and light heartedness/easiness (R2 = 0.03–0.40).A total of 310 inpatients  were included. Using mixed linear models, significant improvements in pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were found (all Results of this study suggest that a 2-week integrative medicine inpatient treatment can benefit patients with chronic pain conditions. Functional improvements are associated with improved ability to change and implementation, disease acceptance, and satisfaction. Patients in integrative medicine settings are perceived as actively contributing to their own healing process, thus integrative medicine treatments are especially effective when the patients’ health-related cognitions and coping skills change during treatment. Lifestyle management, such as changing the patients’ dietary, stress management, and exercise habits, are a major part of these treatment approaches. Thus motivating the patients to adopt a healthier lifestyle during treatment and to maintaining it after discharge is an important predictor of treatment success.,11Integrative pain treatment involves multimodal and complex interventions that strongly depend on the relationship between therapists and patients, the patients’ expectations, and motivations.,10,12,13 Prior studies have shown positive effects of the inpatient treatment on physical and mental health in mixed patients groups. Chronic and therapy-refractory pain is a major reason for referral.The Department for Internal and Integrative Medicine at Kliniken Essen-Mitte, Germany, the University of Duisburg-Essen's academic teaching hospital, was established in 1999 as a governmentally funded model institution. Developed as an integrative medicine inpatient ward from the beginning, the hospital combines conventional medicine, complementary medicine, and mind/body medicine to treat patients with chronic internal medicine diseases.The aim of this cohort study using a process-outcome design was to investigate the effects of a 2-week integrative medicine inpatient treatment at the Department for Internal and Integrative Medicine on chronic pain. A further aim was to investigate the association of treatment success with patient-related process variables, such as ability and motivation for behavioral changes, disease acceptance, and health satisfaction.22.1,15Where applicable, this study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement.Effects of the integrative medicine inpatient treatment were investigated in a prospective single-arm cohort study. Outcome measures were assessed in all participants at admission, at discharge, and 6 months after the end of the inpatient treatment. At 6 months, patients received the respective questionnaires and a franked envelope by mail and were asked to fill in the questionnaire and return it by mail as soon as possible. Problems or questions regarding the questionnaires were solved by phone. Outcome measures included pain intensity, pain-related disability, health-related quality of life, depression, and subjective stress. Furthermore, process variables including ability and will to change, disease acceptance, mindfulness, life and health satisfaction, and easiness of life were assessed. Associations of changes between outcome measures and process variables were analyzed. The study was approved by the Ethics Committee of the University of Duisburg-Essen  and registered at Clinicaltrials.gov (identifier: NCT02038244) before patient recruitment.2.2All patient's with an ICD-10 diagnosis of a chronic pain condition  who were referred to inpatient treatment at the Department of Internal and Integrative Medicine, Faculty of Medicine, University of Duisburg-Essen, Germany between January 2013 and July 2014 were invited to participate in this study. Written informed consent was obtained. The Department was established as a model clinic in 1999 to treat patients with chronic diseases, including those with chronic pain syndromes. Referrals come from specialist and general practitioners, with treatment costs being met by statutory health insurance and many private health insurance companies.2.3 Patients also received several mind/body therapy sessions, focusing on exercise, stress reduction, diet, and self-help, to empower them to adopt healthy lifestyles. These sessions were based on Harvard Medical School's Benson-Henry Institute for Mind/Body Medicine Program and the University of Massachusetts’ Mindfulness-Based Stress Reduction Program.,18 Elements of cognitive restructuring were also added in this study.,20Patients received 2 weeks of integrative inpatient hospital treatment; following individual treatment plans developed from extensive anamneses by physicians, nurses, and mind/body therapists. Treatments included conventional diagnostic and interventional medical approaches, including physiotherapy, and the use of complementary techniques. The latter included the use of traditional medicine  and classical naturopathy .2.4Visual Analog Scales (VAS). Current pain, mean pain intensity and most severe pain intensity during the past 4 weeks were measured on 100-mm VAS ranging from 0  to 100 (worst pain imaginable).Pain Perception Scale (PPS). The PPS measures subjectively felt pain on 2 scales: affective pain and sensory pain by 24 items.Pain Disability Index (PDI). The PDI assesses in how far specific aspects of a person's life are disrupted by chronic pain by.Short Form (36) Health Survey (SF-36). Patients’ health-related quality of life was assessed using the 36-item short form of the health survey questionnaire (SF-36). This tool measures an individual's quality of life on 8 dimensions and 2 main component scales . It has proven validity and reliability. Each scale ranges from 0 to 100, with higher scores indicating higher quality of life.Beck Depression Inventory (BDI). Depression was assessed by the 21-item BDI.Perceived Stress Scale (PSS). Self-perceived stress level in specific situations during the last month was assessed on the 10-item German version of the PSS.2.5Ability and will to Change Questionnaire. This new instrument addresses a person's ability to perceive that changing certain aspects in life might be beneficial to get better with the health situation; their intention to change aspects in their life and behavior; whether or not they have already begun to change life and behavior on the one hand; and the successfully developed strategies how to better deal with health problems. Factor analysis pointed to 2 factors, that is, “Perception and Intention to Change”  and “Ability to Change and Implementation .Emotional/Rational Disease Acceptance (ERDA). The ERDA measures emotional and rational acceptance of a disease on 3 emotional scales , and 2 rational scales .Conscious Presence and Self Control (CPSC). The CPSC is a modified short form of the Freiburg Mindfulness Inventory, measuring mindfulness or situational awareness by 10 items on a 4-point Likert scale ranging from 0 (rarely) to 3 .Brief Multidimensional Life Satisfaction Scale (BMLSS). The BMLSS measures life satisfaction in four domains: intrinsic , social , external , and perspective . Two additional items assess health-related satisfaction.Lightheartedness/easiness. Several patients with chronic diseases experience an affected functional, emotional, and social well being, which may result in a self-protective “emotional withdrawal.” The intention was to make measurable distinct  attitudes associated with a revival of vitality and zest of life, that is, positive internal attitudes, such as “light heartedness/easiness” and subsequent “social interest/contact” to external contacts. These attitudes are seen in the context of an increasing positive health/well being. The 9-item instrument differentiates two factors, light heartedness/easiness , and social interest/contact . The scale light heartedness/easiness was strongly associated with positive mood (r = .61), satisfaction with daily life management (r = 0.53), satisfaction with health situation (r = 0.50), with the mental component of SF-12's health-related quality of life (r = 0.50), and moderately with general life satisfaction (r = 0.47).,312.6Statistical analysis was based on mixed linear models using IBM SPSS software . Values on the respective variable were regressed to the categorical covariate “time” , that is, changes were analyzed across the three time points. To analyze the associations of outcome variables and process variables, linear forward stepwise regression analyses with linear outcome and linear and dichotomous predictors were conducted for all outcomes that significantly improved across time. Process variables were entered as predictors only if they had changed significantly across time. Changes from before to after the intervention and from before intervention to 6-month follow-up were used as outcome variables. Given that the influence of changes in process variables during the inpatient treatment was to be assessed, changes from before to after the intervention were used as predictor variables. To control for possible effects of clinical and sociodemographic variables, disease duration, age, and gender were additionally included in regression analyses.P values <0.05 were regarded as statistically significant for all analyses. Missing data were replaced according to the manuals of the respective questionnaires. Where this was not possible, the respective questionnaire was not analyzed for this patient.33.1A total of 310 patients were included of which 282 (91.0%) were female. Age ranged from 19 to 75 years with a mean age of 50.7 ± 12.4 years. The most common pain conditions included headache, rheumatic pain, and spinal pain; mean pain duration was 11.0 ± 10.7 years  for long-term outcomes.,11 Short-term effects seem to be mainly driven by practitioner-based intervention and/or externally motivated health behavior during the inpatient stay while after discharge, the patients’ intrinsic motivation and self-efficacy expectations become more important. This is in line with prior studies demonstrating that initiating health behavior changes depends on both, motivation for change and the perceived ability to be able to initiate and maintain such changes without extrinsic motivational factors.,39Interestingly, while the patients’ perceived ability to change their lifestyle improved during the inpatient stay, their motivation to do so remained unchanged. Patients completing the 2-week inpatient treatment can be expected to already be relatively motivated for behavioral changes at admission. There is an about half-year long waiting period before patients can enter the inpatient treatment program and patients are required to actively participate in their treatment by attending educational exercise, stress management, dietary, and mind/body medicine sessions.,41 Satisfaction with health even if pain was not completely dissolved can be regarded as a consequence of increased disease acceptance. Specifically mind/body medical interventions such as meditation or yoga have been shown to increase pain acceptance and satisfaction in patients with chronic pain; and both concepts have been proposed as important mechanisms for these interventions’ pain relieving effects.–45 Likewise, life and health satisfaction were important predictors of the effectiveness of an integrative medicine outpatient program for cancer patients that was conducted at the same department as the current study and build up on the same theoretical and practical foundations.Disease acceptance and health satisfaction were further important predictors of short-term and long-term treatment success. This is in line with prior studies showing that pain acceptance, that is, the engagement in keeping up everyday activities and function despite the pain, is associated with less pain intensity, pain disability, and depression in patients with chronic pain syndromes. making it impossible to dismantle the effects of single interventions. Given that participation in the study was not mandatory for inpatients, selection bias by only including patients with at least minimal motivation for participating in the study and treatments cannot be ruled out. Finally, in line with prior studies on integrative medicine inpatient treatment,,32,34 drop-out rates were high at 6-month follow-up, limiting the expressiveness of the long-term findings.Limitations of the study include its observational design lacking a control group. The reported effects might therefore be an overestimation due to unspecific effects and/or regression to the mean. Causal attributions can only be made for the regression analyses at follow-up where changes from admission to discharge were used as predictors. A further limitation is the multimodal approach inherent to the investigation of integrative medicine and other whole medical systems,In conclusion, a 2-week integrative medicine inpatient treatment can improve pain intensity and pain disability, health-related quality of life, and mental health in patients with chronic pain syndromes. These improvements seem to at least partly depend on patient-reported process variables including developing the ability for health behavior change, pain acceptance, and health satisfaction. Conclusions on the effectiveness of the program remain preliminary until comparative effectiveness and cost-effectiveness are adequately investigated.


This article evaluates the long-term outcome of percutaneous balloon compression (PBC) for trigeminal neuralgia (TN) patients elder than 80 years. A total of 138 elderly patients aged above 80 years with primary TN, who were admitted to Neurosurgery Department, Hangzhou First People's Hospital from January 2007 to December 2011 for PBC treatment, were retrospectively analyzed in this study. The postoperative cure rate of immediate pain was 98.6% ; according to the follow-up, the pain cure rates at 1, 2, 3, 4, and 5 years after surgery were 93.5%, 90.4%, 84.7%, 80.4%, and 72.9%, respectively. In our group, postoperative diplopia was reported in 1 case, masticatory muscle weakness in 3 cases, and herpes labialis in 19 cases. A total of 100% of pain-cured patients exhibited facial numbness and facial hypoesthesia. No serious complications occurred in this group of patients. PBC is an effective and safe procedure for TN treatment and can be employed as the preferred regimen for elderly TN patients aged above 80 years in poorer physical condition. Currently, medical treatment requires long-term medication to control or alleviate pain. However, about 30% to 75% of patients eventually have to take surgical treatment due to poor analgesic effect or adverse effects after long-term medication. MVD is the best treatment and the longest duration of remission for the treatment of TN by craniotomy to separate the blood vessel from the compressed trigeminal nerve. Nevertheless, the risk of surgery and anesthesia for elderly patients undergoing craniotomy with MVD are still controversial. Many surgeons prefer older patients to select a more minimally invasive approach.Trigeminal neuralgia (TN) is a clinically common cranial nerve disease characterized by recurrent, transient, and severe pain in the trigeminal nerve area, which is manifested as electric shocking, knife cutting, and tear-like pain. The pain of TN lasts from several seconds to tens of seconds, and the interval is completely normal. An attack of pain is usually evoked by facial movement, chewing, brushing teeth and washing the face, or by touching the face of a region. The prevalence of TN is estimated to be 182/10 million, and the annual incidence is 3 to 5/10 million. invented PBC through modifying the craniotomy nerve compression created by Shelden and Taarnhoj. There is no requirement for craniotomy during PBC and it thus largely avoids the mortality and complications of craniotomy. Although PBC does not treat TN directing at the etiology like MVD, initial studies have shown that PBC is more successful, safe, and less prone to relapse, becoming more and more popular among older patients. The present study aimed to evaluate the long-term outcome of PBC in the treatment of elderly patients over 80 years of age with TN.In 1983, Mullan and Lichtor22.1A total of 138 elderly patients aged above 80 years with primary TN, who were admitted to Neurosurgery Department, Hangzhou First People's Hospital from January 2007 to December 2011 for PBC treatment, were retrospectively analyzed in this study. The study protocol was approved by the institutional review board of Hangzhou First People's Hospital. All patients received informed consent before the procedure and were willing to participate in this clinical study. These 138 patients included 65 males and 73 females with an average age of 86.59 years ± 4.11. Fifty-three patients had pain on the left side and 85 on the right side. Their disease course ranged from 3 to 20 years with the average of 7.2 ± 8.1 years; pain involving branch I was observed in 5 cases, branch II in 37 cases, branch III in 35 cases, branches II and III in 45 cases, branches I and II in 10 cases, and branches I, II, and III in 6 cases; according to the anesthesia risk classification by American Society of Anesthesiologists (ASA), patients of classes I, II, and III were 19, 95, and 24 cases and accounted for 13.77%, 68.84%, and 17.39%, respectively  of nonionic X-ray contrast agent iohexol was injected to the balloon; the puncture was successful when the filled balloon exhibited a pear-like shape as shown by lateral X-ray fluoroscopy  Pain Intensity Score,3Table Of these 138 patients, 1 case failed to complete the path design of straight puncture due to oval foramen deformity, whereas all remaining 137 cases underwent successful puncture upon the first attempt; after the injection of contrast agent, C-arm X-ray device under lateral view showed that the balloon was located near by the posterior clinoid process and sella turcica and filled in a satisfactory pear-like shape with nipple convex to the posterior cranial fossa; the puncture success rate was 99.3%. A total of 112 cases reported trigeminal depressor response manifested by heart rate decline with the incidence of 81.2%, and their heart rate was slowed by 23 beats/minute in average; of them, 1 case developed transient cardiac arrest with the incidence of 0.72%. The postoperative cure rate of immediate pain was 98.6% ; according to the follow-up, the pain cure rates at 1, 2, 3, 4, and 5 years after surgery were 93.5%, 90.4%, 84.7%, 80.4%, and 72.9%, respectively . Montano et al carried out a similar literature study and suggested good early remission rate in patients undergoing different therapeutic procedures, which showed no significant intergroup difference; the efficacy of PBC and MVD was equivalent in terms of the long-term pain remission rate. Providing varying evaluation criteria for surgical efficacy between different authors and considerable heterogeneity between different literature regarding the description of long-term follow-up results and the follow-up duration, the quality of evidence provided by meta-analysis is poor. Therefore, qualified multicenter randomized controlled trials designed to further compare the long-term efficacy between PBC and other surgical procedures may offer firmer evidence-based medical basis for the treatment of TN with PBC.Through reviewing literature reports, Meglio et al named such conditions as trigeminal cardiac reflexes, whose specific mechanism remains unclear; posing a potential life risk to patients undergoing surgery. Trigeminal cardiac reflexes is a common phenomenon in the process of PBC for the treatment of TN, which generally does not affect the treatment process by taking appropriate preventive and therapeutic measures. Surgeons and anesthesiologists must be fully aware of this possible cardiac suppression response, and corresponding preparations must be made for the surgical and pharmaceutical aspects. In the treatment of TN, the common complications of PBC are relatively mild, including hypesthesia, dysesthesia or even hyperesthesia in the trigeminal innervating areas, masticatory muscle weakness, corneal hypoesthesia, and loss of corneal reflex, as well as viral herpes. Other complications, such as aseptic meningitis, oculomotor nerve and/or trochlear nerve palsy, and elevated odor threshold, are relatively less encountered.–20 By summarizing the postoperative complications of PBC in 100 patients, Lichtor and Mullan concluded that hypesthesia, numbness, and even hyperesthesia in the trigeminal innervating areas were the most important complications, whose severity was associated with the duration of pain relief; of these 100 cases, hypesthesia was reported in a majority of patients with dysesthesia in a minority, while hyperesthesia was observed in 4 cases only.Sudden rise in blood pressure, tachycardia, bradycardia, sudden drop in blood pressure, and other hemodynamic changes appear to be the common intraoperative complications. Chowdhury et al5PBC is an effective and safe procedure for TN treatment and can be employed as the preferred regimen for elderly TN patients aged above 80 years in poorer physical condition.


To assess the correlation between the number of excised neural fibers and degree of pain relief following laparoscopic presacral neurectomy (LPSN).In this before and after study, 20 patients with severe midline dysmenorrhea [Visual Analogue Scale (VAS) >80 mm] unresponsive to medical therapy were consecutively enrolled. All patients underwent LPSN. The superior hypogastric plexus was excised and sent for histologic confirmation. Two pathologists counted the number of neural fibers in the surgically removed tissue. VAS was used for pain assessment before and 2nd, 3rd, 6th, and 12th months after the operations.Out of the initial 20 patients undergoing LPSN, eight were excluded from the final analysis due to intraoperative diagnosis of endometriosis; therefore, the remaining 12 patients were evaluated. The pain scores significantly decreased at each follow-up visit compared with the preoperative period (p=0.002). The pathologists, who were blinded, reported the median (minimum-maximum) neural fiber count as 46 (20-85) and 47 (18-83). No significant correlation was demonstrated between the number of excised neural fibers and the amount of pain relief following LPSN.LPSN is an effective surgical procedure to control primary dysmenorrhea. Our preliminary results revealed that the degree of pain relief in cases of severe midline dysmenorrhea was not related to the amount of excised neural tissue in LPSN. The degree of pain relief after laparoscopic presacral neurectomy is not related to the amount of excised neural tissue.,2. Dysmenorrhea is such a challenge that it interferes with the performance of daily activities, and may even lead to job or school absenteeism. Therefore, the main goal of treatment is to provide pain attenuation sufficient to sustain the woman’s daily performance. Medical therapy is the primary treatment of dysmenorrhea, which includes oral contraceptive pills, systemic or local progestins, non-steroidal anti-inflammatory drugs, danazol and gonadotropin-releasing hormone analogues. Surgical therapies stay as the second line of treatment in refractory cases because medical therapies are associated with a failure rate of 20-25%,4. Surgical intervention includes the interruption of a major group of cervical and uterine sensory nerve fibers, known as pelvic denervation. The presumed mechanism of presacral neurectomy (PSN) for pain relief of dysmenorrhea is primarily based on the anatomy of the sensory pathways from the pelvic viscera through the inferior and superior hypogastric plexus to the spinal column. Excision or incision of the superior hypogastric plexus, located in presacral area and so-called PSN, can disrupt many pain sensory pathways. The surgical technique of PSN was first described by Jaboulay and Ruggi as early as 1899. One hundred years after from the first description, Perez reported the first case of laparoscopic PSN (LPSN).Dysmenorrhea, painful menstrual cramps, is a very common gynecologic problem with a prevalence of 43-90% in women of reproductive age,8,9,10; however, some patients still can not benefit from this approach. This diverse clinical response to LPSN has not yet been elucidated. One explanation may be that other sensory pathways not included in the superior hypogastric plexus may be responsible for cases with partial or no pain attenuation. Another possible mechanism is that the amount of excised neural tissue during LPSN may not be sufficient enough to resolve dysmenorrhea. Factors that determine the degree of response to PSN have yet to be enlightened. We hypothesized that there was an association between the amount of excised neural tissue and the response to therapy. The aim of the present study was to assess the correlation between the number of excised neural fibers and the degree of postoperative pain relief following LPSN.LPSN is found to be an effective surgical procedure in most cases refractory to medical treatmentBetween July 2013 and August 2015, patients with the sole symptom of dysmenorrhea  for more than 6 months were consecutively enrolled in the study. All patients underwent multidisciplinary evaluation by the urology, gastroenterology, physical therapy, and psychiatry departments to exclude other potential causes of pelvic pain. All patients were questioned and physically examined to determine the exact location of their pain. Patients with pelvic pain related to specifiable pathologic conditions such as psychiatric disorder, malignant or infectious disease, previous pelvic surgery, large uterine leiomyoma, diagnosis of visually or histologically confirmed endometriosis or adenomyosis, and/or patients with lateral pelvic pain were excluded.The study population consisted of 20 patients, whose most prominent symptoms were severe midline dysmenorrhea [Visual Analogue Scale (VAS) >80 mm] that had been unresponsive to at least two alternate medical therapies for more than 6 months. All patients reported job or school absenteeism in each menstrual period.Six of the 20 patients reported dyspareunia  and three had mild chromic pelvic pain (CPP) (pain that occurs below the umbilicus and lasts for at least six months) along with severe midline dysmenorrhea. Patients assessed for LPSN are summarized in a flow chart . Twenty Prior to the operation, all patients gave written informed consent for the details of surgical procedure including the risks, benefits, and recurrence rate of LPSN. A senior surgeon (M.A Massachusetts) performed all LPSN procedures with no intraoperative complications.The severity of dysmenorrhea was assessed using a 100 mm VAS that ranged from “least possible pain” to “worst possible pain” at the time of hospital admission, and 2, 3, 6, and 12 months following the surgery. At admission, the women were requested to grade the most severe menstrual pain they experienced during the last 6 months using the VAS. The durations of the surgical procedures and hospital stay, blood loss, and intraoperative and postoperative complications were also recorded. All patients were followed up with clinical visits over 12 months to evaluate the degree of pain relief and possible complications. Zeynep Kamil Training and Research Hospital Review Board was approved our study. Written informed consent was provided from all patients to share and publish their medical records.In the steep Trendelenburg position, the small intestines and sigmoid colon over the sacral promontory were pushed out laterally. After identifying the ureter on the right side, the peritoneum overlying the sacral promontory was incised transversally between the sigmoid mesentery on the left side and right ureter on the right side. The tissue on the sacral promontory, presumably the superior hypogastric plexus, was elevated as much to the lateral sides as possible, carefully dissected from the areolar tissue and then, excised approximately 1 cm above and below the L5-S1 disc level using a harmonic scalpel . The removed plexus segment was sent for histologic evaluation.Two pathologists (E.K. and H.Y.), who were blinded to the study interest, counted the neural fibers. The nerve specimens, after routine tissue processing, were cut into 3-μm-thick transverse, oblique, and longitudinal serial sections and deparaffinized in xylol for 10 minutes. They were dehydrated in a graded series of alcohol. The sections were kept in hematoxylin for 5-6 min. and washed with water for 5-10 min. They were then kept in eosin for 3-4 min and cleared in graded series of alcohol. After staining with hematoxylin-eosin, they were left to dry for a few minutes and placed in xylol. The tissues were passed through xylol three times for 10 min. Finally, they were taken out and mounted with a synthetic resin (entella). The sections were examined to determine the most appropriate sample, i.e., the section that included the greatest amount of neural fibers. To prevent repeated counting, the sections were mapped with a pencil .Statistical analyses were performed using the SPSS software version 20 . While investigating the associations between non-normally distributed or ordinal variables, the correlation coefficients and their significance were calculated using the Spearman test. Friedman tests were used to compare the difference between the pre- and post-operative pain scores. In the post-hoc analysis of pairwise comparisons, the Wilcoxon test was performed. The agreement between the two pathologists for the neural fiber count was assessed using Lin’s concordance correlation coefficient (ρc). A 5% type 1 error level was used to infer statistical significance.Out of the initial 20 patients undergoing LPSN, eight were excluded from the final analysis due to an intraoperative diagnosis of endometriosis. All of these eight patients had dyspareunia and/or CPP along with dysmenorrhea. The remaining 12 patients were evaluated for the final analysis. The median age was 29 years. All patients had midline dysmenorrhea with a median (minimum-maximum) duration of 11 (7-15) years. The median body mass index was 24.6 kg/m2. The median (minimum-maximum) operation time for the LPSN was 32 (21-45) minutes. Blood loss was minimal. There were no minor or major vascular trauma, urinary or gastrointestinal complications related to LPSN. The patients were hospitalized for a maximum of 2 days postoperatively (median 1 day). There was no postoperative voiding dysfunction, constipation or other complications reported during the 12 months of follow-up.Two pathologists reported the median (minimum-maximum) neural fiber count as 46 (20-85) and 47 (18-83). There was almost perfect agreement between the pathologists for the neural fiber counts [Lin’s concordance coefficient (pc)=0.99].The median pain scores were 9.2, 3.3, 2.6, 1.7, and 1.6 before, and 2, 3, 6, and 12 months following the operation, respectively. Pain scores significantly decreased at each follow-up visit compared with the preoperative period (p=0.002). The reduction of pain scores remained stable from 6 to 12 months (p=0.08) .No statistically significant correlation was found between the neural fiber count and preoperative or postoperative pain scores . After t. At this point, before deciding on surgical treatment, a detailed evaluation of patients to determine the location of pain has paramount importance in order to identify patients who would benefit from the procedure with the highest efficacy. In our study, we excluded subjects who reported lateral pain.Up to 80% of reproductive aged women are affected by dysmenorrhea, in many cases causing sufficient pain that precludes social and occupational activities. Pain per se is a necessary defense mechanism of the body; however, chronic pain is a disturbing condition that needs to be treated. In persistent pain syndromes, people face distressing situations rather than biologic benefit. The presacral nerve, namely the superior hypogastric plexus, carries pain afferents from the cervix, the body of the uterus, and the proximal fallopian tube, but does not receive fibers from the ovaries and lateral pelvic structures. Therefore, PSN is traditionally performed for midline dysmenorrhea,13,14. In the study by Jedrzejczak et al., the efficacy of LPSN was evaluated in patients with and without endometriosis. Dysmenorrhea decreased at 3 months by 75% in those without endometriosis. Furthermore, these patients reported a significant decline in dyspareunia and pelvic pain unrelated to menses at 3 and 12 months after LPSN. In our cases, the pain scores significantly decreased over months. The median pain scores decreased sharply at the 2nd month, gradually from 2nd to 3rd month and then, remained stable. The patients with dyspareunia and chronic pelvic pain reported substantial pain relief that did not require any analgesic medication. Although the number of our participants is limited to 12 cases, we obtained 100% of efficacy in patients with severe dysmenorrhea and no identifiable pelvic pathology, when nerve bundles were excised.It has been shown that the success rate of PSN in the management of primary dysmenorrhea is 75 to 87%. Furthermore, because the microscopic anatomy of a nerve plexus can not be differentiated during surgical exploration, surgeons only excise or transect the area where it is presumed to be the possible location of the superior hypogastric plexus. However, the architecture of the presacral area, which consists of fat, connective, vascular, and neural tissue, may mislead adequate excision of neural tissue. To ensure that the neural pathway has been included in the surgical area, histologic confirmation of the excised tissue is needed. On the other hand, the amount of removed neural tissue might be a determinant of surgical success. In our study, the number of neural fibers removed per specimen was counted by the pathologists. We detected that the neural fiber count differed from one patient to another and there was no correlation between the number of fibers removed per tissue and the amount of pain relief. This discrepancy can be explained by individual differences in the number of neural fibers or the complexity of pain perception. Moreover, the neural fiber intensity might not make any difference in pain transmission.Previous studies reported that PSN might be ineffective in some cases. There is an on going debate as to whether efficacy could be related to the surgical method used. Some surgeons have asserted that a longer incision should be made on the hypogastric nerve plexus, whereas others claimed that the anatomic variation of nerve fibers at the area below the bifurcation of the aorta caused inconsistency in pain relief,17. Chang et al. compared LPSN with modified LPSN by transecting nerve bundles over different levels to evaluate long-term effectiveness in pain relief. In traditional LPSN, the presacral nerve bundle is transected over the presacral promontory, whereas in the modified method, it is transected over the aortic bifurcation. Although pain relief was sustained for five years in 90% of patients with both methods, recurrent pain was reported by 82% of the patients in LPSN and 43% in modified LPSN eight years after the operations (p=0.04). The authors commented that incomplete resection and re-growth of the nerve fibers might cause this difference. Presacral nerves spread out into a latticework at the level of the first sacral vertebra, where it divides into several branches going to the right and left sides of the pelvis. These nerves lie beneath fatty areolar tissue contained in the anterior longitudinal ligament, the middle sacral artery, and the vein plexus, where it is too difficult to distinguish and dissect them completely. In addition, there are individual variations of pelvic anatomy and neurophysiology, intermingling of afferent fibers, intercommunication among nerve plexuses, and cross-talk. Excision of the nerves may keep these factors under control and contribute to the long-term effectiveness of the LPSN. We observed a reduction of pain in all subjects supporting the theory that segmental resection might increase the effectiveness of the procedure.The method for PSN has been described in different approaches  with different techniques  at different levels. Some preferred to excise a segment of 2-3 cm in diameter to prevent re-anastomosis of nerves, but others only transected without excisionOur study sheds light on the physiology of pain transmission through the superior hypogastric plexus. However, to our knowledge, no studies have identified any association between the efficacy of the procedure and the quantitative or qualitative parameters of excised neural tissue. Inter-observer variability assessment between the pathologists provides the safety of this experimental nerve counting method, which makes it reproducible for further studies.Our hypothesis was tested in a small number of cases. Further, the subtypes of the neural fibers were not differentiated.Our preliminary results revealed that LPSN, if properly performed in selected cases, is an effective surgical procedure to control primary dysmenorrhea. According to the results of our study, the degree of pain relief in severe midline dysmenorrhea is not related to the amount of excised neural tissue in LPSN. The pathophysiology of pain transmission and perception, and the underlying mechanism of the effectiveness of neurectomy need to be further elucidated.


The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a commonly used knee assessment and outcome tool in both clinical work and research. However, it has not been formally translated and validated in Finnish. The purpose of this study was to translate and culturally adapt the KOOS questionnaire into Finnish and to determine its validity and reliability among Finnish middle-aged patients with knee injuries.KOOS was translated and culturally adapted from English into Finnish. Subsequently, 59 patients with knee injuries completed the Finnish version of KOOS, Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short-Form 36 Health Survey (SF-36) and Numeric Pain Rating Scale (Pain-NRS). The same KOOS questionnaire was re-administered 2 weeks later. Psychometric assessment of the Finnish KOOS was performed by testing its construct validity and reliability by using internal consistency, test-retest reliability and measurement error. The floor and ceiling effects were also examined.The cross-cultural adaptation revealed only minor cultural differences and was well received by the patients. For construct validity, high to moderate Spearman’s Correlation Coefficients were found between the KOOS subscales and the WOMAC, SF-36, and Pain-NRS subscales. The Cronbach’s alpha was from 0.79 to 0.96 for all subscales indicating acceptable internal consistency. The test-retest reliability was good to excellent, with Intraclass Correlation Coefficients ranging from 0.73 to 0.86 for all KOOS subscales. The minimal detectable change ranged from 17 to 34 on an individual level and from 2 to 4 on a group level. No floor or ceiling effects were observed.This study yielded an appropriately translated and culturally adapted Finnish version of KOOS which demonstrated good validity and reliability. Our data indicate that the Finnish version of KOOS is suitable for assessment of the knee status of Finnish patients with different knee complaints. Further studies are needed to evaluate the predictive ability of KOOS in the Finnish population.The online version of this article (10.1186/s12891-018-2078-7) contains supplementary material, which is available to authorized users. Knee pain is common complaint affecting people of all ages. In adult populations, the reported prevalence of knee pain has been 25–28% depending on the age of the examined persons and the level of pain chronicity –3. In thTo be able to detect and treat individuals with a variety of knee problems effectively requires reliable and valid outcome measures, preferably at low cost. During recent decades, a few well-validated outcome measures have been developed for the assessment of symptoms and function in subjects with knee or hip OA –11. In tKOOS is a disease-specific, patient-reported outcome (PRO) measure assessing perceived pain, other symptoms, activities of daily living, sport and recreation functions, and knee-related quality of life. It is freely accessible, and intended for use over the short- and long-term for both research and clinical purposes. KOOS has been found to be a valid, reliable and responsive outcome measure in different patient populations with varying knee injuries  , 14, knePrior to the implementation of the KOOS questionnaire, a cross-cultural adaptation of the measure was performed in accordance with the recommendations by Beaton et al. (2000) . The AmeThe study population comprised patients with diverse knee problems, including OA, post-traumatic injuries, meniscus and ligament problems. The patients had been referred to the Department of Orthopedics and Traumatology in Helsinki University Hospital from primary health care centers in the Hospital District of Helsinki and Uusimaa, where, based on clinical and radiographic or Magnetic Resonance Imaging findings, they were diagnosed as having OA or Anterior Cruciate Ligament (ACL), meniscus or combined ACL and meniscus injuries. For this study, all the assessed patients had to be in a clinically stable condition and not expected to undergo urgent surgery. The patients were recruited between March 2014 and May 2015 using a systematic sampling technique. The inclusion criteria were age 18 years or over, unresponsive to conservative treatment, and the ability to communicate in written Finnish. Eligible patients were informed about the study, and indicated their willingness to participate by giving their informed consent. For test-retest purposes, the participants were asked to complete KOOS twice: first, during the hospital visit, and then again 2 weeks later at home. During the hospital visit the patients were asked to fill in the KOOS along with the WOMAC, the SF-36 and the Numeric Rating Scale of Pain forms. One hundred thirty-one patients completed all four questionnaires during the hospital visit. Of these patients, 59 returned the KOOS questionnaire 2 weeks later from home by regular mail in a pre-paid envelope, yielding a sample of 59 patients for the study. The local Medical Ethics Committee of Helsinki University Hospital approved the study plan . Written informed consents were obtained and participants’ rights protected.KOOS is a patient-administered knee-specific questionnaire comprising five subscales: Pain (nine items); Symptoms (seven items); Activities of Daily Living (ADL) (17 items); Sport and Recreation (five items); and Knee-Related Quality of Life (QOL) (four items). Each item is scored from 0 (best) to 4 (worst) using a Likert type scale with 5 boxes. The raw score for each subscale is the sum of the item scores. Scores are then transformed to a 0 to 100 scale. The scores of the five subscales can be expressed as an outcome profile, higher scores indicating fewer problems. A total score has not been validated and is not recommended according to the KOOS Users Guide . When fiThe Western Ontario and McMaster Osteoarthritis Index (WOMAC) is a disease-specific, self-administered health status instrument assessing pain, stiffness, and function in subjects with OA of the hip or knee . The indHealth-related quality of life was measured using the Short-Form 36 Health Survey (SF-36) . SF-36 iThe subjective intensity of pain in general and in different body regions was measured on the numeric pain rating scale (Pain-NRS). The body regions in this study were neck, back, upper limb, lower limb and knee. The Pain-NRS is an 11-point scale ranging from 0 to 10, where 0 represents “no pain” and 10 represents “the most intense pain imaginable”. For this study, however, as with WOMAC we reversed the scoring direction of the Pain-NRS outcomes, meaning that higher scores indicate “no pain” and lower scores indicate “the most intense pain imaginable”. When filling the form, patients are asked to select the value that best describes the intensity of pain that they have experienced during the past week.During their visit to the outpatient clinic, in addition to demographic data, patients were asked for anamnestic information regarding their knee problem, and to describe the intensity of their habitual physical activity .Construct validity was determined by comparing the first administration of the five KOOS subscales against the five WOMAC subscales, the eight SF-36 subscales, and the six Pain-NRS subscales. On the assumption that the highest correlations can be expected to be observed when comparing scales that are intended to measure the same or similar constructs, we posited a priori sets of hypotheses about convergent relationships between physical health properties which are given in Table internal consistency of the first-administered KOOS was determined by defining the degree of inter-relatedness among the items. Test-retest reliability was determined by comparing the scores of the first- and second-administered KOOS questionnaires. Measurement error is the systematic and random error of a patient’s score that is not attributed to true changes in the construct to be measured [floor and ceiling effect of the KOOS was also examined. We checked each questionnaire for missing values prior to further analysis. The KOOS Users Guide 2012 rule was applied for missing items [measured . The stang items .n = 59), as follows: MDCgroup = MDCindividual/√n [Quantitative variables are described using mean and standard deviation (SD) or median and interquartile range (IQR) values, and categorical variables are described using frequency and percentage values. Construct validity was calculated by using Spearman’s correlation coefficient to assess the relationships between the KOOS subscales and the WOMAC, SF-36 and numeric pain rating scales. Correlation coefficients less than 0.2 were considered very weak, between 0.2 and 0.39 weak, between 0.4 and 0.59 moderate, between 0.6 and 0.79 strong, and above 0.79 very strong . Internaidual/√n . The floidual/√n .A total of 59 patients were included in the validity, internal consistency, test-retest, measurement error and floor/ceiling effects assessments. Mean participant age was 49 SD 14), most were women (78%), and the median duration of knee symptoms was 7 months for women  and 6 months for men . Mean self-reported knee pain for all patients was 5.6 (SD 2.6) on a NRS scale of 0 to 10. The characteristics of the study population are presented in Table 4, most wOnly a few individual items 2%), all from the Pain and Sport and Recreation Function subscales, were missing, and hence a total score for all the subscales was available for all patients  the word “stockings” was omitted. In addition, item A13 on the same subscale (“Getting in/out of the bath”) the word “shower” was added as an alternative to bath. The Finnish version of the KOOS questionnaire was well received by the sample of 16 postmenopausal women with mild knee OA. All the questions and response options were considered understandable and applicable. The back-translation of the Finnish version of the KOOS questionnaire is available in the additional file [see Additional file r = 0.86; KOOS Pain vs. WOMAC Pain, r = 0.81). In addition, the KOOS Symptoms and WOMAC Stiffness subscales correlated moderately (r = 0.48). Thus, the set of a priori hypotheses posited for KOOS and WOMAC was supported . The KOOS Sport and Recreation Function and SF-36 Physical Functioning subscales also correlated strongly (r = 0.67), thus supporting the set of a priori hypotheses posited for KOOS and SF-36  and lower limbs (r = 0.37–0.61) (Table r = 0.68), and moderate correlation between KOOS QOL and Pain-NRS Knee (r = 0.53) were both supported. However, KOOS Pain and Pain-NRS Knee showed strong correlation (r = 0.66) instead of expected very strong correlation  of 0.73 (0.59 to 0.83) and 0.72 (0.57 to 0.82), respectively  are compared rather than the constructs. Due to overlapping subscales between the KOOS and WOMAC, it was essential in this study to compare and correlate the subscales of the KOOS also with other questionnaire’s subscales assessing similar constructs than those of the WOMAC.We found, somewhat surprisingly, that the KOOS subscale of Symptoms and the WOMAC subscale of Stiffness showed “only” a moderate correlation. This may partially be due to fact, as referred to above, that the KOOS Symptoms subscale contains five items in addition to the two original WOMAC items, as it also takes symptoms related to knee movement into account. Also noteworthy, alongside the KOOS subscales of Pain, Symptoms and Activities of Daily Living, were the subscales of Sport and Recreation Function and QOL, which showed a moderate or strong correlation with all the WOMAC subscales.When the KOOS and SF-36 were compared for construct validity, we found strong correlations between the KOOS subscales and those of the SF-36 that measured similar constructs. The highest correlations were observed between the SF-36 subscale of Physical Functioning and the KOOS subscales of ADL and Pain. The SF-36 subscale of Bodily Pain and the KOOS subscales of Pain and ADL also showed strong correlations. In contrast, the KOOS subscale of Symptoms showed the lowest correlations with all the SF-36 subscales. This is in line with the findings of Salavati et al. (2008) in patients with knee injuries, and of Roos et al. (1998) in subjects with knee OA. In fact, Roos et al. concluded that the KOOS Symptoms subscale is not as important as the other four subscales as a determinate of Physical Health. The authors suggested that symptoms and functional limitations should be reported separately and not aggregated into a single score . All in The numeric pain rating scale used in this study measures the intensity of pain experienced in general as well as in specific body regions. It contains subscales that make it possible to explore correlations with the KOOS subscales. As expected, we found strong and moderate correlations between all the KOOS and Pain-NRS subscales, particularly those focusing on the lower extremities and the knee region. These findings, in conjunction with the fact that self-reported knee pain was more severe than pain in any other body region, confirm the utility of the KOOS as a lower-extremity PRO measure in subjects with diverse knee problems. Also of note was the finding of strong correlations between the Pain-NRS Knee and lower limb subscales and the KOOS Activities of Daily Living subscale. This is understandable, given that the knee is a large weight-bearing joint with a large range of movements, and that managing the activities of daily living presumes an extensive repertoire of pain-free weight-bearing movements. However, somewhat surprisingly, the KOOS Pain subscale correlated only strongly instead of, as expected, very strongly with the Pain-NRS Knee subscale. This is most likely due to only partial similarity between the constructs in the two subscales. While the nine-item KOOS Pain subscale is designed to elicit the prevalence and degree of pain during different activities and rest, the Pain-NRS Knee subscale consists of a single item in asking about the intensity of pain experienced during the past week. Nevertheless, the use of the Pain-NRS yielded new information, since to our knowledge no previous KOOS validation studies have investigated the correlations between the KOOS and Pain-NRS subscales. From our pre-defined hypotheses altogether 89% could be confirmed.Internal consistency was good for all five subscales, exceeding the cutoff value of 0.70. This result is comparable to observations in other languages and patient populations, such as in the Swedish version with preoperative patients , the DutThe ICC values for test-retest reliability for all the KOOS subscales were good, ranging from 0.72 to 0.86, thereby indicating sufficient standardization of the KOOS questionnaire. Overall, our results are comparable to those of previous methodological studies of KOOS , 13 and The MDC value of 4.4 points at the group level indicates that the Finnish version of the KOOS has an ability to detect a minimum change of 4.5 points between the measurements. The MDC should be smaller than the minimal important change (MIC), which is regarded as the smallest change score needed for the effect to be considered clinically relevant . For theWe recognize some limitations of this study. First, our sample size was rather small. The response rate for the re-test remained low (~ 45%), meaning that a relatively small number of participants were investigated. The reasons why some subjects did not respond to the second KOOS questionnaire remain unknown. Nevertheless, according to the Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN) group , the samThis research effort produced an appropriately translated and culturally adapted version of KOOS. The Finnish version of KOOS is a reliable and valid measure that can be applied as a self-report and disease-specific questionnaire for use in middle-aged patients with knee injuries. The responsiveness of the Finnish version of KOOS in larger groups of patients with knee complaints remains to be tested.Additional file 1:The back-translation of the Finnish version of the KOOS questionnaire “KOOS KNEE QUESTIONNAIRE”. (PDF 87 kb)


This was true for both the TQ and the NPAD. This effect was of transient nature though: the TQ score went back to its baseline level after a follow-up period of 12 weeks. Based on our results we recommend that in studies that investigate tinnitus treatments targeting somatosensory afferents patients should be stratified according to somatic co-morbidities and somatosensory influence on the tinnitus percept.While brain stimulation techniques have been examined as treatment options for chronic tinnitus for many years, they have recently been extended to multimodal treatment approaches. As chronic tinnitus is often accompanied by comorbid muscular tension in the neck and back, we performed a one-arm pilot study to explore the feasibility of a new multimodal treatment approach. In detail, repetitive peripheral magnetic stimulation (rPMS) of the back was performed before and after each session of repetitive transcranial magnetic stimulation (rTMS) of the brain. Data of 41 patients were analyzed, all of which were treated with ten sessions of rTMS of the left prefrontal and left temporoparietal cortex followed by rPMS of the neck and back muscles. Tinnitus severity was measured using the tinnitus questionnaire (TQ). Neck pain was assessed using the neck pain and disability scale (NPAD). The new treatment approach was feasible and well accepted by the majority of patients. However, the overall patient group did not improve significantly in either of the questionnaires. If patients were divided in different subgroups depending on whether they were suffering from neck pain or somatosensory tinnitus, explorative www.clinicaltrials.gov, NCT02306447.Clinical trial registration:  Chronic subjective tinnitus is a very heterogeneous condition with respect to its causes, clinical characteristics and the emotional distress perceived by a patient. Therefore, it has been suggested that there exist various subtypes of tinnitus which might respond to different treatment approaches . Inclusion criteria for study participation were age between 18 and 80 years and presence of chronic subjective tinnitus for at least 6 months. Exclusion criteria were objective tinnitus, a treatable cause of tinnitus and the involvement in other treatments for tinnitus at the same time. Furthermore, patients with clinically relevant psychiatric comorbidities, alcohol or drug abuse, acute neck or back pain, neck or back pain with unknown etiology as well as unstable internal or neurological comorbidities were excluded. In addition, general exclusion criteria for rTMS or rPMS stimulation applied . Patients were recruited during routine clinical tinnitus consultations. All data were collected at the Department of Psychiatry and Psychotherapy, University of Regensburg between September 2014 and April 2016 (last follow-up visit). All research participants provided written, informed consent to participate in this research as well as for the data to be used for analysis and publication. Data were gathered and analyzed within the framework of the Tinnitus Research Initiative database , week 2 , week 4 and week 12 . Tinnitus severity was assessed using the German version of the Tinnitus Questionnaire . Furthermore the change in the neck pain and disability scale (NPAD) from baseline to week 2 was analyzed.The present clinical trial was designed as a one-arm open-label proof of concept study. Therefore, all patients underwent the same treatment procedures during which they were treated in 10 sessions on 10 consecutive working days with a break over the weekend. Each treatment session consisted of four parts which were applied successively without break in between  and (3) were done at a stimulation intensity of 110% resting motor threshold using a Medtronic MagPro X100 stimulator  and a 70 mm figure-of-eight coil. The temporo-parietal cortex was localized using the 10–20 system: The coil was placed between the temporal (T3) and parietal (P3) EEG electrode sites. The DLFPC was targeted by centring the TMS coil 6 cm anterior from the part of the motor cortex which had been used for defining the motor threshold  t-tests with the within-subjects factor measurement time point. To test for changes in tinnitus severity scores, MDI and WHO-QoL over all four measurement time points an analysis of variance (ANOVA) with the within-subjects factor measurement time point  was calculated for all questionnaires and rating scales. For the ANOVAs, the sphericity of data was checked with Mauchly Tests  was used. Four missing values were replaced by using a last observation carried forward (LOCF) procedure: The TQ score of one patient was missing for the final visit and the score for the rating scale “annoying” was missing for another patient for week 2. Furthermore, the MDI score for week 2 was missing for one patient and for week 12 for another patient. Recently, we could demonstrate that the LOCF method induces no statistical bias in comparison to linear mixed effects analyses for missing data <10%  and/or from somatosensory tinnitus , or having your arms/hands or head touched, affect your tinnitus?”), based on their answers in the Tinnitus Sample Case History Questionnaire . Five further patients dropped out of the study after the treatment phase during the follow-up phase, all for unknown reasons. One of them had described a transient loudening of the tinnitus before. All in all, data of 41 patients were left to be statistically analyzed  reported transient headaches and one patient (2.5%) reported headache which was still present at week 12. Furthermore, six patients (14.6%) complained of an increase in tinnitus loudness. In two of them, this increase was still present at week 12. Additionally, one patient reported a transient pain in his fingers.t(40) = −0.27; p = 0.787; d = 0.04]. The ANOVAs testing for changes in the different questionnaire scores and rating scales over all measurement time points were not significant  = 1.80; p = 0.081; d = 0.31).Concerning the primary outcome (change of the TQ score from baseline to week 12), no significant treatment effect was observed . For the three post hoc t-tests, the Bonferroni-corrected significance level has to be set at 0.016. Post hoc t-tests of the mean NPAD differences from baseline to week 2 revealed that patients with both neck pain and somatosensory tinnitus showed more NPAD change  than patients with neck pain only . This difference was marginally significant . Patients with both conditions also showed significantly more NPAD change than patients with neither condition . There was no significant difference between the group with neither condition and the group with neck pain only . See Figure F = 15.73, p < 0.001; eta2 = 0.022]: patients without neck pain or somatosensory tinnitus scored lower on the NPAD than the other two patient groups. If the change of the TQ score from baseline to week 2 was analyzed, there was also a significant time*group interaction effect . Again, post-hoc t-tests of the mean TQ differences from baseline to week 2  revealed that the group with both conditions  was significantly different from the group suffering from neither condition  and different by trend from the group suffering from neck pain only . There was no significant difference between the group with neither condition and the group with neck pain only . Again, the main effect “group” was significant : patients without neck pain or somatosensory tinnitus scored lower on the TQ than the other two patient groups. If the TQ changes of all three subgroups were compared over all four measurement time points, the ANOVA revealed no significant time*group interaction effect . There was no significant main effect of time  but a significant main effect of group . See Figure If the patients with/without neck pain and/ or somatosensory tinnitus were compared, the interaction effect timeThis is the first study to report combined rTMS and rPMS for the treatment of patients suffering from chronic subjective tinnitus. As it was designed as a pilot study, there are some weaknesses which should be kept in mind when interpreting the results. First, in order to examine the feasibility of the combined treatment, a one-arm trial with no control group was chosen. Second, we chose a well-studied standard rTMS protocol in order to combine it with rPMS treatment. This standard rTMS protocol consisted of left-hemispherical treatment and did not account for tinnitus laterality. The question if and how tinnitus laterality should be considered for the choice of the “right” rTMS treatment protocol has partly been examined for unilateral tinnitus  or neck pain (as measured using the NPAD). This outcome is worse than results of previous studies examining combined frontal plus temporal rTMS stimulation protocols (e.g., Kleinjung et al., Nonetheless, a reduction of the TQ score of nearly 6 points from baseline to week 2 is rather large as compared to other rTMS studies. For example, Langguth et al.  reportedImportantly, the subgroups also differed with respect to the treatment outcome concerning neck pain: patients with both neck pain and somatosensory tinnitus improved with respect to the NPAD score while patients with neck pain only did not. All in all, this suggests that tinnitus patients with both conditions might represent a subgroup of patients for which combined rPMS and rTMS might be a promising treatment approach. There are different possible explanations for these findings. There are studies backing the hypothesis that an improvement of muscle tension leads to an improvement of tinnitus severity (Biesinger et al., This result emphasizes the relevance of individualized treatment for tinnitus patients. Tinnitus should be understood as a symptom with diverse causes and variable subgroups all of which might benefit from different treatment approaches (Landgrebe et al., For electromagnetic stimulation, individual differences in the response to different central and peripheral stimulation techniques have already been demonstrated in the past (Vanneste et al., BL and MS conceived the idea of the study. VV, PK, and TP contributed to data acquisition. AL analyzed the data and drafted the manuscript. All authors contributed to the interpretation of the result and revised the manuscript. All authors approved its final version. The authors declare no competing financial interests with respect to the study.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.