A diagnostic support system based on pain drawings: binary and k-disease classification of EDS, GBS, FSHD, PROMM, and a control group with Pain2D.

BACKGROUND AND OBJECTIVE: The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients. METHODS: Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach. RESULTS: Pain2D was able to classify the four rare diseases with an accuracy of 61-77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%. CONCLUSIONS: Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.

[Rare diseases in the differential diagnosis of myalgia]. / Seltene Erkrankungen in der Differenzialdiagnose bei Myalgien.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. This article focuses on rare neurological diseases that are classically associated with myalgia. In this context etiologically different diseases are considered, whereby some genetically linked diseases (fascioscapulohumeral dystrophy, FSHD, dystrophia myotonica, McArdle's disease, Pompe's disease, limb girdle muscular dystrophy) are contrasted with diseases with an (auto)immune-related pathogenesis (stiff-person syndrome, Isaacs syndrome). The aspects relevant for the diagnosis are particularly highlighted. The therapeutic aspects of the diseases are not part of this article.

[Rare diseases in the differential diagnosis of myalgia]. / Seltene Erkrankungen in der Differenzialdiagnose bei Myalgien.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. This article focuses on rare neurological diseases that are classically associated with myalgia. In this context etiologically different diseases are considered, whereby some genetically linked diseases (fascioscapulohumeral dystrophy, FSHD, dystrophia myotonica, McArdle's disease, Pompe's disease, limb girdle muscular dystrophy) are contrasted with diseases with an (auto)immune-related pathogenesis (stiff-person syndrome, Isaacs syndrome). The aspects relevant for the diagnosis are particularly highlighted. The therapeutic aspects of the diseases are not part of this article.

Quantitative sensory testing (QST). English version.

Quantitative sensory testing (QST) is a standardized and formalized clinical sensitivity test. Testing describes a subjective (psychophysical) method that entails a cooperation of the person to be examined. Within its framework, calibrated stimuli are applied to capture perception and pain thresholds, thus providing information on the presence of sensory plus or minus signs. The presented QST battery imitates natural thermal or mechanical stimuli. The aim is to acquire symptom patterns of sensory loss (for the functioning of the thick and thin nerve fibers) as well as a gain of function (hyperalgesia, allodynia, hyperpathia) with a simultaneous detection of cutaneous and deep tissue sensibility. Most of the tested QST parameters are normally distributed only after a logarithmic transformation (secondary normal distribution)-except the number of paradoxical heat sensations, of cold and heat pain thresholds, and vibration detection thresholds. A complete QST profile can be measured within 1 h. QST is suitable not only for clinical trials but also in practice as a diagnostic method to characterize the function of the somatosensory system-from the peripheral nerve fiber receptor to the projection pathways to the brain.

[Pain management in rare diseases]. / Schmerztherapie bei seltenen Erkrankungen.

In this article we address the relevance of rare diseases and their peculiarities with respect to pain therapy. Towards this end, four rare diseases (hemophilia, Morbus Fabry, dermatomyositis, and facioscapulohumeral dystrophy (FSHD)) will be presented and fundamental aspects of their pain therapies described. The diseases were chosen to showcase a pain therapy based on the WHO-step-by-step plan (hemophilia), a complex but established pain therapy (M. Fabry), and two less well established, individually adapted pain therapies (dermatomyositis, FSHD).

Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

[Pain management in sickle cell disease]. / Schmerztherapie bei Sichelzellkrankheit.

Sickle cell disease is associated with numerous symptoms and complications. Acute painful crisis is the most characteristic manifestation of the disease. In addition, many patients report chronic pain. As both acute and chronic pain severely diminish quality of life, adequate pain management is crucial. Recommendations for the treatment of acute painful crises are based on the World Health Organization analgesic ladder, which has been developed for cancer-related pain. Chronic pain can be treated with basic long-acting opioids and on-demand short-acting opioids. If patients show signs of neuropathic pain, administration of anticonvulsants, antidepressants or possibly ketamine should be considered.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

A Combined EEG-fNIRS Study Investigating Mechanisms Underlying the Association between Aerobic Fitness and Inhibitory Control in Young Adults.

The current evidence suggests that aerobic fitness is associated with inhibitory control of executive functioning in children and older adults. However, the relative contributions of different neurophysiological mechanisms to this relation remain unclear and have not yet been examined in young adults. The present study aimed to compare inhibitory control between high and low-fit young adult men, and to investigate a possible mediation of fitness effects by conflict monitoring (N450 component of event-related potentials) and lateralized oxygenation difference (LOD) in the DLPFC. For the present cross-sectional study, participants with different physical activity levels were recruited and divided into low-fit and high-fit participants based on relative power on the PWC170. A Stroop Color-Word task was administered and combined EEG-fNIRS was simultaneously utilized to assess the N450 and LOD, because these parameters are linked with behavioral performance. The results of the statistical analysis showed that high-fitcompared to low-fit participants showed less Stroop interference and lower negativity of the N450, whereas no difference was found for LOD. Path-analyses further revealed that the relation between aerobic fitness levels and Stroop interference was indirect and mediated by N450. In contrast, LOD was inversely correlated with Stroop interference, but did not explain the relation of aerobic fitness with behavioral performance. The present findings indicate that greater inhibitory control in high- compared to low-fit young men can be explained by more effective conflict monitoring. Moreover, young adults with left-lateralizedDLPFC oxygenation also show higher inhibitory control, but this oxygenation pattern is not influenced by aerobic fitness.

[Surgical interventions in patients with systemic mast cell activation disease : Recommendations for perioperative management]. / Chirurgische Eingriffe bei Patienten mit systemischer Mastzellaktivierungserkrankung : Empfehlungen für das perioperative Management.

BACKGROUND: Systemic mast cell activation disease (MCAD, prevalence 5-10%) is a multifactorial, polygenic disease with multisystemic symptoms that is characterized by an unregulated increased release of mast cell mediators and an accumulation of activated mast cells potentially in all organs and tissues. Due to the high prevalence of the disease, physicians involved in surgical, anesthesiological and interventional procedures are often unknowingly faced with MCAD patients experiencing unexpected preoperative, intraoperative and postoperative complications, if no mast cell-specific treatment regimens have been applied. OBJECTIVE: The findings from a literature search, consensus recommendations of the various international expert groups and extensive own experience in the treatment of MCAD patients enable an empirical and evidence-based care of MCAD patients in association with invasive procedures. RESULTS AND CONCLUSION: Due to the high prevalence of MCAD in the population, it can be assumed that patients with MCAD are correspondingly frequently represented in the surgical patient collective. When MCAD-specific peculiarities are preventively considered in the anesthesiological and surgical procedures in patients with proven or suspected mast cell disease, MCAD patients should not be classified as being at risk.

[Cannabis and cannabinoids-easier access, hype and disappointment : What has been confirmed in therapy?] / Cannabis und Cannabinoide ­ erleichterter Zugang, Hype und Enttäuschung : Was ist gesichert in der Therapie?

BACKGROUND: Cannabis products are being increasingly liberalized all over the world and there is a huge interest in cannabis-based medicine. OBJECTIVES: Presentation of current studies on the efficacy of different cannabis-based medicine for the treatment of various diseases CURRENT DATA: In German pharmaceutical legislation, nabiximols is approved for the treatment of moderate to severe therapy-resistant spasticity in multiple sclerosis and nabilone is approved for the treatment of therapy-resistant chemotherapy-associated nausea and vomiting. In case of therapy failure cannabinoids, as part of an individual therapeutic attempt, may be considered for the treatment of chronic pain (neuropathic pain, cancer pain, non-neuropathic noncancer pain), cachexia in human immunodeficiency virus as well as for Dravet and Lennox-Gastaut syndrome. From the authors' perspective there is not enough evidence for the use in chemotherapy-associated nausea and vomiting and chronic non-neuropathic pain. CONCLUSIONS: Currently, a wide use of cannabinoids does not seem probable in the near future. Further studies involving more patients and evaluating long-term effects are necessary.

[Cannabinoid therapy in practice]. / Cannabinoidtherapie in der Praxis.

BACKGROUND: In recent years, the media and scientists have shown increased interest in cannabis-based drugs. OBJECTIVES: Background information about cannabis-based drugs and their mechanism of action as well as discussion of possible applications as supportive therapy or in palliative medicine, respectively, are presented. MATERIALS AND METHODS: The recent literature was examined and evaluated. RESULTS: In many medical fields, we do not have sufficient evidence for the efficacy of cannabinoids. In German pharmaceutical legislation, the use of nabiximols for the treatment of intermediate to severe, therapy-resistant spasticity in multiple sclerosis is the only approved indication for cannabis-based drugs. Furthermore, in view of the current evidence cannabinoids, combined with established treatments and as part of an individual therapeutic attempt, can be used for neuropathic pain, cancer-associated pain and human immunodeficiency virus (HIV)-related cachexia. CONCLUSIONS: In most cases, today's assessment of cannabinoids relies on studies that are classified as low evidence. Therefore, further studies which involve more participants and evaluate long-term effects are needed.

[Cardiovascular Prevention: Acceptance of Enhanced Occupational Health Care]. / Kardiovaskuläre Prävention ­ Akzeptanz einer erweiterten betrieblichen Vorsorge.

BACKGROUND: To date, prevention efforts of company medical officers and general practitioners are largely independent of each other. In a comprehensive model of healthcare management including both sets of doctors, the company doctor should determine the risk of cardiovascular disease in the employees of the company. In case increased risk is detected, there should be exchange of information between the 2 professional groups so that common preventive interventions can be decided upon. AIM: The aim of this pilot study was to determine how well cardiovascular risk assessment is accepted by employees of a midsize company and where prevention is needed. MATERIALS AND METHODS: In a company with 660 employees, risk analysis was conducted among staff in the context of regular preventive measures. In addition to risk factors, primary care, agreement with an interdisciplinary exchange of information and motivation for health promotion activities were investigated. RESULTS: 204 employees (4 females only) were examined. The average age of the participants was 42.9±10.3 years. In 27% (n=55), an increased overall risk was present. Employees with risk requiring medical intervention were under the care of primary care physician and most of them (70%) agreed to the transfer of information to these physicians. In the survey itself, employees showed sufficient motivation (VAS 6.4±2.8) for workplace health promotion. CONCLUSION: The examined company agreed to implementing further health promoting activities. Due to demographic changes, new concepts for effective prevention are needed. The high acceptance of the proposed prevention framework should motivate implementation of this concept. As a next step, studies must be conducted to examine the effectiveness of screening for risk carried out by company medical officers.

Matrix stimulation in cancer pain: Methodology, safety and effectiveness.

BACKGROUND: This feasibility study addresses the applicability of matrix electrodes for the reduction of ongoing pain in cancer patients via low-frequency electrical stimulation (LFS). METHODS: Low-frequency matrix stimulation (4 Hz) was applied to the skin within the 'Head's zones' referring to the tumour localization of cancer pain patients. Pain at baseline was compared to a 3-day treatment interval consisting of 5 min of matrix stimulation in the morning and evening followed by a 3-day follow-up period without therapy. Main outcome parameters included numeric rating scale values (rating scale 0-100), painDETECT, HADS, and German pain questionnaire, as well as the opioid intake, calculated as the oral morphine equivalent (OME). RESULTS: Twenty patients with cancer pain (aged 64.4 ± 10.3; 9 women) were examined. In the majority of patients, the pain was classified as nociceptive. The mean pain reduction achieved by matrix therapy was 30%, under stable daily controlled-release opioid doses between 177 and 184 mg/day (OME). Seventeen patients (85%) were responders, defined by a pain reduction of at least 30%, while four responders experienced a pain reduction of over 50%. The only side effect was short-term erythema. CONCLUSION: Findings are consistent with the concept of synaptic long-term depression in cancer pain induced after conditioning LFS. Despite the short, but well-tolerated, treatment duration of 2 × 5 min/day, effects persisted throughout the 3-day follow-up. SIGNIFICANCE: Cutaneous neuromodulation using LFS via a matrix electrode has been shown to be a safe intervention for effectively reducing cancer pain in palliative care patients.

[Neuromodulation using matrix stimulation : A treatment for acute pain?] / Neuromodulation mittels Matrixstimulation : Ein Therapieansatz für akute Schmerzen?

BACKGROUND: There is currently a lack of studies that evaluate the effects of matrix electrode neuromodulation on acute pain. In this prospective and randomized cross-over study, we investigated the efficacy of 4 Hz-matrix stimulation on venipuncture-induced pain in 30 healthy subjects. METHODS: We compared two conditions of neurostimulation: in EC1 (experimental condition 1), we performed venipuncture during stimulation, with 2.5 min of prestimulation with 600 stimuli; in EC2 (experimental condition 2), the length of stimulation was 5 min, at 1200 stimuli, with subsequent venipuncture. A group with no stimulation was used as control condition. RESULTS: The EC2 group did not only show a 77% reduction in puncture pain when compared to the control group (p < 0.001; effect size [ES] d = 1.45), but also had a significant effect compared with EC1 (p < 0.001; ES d = 1.33). EC1, on the other hand, did not demonstrate a significant difference to the control group. The status of the veins was evaluated based on visibility and did not differ significantly between the conditions. CONCLUSION: The results of this study showed for the first time that pre-emptive matrix stimulation could be an effective way to reduce acute pain. The duration of stimulation seems to play a key role in the effectiveness of the neurophysiological mechanism of action. Matrix stimulation is a therapeutic intervention with very few side effects, which could, in the future, expand our pain-management options for the treatment of acute pain.

Probing ultrafast ππ*/nπ* internal conversion in organic chromophores via K-edge resonant absorption.

Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method's impressive electronic structure sensitivity for excited-state investigations.Many photo-induced processes such as photosynthesis occur in organic molecules, but their femtosecond excited-state dynamics are difficult to track. Here, the authors exploit the element and site selectivity of soft X-ray absorption to sensitively follow the ultrafast ππ*/nπ* electronic relaxation of hetero-organic molecules.