Circadian Rhythms of the Autonomic Nervous System: Scientific Implication and Practical Implementation

Circadian rhythms are omnipresent in almost any biosignal. In this chapter, we join them with the need for practical tools for screening in preventive settings and point out heart rate variability (HRV), a measure of autonomic nervous system activity, as a chronobiologic, unspecific index of mental and physical health. We discuss methods to calculate the circadian variation of HRV measures, particularly the cosinor procedure. We present reference values for circadian variation parameters of HRV and data concerning reproducibility. Furthermore, we show data giving first evidence of HRV as a comprehensive health index by showing altered circadian variation patterns of HRV depending on mental (trait dysthymia) as well as physical (inflammatory markers) health. Finally, we present examples of disturbed chronobiology of HRV in clinical and preventive settings and its practical application in medical consultation

Inter -and intraobserver variation of ultrasonographic cartilage thickness assessments in small and large joints in healthy children

<p>Abstract</p> <p>Background</p> <p>There is an increasing interest among pediatric rheumatologist for using ultrasonography (US) in the daily clinical examination of children with juvenile idiopathic arthritis (JIA). Loss of joint cartilage may be an early feature of destructive disease in JIA. However, US still needs validation before it can be used as a diagnostic bedside tool in a pediatric setting. This study aims to assess the inter- and intraobserver reliability of US measurements of cartilage thickness in the joints of healthy children.</p> <p>Methods</p> <p>740 joints of 74 healthy Caucasian children (27 girls/47 boys), aged 11.3 (7.11 – 16) years were examined with bilateral US in 5 preselected joints to assess the interobserver variability. In 17 of these children (6 girls/11 boys), aged 10.1(7.11–11.1) years, 170 joints was examined in an intraobserver sub study, with a 2 week interval between the first and second examination.</p> <p>Results</p> <p>In this study we found a good inter- and intraobserver agreement expressed as a coefficient of variation (CV) less than 10% in the knee (CV = 9.5%_{interobserver}and 5.9%_{intraobservserI}, 9.3%_{intraobserverII}respectively for the two intraobserver measurements) and fairly good for the MCP joints (CV = 11.9%_{interobserver}, 12.9%_{intraobserverI}and 11.9%_{intraobsevrerII}). In the ankle and PIP joints the inter- and intraobserver agreement was within an acceptable limit (CV<20%) but not for the wrist joint (CV>26%). We found no difference in cartilage thickness between the left and right extremity in the investigated joints.</p> <p>Conclusion</p> <p>We found a good inter -and intraobserver agreement when measuring cartilage thickness with US. The inter- and intraobserver variation seemed not to be related to joint size. These findings suggest that positioning of the joint and the transducer is of major importance for reproducible US measurements. We found no difference in joint cartilage thickness between the left and right extremity in any of the examined joint of the healthy children. This is an important finding giving the opportunity of using the non-affected extremity as a reference when assessing articular joint cartilage damage in JIA.</p

A need for “good eyes”: Experiences told by patients diagnosed with psychosis

This study highlights experiences of psychiatric care described by patients diagnosed with psychosis. The aim was to investigate how patients, based on earlier experiences, described their wishes and needs regarding the psychiatric care system. Data comprised material from four focus groups; analysis used an inductive thematic approach. Relationships with staff emerged as a recurring theme. During periods of psychosis, patients needed staff to act as “parental figures,” providing care, safety, and help in dealing with overwhelming stimulation from the outside word. In the ensuing struggle to devise a livable life, the need for relationships recurred. In this phase, staff needed to give their time, provide support through information, and mirror the patient's capacity and hope. The patient's trials were described as threatened by a lack of continuity and non-listening professionals. It was important for staff to listen and understand, and to see and respect the patients' viewpoints

2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients'and clinicians'values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Variation in neurosurgical management of traumatic brain injury: A survey in 68 centers participating in the CENTER-TBI study

Background Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Plasma Membrane Biophysical Properties Linked to the Antiproliferative Effect of Interferon-α

The relationship of plasma membrane biophysical properties to the antiproliferative effect of interferon-alpha (IFN-a) was investigated in Daudi lymphoblasts cell lines with sensitivity to growth inhibition, parallel clonal variants selected for resistance, and one revertant subclone. Lateral mobility of surface differentiation antigens (I2, CD19, CD20, and sIgM-k) were measured by fluorescence recovery after photobleaching (FRAP). The mean diffusion coefficients, D, values for two clones of IFN-a resistant Daudi cells were significantly higher (D = 8.1-11 × 10-10 cm2/sec) than for parental sensitive cells (D = 4.9-7.4 × 10-10 cm2/sec). Microviscosity of the plasma membranes were probed by electron spin resonance (ESR) spectrometry. These results also indicate a greater degree of molecular motional freedom in resistant cells. Treatment of sensitive lymphoblasts with IFN-a (100-400 U/106 cells) for 5-30 min consistently increased mean values of D and the degree of spin-probe motional freedom, whereas no significant differences were detected in resistant cells. The effect of IFN-a on the membrane potential (Em) of Daudi cells was quantitated by flow cytometry using a voltage-sensitive oxonol dye. Membrane potential of all clones was similar (-50 to -56 mV). Treatment with IFN-a for 8-10 min caused hyperpolarization in the sensitive cells (DEm up to 45 mV), but only minimal hyperpolarization in the resistant ones (DEm up to 7 mV). We concluded that sensitivity to IFN-a and treatment with IFN-a are related to the biophysical status of plasma membranes

Validation of the irritation scale on a representative German sample: new normative data

Abstract The irritation scale is a widely used and reliable self-report scale for measuring cognitive and emotional strain related to the work environment. It extends existing measures by providing a sensitive assessment for pre-clinical stress at work. Existing normative data are based on convenience samples and are therefore not representative. This study provides new normative data for the irritation scale based on a representative German sample (N = 1480). The new normative data indicate that the overall level of irritation in the German workforce is significantly lower compared to previously published data. Convergent and discriminant validity is confirmed by correlations with depression and anxiety (Patient Health Questionnaire-4 for Depression and Anxiety), somatic symptom scales (Bodily Distress Syndrome 25 checklist, Somatic Symptom Scale-8, Giessen Subjective Complaints List-8, comorbidity), psychological functioning (Mini-ICF rating for activity and participation disorders in mental illness), work-related stressors (overcommitment and bullying) and individual resources (self-efficacy). The results confirm the utility of the irritation scale and provide new benchmarks that avoid an underestimation of the levels of irritation in future studies