General practitioners' stay-at-work practices in patients with musculoskeletal disorders: using Intervention Mapping to develop a training program.

OBJECTIVES: To describe current stay-at-work practices among Danish general practitioners (GPs) in relation to patients with musculoskeletal disorders, to identify potential avenues for improvement, and to suggest a training program for the GPs. DESIGN AND SETTING: We followed the principles of Intervention Mapping. Data were collected by means of literature searches, focus group interviews with GPs, and interaction with stakeholder representatives from the Danish labour market. RESULTS: GPs' current stay-at-work practices were influenced by systemic, organisational, and legislative factors, and by personal determinants, including knowledge and skills relating to stay-at-work principles and musculoskeletal disorders, recognition of the patient's risk of long-term work disability, their role as a GP, and expectations of interactions with other stay-at-work stakeholders. GPs described themselves as important partners and responsible for the diagnostic and holistic assessments of the patient but placed themselves on the side line relying on the patient or workplace stakeholders to act. Their practices are influenced both by patients, employers, and by other stakeholders. We propose a training course for GPs that incorporate both concrete tools and behaviour change techniques. CONCLUSIONS: We have identified varied perspectives on the roles and responsibilities of GPs, as well as legislative and organisational barriers, and proposed a training program. Not all barriers identified can be addressed by a training course, and some questions are left unanswered, among others - who are best suited to help patients staying at work?

Musculoskeletal disorders are highly prevalent and one of the most common causes for visiting a GP.In many countries, GPs are important in facilitating that patients stay at work, when they are experiencing musculoskeletal pain and disability.In our research, GPs place themselves on the side line as coaches relying on the patient or workplace to act.Barriers such as role identity, systemic and organisational issues prevent GPs from being more involved in stay-at-work practices.GPs' with knowledge about stay-at-work practices may empower patients to better self-management.

Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Pre-operative femoral nerve block for hip fracture-A systematic review with meta-analysis.

BACKGROUND: Pre-operative pain management of hip fracture patients is complex. Femoral nerve block (FNB) is used for hip fractures to reduce pain and demand for systematic analgesia. The objective of the study was to systematically investigate the efficacy of single-shot FNB for hip fracture patients. METHODS: Five databases were searched from inception until 8 May 2019. We included randomized controlled trials (RCT's) assessing pain relief in patients with hip fractures. Intervention was pre-operative FNB compared to any systemic analgesic (eg opioids, non-steroidal anti-inflammatory drugs or paracetamol). Primary outcomes assessed were pre-operative pain and use of rescue analgesics. Secondary outcome was cognitive impairment. We present a bias assessment, a meta-analysis and a grading of certainty of evidence. RESULTS: We included five trials (n = 254), where participants received FNB 30 minutes or more prior to surgery; all were judged as having high risk of bias. All studies found significantly decreased pain scores at least once in the intervention group compared to the control group. Meta-analysis on the primary outcome of pain showed significance. Mean difference was -2.13 point (in cm) (CI:-3.53,-0.72) on visual analogue scale in the intervention group, but is judged low on certainty. CONCLUSIONS: The quantity of evidence supporting pre-operative single-shot FNB for hip fractures is very low, and the certainty of evidence supporting pre-operative single-shot FNB for hip fractures is low. No studies using ultrasound guided technique were identified. Data on non-ultrasound guided FNB's suggest a decreased pain score compared to the use of systemic analgesia.

Occupational exposure and the risk of new-onset chronic rhinosinusitis â€" a prospective study 2013-2018.

BACKGROUND: The aetiology behind chronic rhinosinusitis (CRS) is still poorly understood. The aim of this study was to investigate the association between the onset of CRS and several common occupational exposures over time. METHODOLOGY: An adult random population from Telemark, Norway, comprising 7,952 subjects, who answered a comprehensive respiratory questionnaire including questions on CRS and occupational exposure first in 2013 and again in 2018. RESULTS: New-onset CRS during the five-year follow-up was independently associated with occupational exposure to hair-care products, cleaning agents among women, super glue, strong acids, cooking fumes and wood dust. CONCLUSION: In this random population cohort from Norway, exposure to several common occupational agents, such as hair-care products, super glue and wood dust, was associated with the onset of CRS. It is important that physicians who see patients with CRS inquire about workplace exposure.

[Sleep-disordered Breathing]. / Atemstörungen im Schlaf.

Sleep disordered breathing disorders in children are of a high clinical relevance. They do not only affect a large proportion of the children's lives in terms of time but they impact on the thriving, cardiovascular function and cognitive development. Different developmental factors have to be considered in the interpretation of sleep studies in children. Adeno-tonsillar hypertrophy is the most frequent reason for paediatric sleep disordered breathing, however the spectrum of aetiologies is very large. Syndromic cranio facial malformations and metabolic disorders are often associated with a very high risk of relevant sleep disordered breathing. Correct and child-oriented diagnostics are essential to enable adequate therapy.

Butyrylcholinesterase deficiency and its clinical importance in anaesthesia: a systematic review.

Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.

Long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of PASI response.

BACKGROUND: Patients with moderate-to-severe psoriasis require long-term treatment, yet few trials compare outcomes beyond a short-term induction period. Quantitative comparisons of long-term outcomes in patients with psoriasis are limited. To our knowledge, no network meta-analysis (NMA) of such data has been performed. OBJECTIVE: To compare novel systemic therapies, both biologic and non-biologic, approved for moderate-to-severe psoriasis by conducting a systematic review (SR) and NMA of Psoriasis Area and Severity Index (PASI) outcomes measured at or around 1 year. METHODS: An SR was conducted to identify studies reporting PASI 75, PASI 90 and PASI 100 responses. Feasibility of an NMA on maintenance phase endpoints was assessed and sources of heterogeneity considered. Data appropriate for analysis were modelled using a Bayesian multinomial likelihood model with probit link. Wherever possible, data corresponding to an intention-to-treat approach with non-responder imputation were used. RESULTS: Twenty-four studies reporting outcomes at 40-64 weeks were identified, but heterogeneity in study design allowed synthesis of only 17. Four 52-week randomized controlled trials (RCTs) comprised the primary analysis, which found brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept. Secukinumab was also more efficacious than ustekinumab and both outperformed etanercept. In a secondary analysis, evidence from 13 additional studies and 4 further therapies (adalimumab, apremilast, infliximab and ixekizumab) was included by comparing long-term outcomes from active interventions to placebo outcomes extrapolated from induction. Results were consistent with the primary analysis: brodalumab was most effective, followed by ixekizumab and secukinumab, then ustekinumab, infliximab and adalimumab. Etanercept and apremilast had the lowest expected long-term efficacy. Results were similar when studies with low prior exposure to biological therapies were excluded. CONCLUSION: Results suggest that brodalumab is associated with a higher likelihood of sustained PASI response, including complete clearance, at week 52 than comparators. Further long-term active-comparator RCT data are required to better assess relative efficacy across therapies.

Systematic review of the effects of fascia iliaca compartment block on hip fracture patients before operation.

BACKGROUND: Fascia iliaca compartment block is used for hip fractures in order to reduce pain, the need for systemic analgesia, and prevent delirium, on this basis. This systematic review was conducted to investigate the analgesic and adverse effects of fascia iliaca block on hip fracture in adults when applied before operation. METHODS: Nine databases were searched from inception until July 2016 yielding 11 randomised and quasi-randomised controlled trials, all using loss of resistance fascia iliaca compartment block, with a total population of 1062 patients. Meta-analyses were conducted comparing the analgesic effect of fascia iliaca compartment block on nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and other nerve blocks, preoperative analgesia consumption, and time to perform spinal anaesthesia compared with opioids and time for block placement. RESULTS: The analgesic effect of fascia iliaca compartment block was superior to that of opioids during movement, resulted in lower preoperative analgesia consumption and a longer time for first request, and reduced time to perform spinal anaesthesia. Block success rate was high and there were very few adverse effects. There is insufficient evidence to conclude anything on preoperative analgesic consumption or first request thereof compared with NSAIDs and other nerve blocks, postoperative analgesic consumption for preoperatively applied fascia iliaca compartment block compared with NSAIDs, opioids and other nerve blocks, incidence and severity of delirium, and length of stay or mortality. CONCLUSIONS: Fascia iliaca compartment block is an effective and relatively safe supplement in the preoperative pain management of hip fracture patients.

Effects of avoidance or use of neuromuscular blocking agents on outcomes in tracheal intubation: a Cochrane systematic review.

Cohort studies have indicated that avoidance of neuromuscular blocking agents (NMBA) is a risk factor for difficult tracheal intubation. However, the impact of avoiding NMBA on tracheal intubation, possible adverse effects, and postoperative discomfort has not been evaluated in a systematic review of randomised trials. We searched several databases for trials published until January 2017. We included randomised controlled trials comparing the effect of avoiding vs using NMBA. Two independent authors assessed risk of bias and extracted data. The risk of random errors was assessed by trial sequential analysis (TSA). We included 34 trials (3565 participants). In the four trials judged to have low risk of bias, there was an increased risk of difficult tracheal intubation with no use of NMBA [random-effects model, risk ratio (RR) 13.27, 95% confidence interval (CI) 8.19-21.49, P<0.00001, TSA-adjusted CI 1.85-95.04]. The result was confirmed when including all trials, (RR 5.00, 95% CI 3.49-7.15, P<0.00001, TSA-adjusted CI 1.20-20.77). There was a significant risk of upper airway discomfort or injury by avoiding NMBA (RR=1.37, 95% CI 1.09-1.74, P=0.008, TSA-adjusted CI 1.00-1.86). None of the trials reported mortality. Avoiding NMBA was significantly associated with difficult laryngoscopy, (RR 2.54, 95% CI 1.53-4.21, P=0.0003, TSA-adjusted CI 0.27-21.75). In a clinical context, one must balance arguments for using NMBA when performing tracheal intubation.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.

BACKGROUND: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. METHODS: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. RESULTS: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. CONCLUSIONS: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

Peripheral nerve block in ankle fracture surgery: a qualitative study of patients' experiences.

Peripheral nerve blocks are popular as a mode of anaesthesia for limb surgery and their beneficial effects are well documented in elective surgery. However, concerns have been raised about potential rebound pain outweighing the benefits in acute ankle fracture surgery. Furthermore, pain scores and morphine consumption do not provide a full picture, as pain is subjective. To evaluate the clinical usefulness of peripheral nerve blocks, we explored patients' expectations and experiences by means of semi-structured interviews analysed with systematic text condensation. We obtained ethical approval and informed consent and sampled purposively among adult patients scheduled for ankle surgery with nerve blocks as the primary mode of anaesthesia. Patients were interviewed within 48 h postoperatively. Data saturation was reached after 13 interviews. We found that, despite pre-emptive ibuprofen and paracetamol, some patients did experience excruciating rebound pain for up to 2 h, although most had little or no pain. The patients had doubts about what to do when the block wore off, which led to a risk of unnecessary pain levels or morphine overuse. Patients had difficulty understanding the effect and course of the nerve blocks. They had misunderstandings regarding the blocks' effect on sensation, resulting in fear of feeling pain during surgery and of permanent nerve damage after surgery. However, patients valued the mental alertness, ability to ambulate and efficient pain relief provided by the blocks. We recommend that patients be given thorough and repeated information as we feel this is crucial in preventing undesirable responses from patients, and is likely to increase the overall clinical usefulness of nerve blocks in acute limb surgery.

'What gets measured gets managed': revisiting the indicators for maternal and newborn health programmes.

BACKGROUND: The health of women and children are critical for global development. The Sustainable Development Goals (SDG) agenda and the Global Strategy for Women's, Children's, and Adolescent's Health 2016-2030 aim to reduce maternal and newborn deaths, disability, and enhancement of well-being. However, information and data on measuring countries' progress are limited given the variety of methodological challenges of measuring care around the time of birth, when most maternal and neonatal deaths and morbidities occur. MAIN BODY: In 2015, the World Health Organization launched Mother and Newborn Information for Tracking Outcomes and Results (MoNITOR), a technical advisory group to WHO. MoNITOR comprises 14 independent global experts from a variety of disciplines selected in a competitive process for their technical expertise and regional representation. MoNITOR will provide technical guidance to WHO to ensure harmonized guidance, messages, and tools so that countries can collect useful data to track progress toward achieving the Sustainable Development Goals. SHORT CONCLUSION: Ultimately, MoNITOR will provide technical guidance to WHO to ensure harmonized guidance, messages, and tools so that countries can collect useful data to track progress toward achieving the Sustainable Development Goals.

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

Viability and expression of sexual ornaments in the barn swallow Hirundo rustica: a meta-analysis.

Sexual selection results in the evolution of exaggerated secondary sexual characters that can entail a viability cost. However, in species where sexual ornaments honestly reflect individual quality, the viability cost of secondary sexual characters may be overwhelmed by variation in individual quality, leading to expect that individuals with the largest secondary sexual characters show higher, rather than lower viability. Here, we used meta-analyses to test whether such expected positive relationship between sexual ornamentation and viability exists in the barn swallow Hirundo rustica, which is one of the most studied model species of sexual selection under field conditions. We found a mean positive effect size of viability in relation to the expression of secondary sexual characters of 0.181 (CI: 0.084-0.278), indicating that in this species the more ornamented individuals are more viable, and therefore of high quality. Analyses of moderator variables showed similar effects in males and females, the H. r. rustica subspecies rather than others and tail length rather than other secondary sexual characters. Future research emphasis on other subspecies than the European one and secondary sexual characters than tail length may help identify the sources of heterogeneity in effect sizes.

Escape from predators and genetic variance in birds.

Predation is a common cause of death in numerous organisms, and a host of antipredator defences have evolved. Such defences often have a genetic background as shown by significant heritability and microevolutionary responses towards weaker defences in the absence of predators. Flight initiation distance (FID) is the distance at which an individual animal takes flight when approached by a human, and hence, it reflects the life-history compromise between risk of predation and the benefits of foraging. Here, we analysed FID in 128 species of birds in relation to three measures of genetic variation, band sharing coefficient for minisatellites, observed heterozygosity and inbreeding coefficient for microsatellites in order to test whether FID was positively correlated with genetic variation. We found consistently shorter FID for a given body size in the presence of high band sharing coefficients, low heterozygosity and high inbreeding coefficients in phylogenetic analyses after controlling statistically for potentially confounding variables. These findings imply that antipredator behaviour is related to genetic variance. We predict that many threatened species with low genetic variability will show reduced antipredator behaviour and that subsequent predator-induced reductions in abundance may contribute to unfavourable population trends for such species.

Morphological constraints on changing avian migration phenology.

Many organisms at northern latitudes have responded to climate warming by advancing their spring phenology. Birds are known to show earlier timing of spring migration and reproduction in response to warmer springs. However, species show heterogeneous phenological responses to climate warming, with those that have not advanced or have delayed migration phenology experiencing population declines. Although some traits (such as migration distance) partly explain heterogeneity in phenological responses, the factors affecting interspecies differences in the responsiveness to climate warming have yet to be fully explored. In this comparative study, we investigate whether variation in wing aspect ratio (reflecting relative wing narrowness), an ecomorphological trait that is strongly associated with flight efficiency and migratory behaviour, affects the ability to advance timing of spring migration during 1960-2006 in a set of 80 European migratory bird species. Species with larger aspect ratio (longer and narrower wings) showed smaller advancement of timing of spring migration compared to species with smaller aspect ratio (shorter and wider wings) while controlling for phylogeny, migration distance and other life-history traits. In turn, migration distance positively predicted aspect ratio across species. Hence, species that are better adapted to migration appear to be more constrained in responding phenologically to rapid climate warming by advancing timing of spring migration. Our findings corroborate the idea that aspect ratio is a major evolutionary correlate of migration, and suggest that selection for energetically efficient flights, as reflected by high aspect ratio, may hinder phenotypically plastic/microevolutionary adjustments of migration phenology to ongoing climatic changes.

Life history, immunity, Peto's paradox and tumours in birds.

Cancer and tumours may evolve in response to life-history trade-offs between growth and duration of development on one hand, and between growth and maintenance of immune function on the other. Here, we tested whether (i) bird species with slow developmental rates for their body size experience low incidence of tumours because slow development allows for detection of rapid proliferation of cell lineages. We also test whether (ii) species with stronger immune response during development are more efficient at detecting tumour cells and hence suffer lower incidence of tumours. Finally, we tested Peto's paradox, that there is a positive relationship between tumour incidence and body mass. We used information on developmental rates and body mass from the literature and of tumour incidence (8468 birds) and size of the bursa of Fabricius for 7659 birds brought to a taxidermist in Denmark. We found evidence of the expected negative relationship between incidence of tumours and developmental rates and immunity after controlling for the positive association between tumour incidence and body size. These results suggest that evolution has modified the incidence of tumours in response to life history and that Peto's paradox may be explained by covariation between body mass, developmental rates and immunity.

Prospective quality control study of a novel gravity-driven whole blood separation system suitable for humanitarian crises.

Centrifugation-based whole blood (WB) separation represents the worldwide standard but it depends on electricity and infrastructure. We have prospectively evaluated a novel hollow-fibre WB separation system that does not require manual priming or blood flow regulation (n = 29). RBC units contained sufficient Hb (50·4 g ± 4·3), low leucocytes (90 000 ± 0·008), exhibited low haemolysis (0·57% ± 0·49) and robust ATP content (51·47% ± 8·2) after 43 days storage. Plasma units contained low leucocytes and mean coagulation factor activities for FV, FVIII and FXI were 47%, 90% and 68%, respectively. RBC met quality specifications but plasma units exhibited reduced FV and FXI activity.

Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial.

BACKGROUND: In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascular Surgery. Restricting RBC transfusion may affect blood O2 transport with a risk for development of tissue ischaemia and postoperative complications. METHODS: In a single-centre, open-label, assessor blinded trial, 58 vascular surgical patients (> 40 years of age) awaiting open surgery of the infrarenal aorta or infrainguinal arterial bypass surgery undergo a web-based randomisation to one of two groups: perioperative RBC transfusion triggered by hb < 8 g/dl or hb < 9.7 g/dl. Administration of fluid follows an individualised strategy by optimising cardiac stroke volume and near-infrared spectroscopy determines tissue oxygenation. Serious adverse event rates are: myocardial injury (troponin-I ≥ 45 ng/l or ischaemic electrocardiographic findings at day 30), acute kidney injury, death, stroke and severe transfusion reactions. A follow-up visit takes place 30 days after surgery and a follow-up of serious adverse events in the Danish National Patient Register within 90 days is pending. DISCUSSION: This trial is expected to determine whether a RBC transfusion triggered by hb < 9.7 g/dl compared with hb < 8 g/dl results in adequate separation of postoperative hb levels, transfusion of more RBC units and maintains a higher tissue oxygenation. The results will inform the design of a multicentre trial for evaluation of important postoperative outcomes.