Functional clinical motor performance tests to assess potential fall risks in patients with haemophilia: A case-control study.

INTRODUCTION: Patients with haemophilia (PwH) are at increased risk of falls due to haemophilic arthropathy. Yet, studies on clinical tests associated with the risk of falling are scarce in PwH. AIMS: (1) To evaluate the feasibility of different clinical motor performance tests associated with the risk of falling in PwH; (2) to evaluate PwH's performance of these tests compared to a control group; (3) to identify possible influencing factors that affect performance. METHODS: Twenty-nine severe and moderate PwH (57.0 years, IQR: 48.0-61.5) and 29 healthy age- and BMI-matched control participants (CG) performed 13 different clinical tests (SPPB, timed up and go, push and release, functional reach, single-leg stance, knee and grip strength). Haemophilia joint health score (HJHS), kinesiophobia (TSK-11), subjective physical performance (HEP-Test-Q), falls efficiency (FES-I) and falls were assessed. RESULTS: No adverse events occurred. PwH showed impaired performance in all clinical tests, a lower falls efficiency and a higher HJHS than CG. PwH with higher HJHS, lower HEP-Test-Q and higher TSK-11 scores showed higher deficits. Largest discrepancies were observed in the single-leg stance with eyes open and knee extensor strength, where orthopaedically majorly affected PwH showed worse performance compared to minorly affected PwH and the CG, respectively. The prevalence of ≥1 fall in the last year was 27.6% (PwH) and 10.3% (CG). CONCLUSION: These clinical tests are feasible in PwH. Impaired joint status, a high kinesiophobia and low physical performance impair performance. These tests can be used by clinicians for gaining specific information on functional motor abilities of patients.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

BACKGROUND: Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. OBJECTIVES: This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. PATIENTS/METHODS: Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. RESULTS: Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p = .001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). CONCLUSION: The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Physical activity and factor VIII levels in patients with haemophilia: A real-world prospective observational study.

INTRODUCTION: Regular physical activity (PA) is recommended for patients with haemophilia (PwH). For PwH it is crucial to ensure a sufficient factor level to prevent PA-induced bleedings. However, there is a gap in the literature dealing with specific factor levels, which are needed when performing specific types of PA. AIM: To provide data on factor VIII (FVIII) levels at the start of PA performed by PwH. METHODS: In this prospective 12-month real-world observational study, 23 PwH recorded every PA they performed and the FVIII levels at the start of the PA using a pharmacokinetic application. PA types were clustered according to the collision and injury risk into three categories (Cat I = low, Cat II = medium, Cat III = high risk). Haemophilia Joint Health Scores (HJHS) were performed at baseline, after 6 and 12 months. RESULTS: 795 PA sessions of Cat I, 193 of Cat II, and 23 of Cat III were documented. FVIII levels at the start of PA were different between categories (Cat I: 29.8 ± 32.1%, Cat II: 38.3 ± 33.4%, Cat III: 86.6 ± 29.2%). Out of all PA sessions, 145 (14%) were performed at a factor level of ≤3%. Three PA-induced bleeding occurred. Baseline HJHS was 14.5 ± 13.6 points and did not change throughout the study. CONCLUSION: This study provides real-life data on FVIII levels at the start of 1011 PA sessions. PwH are mainly active in low-risk sports with higher FVIII levels observed in Cat II and III, respectively. Only three PA-induced bleeding occurred, even though several PA were started with low FVIII levels.

Determination of body composition by dual x-ray absorptiometry in persons with haemophilia.

BACKGROUND: There is limited research on body composition in persons with haemophilia (PwH). The literature describes an increased body fat distribution and decreased lean mass in PwH compared to healthy controls using bioimpedance analysis. Using dual x-ray absorptiometry (DXA), which is known to be the most accurate method, this investigation aims to postulate reference data for body composition parameters within haemophilia severity phenotypes and age groups. METHODS: Persons underwent whole body DXA screening using Horizon. Body fat percentage, estimated visceral adipose tissue (VAT), appendicular fat and lean mass, and lean and fat mass in relation to body height were assessed. Haemophilia severity and five age groups were distinguished. RESULTS: Two hundred and one persons with mild (n = 44), moderate (n = 41), or severe (n = 116) haemophilia A/B (median age 40 [28-55; 1.IQ-3.IQ] years) were analysed. The median body fat percentage was 28.7% [25.5%-33.9%] and median estimated VAT was 657 g [403-954 g] with no significant difference between severity phenotypes (p = .474; p = .781). Persons with severe haemophilia had less lean mass compared to moderate and mild haemophilia (p = .013; p = .034). Total and appendicular fat is increased in older PwH (aged ≥40 years) compared to younger PwH (aged ≤29 years; p < .05). Lean mass did not differ between age groups. CONCLUSION: This study provides valuable reference data for body composition parameters in PwH. Persons with severe haemophilia show significantly less lean mass compared to persons with moderate or mild haemophilia. Body fat percentage and VAT did not differ between severity phenotypes, but increased with age.

Hypoalgesia after aerobic exercise in healthy subjects: A systematic review and meta-analysis.

Exercise-Induced Hypoalgesia (EIH) refers to an acute reduced pain perception after exercise. This systematic review and meta-analysis investigated the effect of a single aerobic exercise session on local and remote EIH in healthy individuals, examining the role of exercise duration, intensity, and modality. Pressure pain thresholds (PPT) are used as the main measure, applying the Cochrane risk of bias tool and GRADE approach for certainty of evidence assessment. Mean differences (MD; Newton/cm²) for EIH effects were analysed. Thirteen studies with 23 exercises and 14 control interventions are included (498 participants). Most studies used bicycling, with only two including running/walking and one including rowing. EIH occurred both locally (MD = 3.1) and remotely (MD = 1.8), with high-intensity exercise having the largest effect (local: MD = 7.5; remote: MD = 3.0) followed by moderate intensity (local: MD = 3.1; remote: MD = 3.0). Low-intensity exercise had minimal impact. Neither long nor short exercise duration induced EIH. Bicycling was found to be effective in eliciting EIH, in contrast to the limited research observed in other modalities. The overall evidence quality was moderate with many studies showing unclear risk biases.

Neuroinflammatory markers in patients with haemophilia and healthy controls: Where are the differences?

INTRODUCTION: People with haemophilia (PwH) suffer from haemophilic arthropathy which is accompanied by acute and chronic inflammation. The aim of this study was to examine the neuroinflammatory network operative in PwH and to compare it to healthy controls. MATERIAL AND METHODS: Blood samples were collected from 41 PwH (age 54.7 ± 11.7 years) and 33 healthy controls (age 50.9 ± 10.5 years) and the levels of 13 neuroinflammatory markers were analyzed by applying an antibody-based detection kit in a flow cytometer. RESULTS: From 13 analyzed markers, three-ß-nerve growth factor (ß-NGF), soluble receptor for advanced glycation endproducts (sRAGE) and Interleukin-18 (IL-18) differed significantly between the groups (ß-NGF p = .045; sRAGE p = .003; IL-18 p = .007). While ß-NGF was downregulated in PwH, sRAGE and IL-18 were upregulated. None of the analyzed markers corelated to the joint status of PwH while CCL2 (C-C motif ligand 2 chemokine) correlated to HIV infections in PwH (r = .313, p = .007). Correlation analyses of the markers studied also revealed many differences between PwH and controls suggesting a number of deregulations in PwH. CONCLUSION: The altered levels of sRAGE and ß-NGF in PwH, which have not been analyzed in PwH before, may help to understand the neuroinflammatory network operative in PwH. The general inflammatory processes in PwH and the involved biomarkers in PwH remain poorly understood. PwH could benefit from new therapies against neuroinflammation which may help to reduce inflammation or also chronic pain.

Endothelial dysfunction and atherosclerosis related miRNA-expression in patients with haemophilia.

INTRODUCTION: Elevated markers of endothelial dysfunction and inflammation indicate worse endothelial function in the aging haemophilia population. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Several miRNAs have been shown to be involved in the process of endothelial dysfunction and atherosclerosis. AIM: The aim of this study was to determine the underlying molecular pathways of endothelial dysfunction and inflammation in haemophilia patients. METHODS: A total of 25 patients with severe or moderate haemophilia A (20 patients) or B (5 patients), 14 controls and 18 patients with coronary artery disease (CAD) after myocardial infarction were included in this study. Expression of miRNA-126, -155, -222, -1, -let7a, -21 and -197 were analysed using a real time polymerase chain reaction. Network-based visualisation and analysis of the miRNA-target interactions were performed using the MicroRNA ENrichment TURned NETwork (MIENTURNET). RESULTS: Expression of miRNA-126 (p < .05) and miRNA-let7a (p < .05) were significantly higher in CAD patients compared to haemophilia patients and controls. MiRNA-21 (p < .05) was significantly elevated in CAD patients compared to controls. MiRNA-155 (p < .05), miRNA-1 (p < .05) and miRNA-197 (p < .05) were significantly higher expressed in CAD and haemophilia patients compared to controls and showed a strong correlation with increased levels of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). The network analysis revealed interactions in the cytokine signalling, focal adhesion and VEGFA-VEGFR2 pathway (Vascular endothelial growth factor, -receptor). CONCLUSION: This study characterises miRNA expression in haemophilia patients in comparison to CAD patients and healthy controls. The results imply comparable biological processes in CAD and haemophilia patients.

Aerobic exercise in patients with haemophilia: A systematic review on safety, feasibility and health effects.

BACKGROUND: Haemophilia is a congenital bleeding disorder going along with disease-specific joint complications and general health implications attributed to the lack of daily movement. Recent guidelines recommend physical activity for people with haemophilia (PwH). Yet, aerobic exercise in PwH is little studied and seldomly prescribed by clinicans. AIM: The aim of this systematic review is to investigate the safety, feasibility and health-related efficiency of AE in PwH. METHODS: A systematic literature search according to the PRISMA guidelines was conducted (PubMed, Web of Science). Inclusion criteria were defined using PICOS. Methodological quality was assessed via TESTEX. RESULTS: Out of 789 studies identified, seven studies (three randomized controlled, two controlled, two single-group prospective trails) were included. The TESTEX mean score was 8.1 (±3.8). AE was realized as aquatic exercise, nordic walking, treadmill running, bicycle riding and swimming. Neither bleeding rates nor the factor amount increased and AE led to diverse health-related improvements. CONCLUSIONS: Little research has been conducted evaluating AE in PwH. Yet, AE can be considered as safe and feasible when being supervised by experts. However, disease-specific recommendations for AE are difficult to provide. Therefore, experts can currently only back AE recommendations on experience and nonhaemophilia-specific general guidelines.

Most subjectively affected joints in patients with haemophilia - what has changed after 20 years in Germany?

BACKGROUND: In patients with haemophilia (PwH), most frequently affected joints are the ankle, knee and elbow. Due to improved factor therapy in the last decades, these previous findings have to be verified in Germany. AIM: The aim of this study is to detect the most affected joint, evaluate the significance of the source of pain and determine the point prevalence of back pain in Germany today. PATIENTS AND METHODS: In a retrospective study, data of n = 300 patients with severe moderate and mild haemophilia were evaluated regarding the most affected joint, the most common source of pain, and the point prevalence of back pain. An anamnesis questionnaire and the German Pain Questionnaire were used for this assessment. RESULTS: The most affected joint in German PwH is still the ankle (41%), followed by the knee (27%) and the elbow (11%). The most common source of pain is also the ankle joint (32%). Back pain was also identified as one of the most common sources of pain, which is comparable to the elbow (elbow:15%; back:13%). The point prevalence in PwH for back pain was significantly higher compared to the general German population (P = .031). CONCLUSION: Our data showed that the ankle is still the most affected joint and the most common source of pain in Germany. These results also showed the relevance of back pain as a pain source. The evaluations also demonstrated the high point prevalence of back pain in PwH. Future therapies should also focus on the spine because joint changes affect posture.

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.

Exercise-induced hypoalgesia (EIH) in response to different exercise intensities.

PURPOSE: Acute physical activity leads to exercise-induced hypoalgesia (EIH). The aim of this study was to investigate the effects of four different exercise intensities on EIH. METHODS: 25 male (age: 24.7 ± 3.0) subjects underwent four different exercise sessions on a bicycle ergometer for 30 min each at 60, 80, 100, and 110% of the individual anaerobic threshold on separate days in a randomized crossover design. Before, as well as 5- and 45-min post-exercise, pain sensitivity was measured employing pain pressure thresholds (PPT) at the elbow, knee, and ankle joints as well as the sternum and forehead. Besides, conditioned pain modulation (CPM) was conducted using thermal test- and conditioned stimuli before, 5-, and 45-min post-exercise. RESULTS: A main time effect was observed regarding PPT at all landmarks except for the forehead with higher values observed 5 and 45 min post-exercise compared to the pre-values. Yet, no interaction effects occurred. CPM did not change in response to any of the intensities used. CONCLUSION: EIH occurs 5 and 45 min after exercise regardless of the intensity used at the joints and sternum which might be explained by local pain-inhibiting pathways and probably to a limited degree by central mechanisms, as no hypoalgesia was observed at the forehead and no changes in CPM occurred.

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.

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.

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.

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.

Effects of high-intensity interval training in a three-week cardiovascular rehabilitation: a randomized controlled trial.

OBJECTIVE: The aim of this study was to assess the benefit of using high-intensity interval training for cardiovascular patients undergoing outpatient rehabilitation in a standard short-term (three-week) program in Germany. DESIGN: This is a randomized controlled trial (RCT). SETTING: This study was conducted at Cardiowell (Wuppertal, Germany), an outpatient rehabilitation center. INTERVENTION: Patients underwent the typical three-week German outpatient rehabilitation program using either moderate continuous training (i.e. the standard training program) or high-intensity interval training. MAIN MEASURES: A total of 50 patients of an outpatient rehabilitation center were randomized into two groups. The control group underwent the standard rehabilitation protocol that applied moderate continuous training, and the intervention group trained according to a high-intensity interval protocol. Patients trained on a bicycle ergometer. Peak power output, oxygen uptake parameters, heart frequencies, and blood pressure were compared at the beginning and at the end of the rehabilitation program. RESULTS: After three weeks, the intervention group had improved to a significantly greater extent in maximal performance parameters than the control group: the peak power output (20.9 (±14.1) W; control 8.8 (±10.4) W), maximum oxygen uptake (0.33 (±0.33) L/min; control 0.05 (±0.29) L/min)), relative maximum oxygen uptake (3.4 (±4.2) mL/kg/min; control 0.9 (±3.1) mL/kg/min), and O2 pulse (1.8 (±2.2) mL/heart beat; control 0.35 (±1.7) mL/heart beat). CONCLUSION: The implementation of high-intensity interval training during a typical three-week German cardiac rehabilitation has the power to increase the outcome for the patients.

Posturographic and ankle muscle activation characteristics in patients with haemophilia.

INTRODUCTION: The objective of this work was to examine the interrelations of posturographic and surface EMG (SEMG) characteristics of ankle muscles in patients with haemophilia while standing naturally. METHODS: Surface EMG of five bilaterally recorded ankle muscles was conducted in 24 patients with haemophilia (PwH, age: 42 [11] years, mean [SD], 22 A, 2 B, 21 severe, 3 moderate) with median (quartiles) WFH orthopaedic joint score of 30 (20/39) points and 24 non-haemophilic controls (Con, age: 42 [12]). Force plate (IBS) signals were captured simultaneously during bipedal stance with eyes open. Load proportion of the left and right sides as well as heel and forefoot were calculated via four independent pressure transducers. Overall, weight distribution (WD) indices are reported with higher results representing a poorer WD. RESULTS: Analyses of WD showed large differences between groups (PwH: 10.2 [5.4], Con: 5.2 [2.9], P < 0.001, d = 1.15). After clustering PwH, large effects (P = 0.02, ηp 2  > 0.16) were found for amplitude ratios of the lateral gastrocnemius (LG) muscle. In PwH, the degree of joint alteration of the right lower limb was associated with load proportion of the left side (ρ > 0.64, P = 0.001). CONCLUSION: Patients with greater dysbalance showed higher forefoot loads and appeared to compensate their altered joint situations with considerably higher amplitude ratios of LG. Further studies should investigate whether therapeutic interventions could alter postural alignment and muscle activation and how these can influence patients' joint function and symptoms.

Coronary Collateral Growth Induced by Physical Exercise: Results of the Impact of Intensive Exercise Training on Coronary Collateral Circulation in Patients With Stable Coronary Artery Disease (EXCITE) Trial.

BACKGROUND: A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear. METHODS AND RESULTS: This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. CONCLUSIONS: A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.

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.

Rowing and pain: does rowing lead to exercise-induced hypoalgesia?

Physical activity acutely alters pain processing known as exercise-induced hypoalgesia (EIH). This randomized controlled crossover study investigated the effects of two different rowing exercises on EIH and to explore whether possible EIH effects are related to individual rowing specific performance. Fifty male experienced rowers conducted two rowing sessions (submaximal: 30 min of moderate rowing (70% of maximum heart rate); maximal: 350 m in an all-out fashion) and a control session. Pre and post exercise pain sensitivity was measured bilaterally using pressure pain thresholds (PPT; Newton (N)) at the elbow, knee, ankle, sternum, and forehead. Individual performance was determined as maximum watt/kg and was tested for correlations with changes in PPT. Higher PPT values were observed after maximal exercise at all landmarks with a mean change ranging from 2.5 ± 7.8 N (right elbow; p = 0.027; dz = 0.323) to 10.0 ± 12.2 N (left knee; p ≤ 0.001; dz = 0.818). The submaximal (range from -1.6 ± 8.8 N (Sternum; p = 0.205; dz = 0.182) to 2.0 ± 10.3 N (right ankle; p = 0.176; dz = 0.194)) and control session (range from -0.5 ± 7.6 N (left elbow; p = 0.627; dz = 0.069) to 2.6 ± 9.1 N (right ankle; p = 0.054; dz = 0.279)) did not induce changes. Relative performance levels were not correlated to EIH (range from: r = -0.129 (p = 0.373) at sternum to r = 0.176 (p = 0.221) at left knee). EIH occurred globally after a short maximal rowing exercise while no effects occurred after rowing for 30 min at submaximal intensity. EIH cannot be explained by rowing specific performance levels in experienced rowers. However, the sample may lack sufficient heterogeneity in performance levels to draw final conclusions.