@article{LewkowiczWohlbrandtBoettinger2022, author = {Lewkowicz, Daniel and Wohlbrandt, Attila M. and B{\"o}ttinger, Erwin}, title = {Digital therapeutic care apps with decision-support interventions for people with low back pain in Germany}, series = {JMIR mhealth and uhealth}, volume = {10}, journal = {JMIR mhealth and uhealth}, number = {2}, publisher = {JMIR Publications}, address = {Toronto}, issn = {2291-5222}, doi = {10.2196/35042}, pages = {17}, year = {2022}, abstract = {Background: Digital therapeutic care apps provide a new effective and scalable approach for people with nonspecific low back pain (LBP). Digital therapeutic care apps are also driven by personalized decision-support interventions that support the user in self-managing LBP, and may induce prolonged behavior change to reduce the frequency and intensity of pain episodes. However, these therapeutic apps are associated with high attrition rates, and the initial prescription cost is higher than that of face-to-face physiotherapy. In Germany, digital therapeutic care apps are now being reimbursed by statutory health insurance; however, price targets and cost-driving factors for the formation of the reimbursement rate remain unexplored. Objective: The aim of this study was to evaluate the cost-effectiveness of a digital therapeutic care app compared to treatment as usual (TAU) in Germany. We further aimed to explore under which circumstances the reimbursement rate could be modified to consider value-based pricing. Methods: We developed a state-transition Markov model based on a best-practice analysis of prior LBP-related decision-analytic models, and evaluated the cost utility of a digital therapeutic care app compared to TAU in Germany. Based on a 3-year time horizon, we simulated the incremental cost and quality-adjusted life years (QALYs) for people with nonacute LBP from the societal perspective. In the deterministic sensitivity and scenario analyses, we focused on diverging attrition rates and app cost to assess our model's robustness and conditions for changing the reimbursement rate. All costs are reported in Euro (euro1=US \$1.12). Results: Our base case results indicated that the digital therapeutic care strategy led to an incremental cost of euro121.59, but also generated 0.0221 additional QALYs compared to the TAU strategy, with an estimated incremental cost-effectiveness ratio (ICER) of euro5486 per QALY. The sensitivity analysis revealed that the reimbursement rate and the capability of digital therapeutic care to prevent reoccurring LBP episodes have a significant impact on the ICER. At the same time, the other parameters remained unaffected and thus supported the robustness of our model. In the scenario analysis, the different model time horizons and attrition rates strongly influenced the economic outcome. Reducing the cost of the app to euro99 per 3 months or decreasing the app's attrition rate resulted in digital therapeutic care being significantly less costly with more generated QALYs, and is thus considered to be the dominant strategy over TAU. Conclusions: The current reimbursement rate for a digital therapeutic care app in the statutory health insurance can be considered a cost-effective measure compared to TAU. The app's attrition rate and effect on the patient's prolonged behavior change essentially influence the settlement of an appropriate reimbursement rate. Future value-based pricing targets should focus on additional outcome parameters besides pain intensity and functional disability by including attrition rates and the app's long-term effect on quality of life.}, language = {en} } @article{WippertPuertoValenciaDriesslein2022, author = {Wippert, Pia-Maria and Puerto Valencia, Laura and Drießlein, David}, title = {Stress and pain}, series = {Frontiers in medicine}, volume = {9}, journal = {Frontiers in medicine}, publisher = {Frontiers Media}, address = {Lausanne, Schweiz}, issn = {2296-858X}, doi = {10.3389/fmed.2022.828954}, pages = {14}, year = {2022}, abstract = {Introduction: Low back pain (LBP) leads to considerable impairment of quality of life worldwide and is often accompanied by psychosomatic symptoms. Objectives: First, to assess the association between stress and chronic low back pain (CLBP) and its simultaneous appearance with fatigue and depression as a symptom triad. Second, to identify the most predictive stress-related pattern set for CLBP for a 1-year diagnosis. Methods: In a 1-year observational study with four measurement points, a total of 140 volunteers (aged 18-45 years with intermittent pain) were recruited. The primary outcomes were pain [characteristic pain intensity (CPI), subjective pain disability (DISS)], fatigue, and depressive mood. Stress was assessed as chronic stress, perceived stress, effort reward imbalance, life events, and physiological markers [allostatic load index (ALI), hair cortisol concentration (HCC)]. Multiple linear regression models and selection procedures for model shrinkage and variable selection (least absolute shrinkage and selection operator) were applied. Prediction accuracy was calculated by root mean squared error (RMSE) and receiver-operating characteristic curves. Results: There were 110 participants completed the baseline assessments (28.2 7.5 years, 38.1\% female), including HCC, and a further of 46 participants agreed to ALI laboratory measurements. Different stress types were associated with LBP, CLBP, fatigue, and depressive mood and its joint occurrence as a symptom triad at baseline; mainly social-related stress types were of relevance. Work-related stress, such as "excessive demands at work"[b = 0.51 (95\%CI -0.23, 1.25), p = 0.18] played a role for upcoming chronic pain disability. "Social overload" [b = 0.45 (95\%CI -0.06, 0.96), p = 0.080] and "over-commitment at work" [b = 0.28 (95\%CI -0.39, 0.95), p = 0.42] were associated with an upcoming depressive mood within 1-year. Finally, seven psychometric (CPI: RMSE = 12.63; DISS: RMSE = 9.81) and five biomarkers (CPI: RMSE = 12.21; DISS: RMSE = 8.94) could be derived as the most predictive pattern set for a 1-year prediction of CLBP. The biomarker set showed an apparent area under the curve of 0.88 for CPI and 0.99 for DISS. Conclusion: Stress disrupts allostasis and favors the development of chronic pain, fatigue, and depression and the emergence of a "hypocortisolemic symptom triad," whereby the social-related stressors play a significant role. For translational medicine, a predictive pattern set could be derived which enables to diagnose the individuals at higher risk for the upcoming pain disorders and can be used in practice.}, language = {en} } @misc{WippertPuertoValenciaDriesslein2022, author = {Wippert, Pia-Maria and Puerto Valencia, Laura and Drießlein, David}, title = {Stress and pain}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {832}, issn = {1866-8364}, doi = {10.25932/publishup-58804}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-588040}, pages = {14}, year = {2022}, abstract = {Introduction: Low back pain (LBP) leads to considerable impairment of quality of life worldwide and is often accompanied by psychosomatic symptoms. Objectives: First, to assess the association between stress and chronic low back pain (CLBP) and its simultaneous appearance with fatigue and depression as a symptom triad. Second, to identify the most predictive stress-related pattern set for CLBP for a 1-year diagnosis. Methods: In a 1-year observational study with four measurement points, a total of 140 volunteers (aged 18-45 years with intermittent pain) were recruited. The primary outcomes were pain [characteristic pain intensity (CPI), subjective pain disability (DISS)], fatigue, and depressive mood. Stress was assessed as chronic stress, perceived stress, effort reward imbalance, life events, and physiological markers [allostatic load index (ALI), hair cortisol concentration (HCC)]. Multiple linear regression models and selection procedures for model shrinkage and variable selection (least absolute shrinkage and selection operator) were applied. Prediction accuracy was calculated by root mean squared error (RMSE) and receiver-operating characteristic curves. Results: There were 110 participants completed the baseline assessments (28.2 7.5 years, 38.1\% female), including HCC, and a further of 46 participants agreed to ALI laboratory measurements. Different stress types were associated with LBP, CLBP, fatigue, and depressive mood and its joint occurrence as a symptom triad at baseline; mainly social-related stress types were of relevance. Work-related stress, such as "excessive demands at work"[b = 0.51 (95\%CI -0.23, 1.25), p = 0.18] played a role for upcoming chronic pain disability. "Social overload" [b = 0.45 (95\%CI -0.06, 0.96), p = 0.080] and "over-commitment at work" [b = 0.28 (95\%CI -0.39, 0.95), p = 0.42] were associated with an upcoming depressive mood within 1-year. Finally, seven psychometric (CPI: RMSE = 12.63; DISS: RMSE = 9.81) and five biomarkers (CPI: RMSE = 12.21; DISS: RMSE = 8.94) could be derived as the most predictive pattern set for a 1-year prediction of CLBP. The biomarker set showed an apparent area under the curve of 0.88 for CPI and 0.99 for DISS. Conclusion: Stress disrupts allostasis and favors the development of chronic pain, fatigue, and depression and the emergence of a "hypocortisolemic symptom triad," whereby the social-related stressors play a significant role. For translational medicine, a predictive pattern set could be derived which enables to diagnose the individuals at higher risk for the upcoming pain disorders and can be used in practice.}, language = {en} } @article{RowleyEngelKulig2020, author = {Rowley, K. Michael and Engel, Tilman and Kulig, Kornelia}, title = {Trunk and hip muscle activity during the Balance-Dexterity task in persons with and without recurrent low back pain}, series = {Journal of electromyography and kinesiology}, volume = {50}, journal = {Journal of electromyography and kinesiology}, publisher = {Elsevier Science}, address = {Amsterdam}, issn = {1050-6411}, doi = {10.1016/j.jelekin.2019.102378}, pages = {7}, year = {2020}, abstract = {Coordination of the trunk and hips is crucial for successful dynamic balance in many activities of daily living. Persons with recurrent low back pain (rLBP), both while symptomatic and during periods of symptom remission, exhibit dysfunctional muscle activation patterns and coordination of these joints. In a novel dynamic balance task where persons in remission from rLBP exhibit dissociated trunk motion, it is unknown how trunk and hip musculature are coordinated. Activation of hip and trunk muscles were acquired from nineteen persons with and without rLBP during the Balance-Dexterity Task, which involves balancing on one limb while compressing an unstable spring with the other. There were no between-group differences in activation amplitude for any muscle groups tested. In back-healthy control participants, hip and trunk muscle activation amplitudes increased proportionally in response to the added instability of the spring (R = 0.837, p < 0.001). Increases in muscle activation amplitudes in the group in remission from rLBP were not proportional (R = 0.113, p = 0.655). Instead, hip muscle activation in this group was associated with task performance, i.e. dexterous control of the spring (R = 0.676, p = 0.002). These findings highlight atypical coordination of hip and trunk musculature potentially related to task demands in persons with rLBP even during remission from pain.}, language = {en} } @article{PuschmannLinWippert2021, author = {Puschmann, Anne-Katrin and Lin, Chiao-I and Wippert, Pia-Maria}, title = {Sustainability of a motor control exercise intervention}, series = {Frontiers in sports and active living}, volume = {3}, journal = {Frontiers in sports and active living}, publisher = {Frontiers Media}, address = {Lausanne, Schweiz}, issn = {2624-9367}, doi = {10.3389/fspor.2021.659982}, pages = {1 -- 8}, year = {2021}, abstract = {Development of chronic pain after a low back pain episode is associated with increased pain sensitivity, altered pain processing mechanisms and the influence of psychosocial factors. Although there is some evidence that multimodal therapy (such as behavioral or motor control therapy) may be an important therapeutic strategy, its long-term effect on pain reduction and psychosocial load is still unclear. Prospective longitudinal designs providing information about the extent of such possible long-term effects are missing. This study aims to investigate the long-term effects of a homebased uni- and multidisciplinary motor control exercise program on low back pain intensity, disability and psychosocial variables. 14 months after completion of a multicenter study comparing uni- and multidisciplinary exercise interventions, a sample of one study center (n = 154) was assessed once more. Participants filled in questionnaires regarding their low back pain symptoms (characteristic pain intensity and related disability), stress and vital exhaustion (short version of the Maastricht Vital Exhaustion Questionnaire), anxiety and depression experiences (the Hospital and Anxiety Depression Scale), and pain-related cognitions (the Fear Avoidance Beliefs Questionnaire). Repeated measures mixed ANCOVAs were calculated to determine the long-term effects of the interventions on characteristic pain intensity and disability as well as on the psychosocial variables. Fifty four percent of the sub-sample responded to the questionnaires (n = 84). Longitudinal analyses revealed a significant long-term effect of the exercise intervention on pain disability. The multidisciplinary group missed statistical significance yet showed a medium sized long-term effect. The groups did not differ in their changes of the psychosocial variables of interest. There was evidence of long-term effects of the interventions on pain-related disability, but there was no effect on the other variables of interest. This may be partially explained by participant's low comorbidities at baseline. Results are important regarding costless homebased alternatives for back pain patients and prevention tasks. Furthermore, this study closes the gap of missing long-term effect analysis in this field.}, language = {en} } @misc{PuschmannLinWippert2021, author = {Puschmann, Anne-Katrin and Lin, I-Chiao and Wippert, Pia-Maria}, title = {Sustainability of a motor control exercise intervention}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, issn = {1866-8364}, doi = {10.25932/publishup-54408}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-544083}, pages = {1 -- 8}, year = {2021}, abstract = {Development of chronic pain after a low back pain episode is associated with increased pain sensitivity, altered pain processing mechanisms and the influence of psychosocial factors. Although there is some evidence that multimodal therapy (such as behavioral or motor control therapy) may be an important therapeutic strategy, its long-term effect on pain reduction and psychosocial load is still unclear. Prospective longitudinal designs providing information about the extent of such possible long-term effects are missing. This study aims to investigate the long-term effects of a homebased uni- and multidisciplinary motor control exercise program on low back pain intensity, disability and psychosocial variables. 14 months after completion of a multicenter study comparing uni- and multidisciplinary exercise interventions, a sample of one study center (n = 154) was assessed once more. Participants filled in questionnaires regarding their low back pain symptoms (characteristic pain intensity and related disability), stress and vital exhaustion (short version of the Maastricht Vital Exhaustion Questionnaire), anxiety and depression experiences (the Hospital and Anxiety Depression Scale), and pain-related cognitions (the Fear Avoidance Beliefs Questionnaire). Repeated measures mixed ANCOVAs were calculated to determine the long-term effects of the interventions on characteristic pain intensity and disability as well as on the psychosocial variables. Fifty four percent of the sub-sample responded to the questionnaires (n = 84). Longitudinal analyses revealed a significant long-term effect of the exercise intervention on pain disability. The multidisciplinary group missed statistical significance yet showed a medium sized long-term effect. The groups did not differ in their changes of the psychosocial variables of interest. There was evidence of long-term effects of the interventions on pain-related disability, but there was no effect on the other variables of interest. This may be partially explained by participant's low comorbidities at baseline. Results are important regarding costless homebased alternatives for back pain patients and prevention tasks. Furthermore, this study closes the gap of missing long-term effect analysis in this field.}, language = {en} } @misc{MolnarKokEngeletal.2018, author = {Molnar, Marco and Kok, Manor and Engel, Tilman and Kaplic, Hannes and Mayer, Frank and Seel, Thomas}, title = {A method for lower back motion assessment using wearable 6D inertial sensors}, series = {21st International Conference on Information Fusion (FUSION)}, journal = {21st International Conference on Information Fusion (FUSION)}, publisher = {IEEE}, address = {New York}, isbn = {978-0-9964-5276-2}, pages = {799 -- 806}, year = {2018}, abstract = {Low back pain (LBP) is a leading cause of activity limitation. Objective assessment of the spinal motion plays a key role in diagnosis and treatment of LBP. We propose a method that facilitates clinical assessment of lower back motions by means of a wireless inertial sensor network. The sensor units are attached to the right and left side of the lumbar region, the pelvis and the thighs, respectively. Since magnetometers are known to be unreliable in indoor environments, we use only 3D accelerometer and 3D gyroscope readings. Compensation of integration drift in the horizontal plane is achieved by estimating the gyroscope biases from automatically detected initial rest phases. For the estimation of sensor orientations, both a smoothing algorithm and a filtering algorithm are presented. From these orientations, we determine three-dimensional joint angles between the thighs and the pelvis and between the pelvis and the lumbar region. We compare the orientations and joint angles to measurements of an optical motion tracking system that tracks each skin-mounted sensor by means of reflective markers. Eight subjects perform a neutral initial pose, then flexion/extension, lateral flexion, and rotation of the trunk. The root mean square deviation between inertial and optical angles is about one degree for angles in the frontal and sagittal plane and about two degrees for angles in the transverse plane (both values averaged over all trials). We choose five features that characterize the initial pose and the three motions. Interindividual differences of all features are found to be clearly larger than the observed measurement deviations. These results indicate that the proposed inertial sensor-based method is a promising tool for lower back motion assessment.}, language = {en} } @article{KamedaZvickVuketal.2019, author = {Kameda, Takuya and Zvick, Joel and Vuk, Miriam and Sadowska, Aleksandra and Tam, Wai Kit and Leung, Victor Y. and B{\"o}lcskei, Kata and Helyes, Zsuzsanna and Applegate, Lee Ann and Hausmann, Oliver N. and Klasen, Juergen and Krupkova, Olga and W{\"u}rtz-Kozak, Karin}, title = {Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc}, series = {International journal of molecular sciences}, volume = {20}, journal = {International journal of molecular sciences}, number = {7}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms20071767}, pages = {23}, year = {2019}, abstract = {Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1) or tumor necrosis factor alpha (TNF-) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 mu M), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20\% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 mu M AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.}, language = {en} } @article{PuschmannDriessleinBecketal.2020, author = {Puschmann, Anne-Katrin and Drießlein, David and Beck, Heidrun and Arampatzis, Adamantios and Moreno Catal{\´a}, Maria and Schiltenwolf, Marcus and Mayer, Frank and Wippert, Pia-Maria}, title = {Stress and Self-Efficacy as Long-Term Predictors for Chronic Low Back Pain}, series = {Journal of Pain Research}, volume = {13}, journal = {Journal of Pain Research}, publisher = {Dove Medical Press}, address = {Albany, Auckland}, issn = {1178-7090}, doi = {10.2147/JPR.S223893}, pages = {613 -- 621}, year = {2020}, abstract = {Purpose: Psychosocial variables are known risk factors for the development and chronification of low back pain (LBP). Psychosocial stress is one of these risk factors. Therefore, this study aims to identify the most important types of stress predicting LBP. Self-efficacy was included as a potential protective factor related to both, stress and pain. Participants and Methods: This prospective observational study assessed n = 1071 subjects with low back pain over 2 years. Psychosocial stress was evaluated in a broad manner using instruments assessing perceived stress, stress experiences in work and social contexts, vital exhaustion and life-event stress. Further, self-efficacy and pain (characteristic pain intensity and disability) were assessed. Using least absolute shrinkage selection operator regression, important predictors of characteristic pain intensity and pain-related disability at 1-year and 2-years follow-up were analyzed. Results: The final sample for the statistic procedure consisted of 588 subjects (age: 39.2 (± 13.4) years; baseline pain intensity: 27.8 (± 18.4); disability: 14.3 (± 17.9)). In the 1-year follow-up, the stress types "tendency to worry", "social isolation", "work discontent" as well as vital exhaustion and negative life events were identified as risk factors for both pain intensity and pain-related disability. Within the 2-years follow-up, Lasso models identified the stress types "tendency to worry", "social isolation", "social conflicts", and "perceived long-term stress" as potential risk factors for both pain intensity and disability. Furthermore, "self-efficacy" ("internality", "self-concept") and "social externality" play a role in reducing pain-related disability. Conclusion: Stress experiences in social and work-related contexts were identified as important risk factors for LBP 1 or 2 years in the future, even in subjects with low initial pain levels. Self-efficacy turned out to be a protective factor for pain development, especially in the long-term follow-up. Results suggest a differentiation of stress types in addressing psychosocial factors in research, prevention and therapy approaches.}, language = {en} } @misc{PuschmannDriessleinBecketal.2020, author = {Puschmann, Anne-Katrin and Drießlein, David and Beck, Heidrun and Arampatzis, Adamantios and Moreno Catal{\´a}, Maria and Schiltenwolf, Marcus and Mayer, Frank and Wippert, Pia-Maria}, title = {Stress and Self-Efficacy as Long-Term Predictors for Chronic Low Back Pain}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, issn = {1866-8364}, doi = {10.25932/publishup-46013}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-460134}, pages = {613 -- 621}, year = {2020}, abstract = {Purpose: Psychosocial variables are known risk factors for the development and chronification of low back pain (LBP). Psychosocial stress is one of these risk factors. Therefore, this study aims to identify the most important types of stress predicting LBP. Self-efficacy was included as a potential protective factor related to both, stress and pain. Participants and Methods: This prospective observational study assessed n = 1071 subjects with low back pain over 2 years. Psychosocial stress was evaluated in a broad manner using instruments assessing perceived stress, stress experiences in work and social contexts, vital exhaustion and life-event stress. Further, self-efficacy and pain (characteristic pain intensity and disability) were assessed. Using least absolute shrinkage selection operator regression, important predictors of characteristic pain intensity and pain-related disability at 1-year and 2-years follow-up were analyzed. Results: The final sample for the statistic procedure consisted of 588 subjects (age: 39.2 (± 13.4) years; baseline pain intensity: 27.8 (± 18.4); disability: 14.3 (± 17.9)). In the 1-year follow-up, the stress types "tendency to worry", "social isolation", "work discontent" as well as vital exhaustion and negative life events were identified as risk factors for both pain intensity and pain-related disability. Within the 2-years follow-up, Lasso models identified the stress types "tendency to worry", "social isolation", "social conflicts", and "perceived long-term stress" as potential risk factors for both pain intensity and disability. Furthermore, "self-efficacy" ("internality", "self-concept") and "social externality" play a role in reducing pain-related disability. Conclusion: Stress experiences in social and work-related contexts were identified as important risk factors for LBP 1 or 2 years in the future, even in subjects with low initial pain levels. Self-efficacy turned out to be a protective factor for pain development, especially in the long-term follow-up. Results suggest a differentiation of stress types in addressing psychosocial factors in research, prevention and therapy approaches.}, language = {en} }