Gaining more insight into ankle pain in haemophilia: A study exploring pain, structural and functional evaluation of the ankle joint.

INTRODUCTION: Ankle arthropathy is highly prevalent among people with haemophilia (PwH), even with prophylaxis, and leads to pain and disability. Mechanisms and consequences of painful symptoms related to ankle arthropathy have not been extensively studied. METHODS: A consecutive sample of 30 adult PwH was included (60 ankles). Ankle structure was assessed with magnetic resonance imaging (IPSG-MRI) and ultrasound (HEAD-US). The HJHS 2.1 assessed function of ankles and knees. Physical functioning was assessed with the Timed Up and Go test, the 2-Minute Walking Test and activity limitations with the HAL questionnaire. Health-related quality of life was evaluated using the EQ-5D-5L questionnaire. Overall pain severity was examined using the Brief Pain Inventory questionnaire and ankle pain intensity with a visual analogue scale. Pressure pain thresholds with an algometer assessed pain sensitivity. Spearman correlations were used to calculate interrelations between joint structure, function and pain. RESULTS: Twenty-five PwH (83%) reported ≥1 painful joint, with 67% reporting the ankle as most painful joint. MRI-confirmed abnormalities were seen in 76% of talocrural and 55% of subtalar joints. HEAD-US abnormalities were seen in 93% of the ankles. A large variation was seen in pain sensitivity at the ankle. While moderate to high correlations were observed between ankle structure and HJHS, no meaningful correlations were found between MRI-scores and pain intensity or sensitivity. CONCLUSIONS: Structural joint damage is present in many ankles but is not related to pain in PwH. Further studies should consider somatosensory nervous system dysfunction in PwH as contributing factor to painful ankle arthropathy.

Prevalence of pain in adult patients with moderate to severe haemophilia: a systematic review.

OBJECTIVES: Patients with haemophilia (PwH) often suffer from joint pain due to repetitive haemarthroses and resulting arthropathy. Literature focuses so far on pain causes, diagnosis or treatment. A summary of prevalence rates, providing facts on the absolute occurrence of pain, is not sufficiently described so far. This review aimed to explore and systematically review different pain conditions, focussing on prevalence rates of pain in adult PwH. METHODS: A review of English articles using PubMed and Web of Science was conducted in February 2020. The search strategy included patients with haemophilia A or B suffering from pain. The articles were selected based on defined PICOS-selection criteria. RESULTS: Out of 606 identified articles, 13 studies matched the given eligibility criteria and indicated pain prevalence rates. The weighted mean (WM) for the prevalence rate (varying timeframes) for chronic pain was 40% whereas for point prevalence the rate was WM=75%. Regarding pain intensity, findings of the EQ-5D-3L revealed moderate pain to be more present (61.0%) compared to extreme (11.6%). The main problem was the inconsistency of the definition of both acute and chronic pain as well as for prevalence types. CONCLUSIONS: Pain is a major problem in patients with haemophilia. Pain therapy should be carried out taking into account the difference between bleeding-related or arthropathy-related causes of pain. In addition, the intensity and duration of pain should be recorded consistently to better monitor therapy and allow comparison with existing data.

Changes of static and dynamic spine alignment in patients with severe haemophilia.

INTRODUCTION: Haemophilic arthropathy results in a restricted range of motion and pain that often affects gait. The effect of these gait changes on spinal posture has not been studied. AIM: To evaluate whether the altered joint situation in patients with haemophilia (PwH) leads to compensatory mechanisms evident in the trunk and spine, considering static and dynamic conditions. METHODS: PwH and healthy controls (20-65 years) were examined using rasterstereography in a controlled cohort study. Analysis was performed in static and dynamic conditions in regard to gait phases. Joint status was determined using the Haemophilia Joint Health Score (HJHS). RESULTS: Static measurements showed no group differences in PwH (n = 40) compared to healthy controls (n = 40) except pelvic torsion (median [25%-quartile;75%-quartile]: -1.9[-3.2;.9]° vs. .5[-1.1;1.9]°; P = .007). In contrast, under dynamic conditions PwH showed significantly higher trunk inclination and lower apex lumbar lordosis in all gait phases. Additionally, pelvic torsion was increased in mid stance and terminal swing. Considering joint status, PwH had a higher global HJHS (23.5[13.0;30.0] vs. 3.0[1.0;5.0]; P<.001). A significant moderate correlation was shown between the HJHS mobility score and spine parameters (r = .228-.588; P<.05). CONCLUSION: Degenerative joint changes in PwH lead to altered spine posture during gait. A reason could be the reduced mobility in the affected joint. Changes in spinal and pelvic posture lead to higher structural burdens; therefore, clinicians should focus on posture of spinal column during gait in daily treatment.

Changes in pain profile of patients with haemophilia during 1-year follow-up.

INTRODUCTION: Patients with haemophilia (PwH) may experience increased sensitivity to pain. Based on the assessment of the somatosensory system, a recent study showed a specific pain profile in PwH when compared to controls by using Quantitative Sensory Testing (QST). AIM: This study aimed to evaluate the pain profile of affected joints (knee or ankle joints) and a non-affected site (dominant hand) in adult PwH over a 1-year period. METHODS: Twenty-four PwH (severe haemophilia A = 19, B = 3; moderate haemophilia A = 1, B = 1; age: 52±8 years) and 21 healthy controls (age: 52±12 years) were examined by QST. Both knee or ankle joints and the hand as reference were examined twice with an interval of 1 year in order to assess several detection (DT) and pain thresholds (PT). RESULTS: Statistically significant altered mechanical (P < .001) and pressure (P < .05) PT were found at affected joints and at a non-affected site in PwH when compared to controls. Mechanical DT showed a significant increase at all assessed sites (e.g., at ankle joints PwH vs. controls at baseline/follow up in mN: 13.9±9.8 vs. 12.0±8.2/19.4±12.4 vs. 13.7±11.1; P < .01) in both cohorts. Nevertheless, changes in most parameters within 1 year occurred similarly in both groups. CONCLUSION: The statistically significant different QST profile between PwH and controls does not seem to deteriorate further over the course of the year. Thus, under prophylactic treatment, the existing difference in the pain profile between PwH and controls at baseline does not appear to be a progressive process within 1 year.

A single bout of coordination training does not lead to EIH in young healthy men - a RCT.

OBJECTIVES: Physical activity can lead to hypoalgesic effects and is often recommended as part of multidisciplinary pain management. Based on the idea, that in future specific and more differentiated sports therapeutic interventions could be used for a multidisciplinary pain management, various type of sports and their effects on pain sensitivity should be analysed. Whereas endurance as well as strengthening exercises are associated with a decrease in pain sensitivity in healthy people as well as people with chronic pain states, the effects of a specific coordination training (CT) on pain sensitivity have not yet been sufficiently investigated. Therefore, aim of the present study was to examine if a single bout of CT leads to exercised-induced hypoalgesia in young healthy men. METHODS: Thirty five healthy men (mean age 27 ± 3 years) were examined in a randomised crossover design before and after a single bout of 45-min CT and a 45-min resting session as control condition by means of Quantitative Sensory Testing (QST). The QST is a validated instrument to assess the function of the somatosensory system, by applying thermal and mechanical stimuli. By doing so, various detection and pain thresholds were determined at the dorsum of one foot. Exercises of CT were chosen to generate high proprioceptive input for the ankle joints. RESULTS: Analysis of the QST data in respect of the factors group (CT/control condition), time (pre/post) and stimuli (parameter of QST) revealed no statistically significant main effects of a single bout of CT on somatosensory system, neither for the factors group*time (p=0.51), nor the factors group*time*stimuli (p=0.32). All stimuli remained constant in the course of both conditions (e.g. mean ± sd of heat pain threshold pre/post in °C: coordination: 44.7 ± 3.1/44.8 ± 2.9; rest: 45.5 ± 3.0/44.9 ± 3.0). CONCLUSIONS: In this setting, a single bout of CT had no effect on the somatosensory system in young healthy men. Therefore, this specific CT did not lead to an exercised-induced hypoalgesia in healthy people. Intensity of sensory input during training intervention might be too low to generate analgesic effects in a non-pathological altered somatosensory system of young healthy men. Further research is needed to clarify if a CT can induce exercised-induced hypoalgesia in people with pathological alterations of the somatosensory system. In addition, it has to examined if analgesic effects can be induced by changing the intensity of CT in healthy people. Detailed knowledge regarding the effects of different training interventions on pain modulation is needed to completely understand the mechanism of exercised-induced hypoalgesia.

The effect of resistance exercise on strength and safety outcome for people with haemophilia: A systematic review.

INTRODUCTION: Haemophilia is a congenital bleeding disorder with severe musculoskeletal complications. Resistance exercise is important to increase joint stability and to improve physical performance. AIM: This review aimed to investigate the safety and efficacy of resistance exercise interventions on people with haemophilia (PwH) and evaluate whether the American College of Sports Medicine resistance exercise criteria for healthy adults are valid for this population. METHODS: A systematic search in literature was conducted, using the databases PubMed, MEDLiNE, CINAHL, SCOPUS, PEDro and Cochrane Library. Out of 2.440 studies published between 1960 and November 2019, 14 studies (9 randomized controlled trials, 1 controlled trial, 4 single-group prospective studies) applying resistance exercise in juvenile and adult PwH corresponded to the inclusion criteria. RESULTS: Studies performed dynamic, isokinetic or a combination of isometric and dynamic resistance training. Most interventions were carried out in the context of a multimodal training. Resistance was provided using fixed and free weights, body weight, resistance bands and water resistance. Study protocols included clinical and home-based settings. Several studies suggest that training intensities lower than those known to increase the strength of healthy people are effective in increasing the strength of PwH. Resistance exercise seems to be a safe intervention if it is adequately monitored, individually adapted and applied with sufficient factor therapy. Due to the heterogeneity of study designs, training interventions and outcome measures a meta-analysis could not be performed. CONCLUSIONS: Further studies of higher methodological quality are needed to determine the optimal types of exercise, optimal dosage and timing.

Understanding the pain profile in patients with haemophilia: Impaired descending pain inhibition as measured by conditioned pain modulation.

INTRODUCTION: Haemophilic arthropathy is associated with pain that often becomes chronic, likely caused by peripheral and central mechanisms. In the field of haemophilia, to our knowledge, the role of the descending pain pathway, which can also be involved in these pain processes, has not been examined to date. AIM: In light of the dearth of existing literature, we sought to evaluate the function of endogenous descending pain modulation in patients with haemophilia. METHODS: Thirty adult patients with moderate to severe haemophilia A or B (median [interquartile range] age 51.0 [42.0-54.0]) and 23 healthy adult controls (age 46.5 [36.8-54.3]) underwent conditioned pain modulation (CPM) in order to examine the function of endogenous pain modulation. The CPM response was determined by scoring a test stimulus (heat) alone as well as under the influence of a conditioning stimulus (cold) on the basis of a numeric rating scale (NRS) (0 = 'no pain' to 100 = 'worst possible pain'). RESULTS: Patients with haemophilia demonstrated a statistically significant reduced CPM response when compared with the age-matched healthy controls (median (interquartile range) NRS score: patients: -10 (-17.5-[-7.5]) vs controls: -20 (-30.0-[-13.75]); P = .002). The determined difference in the CPM response between both cohorts showed a medium effect size of r = .433. CONCLUSION: The results of this study indicate that an impaired degree of endogenous pain modulation could be present in patients with haemophilia. Therefore, the function of the descending pain pathway should be considered regarding an individual and comprehensive pain management.

Establishing an online physical exercise program for people with hemophilia.

BACKGROUND: Hemophilia is a congenital bleeding disorder with an estimated frequency of 1:10,000 births. Repeated joint bleeding is a hallmark of the disorder and leads to painful hemophilic arthropathy. Regular exercise can help improve joint stability and function, reduce the risk of injury and bleeding and improve physical fitness and quality of life. This method paper describes an online training concept aiming to offer access to appropriate exercise instructions for people with hemophilia who are not able to attend regular training at a hemophilia center. METHODS: The online exercise program is accessible through the homepage of the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University Vienna as well as through scanning a QR code printed on information material using a smart phone or tablet. RESULTS: The program contains exercises to improve mobility, coordination, muscular strength and flexibility. A brief introduction is given by a hematologist, a pediatrician and a physiatrist. An introductory video informs about contraindications and essential precautions, such as medical attendance and sufficient factor therapy to consider before starting the training. Another video gives advice on the exercise composition. The demonstrated exercises are explained by a physician and are available for adults and children. To individualize training recommendations and offer further diagnostic tools and physical treatment options as necessary, the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University of Vienna will establish consultation hours for people with hemophilia. CONCLUSION: As hemophilia is an orphan disease, patients are mainly treated in specialized centers. For patients who live far from these centers or have limited access to a training there for other reasons, the physical medicine consultation hour and the implementation of online exercise instructions offer individually adapted exercise information for a regular home-based training to benefit from increased physical fitness and joint stability.

Pain thresholds following maximal endurance exercise.

PURPOSE: Physical exercise causes alterations in pain sensitivity. Many studies verified so-called exercise-induced analgesia caused by submaximal aerobic intensity. This study aimed to determine the effect of an endurance exercise to exhaustion on pain sensitivity of healthy young men. METHOD: Pressure pain thresholds (PPTs) [in Newton, (N)] of 50 healthy males (mean age 26 ± 4 years) were applied to knee, ankle and elbow joints as well as to the sternum and forehead. This was followed by a bout of cycling ergometer exercise to exhaustion. The whole process was repeated after 20 and 60 min respectively. RESULTS: Endurance exercise to exhaustion decreased PPTs at sternum and forehead significantly, while thresholds at the joints were not affected. Pain thresholds at forehead and sternum declined 20 min after exercise with the forehead's threshold being more reduced. PPTs remain decreased until 60 min after exercise (forehead: from 43.6 ± 15.2 N to 36.6 ± 19.8 N to 37.2 ± 13.4 N; sternum: from 46.8 ± 21.0 N to 42.5 ± 17.1 N to 44.8 ± 18.2 N). Modulation of pain sensitivity showed large effect sizes over time for both landmarks (forehead w = 0.65; sternum w = 0.50). CONCLUSION: Exhaustive endurance exercise is followed by a hyperalgetic condition at forehead and sternum. This may be due to either a reduction in pain inhibiting or an activation in pain stimulating pathways.

Investigation of the Storage Behavior of Shredded Lithium-Ion Batteries from Electric Vehicles for Recycling Purposes.

Shredding of the cells is often the first step in lithium-ion battery (LIB) recycling. Thus, LiNi1/3 Mn1/3 Co1/3 O2 (NMC)/graphite lithium-ion cells from a field-tested electric vehicle were shredded and transferred to tinplate or plastic storage containers. The formation of hazardous compounds within, and being released from, these containers was monitored over 20 months. The tinplate cans underwent fast corrosion as a result of either residual charge in the active battery material, which could not fully be discharged because of contact loss to the current collector, or redox reactions between the tinplate surface and metal parts of the shredded material. The headspace compositions of the containers were investigated at room temperature and 150 °C using headspace-gas chromatography-mass spectrometry (HS-GC-MS). Samples of the waste material were also collected using microwave-assisted extraction and the extracts were analyzed over a period of 20 months using ion chromatography-electrospray ionization-mass spectrometry (IC-ESI-MS). LiPF6 was identified as a conducting salt, whereas dimethyl carbonate, ethyl methyl carbonate, and ethylene carbonate were the main solvent components. Cyclohexylbenzene was also detected, which is an additive for overcharge protection. Diethyl carbonate, fluoride, difluorophosphate and several ionic and non-ionic alkyl (fluoro)phosphates were also identified. Importantly, dimethyl fluorophosphate (DMFP) and diethyl fluorophosphate (DEFP) were quantified using HS-GC-MS through the use of an internal standard. DMFP, DEFP, and related compounds are known as chemical warfare agents, and the presence of these materials is of great interest. In the case of this study, these hazardous materials are present but in manageable low concentrations. Nonetheless, the presence of such compounds and their potential release during an accident that may occur during shredding or recycling of large amounts of LIB waste should be considered.