Topical treatment of chemotherapy-induced peripheral neuropathy (CIPN) with high-concentration (179 mg) capsaicin patch in breast cancer patients - results of the QUCIP study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) following oral or intravenous chemotherapy often results in neuropathic pain, accompanied by symptoms such tingling, burning and hypersensitivity to stimuli, with a notable decline in quality of life (QoL). Effective therapies for CIPN are lacking, with a high demand for analgesics to address this issue. The QUCIP study aimed to assess the effectiveness of high concentration (179 mg) capsaicin patch (HCCP) in alleviating neuropathic pain and associated symptoms in breast cancer patients with confirmed CIPN. Methods: QUCIP is a prospective, multi-center observational study spanning 36 weeks with up to three HCCP treatments. Initial treatment (visit V0) was followed by two telephone contacts (T1, T2) and subsequent face-to-face visits every 12 weeks or upon retreatment (visits V1-V3). 73 female patients with painful CIPN post neoadjuvant/adjuvant breast cancer therapy were enrolled. Primary endpoint was the reduction of neuropathic pain symptom score (painDETECT®). Secondary endpoints included improvements in CIPN-specific QoL (QLQ-CIPN20), reductions in pain intensity (numeric pain rating scale, NPRS), and achievement of ≥ 30% and ≥ 50% pain reduction. Results: Median age was 61 years, with 52.0% of patients experiencing peripheral neuropathic pain for > 1 year (> 2 years: 34.2%). The painDETECT® score significantly decreased from baseline (19.71 ± 4.69) to 15.80 ± 6.20 after initial treatment (p < 0.0001) and continued to decrease at follow-up visits. The NPRS indicated significant pain intensity reduction at each time point, particularly pronounced in patients receiving three HCCP treatments. Clinically significant pain relief of ≥ 30% increased from 25.0% at week 4 (T2) to 36.2%, 43.5%, and 40.0% at weeks 12 (V1), 24 (V2), and 36 (V3), respectively. The percentage of patients achieving pain relief of ≥ 50% increased from 14.7% at T2 to 15.5%, 21.7% and 32.5% at V1, V2 and V3, respectively. Patients further reported a significant improvement in their CIPN-related QoL throughout the study. Adverse drug reactions (ADRs) mainly included application site reactions. Conclusion: In this study, HCCP shows benefit in managing CIPN in real-world settings. The data demonstrate a sustained and progressive reduction in neuropathic pain and symptomatology, confirming the clinical benefit of repeated treatment observed in former clinical trials. HCCP treatment has also the potential to significantly improve the QoL associated with CIPN. The safety profile of HCCP was confirmed, supporting its use in clinical practice.

Sex and age-related patterns in pediatric primary headaches: observations from an outpatient headache clinic.

Background: Age reportedly affects headache prevalence differently in boys and girls. However, little empirical data exists regarding pediatric headache prevalence and headache-related burden in children and adolescents according to age and sex. In the present study, we considered age and sex while evaluating the distribution, characteristics, and impairment of primary headache disorders at a pediatric headache center in Germany. Methods: Medical records of children and adolescents attending the headache clinic of the Interdisciplinary Pain Center of the Carl Gustav Carus University Hospital in Dresden during the period 2015-2022 were retrospectively grouped and analyzed depending on age (< or ≥14 years) and sex. Results: The study population consisted of 652 children and adolescents, aged between 3 and 18 years. Almost two-thirds of the patients (≈60%) were females, and almost two-thirds of these females (58%) were ≥14 years of age. Generally, the most prevalent headache diagnoses as defined by the International Classification of Headache Disorders 3rd edition were episodic migraine without aura and the combination of tension-type headache and episodic migraine with or without aura i.e., mixed-type headache (each ≈27%). In the younger group (<14 years), the mixed-type headache was the most prevalent in girls (28.6%), whereas, for boys, episodic migraine without aura was the most prevalent headache diagnosis (47.4%). In the older group (≥14 years), the mixed-type headache continued to be the most prevalent for girls (30%), and it became the most prevalent for boys (26.3%). Before the age of 14, about 16% of children were severely affected by their headaches. After the age of 14, this proportion increased to roughly one-third (33%) of adolescents, driven mainly by teenage girls (26%) who were severely affected by their headaches. Furthermore, the prevalence of comorbidities was significantly higher among girls (67%), particularly in the adolescent group (74%). Conclusions: Our data shows that headache disorders in a specialized pediatric clinic impose a significant burden, especially among teenage girls indicating high therapy needs. Enhancing awareness of early diagnosis and preventive care is crucial to mitigate the development of chronic headaches, and mitigate their adverse effects on life quality and educational capability.

Evidence-based and Patient-centered Indication for Knee Arthroplasty - Update of the Guideline. / Evidenzbasierte und patientenorientierte Indikationsstellung zur Knieendoprothese ­ Update der Leitlinie.

Knee arthroplasty is one of the most frequently performed operations in Germany, with approximately 170000 procedures per year. It is therefore essential that physicians should adhere to an appropriate, and patient-centered indication process. The updated guideline indication criteria for knee arthroplasty (EKIT-Knee) contain recommendations, which are based on current evidence and agreed upon by a broad consensus panel. For practical use, the checklist has also been updated.For this guideline update, a systematic literature research was conducted in order to analyse (inter-)national guidelines and systematic reviews focusing on osteoarthritis of the knee and knee arthroplasty, to answer clinically relevant questions on diagnostic, predictors of outcome, risk factors and contraindications.Knee arthroplasty should solely be performed in patients with radiologically proven moderate or severe osteoarthritis of the knee (Kellgren-Lawrence grade 3 or 4), after previous non-surgical treatment for at least three months, in patients with high subjective burden with regard to knee-related complaints and after exclusion of possible contraindications (infection, comorbidities, BMI ≥ 40 kg/m2). Modifiable risk factors (such as smoking, diabetes mellitus, anaemia) should be addressed and optimised in advance. After meeting current guideline indications, a shared decision-making process between patients and surgeons is recommended, in order to maintain high quality surgical management of patients with osteoarthritis of the knee.The update of the S2k-guideline was expanded to include unicondylar knee arthroplasty, the preoperative optimisation of modifiable risk factors was added and the main indication criteria were specified.

[Booster treatments in interdisciplinary multimodal pain therapy : Preparing structural and process parameters for the implementation of cross-sectoral booster treatments]. / Boosterbehandlungen in der interdisziplinären multimodalen Schmerztherapie : Vorbereitung von Struktur- und Prozessparametern zur Umsetzung von sektorenübergreifenden Boosterbehandlungen.

Interdisciplinary multimodal pain therapy (IMPT) is an established procedure in the treatment of chronic pain. In daily practice, many institutions regard so-called booster units as an integral part of IMPT. However, no consensual recommendations and evidence for booster concepts are available to date. This article uses the results of a discussion between clinical experts in the field of IMPT at the German Pain Congress in 2022 in order to show the status quo in care. It has been shown that currently applied booster offers vary greatly in terms of time intervals, intensities, therapy content and patient selection and that there is a need for structural and process parameters for the implementation of cross-sectoral booster treatments. In conclusion, the authors outline how the development of these parameters will be planned as an expert consensus with the participation of interested institutions and the inclusion of the patient perspective and offer opportunities for participation in this process.

[Self-efficacy expectation as a central concept in interdisciplinary multimodal pain therapy : Conceptual horizon, implementation, recording and limits]. / Selbstwirksamkeitserwartung als zentrales Konzept in der interdisziplinären multimodalen Schmerztherapie : Begriffshorizont, Umsetzung, Erfassung und Grenzen.

The concept of self-efficacy expectation shows high relevance for interdisciplinary multimodal pain therapy (IMST) aimed at activity and self-regulation due to its theoretical embedding and empirical correlations to the experience of pain. Several issues limit this potential: At the level of the construct definition, there are ambiguities and overlaps with other concepts. A pain-specific transfer to IMST has not yet been performed. With the help of existing instruments, only a small part of what an IMST can achieve in terms of increasing pain-specific competence seems to be detectable. In perspective, a clarification of terms by including patients and the conception of a questionnaire based on this is indicated.

[Gender-specific results of the Dresden children and adolescents headache program DreKiP]. / Geschlechtsspezifische Ergebnisse des Dresdner Kinder- und Jugendkopfschmerzprogrammes DreKiP.

BACKGROUND: Girls and women are more frequently affected by headache than boys and men. The influence of gender on the effectiveness of headache therapies has so far been hardly investigated. We examined gender differences in the outpatient multimodal Dresden Child and Adolescent Headache Program DreKiP. METHODS: We treated 140 patients with primary headache in a 15-hour structured group program. At baseline (T0) and six (T1) and twelve months (T2) after the end of the program, data on headache-related limitation of daily activities (PedMIDAS) as well as headache frequency, intensity, and pain-related disability (P-PDI) were collected. Retrospectively, these data were analyzed separately for girls and boys. RESULTS: For 91 patients (9-19 years, median = 15; 71.4 % female) data were available for at least two measurement time points. Girls showed significantly higher headache frequency than boys at all time points (median headache days/last three months at T0: ♀ 43, ♂ 20; T1: ♀ 32, ♂ 12; T2: ♀ 28, ♂ 9) as well as numerically higher headache-related limitation of daily life. There were significant effects over time with a decrease in headache frequency (F (2.88) = 5.862; p = 0.004) and improvement in daily functioning (F (2.92) = 5.340; p = 0.006). There was no gender-specific treatment response. DISCUSSION: The DreKiP therapy shows effects in girls and boys with primary headache. Higher headache frequencies and everyday life restrictions in girls may have hormonal but also psychosocial causes and should be addressed in educational measures.

[Emotional competence of patients with chronic pain : A self- and third-party assessment]. / Emotionale Kompetenzen bei Menschen mit chronifizierten Schmerzen : Ein Selbst- und Fremdbild.

RESEARCH QUESTION: The aim of the study is to assess the status quo of emotional competence in people with chronic pain. How do patients experience themselves regarding to their ability to perceive, express, and regulate emotions? And does this assessment coincide with the assessment of emotional competence (EC) by mental health professionals? METHODS: The study took place in the context of interdisciplinary multimodal pain therapy at an outpatient clinic in N = 184 adult German-speaking individuals with non-cancer-related chronic pain. EC was assessed at the end of therapy using the self- and third-party assessment scales of the Emotional Competence Questionnaire. The external assessment was performed by the mental health team. Standard scores were created using the norm sample provided by questionnaires. These were analyzed descriptively and inferentially. RESULTS: Self-perceived EC was average (Mself_total = 99.31; SD = 7.78). The mental health professionals predominantly rated the emotional competence of the patients significantly lower (Mexternal_total = 94,70; SD = 7,81; F(1.179) = 35,73; p < 0.001; η2 = 0.17). Emotional expressivity, as a component of EC, was externally rated as below average (Mexpressivity_external = 89.14, SD = 10.33). DISCUSSION: Patients with chronic pain rate themselves as unimpaired in terms of their daily emotional awareness, expression, and regulation abilities. At the same time, mental health professionals rate these same individuals as significantly less emotionally competent. The question remains open as to what extent the divergent assessments can be explained by assessment bias.

[Emotions in chronic pain : Changes in the course of day clinic interdisciplinary multimodal pain therapy]. / Emotionen bei chronifiziertem Schmerz : Veränderungen im Verlauf einer tagesklinischen interdisziplinären multimodalen Schmerztherapie.

RESEARCH QUESTION: The present study examined the extent to which emotional experience and emotional competence (EC) change in people with chronic pain during interdisciplinary multimodal pain treatment (IMPT). METHODS: The study included N = 184 adult German-speaking individuals with non-cancer-related chronic pain. They completed a day clinic IMPT. The frequency of specific emotions (anger, etc.) and EC was assessed at three measurement time points using the Questionnaire for Emotion-Specific Self-Assessment of Emotional Competencies (ERSQ-ES) and the Emotional Competency Questionnaire (ECQ). The course results were analyzed descriptively, inferentially, and using linear regression. RESULTS: Positive emotions were experienced more frequently (effect size r = 0.40; p < 0.001) and negative emotions less frequently (r = 0.39, p < 0.001) at end of therapy. The experience of anger decreased particularly strongly (r = 0.52; p < 0.001). Self-assessed EC did not change during the IMPT (χ2ECQ_total (2) = 0.09; p = 0.956). EC largely explained the variance in the frequency experience of positive (R2 = 0.468) and negative emotions (R2 = 0.390). DISCUSSION: Improvements in patient-reported frequencies of positive and negative emotions during IMPT were demonstrated. Further research should validate these results using a control group. Even though no explicit increase in competence was perceivable for the studied subjects, EC had a high predictive value for emotion frequency. Future therapy designs and evaluations should focus more on changes of emotional experience.

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches.

Objective: Headache prevalence among children and adolescents has increased over the last few years. Evidence-based treatment options for pediatric headaches remain limited. Research suggests a positive influence of odors on pain and mood. We investigated the effect of repeated exposure to odors on pain perception, headache-related disability, and olfactory function in children and adolescents with primary headaches. Methods: Eighty patients with migraine or tension-type headache (mean 13.1 ± 3.29 years) participated, of whom 40 underwent daily olfactory training with individually selected pleasant odors for 3 months and 40 received state-of-the-art outpatient therapy as a control group. At baseline and after a 3-month follow-up, olfactory function [odor threshold; odor discrimination; odor identification; comprehensive Threshold, Discrimination, Identification (TDI) score], mechanical detection and pain threshold (quantitative sensory testing), electrical pain threshold, patient-reported outcomes on headache-related disability [Pediatric Migraine Disability Assessment (PedMIDAS)], pain disability [Pediatric Pain Disability Index (P-PDI)], and headache frequency were assessed. Results: Training with odors significantly increased the electrical pain threshold compared to the control group (U = 470.000; z = -3.177; p = 0.001). Additionally, olfactory training significantly increased the olfactory function (TDI score [t(39) = -2.851; p = 0.007], in particular, olfactory threshold, compared to controls (U = 530.500; z = -2.647; p = 0.008). Headache frequency, PedMIDAS, and P-PDI decreased significantly in both groups without a group difference. Conclusions: Exposure to odors has a positive effect on olfactory function and pain threshold in children and adolescents with primary headaches. Increased electrical pain thresholds might reduce sensitization for pain in patients with frequent headaches. The additional favorable effect on headache disability without relevant side effects underlines the potential of olfactory training as valuable nonpharmacological therapy in pediatric headaches.

Functional improvement in children and adolescents with primary headache after an interdisciplinary multimodal therapy program: the DreKiP study.

BACKGROUND: More than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing. METHODS: One hundred eleven patients with frequent migraine and/or tension type headache were treated in a 15 hour group program in afternoons, parallel with school, parents received 7 hours of therapy. At the beginning of the program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were prospectively collected to investigate the effects of the therapy. RESULTS: Seventy-five patients (9-19 years, median = 14; 66.7% female) and their parents provided patient reported outcome measures showing at T1 (65 patients) and T2 (47 patients) reduced headache frequency (last 3 months headache days median T0: 30 days; T1: 18 days, reduction of median 12 days since T0; T2: 13 days, reduction of median 17 days since T0). Linear mixed models revealed significant reduction (T0/T1 p = 0,002; T0/T2 p = 0,001). Reduced headache disability has been reported at T1 and T2 (PedMidas median T0 = 30, T1 = 15, T2 = 7; p < 0,001, p < 0,001 respectively). Follow up data of a subgroup of patients 24 months after the treatment point to sustainable effects. CONCLUSIONS: The interdisciplinary multimodal headache therapy program DreKiP reduces headache frequency and headache related disability significantly 6-12 months following its completion. TRIAL REGISTRATION: DRKS00027523, retrospectively registered.

Interictal osmophobia is associated with longer migraine disease duration.

BACKGROUND: Sensitization to sensory stimuli is an essential feature of migraine attacks. The relationship between the clinical course of migraine and increased sensitivity to olfactory stimuli has been little studied so far. METHODS: We analyzed the frequency and quality of osmophobia depending on the phase of migraine in patients with episodic and chronic migraine treated in an tertiary headache center with regard to gender, age, medical history and migraine disability assessment score (MIDAS). Standardized diagnostic questions were used for the assessment of osmophobia. RESULTS: In our cross-sectional investigation (n = 113), 38.1% of the patients showed an increased preictal hypersensitivity to odors, whereas 61.9% described ictal and 31.9% interictal hypersensitivity to odors, odor-triggered migraine was described in 30.1%. Median migraine disease duration has been statistically significantly longer in patients who suffered from interictal hypersensitivity to odors (28.5 years vs. 20 years; p = 0.012). There was a significant correlation between interictal hypersensitivity and higher age (54.50 vs. 45; p = 0.015). Patients with higher migraine disability in MIDAS experienced more frequently preictal and interictal olfactory sensitization and odor triggered migraine attacks. CONCLUSIONS: In patients with longer migraine disease duration and higher migraine-related impairment, osmophobia was more frequently observed. These results might support the hypothesis of increasing sensitization with increasing burden of migraine.

C-tactile touch perception in patients with chronic pain disorders.

INTRODUCTION: Slow brushing over the skin activates C-tactile nerve fibers that transmit pleasant tactile experiences in healthy subjects, leading to an inverted U-shaped velocity dependence of ratings: C-tactile optimal stroking stimulations are rated as more pleasant than slower or faster stimulations. Chronic pain diseases such as postherpetic neuralgia (PHN) and complex regional pain syndrome show altered C-fiber innervation density, sensory loss, and pain sensitization. OBJECTIVES: We aimed to investigate whether C-tactile function is affected in painful conditions. METHODS: We assessed psychophysically C-tactile function and sensory perception thresholds in 16 patients with PHN, 19 patients with complex regional pain syndrome, and 22 healthy controls. RESULTS: Assessment of C-tactile function showed a significantly altered perceived pleasantness of CT stimulation between healthy controls and patients with chronic pain. In specific, tactile stimulation was perceived less pleasant on the affected and contralateral side when compared with controls. In patients with PHN, velocity-dependent pleasantness ratings could not be obtained, suggesting highly impaired C-tactile function with functional loss of pleasant touch perception. CONCLUSIONS: In conclusion, this is the first report of impaired C-tactile function in patients with PHN. Reduced pleasantness resulting from gentle touch can reflect defective C-fiber function or result from central nervous system effects in a chronic pain state.

Exposure to Odors Increases Pain Threshold in Chronic Low Back Pain Patients.

OBJECTIVES: Structured exposure to odors is an acknowledged therapy in patients with smell loss but has also been shown to be effective in depression. The latter might rely on connections between olfactory and emotional structures, suggesting possible effects of a similar approach in pain patients. Based on neuroanatomy, there are several interfaces between the "pain matrix" and olfactory system, such as the limbic system, hypothalamus, and mediodorsal thalamus. We aimed to investigate whether structured exposure to odors may impact perceived pain in patients with chronic low back pain. DESIGN: Randomized controlled parallel-group design. Subjects were tested on two occasions, at baseline and after four weeks. SETTING: Ambulatory. SUBJECTS: Forty-two patients with chronic low back pain. METHODS: For all patients, olfactory function (using the "Sniffin'Sticks" test kit), detection, and pain thresholds for cutaneous electrical stimuli (applied to the forearm) were tested at baseline and after four weeks. Twenty-eight patients exposed themselves to four odors (rose, vanilla, chocolate, peach) every two hours over a period of four weeks (training group). Control patients (N = 14) underwent no such "olfactory training" (nontraining group). RESULTS: Pain thresholds were significantly increased in patients who performed olfactory training compared with patients who did not train with odors. Detection thresholds and olfactory function remained unchanged. CONCLUSIONS: The present results indicate that regular exposure to odors increases pain thresholds in patients with chronic back pain and could be useful for general pain control in these patients. Furthermore, olfactory training in chronic pain patients might help to reduce chronification of pain by desensitization.

C-tactile touch perception in migraineurs - a case-control study.

BACKGROUND: Migraine is characterized by sensory hypersensitivity and habituation deficits. Slow brushing over the skin activates C-tactile nerve fibers, which mediate pleasant touch and analgesic effects in healthy subjects. As this function is altered in painful conditions, we aimed to examine whether the C-tactile processing is disrupted in migraines. METHODS: To psychophysically assess C-tactile function, we applied optimal and suboptimal C-tactile stroking stimuli on the dorsal forearm (body reference area) and the trigeminally innervated skin of 52 interictal migraineurs and 52 matched healthy controls. For habituation testing, 60 repeated C-tactile optimal stimuli were presented in both test areas. The participants rated each stimulus on a visual analogue scale by intensity, pleasantness, and painfulness. RESULTS: Regarding C-tactile function, migraineurs showed unphysiological rating patterns but no significantly different pleasantness ratings than controls. During repeated stimulation, controls showed stable pleasantness ratings while migraineurs' ratings decreased, especially in those experiencing tactile allodynia during headaches. Migraineurs taking triptans responded like controls. CONCLUSION: The C-tactile function of migraineurs is subclinically altered. Repeated C-tactile stimulation leads to altered habituation but differs from previous work by the direction of the changes. Although the pathophysiology remains unknown, causative mechanisms could include central and peripheral neuronal sensitization, tactile allodynia and hedonic stimulus attributions.

The prevalence of headache in German pupils of different ages and school types.

BACKGROUND/OBJECTIVE: Headache in pupils is underestimated and has a negative impact on learning and life. The aim of this study was to investigate headache prevalence and its collateral effects, in pupils of different ages and school types in a German city. METHODS: Anonymized questionnaires were distributed to 5419 pupils attending primary and secondary schools. Demographics, headache frequency, analgesic use, school absence and, for secondary school children, data on lifestyle were collected. RESULTS: The questionnaire was returned by 2706 children (49%), 1362 (50.3%) girls, 1344 (49.7%) boys. Of these, 36.6% indicated a frequency of 1, and 31.5% a frequency of ≥ 2 headache days per month within the last 3 months. Headache prevalence increased with school grade, age and secondary school type: 63.6%, 67.2% and 79.5% for primary school children, pupils attending 8-year and pupils attending 6-year secondary schools, respectively. With secondary school level I certificates, pupils are prepared for general professional training in 6 years. Secondary school level II results, after 8 years of training, in university entrance level II certificates, which are the precondition for university studies. Girls reported significantly more headache than boys (73% vs. 63.1%). A significant relationship has been observed between headache frequency and school absence and between headache intensity and headache frequency. Of pupils with headache at least twice a month, 48.1% reported analgesic intake. Ibuprofen (49.1%) and paracetamol (32.8%) were the most frequently used analgesics. Of those pupils with headache ≥ 2 days/month, 68.3% did not have a specific headache diagnosis. Concomitant diseases and regular drug intake, analgesic intake for another reason than headache, caffeine consumption and lack of participation in sports were positively correlated with headache. CONCLUSIONS: The majority of pupils suffer from headache at least once a month. Since frequent headache results in educational and social limitations, pupils at risk should be identified and referred to headache education programs. Efforts are needed to improve the management of juvenile headache patients.

Sleep quality with WHO Step III opioid use for cancer pain.

OBJECTIVE: Sleep is often disturbed in patients with advanced cancer. There is limited knowledge about sleep in patients with cancer treated with strong opioids. This study examines sleep quality in patients with advanced cancer who are treated with a WHO Step III opioid for pain. METHODS: An international, multicentre, cross-sectional study with 604 adult patients with cancer pain using WHO Step III opioids. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) global score (range; 0-21; score >5 indicates poor sleep). PSQI includes sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medications and daytime dysfunction. Pain and quality of life were assessed by Brief Pain Inventory and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core30. RESULTS: The median age was 62 years, 42% were female, mean Karnofsky performance score (KPS) was 62.5 (±14.2) and mean oral daily morphine equivalent dose was 303 mg/24 hours (±543.8 mg). The mean PSQI global score was 8.8 (±4.2) (range 0-20). Seventy-eight per cent were poor sleepers. All PSQI components were affected, and 44% reported trouble sleeping caused by pain. In the multiple regression model, predictors of PSQI global scores were pain intensity, emotional function, constipation, financial difficulties and KPS (adjusted R2=0.21). CONCLUSION: The majority (78%) of these patients with cancer treated with Step III opioids experienced poor sleep quality. Pain intensity, emotional function, constipation, financial difficulties and KPS predicted poor PSQI global scores. The clinical implication is that healthcare personnel should routinely assess and treat sleep disturbance in patients with advanced cancer disease.

Developing a core outcome domain set to assessing effectiveness of interdisciplinary multimodal pain therapy: the VAPAIN consensus statement on core outcome domains.

Interdisciplinary multimodal pain therapy (IMPT) is a biopsychosocial treatment approach for patients with chronic pain that comprises at least psychological and physiotherapeutic interventions. Core outcome sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcome domains, and measurement instruments in clinical trials, to make trial results meaningful, to pool trial results, and to allow indirect comparison between interventions. The objective of this study was to develop a COS of patient-relevant outcome domains for chronic pain in IMPT clinical trials. An international, multiprofessional panel (patient representatives [n = 5], physicians specialized in pain medicine [n = 5], physiotherapists [n = 5], clinical psychologists [n = 5], and methodological researchers [n = 5]) was recruited for a 3-stage consensus study, which consisted of a mixed-method approach comprising an exploratory systematic review, a preparing online survey to identify important outcome domains, a face-to-face consensus meeting to agree on COS domains, and a second online survey (Delphi) establishing agreement on definitions for the domains included. The panel agreed on the following 8 domains to be included into the COS for IMPT: pain intensity, pain frequency, physical activity, emotional wellbeing, satisfaction with social roles and activities, productivity (paid and unpaid, at home and at work, inclusive presentism and absenteeism), health-related quality of life, and patient's perception of treatment goal achievement. The complexity of chronic pain in a biopsychosocial context is reflected in the current recommendation and includes physical, mental, and social outcomes. In a subsequent step, measurement instruments will be identified via systematic reviews.

Indication Criteria for Total Knee Arthroplasty in Patients with Osteoarthritis - A Multi-perspective Consensus Study.

Background and Objectives Knee osteoarthritis (OA) is a significant public health burden. Rates of total knee arthroplasty (TKA) in OA vary substantially between geographical regions, most likely due to the lack of standardised indication criteria. We set out to define indication criteria for the German healthcare system for TKA in patients with knee OA, on the basis of best evidence and transparent multi-stakeholder consensus. Methods We undertook a complex mixed methods study, including an iterative process of systematic appraisal of existing evidence, Delphi consensus methods and stakeholder conferences. We established a consensus panel representing key German national societies of healthcare providers (orthopaedic surgeons, rheumatologists, pain physicians, psychologists, physiotherapists), payers, and patient representatives. A priori defined consensus criteria were at least 70% agreement and less than 20% disagreement among the consensus panel. Agreement was sought for (1) core indication criteria defined as criteria that must be met to consider TKA in a normal patient with knee OA, (2) additional (not obligatory) indication criteria, (3) absolute contraindication criteria that generally prohibit TKA, and (4) risk factors that do not prohibit TKA, but usually do not lead to a recommendation for TKA. Results The following 5 core indication criteria were agreed within the panel: 1. intermittent (several times per week) or constant knee pain for at least 3 - 6 months; 2. radiological confirmation of structural knee damage (osteoarthritis, osteonecrosis); 3. inadequate response to conservative treatment, including pharmacological and non-pharmacological treatment for at least 3 - 6 months; 4. adverse impact of knee disease on patient's quality of life for at least 3 - 6 months; 5. patient-reported suffering/impairment due to knee disease. Additional indication criteria, contraindication criteria, and risk factors for adverse outcome were also agreed by a large majority within the multi-perspective stakeholder panel. Conclusion The defined indication criteria constitute a prerequisite for appropriate provision of TKA in patients with knee OA in Germany. In eligible patients, shared-decision making should eventually determine if TKA is performed or not. The next important steps are the implementation of the defined indication criteria, and the prospective investigation of predictors of success or failure of TKA in the context of routine care provision in Germany.

[Patient first - The impact of characteristics of target populations on decisions about therapy effectiveness of complex interventions: Psychological variables to assess effectiveness in interdisciplinary multimodal pain therapy]. / Patient first - Die Bedeutung spezifischer Zielpopulationscharakteristika für die Bewertung von Therapieeffektivität bei komplexen Interventionen: Psychologische Variablen in der Effektivitätsbestimmung interdisziplinärer multimodaler Schmerztherapie.

INTRODUCTION: The assessment of treatment effectiveness in public health settings is ensured by indicators that reflect the changes caused by specific interventions. These indicators are also applied in benchmarking systems. The selection of constructs should be guided by their relevance for affected patients (patient reported outcomes). The interdisciplinary multimodal pain therapy (IMPT) is a complex intervention based on a biopsychosocial understanding of chronic pain. For quality assurance purposes, psychological parameters (depression, general anxiety, health-related quality of life) are included in standardized therapy assessment in pain medicine (KEDOQ), which can also be used for comparative analyses in a benchmarking system. The aim of the present study was to investigate the relevance of depressive symptoms, general anxiety and mental quality of life in patients undergoing IMPT under real life conditions. METHODS: In this retrospective, one-armed and exploratory observational study we used secondary data of a routine documentation of IMST in routine care, applying several variables of the German Pain Questionnaire and the facility's comprehensive basic documentation. 352 participants with IMPT (from 2006 to 2010) were included, and the follow-up was performed over two years with six assessments. Because of statistically heterogeneous characteristics a complex analysis consisting of factor and cluster analyses was applied to build subgroups. These subgroups were explored to identify differences in depressive symptoms (HADS-D), general anxiety (HADS-A), and mental quality of life (SF 36 PSK) at the time of therapy admission and their development estimated by means of effect sizes. Analyses were performed using SPSS 21.0®. RESULTS: Six subgroups were derived and mainly proved to be clinically and psychologically normal, with the exception of one subgroup that consistently showed psychological impairment for all three parameters. The follow-up of the total study population revealed medium or large effects; changes in the subgroups were consistently caused by two subgroups, while the other four showed little or no change. In summary, only a small proportion of the target population (20 %) demonstrated clinically relevant scores in the psychological parameters applied. DISCUSSION: When selecting indicators for quality assurance, the heterogeneity of the target populations as well as conceptual and methodological aspects should be considered. The characteristics of the parameters intended, along with clinical and personal relevance of indicators for patients, should be investigated by specific procedures such as patient surveys and statistical analyses.