Nocturia in Menopausal Women: The Link Between Two Common Problems of the Middle Age.

INTRODUCTION AND HYPOTHESIS: The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors, treatment needs and options for nocturia in peri-menopausal women. METHODS: This opinion article is a narrative review based on the expertise and consensus of a variety of key opinion leaders, in combination with an extensive literature review. This literature search included a thorough analysis of potential publications on both the PubMed Database and the Web of Science and was conducted between November 2022 and December 2022. The following key words were used "nocturia" and "menopause" or "nocturnal frequency and menopause." Moreover, key words including "incidence," "prevalence," "insomnia," "estrogen therapy," "metabolic syndrome," and "hot flushes" were used in combination with the aforementioned key words. Last, the reference lists of articles obtained were screened for other relevant literature. RESULTS: The perimenopause can be a trigger for inducing nocturia. Typically, obesity, body mass index (BMI), and waist circumference are risk factors for developing peri-menopausal nocturia. Presumably the development of peri-menopausal nocturia is multifactorial, with interplay among bladder, sleep, and kidney problems due to estrogen depletion after the menopause. First, impaired stimulation of estrogen receptors in the urogenital region leads to vaginal atrophy and reduced bladder capacity. Moreover, menopause is associated with an increased incidence of overactive bladder syndrome. Second, estrogen deficiency can induce salt and water diuresis through blunted circadian rhythms for the secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone system. Additionally, an increased incidence of sleep disorders, including vasomotor symptoms and obstructive sleep apnea signs, is observed. Oral dryness and a consequent higher fluid intake are common peri-menopausal symptoms. Higher insulin resistance and a higher risk of cardiovascular diseases may provoke nocturia. Given the impact of nocturia on general health and quality of life, bothersome nocturia should be treated. Initially, behavioral therapy should be advised. If these modifications are inadequate, specific treatment should be proposed. Systemic hormone replacement is found to have a beneficial effect on nocturia, without influencing sodium and water clearance in patients with nocturnal polyuria. It is presumed that the improvement in nocturia from hormonal treatment is due to an improvement in sleep disorders.

Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a high risk of vascular complications. Interestingly, cocoa flavanols (CF) can exert beneficial vascular effects in non-diabetic subjects. However, these effects have only been scarcely studied in T2DM. Therefore, we performed a study to assess the effects on vascular reactivity of a single dose of CF (790 mg) in T2DM and whether certain antihypertensive drugs may modulate these effects. METHODS: 24 non-diabetic and 11 T2DM subjects were studied in a cross-over design. Fasting blood samples, blood pressure (BP), and arterial vasoreactivity (flow-mediated dilation) were assessed before and 70 min after capsule ingestion. Muscle microvascular reactivity was only assessed after capsule ingestion. Age, waist-to-hip ratio, BP at baseline, and the use of antihypertensive drugs were regarded as covariates in a mixed models analysis. RESULTS: CF ingestion did not affect any parameter. However, independent of the type of capsules ingested, a decrease in diastolic BP by 3 mmHg (95% CI: -4.0; -2.0) and an increase in the change in brachial artery diameter (pre vs. post occlusion) by 0.06 mm (95% CI: 0.01; 0.12) were detected in the non-diabetic group, while they remained unchanged in the T2DM group. CONCLUSION: No beneficial effects of CF were detected on vascular reactivity parameters in T2DM and non-diabetic participants.

Societal participation in ehlers-danlos syndromes and hypermobility spectrum disorder, compared to fibromyalgia and healthy controls.

Ehlers-Danlos syndrome and hypermobility spectrum disorder affect daily life. There is a lack of research that investigates how the disease affects aspects of participation. This study investigates whether there is a difference in the level of participation in society in persons with vascular EDS (N = 18), hypermobile EDS (N = 20), classical EDS (N = 4) and Hypermobility Spectrum Disorder (N = 27), compared to a healthy control group (N = 69) and fibromyalgia (N = 69). In this retrospective case-control study, the Ghent Participation Scale was completed by all participants. Each patient with EDS and HSD was matched by age and sex to healthy controls. The hEDS and HSD group were compared with the healthy control group and a positive control group (persons with fibromyalgia). The results show that there was a significant lower overall participation score for persons with hEDS/HSD compared to the healthy control group. In addition, significant differences were observed in the subscores self-performed activities and delegated activities in the hEDS/HSD group compared to healthy controls, being HEDS/HSD patients who obtained the lower scores. Further research is needed to obtain representative results of the participation level for the EDS/HSD population. In this way, interventions can be set up for patients with EDS in an evidence-based way and that are appropriate to the patient's level of participation.

Markers of protein-energy wasting and physical performance in haemodialysis patients: A cross-sectional study.

BACKGROUND: Physical impairments are common in uraemia, as reflected by the high risk of falls of haemodialysis (HD) patients. Furthermore, these patients often suffer from malnutrition. OBJECTIVE: Up to now, it is unknown which aspects of physical performance are predominantly driven by malnutrition in HD patients. As this answer could steer different interventions, the aim of this study was to evaluate the cross-sectional relationship between nutritional status, muscle strength, exercise capacity and the risk of falls. METHODS: This study recruited HD patients between December 2016 and March 2018 from two hospital-based and five satellite dialysis units (registration number on clinicaltrial.gov: NCT03910426). The mini-nutritional assessment scale as well as objective measures of protein-energy wasting were obtained (total iron-binding capacity, total protein levels, and CRP). Physical assessment included muscle strength (quadriceps, handgrip force, and sit-to-stand test), exercise capacity (six-minute walking test) and the risk of falls (Tinetti, FICSIT, and dialysis fall index). Their interrelationship was analysed by ridge regression models. RESULTS: Out of 113 HD patients (mean age 67 years ± 16.1, 57.5% male) 36.3% were malnourished according to the mini-nutritional assessment scale and a majority had impaired quadriceps force (86.7%), six-minute walking test (92%), and an increased risk of falls (73.5%). Total protein and CRP levels were identified as relevant nutritional factors in the association with physical performance. Nutritional parameters explained 9.2% of the variance in the risk of falls and 7.6% of the variance in exercise capacity. No conclusive association was found between nutritional status and muscle strength. CONCLUSION: Protein-energy wasting is a determinant of the risk of falls and exercise capacity in patients on HD. The association between malnutrition and muscle weakness remains inconclusive.

Foci of Segmentally Contracted Sarcomeres in Trapezius Muscle Biopsy Specimens in Myalgic and Nonmyalgic Human Subjects: Preliminary Results.

OBJECTIVE: The myofascial trigger point hypothesis postulates that there are small foci of contracted sarcomeres in resting skeletal muscle. Only one example, in canine muscle, has been published previously. This study evaluated human muscle biopsies for foci of contracted sarcomeres. SETTING: The Departments of Rehabilitation Sciences and Physiotherapy at Ghent University, Ghent, Belgium. SUBJECTS: Biopsies from 28 women with or without trapezius myalgia were evaluated, 14 in each group. METHODS: Muscle biopsies were obtained from regions of taut bands in the trapezius muscle and processed for light and electron microscopy and for histochemical analysis. Examination of the biopsies was blinded as to group. RESULTS: A small number of foci of segmentally contracted sarcomeres were identified. One fusiform segmental locus involved the entire muscle fiber in tissue from a myalgic subject. Several transition zones from normal to contracted sarcomeres were found in both myalgic and nonmyalgic subjects. The distance between Z-lines in contracted sarcomeres was about 25-45% of the same distance in normal sarcomeres. Z-lines were disrupted and smeared in the contracted sarcomeres. CONCLUSIONS: A small number of foci of segmentally contracted sarcomeres were found in relaxed trapezius muscle in human subjects, a confirmation of the only other example of spontaneous segmental contraction of sarcomeres (in a canine muscle specimen), consistent with the hypothesis of trigger point formation and with the presence of trigger point end plate noise.

Differences in the Mitochondrial and Lipid Droplet Morphology in Female Office Workers With Trapezius Myalgia, Compared With Healthy Controls: A Muscle Biopsy Study.

OBJECTIVE: Trapezius myalgia or, more specifically, myofascial dysfunction of the upper trapezius mainly affects women performing jobs requiring prolonged low level activation of the muscle. This continuous low muscle load can be accompanied by a shift to a more anaerobic energy metabolism, causing pain. The aim of the study was to investigate whether morphological signs of an impaired aerobic metabolism are present in female office workers with trapezius myalgia. DESIGN: Muscle biopsy analysis, using electron and light microscopy, was performed to compare mitochondrial and fat droplet morphology, and irregular muscle fibers, between female office workers with (n = 17) and without (n = 15) work-related trapezius myalgia. RESULTS: The patient group showed a significantly higher mean area (P = 0.023) and proportion (P = 0.029) for the subsarcolemmal and intermyofibrillar mitochondria respectively, compared with the control group. A significantly lower mean area of subsarcolemmal lipid droplets was found in the patient group (P = 0.015), which also displayed a significantly higher proportion of lipid droplets touching the mitochondria (P = 0.035). A significantly higher amount of muscle fibers with cytochrome c oxidase-deficient areas were found in the patient group (P = 0.030). CONCLUSIONS: The results of the present study may be indicative for an impaired oxidative metabolism in work-related trapezius myalgia. However, additional research is necessary to confirm this hypothesis.

Morphological Differences in the Upper Trapezius Muscle Between Female Office Workers With and Without Trapezius Myalgia: Facts or Fiction?: A Cross-Sectional Study.

OBJECTIVE: Work-related trapezius myalgia is a common musculoskeletal disorder in office workers. Prolonged low-level muscle activity during office work may lead to morphological changes in the muscle tissue, causing pain and fatigue. The aim of the present study was to investigate differences in muscle morphology between office workers with and without trapezius myalgia. DESIGN: Muscle biopsy samples were obtained from the upper trapezius of female office workers with trapezius myalgia (n = 17) and healthy controls (n = 15). Myosin heavy chain immunohistochemistry and Gomori trichrome stainings were performed to identify differences in muscle fiber type proportion, Feret's diameter, and internal nuclear proportion. RESULTS: The myalgia group showed significantly more type IIA and IIA/IIX fibers and less type I and IIX fibers, compared with the control group (P < 0.001 to P = 0.005). No significant differences were found for Feret's diameter and internal nuclear proportion (P > 0.05). However, a significantly higher Feret's diameter was found for type I fibers, compared with type II fibers in both groups (P < 0.001 to P = 0.002). Several subjects of both groups displayed an internal nuclear proportion of more than 3%. CONCLUSIONS: Female office workers with trapezius myalgia show a different fiber type distribution compared with their healthy colleagues but display no differences in fiber size and internal nuclear proportion.

Short and long-term impairments of cardiopulmonary fitness level in previous childhood cancer cases: a systematic review.

PURPOSE: To describe the impairments in physical fitness in individuals who were previously diagnosed and treated for childhood cancer. METHODS: Using the PRISMA-guidelines, a systematic search was performed in PubMed, Web of Science, and Embase using a combination of the following predefined keywords: "exercise capacity" OR "aerobic capacity" OR "fitness" OR "cardiorespiratory fitness" OR "cardiopulmonary fitness" OR "physical fitness" OR "exercise testing" OR "exercise tolerance" OR "exercise" OR "oxygen consumption" AND "leukemia" OR "childhood cancer" OR "childhood cancer survivors (CCS)". Studies that met our inclusion criteria were reviewed on methodological quality, while the Newcastle-Ottawa Scale was used for evidence synthesis. RESULTS: A total of 2644 articles were identified from the database search. After screening based on the eligibility (abstracts) and inclusion (full texts) criteria, 49 articles remained. Even though the risk-of-bias scores in the studies were generally low, yet the results from those with high-quality studies revealed that poor fitness levels were prevalent in individuals with acute lymphoblastic leukemia, brain tumor, and mixed cancer histories, compared to healthy controls. CONCLUSIONS: A global glance at CCS shows poor levels of fitness that is continuous and life-long even after active cancer treatment has ended. Nevertheless, the results presented in this review were based on a limited number of high-quality studies suggesting the need to for additional clinical trials in the topic area.

Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis.

OBJECTIVES: The purposes were to (i) determine the effect of diet-only treatments and combined diet and exercise treatments on pain and physical function and (ii) explore the effect of these treatments on inflammatory biomarkers in overweight and obese adults with knee osteoarthritis. METHODS: Five electronic databases were searched until March 2017. Randomised controlled trials investigating the effect of non-surgical non-pharmacological weight loss treatment, with or without exercise, on self-reported pain and/or physical function and/or inflammatory biomarkers were selected. Two review authors independently extracted data and assessed risk of bias for each study. Standardised mean differences (SMD) of outcomes were pooled as appropriate, using a random effects approach. RESULTS: 2676 articles were identified, 19 met review criteria and 9 met criteria for meta-analyses. Diet-only treatments did not reduce pain (SMD -0.13; 95% confidence interval, CI: -0.37, 0.10; I2 = 49%) while a combination of diet and exercise treatments did reduce pain moderately (SMD -0.37; 95%CI: -0.69, -0.04; I2 = 54%). Physical function improved moderately with diet treatments (SMD -0.30; 95%CI: -0.52, -0.08; I2 = 47%) and combined diet and exercise treatments (SMD -0.32; 95%CI: -0.56, -0.08; I2 = 24%). Of the inflammatory markers assessed, only IL-6 reduced with diet-only treatments (SMD -0.23; 95%CI: -0.45, -0.02; I2 = 0%). CONCLUSION: Overall, moderate pain-relief is achievable with a combination of diet and exercise, but potentially not with diet-only treatments. Findings support that either diet-only treatments or combined diet and exercise treatments moderately improve physical function. Overall, treatment effects on inflammatory biomarkers are questionable.

Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study.

BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown. METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten chronic fatigue syndrome (CFS)/fibromyalgia (FM) patients, 11 rheumatoid arthritis (RA) patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/mL Naloxone) and placebo (2 mL Aqua) group. Pressure pain thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned pain modulation (CPM) efficacy and deep tissue pain pressure were assessed by adding ischemic occlusion at the opposite upper arm. RESULTS: Deep tissue pain pressure was lower and temporal summation higher in CFS/FM (P = 0.002 respectively P = 0.010) and RA patients (P = 0.011 respectively P = 0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (P time = 0.034). Accordingly, PPTs increased after placebo (P time = 0.015), and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, deep tissue pain, temporal summation or CPM in the control group. CONCLUSIONS: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

Morphological and physiological differences in the upper trapezius muscle in patients with work-related trapezius myalgia compared to healthy controls: A systematic review.

BACKGROUND: Trapezius myalgia is a common musculoskeletal complaint, characterized by pain, stiffness and tightness of the upper trapezius muscle. It is often work-related and caused by prolonged static and repetitive work tasks. It is hypothesized that this leads to various morphological and physiological alterations in muscle tissue but the pathophysiology is poorly understood. These alterations can be investigated by analysing muscle biopsies in order to reveal the underlying cellular mechanisms. OBJECTIVES: This systematic review aimed at providing a summary of the existing literature regarding morphological and physiological differences between people with work-related trapezius myalgia and healthy controls, obtained by analysing muscle biopsies. DESIGN: Systematic review. METHODS: A systematic literature search was performed in following databases: Pubmed, Web of Science and Embase by using different keyword combinations. This systematic review is reported following the PRISMA guidelines. RESULTS: Generally, low to moderate evidence was found for the absence of differences in muscle morphology in people with trapezius myalgia, compared to healthy controls. However, significant differences were mainly found in comparison with the control group with another occupation than the myalgic group. It can thus be hypothesized that morphological alterations in muscle tissue are related to work load and not to pain. Low to moderate evidence was also found for the absence of differences at the physiological level. CONCLUSIONS: Based on this systematic review, there are no clear differences in muscle morphology and physiology between subjects with trapezius myalgia and healthy controls.

Determinants of testosterone levels in human male obesity.

Testosterone (T) levels are decreased in obese men, but the underlying causes are incompletely understood. Our objective was to explore the relation between low (free) T levels and male obesity, by evaluating metabolic parameters, subcutaneous adipose tissue (SAT) aromatase expression, and parameters of the hypothalamic-pituitary-gonadal axis. We recruited 57 morbidly obese men [33 had type 2 diabetes (DM2)] and 25 normal-weight men undergoing abdominal surgery. Fourteen obese men also attended a follow-up, 2 years after gastric bypass surgery (GBS). Circulating T levels were quantified by LC-MS/MS, whereas free T levels were measured using serum equilibrium dialysis and sex hormone-binding globulin, luteinizing hormone, and follicle-stimulating hormone by immunoassay. SAT biopsies were used to determine adipocyte cell size and aromatase expression by real-time PCR. Total and free T levels were decreased in obese males versus controls, with a further decrease in obese men with DM2 versus obese men without DM2. There were no differences in aromatase expression among the study groups, and sex steroids did not correlate with aromatase expression. Pearson analysis revealed an inverse association between (free) T and SAT cell size, triglycerides, and HOMA-IR. Multivariate analysis confirmed the inverse association between (free) T and SAT cell size (ß = -0.321, P = 0.037 and ß = -0.441, P = 0.011, respectively), independent of age, triglycerides, HOMA-IR, obesity, or diabetes. T levels were normalized 2 years after GBS. These data suggest that SAT cell size rather than SAT aromatase expression or parameters of the hypothalamic-pituitary-gonadal axis is related to low T in male obesity, which points to adipose cell size-related metabolic changes as a major trigger in decreased T levels.

Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls.

AIM: This study provides insight into the profile and importance of autonomic symptoms in the hypermobility type (HT) of Ehlers-Danlos syndrome (EDS). The impact of these symptoms is put into perspective by comparing with fibromyalgia (FM) and two other EDS types. METHODS: Overall, 80 patients with EDS-HT participated, as well as 11 with classical EDS (cEDS), seven with vascular EDS (vEDS), 38 with FM, and 43 healthy controls. All participants filled out the autonomic symptom profile (ASP). Furthermore, they were inquired about quality of life (QOL, SF-36) and factors contributing to the EDS disease burden, e.g., hypermobility (5-point questionnaire, GHQ), fatigue (checklist individual strength, CIS), pain (pain detect questionnaire, PDQ), affective distress (hospital anxiety and depression scale, HADS), and physical activity (Baecke). RESULTS: The total autonomic symptom burden was higher in EDS-HT (57.9 ± 21.57) than in controls (11.3 ± 19.22), cEDS (32.3 ± 19.47), and vEDS (29.1 ± 19.18), but comparable to FM (53.8 ± 19.85). Especially orthostatic and gastrointestinal complaints were prevalent. The importance of autonomic symptoms in EDS-HT was emphasized by the correlation with lowered QOL (r = -0.402), fatigue (r = 0.304), and pain severity (r = 0.370). Although affective distress and decreased physical activity are often suggested as possible causes for dysautonomia, the ASP did not correlate with the HADS and Baecke score. By contrast, the correlation of the GHQ (r = 0.298) and PDQ (r = 0.413) with the ASP supports the hypothesis that joint hypermobility and neuropathy may play a role in the development of autonomic symptoms. CONCLUSION: Autonomic symptoms, especially orthostatic and gastrointestinal complaints, are frequent extraarticular manifestations of EDS-HT and contribute to the disease burden.

Impact of the preoperative risk and the type of surgery on exercise capacity and training after valvular surgery.

Information on exercise capacity and training in patients who underwent valvular surgery is scarce. The aim of this study is to evaluate postoperative exercise capacity and functional improvement after exercise training according to the preoperative risk and type of surgery. In this prospective study, 145 patients who underwent aortic valve surgery (AVS) or mitral valve surgery (MVS) and who were referred for cardiac rehabilitation were stratified according to the preoperative risk (European System for Cardiac Operative Risk Evaluation [EuroSCORE]) and type of surgery (sternotomy vs ministernotomy or port access). Exercise capacity was evaluated at the start and end of cardiac rehabilitation. Postoperative exercise capacity and the benefit from exercise training were compared between the groups. Patients with a higher preoperative risk had a worse postoperative exercise capacity, with a lower load, peak VO2, anaerobic threshold and 6-minute walking distance (all p<0.001), and a higher VE/VCO2 slope (p=0.01). In MVS, port access patients performed significantly better at baseline (all p<0.05), but in AVS, ministernotomy patients performed better than sternotomy patients with a concomitant coronary artery bypass graft (p<0.05). Training resulted in an improvement in exercise capacity in each risk group and each type of surgery (all p<0.05). This gain in exercise capacity was comparable for the EuroSCORE risk groups and for the types of surgery, for patients after AVS or MVS. In conclusion, exercise capacity after cardiac surgery is related to the preoperative risk and the type of surgery. Despite these differences in postoperative exercise capacity, a similar benefit from exercise training is obtained, regardless of their preoperative risk or type of surgery.

The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?

INTRODUCTION: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are characterized by persistent pain and fatigue. It is hypothesized that reactive oxygen species (ROS), caused by oxidative and nitrosative stress, by inhibiting mitochondrial function can be involved in muscle pain and central sensitization as typically seen in these patients. AREAS COVERED: The current evidence regarding oxidative and nitrosative stress and mitochondrial dysfunction in CFS and FM is presented in relation to chronic widespread pain. Mitochondrial dysfunction has been shown in leukocytes of CFS patients and in muscle cells of FM patients, which could explain the muscle pain. Additionally, if mitochondrial dysfunction is also present in central neural cells, this could result in lowered ATP pools in neural cells, leading to generalized hypersensitivity and chronic widespread pain. EXPERT OPINION: Increased ROS in CFS and FM, resulting in impaired mitochondrial function and reduced ATP in muscle and neural cells, might lead to chronic widespread pain in these patients. Therefore, targeting increased ROS by antioxidants and targeting the mitochondrial biogenesis could offer a solution for the chronic pain in these patients. The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area.

Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review.

OBJECTIVE: The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia (FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects. METHODS: To obtain relevant articles, PubMed and Web of Knowledge were searched for case-control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined. RESULTS: Sixteen case-control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, as well as increased sympathetic activity and a blunted autonomic response to stressors. Resistance training improved HRV in FM patients. In CFS patients HRV was only reduced during sleep. CONCLUSION: FM patients show more HRV aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV.

Endogenous oestradiol and cardiovascular disease in healthy men: a systematic review and meta-analysis of prospective studies.

CONTEXT: The literature provides no clear answer as to whether total oestradiol (E2) concentrations increase the risk of incident cardiovascular disease (CVD) in healthy men. OBJECTIVE: The authors conducted a systematic review and meta-analysis to estimate the predictive value of E2 for CVD, and to identify study features explaining conflicting results. DATA SOURCES: Articles were identified by a Medline and Embase search and citation tracking. STUDY SELECTION: Eligible articles were prospective population-based cohorts and nested case-control studies on E2 and incident cardiovascular disease (CVD), including myocardial infarction, stroke or death from coronary heart disease. DATA-EXTRACTION: Independent researchers re-expressed associations of E2 and incident CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of E2 for CVD. RESULTS AND CONCLUSIONS: 14 studies out of 128 electronically identified articles were eligible. Data to be used for meta-analysis could be calculated in seven cases, and in the remaining seven cases, data of three more became available by contacting those authors. Overall, a non-significant association was found with an estimated summary RR of 0.98 for a change of >75th versus <25th percentile in E2 (95% CI 0.74 to 1.31). Mean body mass index (BMI) of the study population (ßs -0.8, p<0.004), and quality of E2 assay (ßs -0.6, p<0.08) may have modified the relationship between E2 and incident CVD. The present systematic review does not provide evidence for a pronounced harmful or beneficial effect of E2 on risk for incident CVD in healthy men. If present, an effect of E2 on risk for CVD might be modulated by BMI.

Medication, surgery, and physiotherapy among patients with the hypermobility type of Ehlers-Danlos syndrome.

OBJECTIVES: To describe medication use, surgery, and physiotherapy, and to examine the effect of these treatment modalities on functional impairment and amount of complaints among patients with the hypermobility type of Ehlers-Danlos syndrome (EDS-HT). DESIGN: Cross-sectional study. SETTING: Physical and rehabilitation medicine department and center for medical genetics. PARTICIPANTS: Patients with EDS-HT (N=79; 8 men, 71 women) were recruited for this study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients filled out questionnaires regarding type of complaints, medication use, surgery, physiotherapy, and outcome of treatment. Functional impairment in daily life was measured by the Sickness Impact Profile. Pain severity was assessed with visual analog scales. RESULTS: Patients reported a large number of complaints, a considerable presence of severe pain, and a clinically significant impact of disease on daily functioning. Most patients (92.4%) used medications, among which analgesics were the most prevalent. Fifty-six patients (70.9%) underwent surgery, including mainly interventions of the extremities and abdomen. Forty-one patients (51.9%) are currently enrolled in a physical therapy program, mainly comprising neuromuscular exercises, massage, and electrotherapy. Patients with a high consumption of analgesics, who visited the physiotherapist, or who underwent surgery had a higher dysfunction in daily life. Only 33.9% of the patients who underwent surgery and 63.4% of patients in physical therapy reported a positive outcome. CONCLUSIONS: Patients with EDS-HT have numerous complaints and an impaired functional status that strongly determine their high rate of treatment consumption. The outcome of surgical and physiotherapy treatment is disappointing in a large percentage, which illustrates a strong need for evidence-based therapy.

Impairment and impact of pain in female patients with Ehlers-Danlos syndrome: a comparative study with fibromyalgia and rheumatoid arthritis.

OBJECTIVE: The purpose of this study was to investigate functional impairment and the impact of pain in patients with Ehlers-Danlos syndrome, hypermobility type (EDS-HT), and to compare the burden of disease with that in women with fibromyalgia (FM) and rheumatoid arthritis (RA). METHODS: A total of 206 female patients were compared (72 with EDS-HT, 69 with FM, and 65 with RA). Functional impairment was assessed with the Sickness Impact Profile (SIP), and the psychosocial impact of chronic pain was quantified with the Multidimensional Pain Inventory (MPI). Data on symptoms were collected. RESULTS: SIP results showed clinically relevant health-related dysfunction in all groups. Significantly poorer physical, psychosocial, and overall function was found in the EDS-HT group compared with the RA group. In comparison with the FM group, the EDS-HT group reported similar physical and overall function, but better psychosocial function. T scores from the MPI revealed significantly higher levels of pain severity and life interference due to pain, and a lower level of perceived life control, in the EDS-HT group compared to the RA group. In contrast, the EDS-HT group showed significantly lower levels of pain severity, life interference, and affective distress in comparison with the FM group. Social support for help in coping with pain was similar between the 3 groups. CONCLUSION: EDS-HT is associated with a consistent burden of disease, similar to that of FM and worse than that of RA, as well as a broad impact of chronic pain on daily life, which needs to be addressed in the health care system.

Physical fitness in morbidly obese patients: effect of gastric bypass surgery and exercise training.

BACKGROUND: There is a growing consensus that bariatric surgery is currently the most efficacious and long-term treatment for clinically severe obesity. However, it remains to be determined whether poor physical fitness, an important characteristic of these patients, improves as well. The purpose of this pilot study is to investigate the effect of gastric bypass surgery on physical fitness and to determine if an exercise program in the first 4 months is beneficial. METHODS: Fifteen morbidly obese patients (BMI 43.0 kg/m(2)) were tested before and 4 months after gastric bypass surgery. Eight of them followed a combined endurance and strength training program. Before and after 4 months the operation, anthropometrical characteristics were measured, and an extensive assessment of physical fitness (strength, aerobic, and functional capacity) was performed. RESULTS: Large-scale weight loss through gastric bypass surgery results in a decrease in dynamic and static muscle strength and no improvement of aerobic capacity. In contrast, an intensive exercise program could prevent the decrease and even induced an increase in strength of most muscle groups. Together with an improvement in aerobic capacity, functional capacity increased significantly. Both groups evolved equally with regard to body composition (decrease in fat mass and fat-free mass). CONCLUSIONS: An exercise training program in the first 4 months after bariatric surgery is effective and should be promoted, considering the fact that physical fitness does not improve by weight loss only.