Application and accuracy of the EAPC/IASP diagnostic algorithm for neuropathic cancer pain and quantitative sensory testing profile in patients with pain due to cancer.

Introduction: Better diagnosis and treatment of neuropathic cancer pain (NcP) remains an unmet clinical need. The EAPC/IASP algorithm was specifically designed for NcP diagnosis; yet, to date, there is no information on its application and accuracy. Objectives: Our aim was to determine the accuracy of the EAPC/IASP algorithm compared with the Neuropathic Special Interest Group grading system (gold standard) and to describe patients' sensory profile with quantitative sensory testing (QST). Methods: This is a cross-sectional observational study conducted in a palliative care and pain outpatient clinic. Patients with cancer pain intensity ≥3 (numerical rating scale 0-10) were eligible. The palliative care physician applied the EAPC/IASP algorithm as a grading system to diagnose probable or definite NcP, and an independent investigator applied the gold standard and performed the QST. Sensitivity and specificity of the EAPC/IASP algorithm were measured in comparison with the gold standard results. Kruskal-Wallis and unequal variance independent-samples t tests were used to compare the QST parameters in patients with and without NcP. Results: Ninety-eight patients were enrolled from August 2020 to March 2023. Sensitivity and specificity for the EAPC/IASP algorithm were 85% (95% CI 70.2-94.3) and 98.3% (95% CI 90.8-100), respectively. Patients with NcP in contrast to patients without NcP showed cold hypoesthesia (P = 0.0032), warm hypoesthesia (P = 0.0018), pressure hyperalgesia (P = 0.02), and the presence of allodynia (P = 0.0001). Conclusion: The results indicate a good performance of the EAPC/IASP algorithm in diagnosing NcP and the QST discriminated well between patients with and without NcP.

[Neuropathic pain as a symptom in autonomic neuropathies and other rare diseases : Small fiber neuropathy: its recognition, diagnosis, and treatment]. / Neuropathische Schmerzen als Symptom bei autonomen Neuropathien und anderen seltenen Erkrankungen : Kleinfaserneuropathie erkennen, diagnostizieren und behandeln.

BACKGROUND: Neuropathic pain is difficult to diagnose and treat. Small fiber neuropathy (SFN) flies under the radar of nerve conduction studies. OBJECTIVES: The importance of a structured patient history and physical examination in the context of neuropathic pain is emphasized. Describing SFN as an important cause, the authors consider rare but partially treatable differential diagnoses. They conclude that autonomic symptoms are frequently associated, often presenting with diverse symptoms. METHODS: A selective literature research to present SFN symptoms as well as differential diagnostic and therapeutic steps in the context of SFN and rare diseases focusing on the autonomic nervous system. RESULTS: Neuropathic pain significantly reduces quality of life. To shorten the time until diagnosis and to initiate therapy, the authors recommend a structured patient history including sensory plus and minus symptoms and non-specific autonomic signs. If the initial search for the cause is not successful, rare causes such as treatable transthyretin (ATTR) amyloidosis and Fabry's disease or autoimmune causes should be considered, particularly in the case of progressive and/or autonomic symptoms. CONCLUSION: The diagnosis and therapy of rare SFN requires interdisciplinary collaboration and, in many cases, a referral to specialized centers to achieve the best patient care.

Interindividual variability in cold-pressor pain sensitivity is not explained by peripheral vascular responding and generalizes to a C-nociceptor-specific pain phenotype.

ABSTRACT: Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor-sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex-mediated microcirculatory responses. Cold-pressor-sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor-mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber-mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water-exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.

Reduced Gray Matter Volume and Cortical Thickness in Patients With Small-Fiber Neuropathy.

Small-fiber neuropathy (SFN) is defined by degeneration or dysfunction of peripheral sensory nerve endings. Central correlates have been identified on the level of gray matter volume (GMV) and cortical thickness (CT) changes. However, across SFN etiologies knowledge about a common structural brain signature is still lacking. Therefore, we recruited 26 SFN patients and 25 age- and sex-matched healthy controls to conduct voxel-based- and surface-based morphometry. Across all patients, we found reduced GMV in widespread frontal regions, left caudate, insula and superior parietal lobule. Surface-based morphometry analysis revealed reduced CT in the right precentral gyrus of SFN patients. In a region-based approach, patients had reduced GMV in the left caudate. Since pathogenic gain-of-function variants in voltage-gated sodium channels (Nav) have been associated with SFN pathophysiology, we explored brain morphological patterns in a homogenous subsample of patients carrying rare heterozygous missense variants. Whole brain- and region-based approaches revealed GMV reductions in the bilateral caudate for Nav variant carriers. Further research is needed to analyze the specific role of Nav variants for structural brain alterations. Together, we conclude that SFN patients have specific GMV and CT alterations, potentially forming potential new central biomarkers for this condition. Our results might help to better understand underlying or compensatory mechanisms of chronic pain perception in the future. PERSPECTIVE: This study reveals structural brain changes in small-fiber neuropathy (SFN) patients, particularly in frontal regions, caudate, insula, and parietal lobule. Notably, individuals with SFN and specific Nav variants exhibit bilateral caudate abnormalities. These findings may serve as potential central biomarkers for SFN and provide insights into chronic pain perception mechanisms.

[Transition from intensive care to palliative care : A retrospective analysis of 102 consultation requests]. / Transition von der Intensivmedizin zur Palliativmedizin : Eine retrospektive Analyse von 102 Konsilanforderungen.

BACKGROUND: The transition of patients from the intensive care unit (ICU) to the palliative care (PC) ward often implies changes including establishing a palliative concept. Adaptation of therapeutic goals can be challenging for medical staff, patients and relatives; however, descriptions of these transition trajectories are rare. OBJECTIVE: The aim of this retrospective study was to characterize the consultation requests of the ICU to the PC consultation team as well as the patients by a description of trajectories and interventions. METHODS: Retrospective analysis of all patients receiving intensive care at RWTH Aachen University Hospital in 2019 for whom a PC consultation was requested. The patient population transferred from the ICU to the PC ward was compared with the non-transferred population. In each case, the primary consultation was evaluated regarding the following factors: question, vigilance, length of time from consultation request to its performance, and primary focus of the question. The question focus was categorized into "symptom control", "counselling" and "transfer" (tick options). In addition, a free text field was available for further notes. Exploration of diagnoses was complemented by accessing the electronic health records. RESULTS: A total of 102 consultation requests from the ICU to the PC ward were evaluated. The morbidity of patients was high, and most patients had at least one of the following diagnoses: pulmonary (62%), cardiovascular (61%), and/or neurological disease (55%). Of the patients 32 (31%) were transferred to the PC ward, among whom weakness (94%), fatigue (77%), anxiety (55%), pain (53%), and dyspnea (48%) were the most frequently noted symptoms. Of the transferred patients 5 (16%) could be discharged to home, nursing home, hospice or other. In total, 35 (34%) of all patients who were seen by palliative care specialists on ICUs in 2019 could be discharged alive. The most frequent reasons for nonadmission were lack of capacity of the PC ward (33%), dying while being on the waiting list (20%), and refusal by the patient (20%). Of the patients, 7 (26%) died within 48 h after they had been transferred to the PC ward. Performed consultation services "symptom control" (χ2 = 10.17; p < 0.05) and "counselling" (χ2 = 12.82; p < 0.001), which were requested by the intensive care physicians, showed a significant linkage with the respective intervention performed by the palliative care team. On the other hand, no statistically significant difference was found for requested and performed "transfer" of patients from ICUs to PC ward. Comparing the transferred versus non-transferred patient population, a significantly more frequent transfer of patients with malignant tumors (p = 0.00) was observed. CONCLUSION: The need for palliative care support in the ICUs exceeded the admission capacity of the PC ward. Future studies should further examine palliative care models in intensive care medicine.

Carbamazepine for Chronic Muscle Pain: A Retrospective Assessment of Indications, Side Effects, and Treatment Response.

Myopathies fall under the umbrella of rare diseases, however, muscle pain is a relevant, under-recognized symptom with limited treatment options. Carbamazepine is an oral sodium channel blocker approved for the treatment of seizures and neuropathic pain. In 54 individuals receiving carbamazepine for muscle pain, we retrospectively assessed the subjective treatment response, side effects, and reasons for carbamazepine discontinuation. The underlying diagnoses leading to muscle pain were diverse, ranging from metabolic (n = 5) and other hereditary (n = 9) to acquired (n = 2) myopathies and myotonia syndromes (n = 22). Under carbamazepine (daily dose 254 ± 138 mg), patients reported a significant reduction of pain, quantified by an 11-point numeric rating scale (−1.9 ± 1.8, p < 0.001). Compared to age- and sex-matched controls, our sensory assessment revealed a significant dysfunction of Aδ-nerve fibers in patients with chronic muscle pain. Neuropathic pain components identified by the painDETECT questionnaire or quantitative sensory testing did not seem to influence the reported treatment response. Side effects (n = 18) such as fatigue, elevated liver enzymes, and diarrhea, as well as lack of pain improvement (n = 6), led to carbamazepine discontinuation in 44.4% (24/54). Mediated by dysfunctional Aδ-nerve fibers, muscle pain is common in a variety of myopathies. Carbamazepine may reduce pain levels, but comes with therapy-limiting side effects.

Neural correlates of multisensory integration in the human brain: an ALE meta-analysis.

Previous fMRI research identified superior temporal sulcus as central integration area for audiovisual stimuli. However, less is known about a general multisensory integration network across senses. Therefore, we conducted activation likelihood estimation meta-analysis with multiple sensory modalities to identify a common brain network. We included 49 studies covering all Aristotelian senses i.e., auditory, visual, tactile, gustatory, and olfactory stimuli. Analysis revealed significant activation in bilateral superior temporal gyrus, middle temporal gyrus, thalamus, right insula, and left inferior frontal gyrus. We assume these regions to be part of a general multisensory integration network comprising different functional roles. Here, thalamus operate as first subcortical relay projecting sensory information to higher cortical integration centers in superior temporal gyrus/sulcus while conflict-processing brain regions as insula and inferior frontal gyrus facilitate integration of incongruent information. We additionally performed meta-analytic connectivity modelling and found each brain region showed co-activations within the identified multisensory integration network. Therefore, by including multiple sensory modalities in our meta-analysis the results may provide evidence for a common brain network that supports different functional roles for multisensory integration.

[Postoperative pain experience after proximal femur fracture in dementia]. / Postoperatives Schmerzerleben nach proximaler Femurfraktur bei Demenz.

BACKGROUND: The present study aimed to assess the postoperative pain experience in cognitive deficit patients with special reference to sensory or affective pain quality. METHODS: Nineteen patients with normal cognition up to cognitive impairments according to the DemTect screening-tool were studied regarding their postoperative pain experience after proximal femur fracture. The numerical rating scale (NRS), the cognitive DemTect questionnaire, the pain sensation questionnaire (SES), and a quantitative sensory test (QST) were used as examination instruments. RESULTS: The mean ± SD age of the patients was 83.8 ± 10.0 years. Of the 19 patients, 6 (31.6%) had normal cognitive abilities. In 4 patients (21.1%) there were indications of mild cognitive impairments, and in 9 patients (47.4%) the suspicions of the presence of dementia arose. The mean postoperative pain intensity (NRS) was 4.0 (1.6). With comparable analgesic therapy, the reported pain intensities did not differ between the three patient groups with different cognitive impairments and the first three postoperative treatment days. There were no statistically significant differences between the groups for the sensory or affective total scores of the pain sensation scale. The QST parameters deep pain (PPT), superficial mechanical pain after needle stimulation (MPT), and the superficial sensitivity to light touch stimuli (MDT) showed a significantly increased sensitivity of the operated side. For the sensation of vibration (VDT) no differences between operated and healthy extremities could be proven. DISCUSSION: The postoperative pain experience does not differ between patients with normal and limited cognition. The quantitative sensory testing showed mechanical hyperalgesia in the operated area. The study points to the importance of adequate postoperative pain management even in those with dementia.

Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromes.

BACKGROUND AND PURPOSE: Ehlers-Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres, with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome (PoTS) are frequently reported features in patients with hypermobile Ehlers-Danlos syndrome (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood. STUDY PURPOSE: To better understand pathophysiological mechanisms of small fiber neuropathy and autonomic neuropathy in hypermobile Ehlers-Danlos Syndromes. METHODS: We prospectively investigated 31 patients with hEDS compared to 31 healthy controls by using skin biopsy, quantitative sensory testing, tilt-table testing, the painDetect, Small Fibre Neuropathy Screening List and the COMPASS-31 (Composite Autonomic Symptom Score 31) questionnaire. RESULTS: Nineteen (61%) patients with hEDS were diagnosed with SFN, and 10 (32%) fulfilled the criteria for PoTS. Patients with hEDS had significantly higher heart rates than controls. According to quantitative sensory testing, these patients had generalized thermal and tactile hypesthesia. Skin biopsy revealed significantly reduced intraepithelial nerve fibre density proximally (thigh) and distally (lower leg) in patients compared to controls. This was consistent with various complaints of pain and sensory disturbances in both the proximal and distal body regions. CONCLUSION: These results confirm histologically proven SFN as a common feature in patients with hEDS, revealing a generalized distribution of nerve fibre loss. Regarding the frequently reported autonomic and neuropathic dysfunctions, the findings support SFN as an important, but not the only, underlying pathomechanism.

Influence of Palliative Care Qualifications on the Job Stress Factors of General Practitioners in Palliative Care: A Survey Study.

Due to demographic change, the number of patients in palliative care (PC) is increasing. General Practitioners (GPs) are important PC providers who often have known their patients for a long time. PC can be demanding for GPs. However, there are few studies on the job stress factors of GPs performing PC and the potential influence of their PC training. To get more insights, a postal survey was performed with GPs in North Rhine, Germany. The questionnaire was based on a literature search, qualitative pre-studies, and the Hospital Consultants' Job Stress & Satisfaction Questionnaire (HCJSSQ). Participants state that a high level of responsibility, conflicting demands, and bureaucracy are the most important stressors they experienced in PC. The influence of PC qualification level on their perceived job stress factors is low. Only advanced but not specialist qualification shows a correlation with renumeration-related stress. Gender and work experience are more dominant influences. In our study, female GPs and physicians with more work experience tend to be more stressed. In conclusion, organisational barriers, such as administration, should be reduced and renumeration should be increased to facilitate the daily work of GPs.

GPs' involvement in specialised palliative home care: A mixed methods study in Germany.

BACKGROUND: General practitioners (GPs) are important providers of palliative home care (PHC). To deliver adequate palliative care, cooperation with specialised PHC teams is necessary. Specialised PHC is a type of care for severely ill patients by specialised providers. Little is known about the involvement of German GPs in specialised PHC. OBJECTIVES: To analyse GPs' experience with realised and desired involvement in specialised PHC. Realised involvement means GPs took part in specialised PHC patients' care. Desired involvement is GPs' hoped-for cooperation with specialised PHC teams: GPs could state whether they want to stay involved, be informed, or provide medical services themselves after referral to specialised PHC. METHODS: Mixed methods design (focus group with 6 GPs; survey of 445 GPs in North Rhine, Germany, about their experiences in PHC/specialised PHC): Qualitative data was interpreted using content analysis. The authors developed a questionnaire and performed descriptive analysis based on qualitative results. RESULTS: GPs are mostly satisfied with specialised PHC teams' care, although they report cooperation is not always optimal. GPs describe a high satisfaction with quality of care by specialised PHC teams. However, physicians with higher PC knowledge are less satisfied with specialised PHC. Also, GPs are often less involved in specialised PHC than they wish, especially when they have a higher PC qualification. CONCLUSION: In general, GPs are satisfied with the quality of care provided by specialised PHC teams but GPs do not always perceive cooperation as optimal. Involvement of GPs in specialised PHC needs to be improved.

Prepared to Accompany the End of Life during Pandemics in Nursing Homes.

BACKGROUND: The COVID-19 pandemic confronted nursing homes with a variety of challenges to ensure the provision of palliative care for residents. PallPan-Implement aimed to adapt the recommendations of the National Strategy for the Care of Seriously Ill, Dying Adults and their Families in Times of Pandemic (PALLPAN) in such a way that nursing facilities can use and implement them. METHODS: Based on 33 PALLPAN recommendations, we developed a questionnaire, conducted a pilot implementation for selected nursing homes, and asked for qualitative feedback. RESULTS: The developed questionnaire contains 22 main questions. A three-stage pilot implementation with an introductory event, processing phase, and evaluation event took place in seven facilities. The facilities evaluated the developed questionnaire as helpful. Feedback from the facilities identified three major categories: (a) requirements for facilities should be realistic to avoid frustration, (b) the creation of a pandemic plan for palliative care only is impractical, (c) measures for the psychosocial support of staff is particularly necessary, but was perceived as difficult to implement. CONCLUSIONS: The practical implementation of recommendations requires a concept and material tailored to facilities and areas. The strategy of PallPan Implement developed in this project appears to be target-oriented, well-received, and can be recommended for further implementation.

Nonregional small fibre neuropathy in cases of autoimmune autonomic neuropathy.

OBJECTIVE: Autonomic small fibre neuropathy is described in patients with autoimmune autonomic neuropathy (AAN). Few data are available on somatosensory function and skin biopsies in AAN. METHODS: Retrospective analysis of 17 patients (51.2 ± 6.8 years, n = 7 males) with AAN, including autoantibodies, quantitative sensory testing (QST, n = 13) and intraepithelial nerve fibre density (IENFD) in skin biopsy (n = 16). QST was performed according to the DFNS protocol over hands and feet dorsum. QST data were compared to healthy controls. Comparison of antibody-positive and antibody-negative cases. RESULTS: 70.6% of patients were antibody positive. 82.4% described at least one episode with sensory symptoms. Skin biopsies revealed reduced IENFD in 58.8% of patients, whereas neuropathic pain was only present in 41.2%. QST showed a nonregional increase for nonpainful thermal and mechanical detection rather than for mechanical pain thresholds. Compared to healthy controls, sensory loss for cold and warm detection thresholds and for the thermal sensory limen-the temperature difference between alternating warm and cold stimuli-was found on hands and feet (all p < 0.05). For nonpainful mechanical stimuli, the vibration detection threshold on the hand was increased (p < 0.05). Of all pain thresholds, only the mechanical pain threshold was elevated for pinprick stimuli to the feet (p < 0.05). INTERPRETATION: Findings are consistent with a sensory small fibre more than large fibre neuropathy in AAN. Sensory loss was comparably distributed across hands and feet, indicating that nerve fibre dysfunction was rather generalized. Serostatus was not a significant predictor of the small fibre deficit present in AAN.

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study.

BACKGROUND: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. PATIENTS AND METHODS: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. RESULTS: In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (ρ = -0.51), warm detection (ρ = -0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). CONCLUSIONS: The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

[Perceptions on handling of opioids: focus COVID-19 : A survey among anesthesiologists via the specialist societies DGAI/BDA]. / Wahrnehmungen zum Umgang mit Opioiden: Fokus COVID-19 : Eine Umfrage unter Anästhesist:innen über die Fachgesellschaften DGAI/BDA.

BACKGROUND: Opioids are part of the daily routine in anesthesiology and palliative care; however, treatment of dyspnea with opioids is presented heterogeneously in guidelines. This may result in an uncertainty concerning opioid indications and ethical concerns, especially when caring for COVID-19 patients. OBJECTIVE: We aimed to examine the perception of anesthesiologists concerning the handling of morphine as the reference opioid (subsequently termed M/O) for symptom control within and outside of a palliative care setting, including care for COVID-19 patients. MATERIAL AND METHODS: Members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Professional Association of German Anesthesiologists (BDA) received an anonymized online questionnaire (Survey Monkey®; Momentive Inc., San Mateo, CA, USA) in October 2020, containing questions regarding their perception of symptom management with M/O in general, and in particular concerning COVID-19 patients. Participants were asked to rate their perception within and outside a palliative care setting. RESULTS AND DISCUSSION: A total of 1365 anesthesiologists participated; 46% women. Most anesthesiologists were 41-60 years old (58%), worked in a hospital setting (78%), in the operating theatre (63%) and in intensive care units (49%). The majority (57%) reported > 20 years of professional experience (52%) and partial involvement in palliative care (57%). Perception of M/O handling was mostly "certain and confident" (88%) and "clearly regulated" (85%) within a palliative care setting but rated substantially lower for outside palliative care (77%/63%). When caring for COVID-19 patients, handling of M/O was even less often rated "certain and confident" (40%) or "clearly regulated" (29%) outside palliative care. Dyspnea (95%/75%), relief of the dying process (84%/51%), agitation (59%/27%) and anxiety/panic (61%/33%) were more frequently rated as general indications for morphine within versus outside palliative care. The majority of anesthesiologists disputed that M/O is given with the intention to hasten death within (87%) and outside (93%) palliative care. Highest difference in route of administration was reported for the subcutaneous administration of M/O within (76%) versus outside (33%) palliative care, followed by the intravenous route (57%/79%), while oral (66/62%) and transdermal (48%/39%) administration were reported to be used comparatively frequently. Most participants (85%) wanted more frequent involvement of palliative care consultation teams but also more team conferences (75%), supervision (72%), and training on opioid management (69%). CONCLUSION: Anesthesiologists perceived considerable uncertainty in using M/O for nonpalliative care medical settings. Highest uncertainty was seen for the care of patients with COVID-19. The prevalent use of the subcutaneous route for M/O application in palliative care can serve as inspiration for areas outside palliative care as well. Uniform interdisciplinary guidelines for symptom control including dyspnea, education and involvement of a palliative care consultation team should be more considered in the future.

Deoxy-sphingolipids, oxidative stress, and vitamin C correlate with qualitative and quantitative patterns of small fiber dysfunction and degeneration.

ABSTRACT: Defined by dysfunction or degeneration of Aδ and C fibers, small fiber neuropathies (SFNs) entail a relevant health burden. In 50% of cases, the underlying cause cannot be identified or treated. In 100 individuals (70% female individuals; mean age: 44.8 years) with an idiopathic, skin biopsy-confirmed SFN, we characterized the symptomatic spectrum and measured markers of oxidative stress (vitamin C, selenium, and glutathione) and inflammation (transforming growth factor beta, tumor necrosis factor alpha), as well as neurotoxic 1-deoxy-sphingolipids. Neuropathic pain was the most abundant symptom (95%) and cause of daily life impairment (72%). Despite the common use of pain killers (64%), the painDETECT questionnaire revealed scores above 13 points in 80% of patients. In the quantitative sensory testing (QST), a dysfunction of Aδ fibers was observed in 70% and of C fibers in 44%, affecting the face, hands, or feet. Despite normal nerve conduction studies, QST revealed Aß fiber involvement in 46% of patients' test areas. Despite absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2 , plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia ( P < 0.01) or those in the healthy category ( P < 0.1), correlating inversely with the intraepidermal nerve fiber density (1-deoxy-SA: P < 0.05, 1-deoxy-SO: P < 0.01). Patients with arterial hypertension, overweight (body mass index > 25 kg/m 2 ), or hyperlipidemia showed significantly lower L-serine (arterial hypertension: P < 0.01) and higher 1-deoxy-sphingolipid levels (arterial hypertension: P < 0.001, overweight: P < 0.001, hyperlipidemia: P < 0.01). Lower vitamin C levels correlated with functional Aß involvement ( P < 0.05). Reduced glutathione was lower in patients with Aδ dysfunction ( P < 0.05). Idiopathic SFNs are heterogeneous. As a new pathomechanism, plasma 1-deoxy-sphingolipids might link the metabolic syndrome with small fiber degeneration.

[Perceptions on the use of opioids: focus on COVID-19 : Free-text analysis of a survey in anesthesiology/intensive care, internal medicine, and palliative care]. / Wahrnehmungen zum Umgang mit Opioiden: Fokus COVID-19 : Freitext-Analyse einer Umfrage in Anästhesiologie/Intensivmedizin, Innerer Medizin und Palliativmedizin.

BACKGROUND: Opioids efficiently manage pain and dyspnea. However, guidelines on symptom management with opioids differ, which may lead to uncertainty among medical staff concerning opioid indication and ethical implication, especially when caring for COVID-19 patients. AIMS: We aimed to examine the perception of morphine/opioid (M/O) administration for symptom control within and outside palliative care, including care for COVID-19 patients, among members of the German associations for palliative medicine, internal medicine, anesthesiology and intensive care. METHODS: Participants received an anonymized online questionnaire via Survey Monkey® (Momentive Inc., San Mateo, CA, USA) regarding their general perception of symptom management with M/O. These results have been published elsewhere. For systematic and structural analysis of comments in the free-text field, we chose Phillip Mayring's method of summarizing qualitative content analysis. RESULTS: Of the n = 2202 persons who participated, 339 wrote comments in the free-text field which were categorized as follows: main categories 1) personal perceptions of COVID-19 patients, 2) administration and effect of M/O, 3) observations within the palliative care field, 4) imparting knowledge concerning M/O usage and palliative care, and 5) others. CONCLUSIONS: Some participants reported very personal perceptions and deficits of the healthcare system, especially when caring for COVID-19 patients. Uniform interdisciplinary guidelines for symptom control, more education, and support by trained staff confident in symptom control should be increasingly considered in the future.

[Perceptions on the use of opioids in COVID-19 : A survey of members of the German Association for Palliative Medicine]. / Wahrnehmungen zum Umgang mit Opioiden bei COVID-19 : Eine Umfrage unter Mitgliedern der Deutschen Gesellschaft für Palliativmedizin.

BACKGROUND: Opioids efficiently alleviate pain and dyspnea. However, guidelines on symptom management with opioids differ, which may lead to an uncertainty concerning opioid indication and ethical implication among medical staff, especially when caring for COVID-19 patients. AIMS: We aimed to examine the perception of members of the German Association for Palliative Medicine (DGP) concerning the administration of morphine as the gold standard opioid (subsequently termed M/O) for symptom control within and outside of a palliative care (PC) setting, including care for COVID-19 patients. METHODS: DGP members received an anonymized online questionnaire (Survey Monkey®) containing questions regarding their perception of symptom management with M/O in general and in particular concerning COVID-19 patients. Participants were asked to rate their perception within and outside of a PC setting. RESULTS: Of the 6129 DGP members, N = 506 participated. DGP physicians and nurses perceived handling of M/O as "certain and confident" (98%) and "clearly regulated" within PC (95%) but rated it significantly lower for outside PC (48%/38%). When caring for COVID-19 patients, handling of M/O was even less often rated "certain and confident" (26%) or "clearly regulated" (23%) for outside PC. Dyspnea (99%/52%), relief from the dying process (62%/37%), restlessness (30%/15%) and fear or panic (27%/13%) were more frequently rated as general indications for morphine within versus outside PC. Most participants (89%) wished to involve palliative care consultation teams. CONCLUSIONS: DGP members perceived substantial uncertainty in the handling of M/O for medical fields outside PC. Uniform interdisciplinary guidelines for symptom control, more education, and involvement of a PC consultation team should be increasingly considered in the future.