Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

The effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis - A systematic review with meta-analysis.

This systematic review aimed to systematically investigate the literature on the effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis. For that, seven databases were searched for relevant randomized controlled trials. After the searches, 36 studies investigating 2281 participants were included. Risk of bias assessments were done by two independent reviewers using the Cochrane Risk of Bias tool 2. Random-effects meta-analyses were performed, and the Grading of Recommendations Assessment, Development and Evaluation framework was used to judge the certainty of evidence. The evidence on benefits of exercise and physical activity programs on fatigue and sleep parameters in people with osteoarthritis and psoriatic arthritis was either lacking or inconclusive. There was very low to low certainty evidence for a slight benefit of exercise and physical activity programs on fatigue at short-term in people with ankylosing spondylitis and rheumatoid arthritis. However, the evidence was very uncertain for the medium- and long-term as well as for any sleep parameters. The results indicate that exercise and physical activity programs may offer some benefits on fatigue for people with arthritis in the short-term, although the best type of exercise remains uncertain. The available evidence on improvements in sleep was insufficient to draw strong conclusions.

Do sociodemographic features, pain sensitivity or pain catastrophizing relate to clinic-based adherence to physiotherapy in people suffering from chronic spinal pain? Secondary analysis of a randomized clinical trial.

PURPOSE: Examining whether socio-demographic variables, pain or functionality are related to the degree of clinic-based therapy adherence in patients suffering from nonspecific chronic spinal pain (nCSP). DESIGN: Secondary analysis of a randomized clinical trial. SETTING: University hospital of Ghent and Brussels. METHODS: Dutch speakers, 18-65 years old, experiencing nCSP for at least 3 months. 120 participants were randomly allocated to two interventional groups, of which 94 completed all therapy sessions. MAIN OUTCOME MEASURES: Degree of clinic-based adherence, defined as the amount of completed therapy sessions. RESULTS: Demographic data (sex, age or education) were not significantly associated with adherence in the total sample or the neuroscience group. For the traditional physiotherapy group, educational level was associated with attendance of at least 50% of the therapy sessions. Regarding pain-, belief- and function-related measures, only the association between change in kinesiophobia and adherence was significant for the traditional physiotherapy group. CONCLUSIONS: Factors related to therapy adherence in the total group or the neuroscience group could not be found. Educational level and change in kinesiophobia were however related to therapy adherence in the traditional physiotherapy group.

Reward-related brain structures are smaller in patients with schizophrenia and comorbid metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MS) is highly prevalent in schizophrenia and often a consequence of unhealthy behaviour. Reward-related brain areas might be associated with MS, since they play a major role in regulating health behaviour. This study examined the relationship between MS and brain volumes related to the reward system in schizophrenia. METHOD: We included patients with schizophrenia, with MS (MS+; n = 23), patients with schizophrenia, without MS (MS-; n = 48), and healthy controls (n = 54). Global brain volumes and volumes of (sub)cortical areas, part of the reward circuit, were compared between patients and controls. In case of a significant brain volume difference between patients and controls, the impact of MS in schizophrenia was examined. RESULTS: Patients had smaller total brain (TB; P = 0.001), GM (P = 0.010), larger ventricles (P = 0.026), and smaller reward circuit volume (P < 0.001) than controls. MS+ had smaller TB (P = 0.017), GM (P = 0.008), larger ventricles (P = 0.015), and smaller reward circuit volume (P = 0.002) than MS-. MS+ had smaller orbitofrontal cortex (OFC; P = 0.002) and insula volumes (P = 0.005) and smaller OFC (P = 0.008) and insula cortical surface area (P = 0.025) compared to MS-. CONCLUSION: In schizophrenia, structural brain volume reductions in areas of the reward circuitry appear to be related to comorbid MS.

Sensory processing and central pain modulation in patients with chronic shoulder pain: A case-control study.

Chronicity and recurrence in musculoskeletal shoulder pain are highly prevalent and can possibly be attributed to the concept of central sensitization. Available studies suggest a role for central sensitization in explaining chronic shoulder pain, but so far a comprehensive quantitative sensory testing (QST) protocol has not been used. The aim of this study was to gain knowledge on sensory processing and central pain modulatory mechanisms in patients suffering from chronic shoulder pain using such a QST protocol. Fifty study participants, including chronic shoulder pain patients and healthy controls, underwent a standardized, comprehensive psychophysical testing procedure. A static adapted QST protocol (including pressure algometry, vibration and mechanical detection) was applied. Thereafter, all subjects underwent dynamic measures of temporal summation and conditioned pain modulation. Questionnaires assessing psychosocial factors were completed by each subject. No significant differences (P >= .05) were found between patients and controls based on pressure algometry, vibration detection, mechanical detection, temporal summation, and conditioned pain modulation. Moderate positive correlations (r = .5) were found between pressure pain thresholds (PPTs) and the amount of sports participation. Weak-to-moderate negative correlations (r = -.3 à -.5) were found between PPTs and psychosocial factors such as pain catastrophizing. Based on these findings, we can conclude that central sensitization is no characteristic feature in chronic musculo-skeletal shoulder pain but can be present in individual cases.

Does pre-surgical central modulation of pain influence outcome after total knee replacement? A systematic review.

The aim of this study is to systematically review whether the presence of altered central pain modulation pre-surgical influences outcome after total knee replacement (TKR) in patients with knee osteoarthritis (OA), and if so which indices of central pain modulation predict poor outcome after TKR. To identify relevant articles, PubMed and Web of Science were searched. The search strategy was a combination of key words related to "Knee Osteoarthritis and Total Knee Replacement", "Central Pain Modulation" and "Post-Surgical Outcome Measures". Articles fulfilling the inclusion criteria were screened for methodological quality and results were analyzed and summarized. Sixteen prospective cohort studies were included. Strong evidence is available that presence of catastrophic thinking and poor coping strategies predict more pain after TKR and that there is no association between fear of movement and post-surgical pain or function. Evidence on other psychosocial influences is limited or conflicting. Literature on the influence of other signs of altered central pain modulation on post-surgical outcome is scarce. It is plausible that pre-surgical signs of altered central pain modulation, such as joint pain at rest or widespread pain sensitization, predict more post-surgical pain. Surgeons should be attentive for patients with signs of altered central pain modulation before surgery as they might be at risk for unfavorable outcome. A broader therapeutic approach aiming to desensitize the central nervous system can be adapted in these patients. Further research is however needed to identify the influence of central pain modulation pre-surgical in predicting outcome after TKR.

Metabolic syndrome in schizophrenia patients associated with poor premorbid school performance in early adolescence.

OBJECTIVE: More than 40% of patients with schizophrenia have an additional diagnosis of the metabolic syndrome (MS), possibly related to poor cognition. This study investigated premorbid and current cognitive functioning in schizophrenia and co-occurrence of MS. METHOD: A total of 104 participants with schizophrenia with MS and 142 without MS were included. Neuropsychological assessment was carried out using the Wechsler Adult Intelligence Scale-III, Word Learning Task, and Continuous Performance Test-HQ. Premorbid functioning was assessed retrospectively with the Premorbid Adjustment Scale. anovas were used to examine differences between participants with and without MS. RESULTS: Subjects with and without MS did not differ concerning current, lifetime and amount substance use, duration/severity of illness, parental socioeconomic status (SES), and type/amount of antipsychotic medication. We found that poor school performance between the ages 12 and 16 is associated with MS in schizophrenia. Educational level and current cognitive functioning in participants with MS deviate as compared to those without MS. CONCLUSION: Subjects with MS had impaired premorbid cognition in adolescence and lower educational achievement, irrespective of parental SES. This suggests poor premorbid cognitive functioning is a risk factor for metabolic complications later in life. Future studies are needed to examine whether cognitive interventions have beneficial effects on general health in schizophrenia.

Connectome organization is related to longitudinal changes in general functioning, symptoms and IQ in chronic schizophrenia.

Emerging evidence suggests schizophrenia to involve widespread alterations in the macroscale wiring architecture of the human connectome. Recent findings of attenuated connectome alterations in unaffected siblings of schizophrenia patients suggest that altered connectome organization may relate to the vulnerability to develop the disorder, but whether it relates to progression of illness after disease onset is currently unknown. Here, we examined the interaction between connectome structure and longitudinal changes in general functioning, clinical symptoms and IQ in the 3years following MRI assessment in a group of chronically ill schizophrenia patients. Effects in patients were compared to associations between connectome organization and changes in subclinical symptoms and IQ in healthy controls and unaffected siblings of schizophrenia patients. Analyzing the patient sample revealed a relationship between structural connectivity-particularly among central 'brain hubs'-and progressive changes in general functioning (p=0.007), suggesting that more prominent impairments of hub connectivity may herald future functional decline. Our findings further indicate that affected local connectome organization relates to longitudinal increases in overall PANSS symptoms (p=0.013) and decreases in total IQ (p=0.003), independent of baseline symptoms and IQ. No significant associations were observed in controls and siblings, suggesting that the findings in patients represent effects of ongoing illness, as opposed to normal time-related changes. In all, our findings suggest connectome structure to have predictive value for the course of illness in schizophrenia.

The effect of docetaxel on developing oedema in patients with breast cancer: a systematic review.

Docetaxel is extensively used in chemotherapy for the treatment of breast cancer. Little attention has been given to oedema as a possible side effect of docetaxel-containing therapies. Until now, no review was conducted to evaluate docetaxel-containing therapies versus docetaxel-free therapies on the magnitude of the risk of developing oedema. In this systematic review, we investigated the risk of developing oedema in patients being treated for breast cancer with or without docetaxel. In this systematic literature review, we searched PubMed and Web of Knowledge for studies on breast cancer patients treated with chemotherapy containing docetaxel. We included clinical trials comparing docetaxel versus docetaxel-free chemotherapy. Oedema had to be reported and measured as a key outcome or an adverse effect. Methodological checklists were used to assess the risk of bias within the selected studies. Seven randomised clinical trials were included. Six trials were of moderate methodological quality. All trials showed an increased rate of oedema in the docetaxel-treatment arm. The trial of weakest methodological quality reported the highest incidence of oedema. The results moderately suggest that adjuvant chemotherapy containing docetaxel is related to a significantly increased risk of developing oedema, compared with docetaxel-free chemotherapy.

Measuring resting energy expenditure during extracorporeal membrane oxygenation: preliminary clinical experience with a proposed theoretical model.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe respiratory failure. Indirect calorimetry (IC) is a safe and non-invasive method for measuring resting energy expenditure (REE). No data exist on the use of IC in ECMO-treated patients as oxygen uptake and carbon dioxide elimination are divided between mechanical ventilation and the artificial lung. We report our preliminary clinical experience with a theoretical model that derives REE from IC measurements obtained separately on the ventilator and on the artificial lung. METHODS: A patient undergoing veno-venous ECMO for acute respiratory failure due to bilateral pneumonia was studied. The calorimeter was first connected to the ventilator and oxygen consumption (VO2 ) and carbon dioxide transport (VCO2 ) were measured until steady state was reached. Subsequently, the IC was connected to the membrane oxygenator and similar gas analysis was performed. VO2 and VCO2 values at the native and artificial lung were summed and incorporated in the Weir equation to obtain a REEcomposite . RESULTS: At the ventilator level, VO2 and VCO2 were 29.5 ml/min and 16 ml/min. VO2 and VCO2 at the artificial lung level were 213 ml/min and 187 ml/min. Based on these values, a REEcomposite of 1703 kcal/day was obtained. The Faisy-Fagon and Harris-Benedict equations calculated a REE of 1373 and 1563 kcal/day. CONCLUSION: We present IC-acquired gas analysis in ECMO patients. We propose to insert individually obtained IC measurements at the native and the artificial lung in the Weir equation for retrieving a measured REEcomposite .

Balancing "hands-on" with "hands-off" physical therapy interventions for the treatment of central sensitization pain in osteoarthritis.

Traditional understanding of osteoarthritis-related pain has recently been challenged in light of evidence supporting a key role of central sensitization in a subgroup of this population. This fact may erroneously lead musculoskeletal therapists to conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied exclusively. The aim of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are also addressed. Future studies should explore the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes against current approaches for chronic osteoarthritis-related pain.

Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review.

Hyperexcitability of the central nervous system (CNS) has been suggested to play an important role in the chronic pain experienced by osteoarthritis (OA) patients. A systematic review following PRISMA guidelines was performed to evaluate the existing evidence from the literature related to the presence of central sensitization (CS) in patients with OA.Electronic databases PubMed and Web of Science were searched to identify relevant articles using pre-defined keywords regarding CS and OA. Full-text clinical reports addressing studies of CS in human adults with chronic complaints due to osteoarthritis were included and screened for methodological quality by two independent reviewers. From the 40 articles that were initially eligible for methodological quality assessment, 36 articles achieved sufficient scores and therefore were discussed. The majority of these studies were case-control studies and addressed OA of the knee joint. Different subjective and objective parameters considered manifestations of CS, which have been previously reported in other chronic pain conditions such as whiplash or rheumatoid arthritis, were established in subjects with OA pain. Overall results suggest that, although peripheral mechanisms are involved in OA pain, hypersensitivity of the CNS plays a significant role in a subgroup of subjects within this population. Although the majority of the literature provides evidence for the presence of CS in chronic OA pain, clinical identification and treatment of CS in OA is still in its infancy, and future studies with good methodological quality are necessary.

Does scapular positioning predict shoulder pain in recreational overhead athletes?

The objective of this prospective study is to investigate possible scapular related risk factors for developing shoulder pain. Therefore, a 2-year follow-up study in a general community sports centre setting was conducted. A sample of convenience of 113 recreational overhead athletes (59 women and 54 men) with a mean age of 34 (17-64; SD 12) years were recruited. At baseline, visual observation for scapular dyskinesis, measured scapular protraction, upward scapular rotation and dynamic scapular control were evaluated. 22% (n=25) of all athletes developed shoulder pain during the 24 months following baseline assessment. The Mean Shoulder Disability Questionnaire (SDQ) score for the painful shoulders was 34.8 (6.3-62.5; SD 17.4). None of the scapular characteristics predicted the development of shoulder pain. However, the athletes that developed shoulder pain demonstrated significantly less upward scapular rotation at 45° (p=0.010) and 90° (p=0.016) of shoulder abduction in the frontal plane at baseline in comparison to the athletes that remained pain-free. In conclusion, although these scapular characteristics are not of predictive value for the development of shoulder pain, this study increases our understanding of the importance of a scapular upward rotation assessment among recreational overhead athletes.

Does acupuncture activate endogenous analgesia in chronic whiplash-associated disorders? A randomized crossover trial.

BACKGROUND: Many patients with chronic pain, including those with chronic whiplash-associated disorders (WAD), show features of central sensitization. Randomized trials examining whether treatments are able to influence the process of central sensitization in patients with chronic WAD are emerging. Therefore, the present study aimed at examining whether acupuncture results in activation of endogenous analgesia and relief in symptoms in patients with chronic WAD. METHODS: In this randomized crossover pilot trial with blinded assessors, each patient (n = 39) received two treatment sessions of identical duration, with acupuncture and relaxation therapy randomly crossed over in visit 2. Primary outcome measurement included immediate activation of endogenous analgesia i.e., pressure pain sensitivity and conditioned pain modulation. Secondary outcome measurements included pain relief and reduced disability level. RESULTS: Local pressure pain sensitivity at baseline and during conditioned pain modulation decreased significantly more following acupuncture compared with relaxation (time × group interactions: p < 0.001), both in the neck and at a site distinct from the painful region. When comparing the effects of acupuncture versus relaxation, no differences were observed on conditioned pain modulation, temporal summation of pressure pain, neck disability or symptom severity (all p-values >0.05). CONCLUSION: It was shown that one session of acupuncture treatment results in acute improvements in pressure pain sensitivity in the neck and calf of patients with chronic WAD. Acupuncture had no effect on conditioned pain modulation or temporal summation of pressure pain. Both acupuncture and relaxation appear to be well-tolerated treatments for people with chronic WAD. These findings suggest that acupuncture treatment activates endogenous analgesia in patients with chronic WAD.

Scapular-focused treatment in patients with shoulder impingement syndrome: a randomized clinical trial.

The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome. Therefore, a randomized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome. The primary outcome measures included self-reported shoulder disability and pain. Next, patients were evaluated regarding scapular positioning and shoulder muscle strength. The scapular-focused treatment included stretching and scapular motor control training. The control therapy included stretching, muscle friction, and eccentric rotator cuff training. Main outcome measures were the shoulder disability questionnaire, diagnostic tests for shoulder impingement syndrome, clinical tests for scapular positioning, shoulder pain (visual analog scale; VAS), and muscle strength. A large clinically important treatment effect in favor of scapular motor control training was found in self-reported disability (Cohen's d = 0.93, p = 0.025), and a moderate to large clinically important improvement in pain during the Neer test, Hawkins test, and empty can test (Cohen's d 0.76, 1.04, and 0.92, respectively). In addition, the experimental group demonstrated a moderate (Cohen's d = 0.67) improvement in self-experienced pain at rest (VAS), whereas the control group did not change. The effects were maintained at three months follow-up.

Evidence for central sensitization in chronic whiplash: a systematic literature review.

BACKGROUND AND OBJECTIVES: It has been suggested that sensitization of the central nervous system plays an important role in the development and maintenance of chronic (pain) complaints experienced by whiplash patients. According to the PRISMA guidelines, a systematic review was performed to screen and evaluate the existing clinical evidence for the presence of central sensitization in chronic whiplash. DATABASES AND DATA TREATMENT: Predefined keywords regarding central sensitization and chronic whiplash were combined in electronic search engines PubMed and Web of Science. Full text clinical reports addressing studies of central sensitization in human adults with chronic complaints due to a whiplash trauma were included and reviewed on methodological quality by two independent reviewers. RESULTS: From the 99 articles that were identified, 24 met the inclusion criteria, and 22 articles achieved sufficient scores on methodological quality and were discussed. These studies evaluated the sensitivity to different types of stimuli (mechanical, thermal, electrical). Findings suggest that although different central mechanisms seem to be involved in sustaining the pain complaints in whiplash patients, hypersensitivity of the central nervous system plays a significant role. Persistent pain complaints, local and widespread hyperalgesia, referred pain and (thoracic) allodynia, decreased spinal reflex thresholds, inefficient diffuse noxious inhibitory controls activation and enhanced temporal summation of pain were established in chronic whiplash patients. CONCLUSIONS: Although the majority of the literature provides evidence for the presence of central sensitization in chronic whiplash, underlying mechanisms are still unclear and future studies with good methodological quality are necessary. In addition, international guidelines for the definition, clinical recognition, assessment and treatment of central sensitization are warranted.