Five-Year PTSD Symptom Remission in Two Patients Following Treatment With Rivastigmine.

INTRODUCTION: The beneficial effect of rivastigmine, an acetylcholinesterase inhibitor (AChEi), which increases levels of acetylcholine (ACh), was first reported in 2013. This paper replicates those findings and reports sustained symptom remission. METHODS AND MATERIALS: The high-frequency (HF) component of heart rate variability (HRV) is a measure of cholinergic withdrawal and was measured using a Zephyr Bioharness HR monitor, pre- and post-commencement of treatment. Data analysis was performed using Kubios HRV software. PTSD symptom severity was assessed using the Post-Traumatic Checklist-Civilian (PCL-C). RESULTS: Low HF HRV was observed in both patients before rivastigmine treatment and reductions in PCL-C scores paralleled increases in HF HRV values. Follow-up revealed low HF HRV values in both patients despite PCL-C scores indicating remission. Sympathetic nervous system hyperactivity was observed in one patient, just before a suicide attempt. Following rivastigmine treatment, the patient had no further suicidal ideation or attempts. Another patient reported worsening of her PTSD symptoms in the peri-menstrual period, which was abolished by rivastigmine. She also experienced symptom relapse following prolonged infections. CONCLUSION: Low HF HRV has been reported in PTSD patients, but findings have been inconsistent. Cholinergic withdrawal could explain the disturbances in sleep, learning, and memory seen in PTSD patients. The relapse of symptoms following prolonged infection implicates the immune system as a possible initiator of the disorder. ACh and estrogen have anti-inflammatory properties, supporting a possible role of inflammation in initiating PTSD. The effect of rivastigmine treatment should be tested in properly controlled clinical trials.

Key viral immune genes and pathways identify elite athletes with URS.

PURPOSE: Habitual intense exercise may increase the incidence of upper respiratory symptoms (URS) in elite athletes. This study investigated whether immune gene expression could identify gene markers that discriminate athletes with a higher prevalence of URS. METHODS: This cross-sectional analysis of elite Australian athletes from various sports investigated whether athletes retrospectively reporting URS for two days or more in a month (n=38), had an altered immune gene expression profile compared with asymptomatic athletes (n=33). Peripheral blood samples were collected during Olympic selection events with corresponding URS data collected for the one-month period before sampling. Digital immune gene expression analysis was undertaken using the NanoString PanCancer Immune Profiling panel. RESULTS: Fifty immune genes were differentially expressed between the groups (p<0.05) and approximately 78% of these genes were more highly expressed in athletes reporting URS. Many of these genes were interferon-stimulated genes or genes involved in the Jak/Stat signalling pathway. Only interferon alpha inducible protein 27 (IFI27), an interferon stimulated gene involved in viral response, remained significantly higher in athletes reporting URS (log2 fold-difference=2.49, odds ratio 1.02 per unit increase; p<0.01) post-adjustment and discriminated athletes reporting URS from asymptomatic athletes with 78% accuracy. CONCLUSIONS: Expression of IFI27 could differentiate athletes reporting URS from asymptomatic athletes, a gene that is upregulated in the immune response to viral infection. Upregulation of viral signalling pathways provides novel information on the potential aetiology of URS in elite Olympic athletes.

Oral Supplementation of Specific Collagen Peptides Combined with Calf-Strengthening Exercises Enhances Function and Reduces Pain in Achilles Tendinopathy Patients.

The current pilot study investigates whether oral supplementation of specific collagen peptides improves symptoms and tendon vascularisation in patients with chronic mid-portion Achilles tendinopathy in combination with structured exercise. Participants were given a placebo or specific collagen peptides (TENDOFORTE®) in combination with a bi-daily calf-strengthening program for 6 months. Group AB received specific collagen peptides for the first 3 months before crossing over to placebo. Group BA received placebo first before crossing over to specific collagen peptides. At baseline (T1), 3 (T2) and 6 (T3) months, Victorian Institute of Sports Assessment⁻Achilles (VISA-A) questionnaires and microvascularity measurements through contrast-enhanced ultrasound were obtained in 20 patients. Linear mixed modeling statistics showed that after 3 months, VISA-A increased significantly for group AB with 12.6 (9.7; 15.5), while in group BA VISA-A increased only by 5.3 (2.3; 8.3) points. After crossing over group AB and BA showed subsequently a significant increase in VISA-A of, respectively, 5.9 (2.8; 9.0) and 17.7 (14.6; 20.7). No adverse advents were reported. Microvascularity decreased in both groups to a similar extent and was moderately associated with VISA-A (Rc²:0.68). We conclude that oral supplementation of specific collagen peptides may accelerate the clinical benefits of a well-structured calf-strengthening and return-to-running program in Achilles tendinopathy patients.

Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4): a multicentre, randomised, controlled phase III study protocol.

INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. ETHICS AND DISSEMINATION: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation. TRIAL REGISTRATION NUMBER: NCT02730338.

Prevalence of illness, poor mental health and sleep quality and low energy availability prior to the 2016 Summer Olympic Games.

OBJECTIVE: Establish the prevalence of illness symptoms, poor sleep quality, poor mental health symptoms, low energy availability and stress-recovery state in an Olympic cohort late in the 3 months prior to the Summer Olympic Games. METHODS: Olympic athletes (n=317) from 11 sports were invited to complete questionnaires administered 3 months before the Rio 2016 Olympic Games. These questionnaires included the Depression, Anxiety and Stress Questionnaire, Perceived Stress Scale, Dispositional Resilience Scale, Recovery-Stress Questionnaire (REST-Q-52 item), Low Energy Availability in Females Questionnaire (LEAF-Q), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and custom-made questionnaires on probiotic usage and travel. Multiple illness (case) definitions were applied. ORs and attributable fractions in the population were used. Factor analyses were used to explore the relationships between variables. RESULTS: The response rate was of 42% (male, n=47, age 25.8±4.1 years; female, n=85, age 24.3±3.9 years). Low energy availability was associated with sustaining an illness in the previous month (upper respiratory, OR=3.8, 95% CI 1.2 to 12). The main factor relating to illness pertained to a combination of anxiety and stress-recovery states (as measured by the REST-Q-52 item). All participants reported at least one episode of illness in the last month (100% prevalence). CONCLUSIONS: All participants reported at least one illness symptom in the previous month. Low energy availability was a leading variable associated with illness in Olympic-class athletes. The estimates duration of symptoms ranged from 2 to 7 days. Factor analyses show the interdependence of various health domains and support multidisciplinary care.

A multifactorial evaluation of illness risk factors in athletes preparing for the Summer Olympic Games.

OBJECTIVES: Illness can disrupt training and competition performance of athletes. Few studies have quantified the relative contribution of the known medical, behavioural and lifestyle risk factors. DESIGN: Cross-sectional. METHODS: Olympic athletes from 11 sports (n=221) were invited to complete questionnaires administered nine months before the Rio 2016 Olympic Games. These included the Depression, Anxiety and Stress Questionnaire (DASS-21), Perceived Stress Scale (PSS), Dispositional Resilience Scale (DRS), Recovery-Stress Questionnaire (REST-Q-52 item), Low Energy in Females Questionnaire (LEAF-Q), a modified Personal and Household Hygiene questionnaire, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and custom-made questionnaires on probiotic usage and travel. An illness (case) was defined as an event which limited training or competition for greater hours in the prior month. Odds ratios and attributable fractions in the population (AFP) were utilised for categorical variables with independent t-tests or Wilcoxon rank-sum for continuous variables. RESULTS: Eighty-one athletes responded (male, n=26; female, n=55). There were 16 illness cases and 65 controls. Female athletes were at higher odds of illness (OR=9.4, 95%CI 1.3-410, p=0.01, AFP=0.84). Low energy availability (LEAF-Q score ≥8: OR=7.4, 95%CI 0.78-352, p=0.04, AFP=0.76), depression symptoms (DASS-21: depression score >4, OR=8.4, 95%CI 1.1-59, p<0.01; AFP=0.39) and higher perceived stress (PSS: 10-item, p=0.04) were significantly associated with illness. CONCLUSIONS: Female sex, low energy availability, and mental health are associated with sports incapacity (time loss) due to illness. Low energy availability had high attributable fractions in the population and stands out as a primary association with illness.

Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy.

Muscle weakness and exercise intolerance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min-1·kg body wt-1, maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt-1·day-1 inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50% of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using 31P-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.

Skin autofluorescence is associated with arterial stiffness and insulin level in endurance runners and healthy controls - Effects of aging and endurance exercise.

BACKGROUND: Life-long regular endurance exercise yields positive effects on cardiovascular and metabolic function, disease and mortality rate. Glycation may be a major mechanism behind age-related diseases. However, it remains unknown if skin autofluorescence (SAF), which reflects glycation, is related to arterial and metabolic function in life-long endurance runners and sedentary controls. METHODS: Healthy elderly men: 15 life-long endurance runners (OT) (64±4years) and 12 old untrained (OU) (66±4years), and healthy young men; ten young athletes (YT) (26±4years) matched to OT for running distance, and 12 young untrained (YU) (24±3years) were recruited. Endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI@75 and AI) were measured by an operator-independent PAT 2000. SAF was non-invasively determined using an autofluorescence spectrometer. RESULTS: For AI@75 there was an effect of age (p<0.0001), but not training (p=0.71). There was an interaction for endothelial function (p<0.05): YT had higher RHI than YU (p<0.05) and OU (p<0.01). SAF was associated with arterial stiffness (r2=0.57, p<0.001), insulin and HOMA-index levels after age correction (both r2=0.19, p<0.05). CONCLUSIONS: To our knowledge, these are the first data to show that skin autofluorescence (SAF) is linked to human arterial stiffness and insulin resistance in well-trained elderly and young men as well as sedentary controls. SAF may in the future be a helpful tool to predict vascular and metabolic dysfunction (early signs of aging and pathology). Surprisingly, endurance running only had modest effects on cardiovascular function compared to lean healthy controls.

Oxygen delivery is not a limiting factor during post-exercise recovery in healthy young adults.

PURPOSE: It is still equivocal whether oxygen uptake recovery kinetics are limited by oxygen delivery and can be improved by supplementary oxygen. The present study aimed to investigate whether measurements of muscle and pulmonary oxygen uptake kinetics can be used to assess oxygen delivery limitations in healthy subjects. METHODS: Sixteen healthy young adults performed three sub-maximal exercise tests (6 min at 40% Wmax) under hypoxic (14%O2), normoxic (21%O2) and hyperoxic (35%O2) conditions on separate days in randomized order. Both Pulmonary VO2 and near infra red spectroscopy (NIRS) based Tissue Saturation Index (TSI) offset kinetics were calculated using mono-exponential curve fitting models. RESULTS: Time constant τ of VO2 offset kinetics under hypoxic (44.9 ± 7.3s) conditions were significantly larger than τ of the offset kinetics under normoxia (37.9 ± 8.2s, p = 0.02) and hyperoxia (37±6s, p = 0.04). TSI mean response time (MRT) of the offset kinetics under hypoxic conditions (25.5 ± 13s) was significantly slower than under normoxic (15 ± 7.7, p = 0.007) and hyperoxic (13 ± 7.3, p = 0.008) conditions. CONCLUSION: The present study shows that there was no improvement in the oxygen uptake and muscle oxygenation recovery kinetics in healthy subjects under hyperoxic conditions.Slower TSI and VO2 recovery kinetics under hypoxic conditions indicate that both NIRS and spiro-ergometry are appropriate non-invasive measurement tools to assess the physiological response of a healthy individual to hypoxic exercise.

Heart-Rate Variability Threshold as an Alternative for Spiro-Ergometry Testing: A Validation Study.

Mankowski, RT, Michael, S, Rozenberg, R, Stokla, S, Stam, HJ, and Praet, SFE. Heart-rate variability threshold as an alternative for spiro-ergometry testing: a validation study. J Strength Cond Res 31(2): 474-479, 2017-Although spiro-ergometry is the established "gold standard" for determination of the second ventilatory threshold (VT2), it is a costly and rather time-consuming method. Previous studies suggest that assessing the second anaerobic threshold (AT2) on the basis of heart rate variability (HRV) during exercise may be a more cost-effective and noninvasive manner. However, appropriate validation studies, are still lacking. Eleven healthy, moderately trained subjects underwent 3 incremental exercise tests. Ventilation, oxygen uptake (V[Combining Dot Above]O2), CO2 production (V[Combining Dot Above]CO2), and HRV were measured continuously. Exercise testing was performed in 3 oxygen (FiO2) conditions of inspired air (14, 21, and 35% of oxygen). Participants and assessors were blinded to the FiO2 conditions. Two research teams assessed VT2s and HRVT2s independently from each other. Mean workloads corresponding to VT2 and HRVT2 in hypoxia were, respectively, 19 ± 17% (p = 0.01) and 15 ± 15% (p = 0.1) lower in comparison with hyperoxic conditions. Bland-Altman analysis showed low estimation bias (2.2%) and acceptably precise 95% limits of agreement for workload -15.7% to 20.1% for all FiO2 conditions. Bias was the lowest under normoxic conditions (1.1%) in comparison with hypoxia (3.7%) and hyperoxia (4.7%). Heart rate variability-based AT2 assessment had a most acceptable agreement with VT2 under normoxic conditions. This simple HRVT2 assessment may have potential applications for exercise monitoring in commercial fitness settings.

Impaired muscle strength may contribute to fatigue in patients with aneurysmal subarachnoid hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (a-SAH) show long-term fatigue and face difficulties in resuming daily physical activities. Impaired muscle strength, especially of the lower extremity, impacts the performance of daily activities and may trigger the onset of fatigue complaints. The present study evaluated knee muscle strength and fatigue in patients with a-SAH. This study included 33 patients, 6 months after a-SAH, and 33 sex-matched and age-matched healthy controls. Isokinetic muscle strength of the knee extensors and flexors was measured at 60 and 180°/s. Maximal voluntary muscle strength was defined as peak torque and measured in Newton-meter. Fatigue was examined using the Fatigue Severity Scale. In patients with a-SAH, the maximal knee extension was 22% (60°/s) and 25% (180°/s) lower and maximal knee flexion was 33% (60°/s) and 36% (180°/s) lower compared with that of matched controls (P≤0.001). The Fatigue Severity Scale score was related to maximal knee extension (60°/s: r=-0.426, P=0.015; 180°/s: r=-0.376, P=0.034) and flexion (60°/s: r=-0.482, P=0.005; 180°/s: r=-0.344, P=0.083). The knee muscle strength was 28-47% lower in fatigued (n=13) and 11-32% lower in nonfatigued (n=20) patients; deficits were larger in fatigued patients (P<0.05), particularly when the muscle strength (peak torque) was measured at 60°/s. The present results indicate that patients with a-SAH have considerably impaired knee muscle strength, which is related to more severe fatigue. The present findings are exploratory, but showed that knee muscle strength may play a role in the severity of fatigue complaints, or vice versa. Interventions targeting fatigue after a-SAH seem necessary and may consider strengthening exercise training in order to treat a debilitating condition.

Anterior cruciate ligament rupture is associated with abnormal and asymmetrical lower limb loading during walking.

OBJECTIVES: Anterior Cruciate Ligament (ACL) deficiency may result in abnormal lower limb loading with increased foot pronation. This study evaluated spatiotemporal parameters and plantar pressure distribution during walking in participants with and without an ACL rupture. DESIGN: Cross-sectional. METHODS: Plantar pressure was measured in 42 unilateral ACL deficient (ACLD) participants and 32 healthy controls while walking barefoot. Spatiotemporal parameters, pressure distribution and center of pressure (CoP) during foot roll off were determined. Differences in spatiotemporal parameters and pressure distribution were analyzed using a Linear Mixed Model. CoP position was analyzed with one-way ANOVA. RESULTS: ACLD participants had a longer contact time and earlier forefoot contact compared to controls. The ACLD side showed a shorter contact time and a faster roll off toward the forefoot compared to the ACL intact side. Compared to controls, ACLD participants had increased pressure under the medioproximal side of the midfoot. Within ACLD participants, the ACLD side had decreased pressure under the heel and increased pressure under the forefoot. Foot pronation was not different between groups or within ACLD participants. CoP of the ACLD participants was significantly more toward the toes during initial contact and toward the heel during foot flat. CONCLUSIONS: Changes in lower limb loading during barefoot walking in ACLD participants are due to changes in roll off pattern, most likely in order to reduce anterior shear forces on the knee. Dynamic plantar pressure measurements may assist in evaluating and guiding interventions aimed at normalizing lower limb and knee biomechanics in ACL deficiency.

Hyperoxia increases arterial oxygen pressure during exercise in type 2 diabetes patients: a feasibility study.

OBJECTIVE: The study investigated the feasibility and potential outcome measures during acute hyperoxia in type 2 diabetes patients (DM2). METHODS: Eleven DM2 patients (7 men and 4 women) were included in the study. The patients cycled (30 min at 20% Wmax) whilst breathing three different supplemental oxygen flows (SOF, 5, 10, 15 L min(-1)). During hyperoxic exercise, arterial blood gases and intra-arterial blood pressure measurements were obtained. RESULTS: Arterial pO2 levels increased significantly (ANOVA, p < 0.05) with SOF: 13.9 ± 1.2 (0 L min(-1)); 18.5 ± 1.5 (5 L min(-1)); 21.7 ± 1.7 (10 L min(-1)); 24.0 ± 2.3 (15 L min(-1)). Heart rate (HR) and pH increased significantly after terminating administration of hyperoxic air. CONCLUSIONS: An SOF of 15 L min(-1) appears to be more effective than 5 or 10 L min(-1). Moreover, HR, blood pressure, blood lactate and pH are not recommended as primary outcome measures.

Safety and efficacy of exercise training in adults with Pompe disease: evalution of endurance, muscle strength and core stability before and after a 12 week training program.

BACKGROUND: Pompe disease is a proximal myopathy. We investigated whether exercise training is a safe and useful adjuvant therapy for adult Pompe patients, receiving enzyme replacement therapy. METHODS: Training comprised 36 sessions of standardized aerobic, resistance and core stability exercises over 12 weeks. Before and after, the primary outcome measures safety, endurance (aerobic exercise capacity and distance walked on the 6 min walk test) and muscle strength, and secondary outcome measures core stability, muscle function and body composition, were evaluated. RESULTS: Of 25 patients enrolled, 23 successfully completed the training. Improvements in endurance were shown by increases in maximum workload capacity (110 W before to 122 W after training, [95 % CI of the difference 6 · 0 to 19 · 7]), maximal oxygen uptake capacity (69 · 4 % and 75 · 9 % of normal, [2 · 5 to 10 · 4]), and maximum walking distance (6 min walk test: 492 meters and 508, [-4 · 4 to 27 · 7] ). There were increases in muscle strength of the hip flexors (156 · 4 N to 180 · 7 N [1 · 6 to 13 · 6) and shoulder abductors (143 · 1 N to 150 · 7 N [13 · 2 to 35 · 2]). As an important finding in secondary outcome measures the number of patients who were able to perform the core stability exercises rose, as did the core stability balancing time (p < 0.05, for all four exercises). Functional tests showed small reductions in the time needed to climb four steps (2 · 4 sec to 2 · 1, [- 0 · 54 to -0 · 04 ]) and rise to standing position (5 · 8 sec to 4 · 8, [-2 · 0 to 0 · 0]), while time to run, the quick motor function test results and body composition remained unchanged. CONCLUSIONS: Our study shows that a combination of aerobic, strength and core stability exercises is feasible, safe and beneficial to adults with Pompe disease.

Achilles tendons in people with type 2 diabetes show mildly compromised structure: an ultrasound tissue characterisation study.

BACKGROUND: Musculotendinous overuse injuries are prevalent in people with type 2 diabetes. Non-enzymatic glycosylation of collagen resulting in tendon stiffening may play a role. In this case-control study we determined whether patients with diabetes had poorer ultrasonographic structure in their Achilles tendons compared to age-matched controls. METHODS: People with type 1 diabetes or type 2 diabetes, and age-matched controls, had computerised ultrasound tissue characterisation of both Achilles tendons. In contiguous ultrasonographic images of the tendon, echopatterns were quantified and categorised into four echo-types. Tendon abnormality was quantified as sum of echo-types III+IV. Furthermore, skin autofluorescence (AF) of the forearm (AF-value) was gathered. RESULTS: Twenty four type 2 diabetes patients, 24 controls, 24 type 1 diabetes patients and 20 controls were included. AF-value was higher in type 1 diabetes (1.55±0.17) than in their controls (1.39±0.18, p<0.001) and in type 2 diabetes (2.28±0.38) compared to their controls (1.84±0.32, p<0.001) Achilles tendons of type 2 diabetes patients contained more echo-types III+IV (14.1±7.9%) than matched controls (8.0±5.4%, p<0.001). There was a trend towards a difference in echo-types III+IV between type 1 diabetes patients (9.5±5.3%) and their controls (6.5±3.7%, p=0.055). In a stepwise linear regression analysis, body mass index (BMI) was moderately associated with tendon abnormality in patients with diabetes and controls (ß=0.393, p<0.001). CONCLUSIONS: Type 2, and possibly type 1, diabetes patients showed poorer ultrasonographic Achilles tendon structure that may be a risk factor for tendinopathy. Although markers for accumulation of advanced glycation end products were elevated in both diabetes populations, only BMI was associated with these abnormalities. TRIAL REGISTRATION NUMBER: NTR2209.

Exercise training in adults with Pompe disease: the effects on pain, fatigue, and functioning.

OBJECTIVE: To assess if a 12-week exercise intervention to improve aerobic fitness, muscle strength, and core stability also had an impact on fatigue, pain, activity, and participation in adults with Pompe disease, an inherited neuromuscular disorder. DESIGN: Open-label trial. Change was assessed by the chi-square test and Wilcoxon signed-rank test. SETTING: Physiotherapy practices. PARTICIPANTS: Mildly affected adult patients with Pompe disease who were not dependent on ventilators and/or walking devices and were receiving enzyme replacement therapy. INTERVENTION: Patients participated in a 12-week exercise program, which included 36 sessions of standardized aerobic, resistance, and core stability exercises. MAIN OUTCOME MEASURES: Before and after the training program we evaluated fatigue (Fatigue Severity Scale), pain (yes/no), motor function (Quantitative Muscle Function Test, Rasch-built Pompe-specific Activity Scale), amount of physical activity (activity monitor), and health status (Medical Outcomes Study 36-Item Short-Form Health Survey). RESULTS: Of the 25 patients enrolled, 23 completed the program. At the end of the program, levels of fatigue (median, 5.33 to 4.78, P=.01) and pain (56.5% to 21.7%, P=.04) improved. The quality of motor function and the amount of physical activity patients engaged in did not change. Changes in pain and fatigue were not related to improvements in aerobic fitness or muscle strength. CONCLUSIONS: This study in mildly affected adult patients with Pompe disease suggests that a combined training program aiming to increase aerobic fitness, muscle strength, and core stability also leads to improvements in fatigue and pain.

Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue.

Life-long regular endurance exercise is known to counteract the deterioration of cardiovascular and metabolic function and overall mortality. Yet it remains unknown if life-long regular endurance exercise can influence the connective tissue accumulation of advanced glycation endproducts (AGEs) that is associated with aging and lifestyle-related diseases. We therefore examined two groups of healthy elderly men: 15 master athletes (64 ± 4 years) who had been engaged in life-long endurance running and 12 old untrained (66 ± 4 years) together with two groups of healthy young men; ten young athletes matched for running distance (26 ± 4 years), and 12 young untrained (24 ± 3 years). AGE cross-links (pentosidine) of the patellar tendon were measured biochemically, and in the skin, it was assessed by a fluorometric method. In addition, we determined mechanical properties and microstructure of the patellar tendon. Life-long regular endurance runners (master athletes) had a 21 % lower AGE cross-link density compared to old untrained. Furthermore, both master athletes and young athletes displayed a thicker patellar tendon. These cross-sectional data suggest that life-long regular endurance running can partly counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurance running yields tendon tissue hypertrophy that may serve to lower the stress on the tendon and thereby reduce the risk of injury.

Functional outcome after successful internal fixation versus salvage arthroplasty of patients with a femoral neck fracture.

OBJECTIVES: To determine patient independency, health-related and disease-specific quality of life (QOL), gait pattern, and muscle strength in patients after salvage arthroplasty for failed internal fixation of a femoral neck fracture. DESIGN: Secondary cohort study to a randomized controlled trial. SETTING: Multicenter trial in the Netherlands, including 14 academic and nonacademic hospitals. PATIENTS: Patients after salvage arthroplasty for failed internal fixation of a femoral neck fracture were studied. A comparison was made with patients who healed uneventfully after internal fixation. INTERVENTION: None (observatory study). MAIN OUTCOME MEASUREMENTS: Patient characteristics, SF-12, and Western Ontario McMaster osteoarthritis index scores were collected. Gait parameters were measured using plantar pressure measurement. Maximum isometric forces of the hip muscles were measured using a handheld dynamometer. Differences between the fractured and contralateral leg were calculated. Groups were compared using univariate analysis. RESULTS: Of 248 internal fixation patients (median age, 72 years), salvage arthroplasty was performed in 68 patients (27%). Salvage arthroplasty patients had a significantly lower Western Ontario McMaster osteoarthritis index score (median, 73 vs. 90; P = 0.016) than patients who healed uneventfully after internal fixation. Health-related QOL (SF-12) and patient independency did not differ significantly between the groups. Gait analysis showed a significantly impaired progression of the center of pressure in the salvage surgery patients (median ratio, -8.9 vs. 0.4, P = 0.013) and a significant greater loss of abduction strength (median, -25.4 vs. -20.4 N, P = 0.025). CONCLUSIONS: Despite a similar level of dependency and QOL, salvage arthroplasty patients have inferior functional outcome than patients who heal after internal fixation of a femoral neck fracture. LEVEL OF EVIDENCE: Therapeutic level III.

Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

BACKGROUND: Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. METHODS: 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. RESULTS: The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. CONCLUSIONS: VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

Femoral neck shortening after internal fixation of a femoral neck fracture.

This study assesses femoral neck shortening and its effect on gait pattern and muscle strength in patients with femoral neck fractures treated with internal fixation. Seventy-six patients from a multicenter randomized controlled trial participated. Patient characteristics and Short Form 12 and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were collected. Femoral neck shortening, gait parameters, and maximum isometric forces of the hip muscles were measured and differences between the fractured and contralateral leg were calculated. Variables of patients with little or no shortening, moderate shortening, and severe shortening were compared using univariate and multivariate analyses. Median femoral neck shortening was 1.1 cm. Subtle changes in gait pattern, reduced gait velocity, and reduced abductor muscle strength were observed. Age, weight, and Pauwels classification were risk factors for femoral neck shortening. Femoral neck shortening decreased gait velocity and seemed to impair gait symmetry and physical functioning. In conclusion, internal fixation of femoral neck fractures results in permanent physical limitations. The relatively young and healthy patients in our study seem capable of compensating. Attention should be paid to femoral neck shortening and proper correction with a heel lift, as inadequate correction may cause physical complaints and influence outcome.