Systemic treatment of children and adolescents with atopic dermatitis aged ≥2 years: a Delphi consensus project mapping expert opinion in Northern Europe.

BACKGROUND: Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication. OBJECTIVES: This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision-making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate-to-severe AD. METHODS: Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two-round Delphi process, they reached full or partial consensus on 37 statements. RESULTS: Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non-systemic therapy. Systemic therapy should achieve long-term disease control and reduce short-term interventions. Recommended are cyclosporine A for short-term use (all ages) and dupilumab or methotrexate for long-term use (ages ≥6 years). Consensus was not reached on the best long-term systemics for children aged 2-6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real-world data will become available. CONCLUSIONS: This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate-to-severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.

Minimal important change in physical function in trauma patients: a study using the short musculoskeletal function assessment.

PURPOSE: The Short Musculoskeletal Function Assessment (SMFA) questionnaire can be used to evaluate physical functioning in patients with traumatic injuries. It is not known what change in score reflects a meaningful change to patients. The aim was to determine minimal important change (MIC) values of the subscales (0-100) of the Dutch SMFA-NL in a sample of patients with a broad range of injuries. METHODS: Patients between 18 and 65 years of age completed the SMFA-NL and the Global Rating of Effect (GRE) questions at 6-week and 12-month post-injury. Anchor-based MIC values were calculated using univariable logistic regression analyses. RESULTS: A total of 225 patients were included (response rate 67%). The MIC value of the Upper Extremity Dysfunction (UED) subscale was 8 points, with a misclassification rate of 43%. The Lower Extremity Dysfunction subscale MIC value was 14 points, with a misclassification rate of 29%. The MIC value of the Problems with Daily Activities subscale was 25 points, with a misclassification rate of 33%. The MIC value of the Mental and Emotional Problems (MEP) subscale was 7 points, with a misclassification rate 37%. CONCLUSION: MIC values of the SMFA-NL were determined. The MIC values aid interpreting whether a change in physical functioning can be considered clinically important. Due to the considerable rates of misclassification, the MIC values of the UED and MEP subscales should be used with caution.

Guttate psoriasis triggered by perianal streptococcal infection.

The association of guttate psoriasis (GP) with streptococcal pharyngitis is well accepted. However, less is known about the association with perianal streptococcal infection. We report a case of a 19-month-old boy with GP after a preceding perianal streptococcal dermatitis, with no clinical signs of a streptococcal pharyngitis. Treatment with phenethicillin was given together with mometasone ointment. After 4 weeks, the perianal redness was reduced and the psoriasis had improved significantly. A review of the literature revealed nine previous case reports, comprising a total of 15 patients. In all cases, the perianal dermatitis and the GP improved after treatment with oral antibiotics, sometimes in combination with topical corticosteroids. We conclude that in cases of GP in children, the perianal area must be examined for streptococcal infection.

Evaluation of measurement properties of self-administered PROMs aimed at patients with non-specific shoulder pain and "activity limitations": a systematic review.

OBJECTIVE: To critically appraise and compare the measurement properties of self-administered patient-reported outcome measures (PROMs) focussing on the shoulder, assessing "activity limitations." STUDY DESIGN: Systematic review. The study population had to consist of patients with shoulder pain. We excluded postoperative patients or patients with generic diseases. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist. RESULTS: Out of a total of 3427 unique hits, 31 articles, evaluating 7 different questionnaires, were included. The SPADI is the most frequently evaluated PROM and its measurement properties seem adequate apart from a lack of information regarding its measurement error and content validity. CONCLUSION: For English, Norwegian and Turkish users, we recommend to use the SPADI. Dutch users could use either the SDQ or the SST. In German, we recommend the DASH. In Tamil, Slovene, Spanish and the Danish languages, the evaluated PROMs were not yet of acceptable validity. None of these PROMs showed strong positive evidence for all measurement properties. We propose to develop a new shoulder PROM focused on activity limitations, taking new knowledge and techniques into account.

Short Musculoskeletal Function Assessment: normative data of the Dutch population.

BACKGROUND: The Short Musculoskeletal Function Assessment (SMFA) is widely used in both research and clinical practice. Despite its frequent use, normative data of the SMFA have remained limited. Aim of this study was to gather normative data for the Dutch SMFA (SMFA-NL). METHODS: The SMFA-NL consists of two indices (function index and bother index) and four subscales (upper extremity dysfunction, lower extremity dysfunction, mental and emotional problems, and problems with daily activities). A total of 900 patients were invited to fill in the SMFA-NL. Six age groups (18-24, 25-34, 35-44, 45-54, 55-64, and 65-75 years) were constructed. Analysis of variance, t tests, and regression analyses were used to assess age and gender effects. RESULTS: The response rate was 97 %. There was a significant difference between men and women in scores on all indices and subscales (range p < 0.001 to p = 0.002), except for the upper extremity dysfunction subscale (p = 0.06). A significant interaction effect was found between gender and age for the upper extremity dysfunction subscale; a larger decrease in score with increasing age was observed for women, compared with men. Significant differences were found between age groups for the bother index (p < 0.001), lower extremity dysfunction subscale (p = 0.001), and the problems with daily activities subscale (p = 0.002). CONCLUSION: Significant differences in SMFA-NL scores were found between men and women and between different age groups. These SMFA-NL normative data provide an opportunity of benchmarking health status of participants with musculoskeletal disorders or injuries against their age- and gender-matched peers in the Dutch population.

Emergence of a novel GII.17 norovirus ­ End of the GII.4 era?

In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.

Shallow genetic divergence and species delineations in the endemic Labeobarbus species flock of Lake Tana, Ethiopia.

To assess whether the species distinctions of Lake Tana's Labeobarbus spp. are supported by genetic information, microsatellite markers were used. A total of 376 Labeobarbus spp., belonging to 24 populations of 11 species from three regions of the lake (north, south and east), were sampled. Eight microsatellite markers were analysed. In general, differences between conspecific populations were smaller than differences between populations of different species. For six species, conspecific populations from different regions in the lake were consistently more similar than populations of other species from the same region. For four species this was not the case, while for one species two populations were similar, but different from the third population. River-spawning species appeared to be more distinct than presumed lake spawners. On the species level, there was a significant correlation between genetic and morphological differentiation, especially in morphological aspects associated with ecological functioning. This suggests that genetic differentiation arose together with adaptive radiation, although the overall genetic differentiation among the Lake Tana Labeobarbus spp. is small.

Screening for coronary artery disease after mediastinal irradiation in Hodgkin lymphoma survivors: phase II study of indication and acceptance†.

BACKGROUND: Cardiovascular diseases are the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. We investigated the role of computed tomographic coronary angiography (CTA) as a screening tool for coronary artery disease (CAD) in asymptomatic HL survivors, and related CTA findings to exercise testing and subsequent interventions. PATIENTS AND METHODS: Patients were eligible for this phase II study if at least 10 years disease-free and treated with mediastinal radiotherapy. Screening consisted of electrocardiogram, exercise testing and CTA. Primary end point was significant CAD (stenosis >50%) on CTA. CTA screening was considered to be indicated for testing in a larger population if ≥6 of 50 CTA scanned patients (12%) would need revascularization. Screening was evaluated with a questionnaire before and after screening. RESULTS: Fifty-two patients were included, and 48 patients underwent CTA. Median age was 47 years, time since HL diagnosis 21 years. There were 45 evaluable scans. Significant CAD on CTA was found in 20% (N = 9), significantly increased compared with the 7% expected abnormalities (P = 0.01, 95% confidence interval 8.3% to 31.7%). In 11% (N = 5), significant stenosis was confirmed at coronary angiography, and revascularization was carried out. Additionally, two patients were treated with optimal medical therapy. Ninety percent of patients were content with screening, regardless whether the CTA showed abnormalities. CONCLUSIONS: Prevalence of significant CAD among HL survivors is high, while asymptomatic even in the presence of life-threatening CAD. This might justify screening by CTA in asymptomatic HL survivors who had mediastinal radiotherapy, but needs to be evaluated in a larger cohort. The trial protocol was approved by the Ethics Committee of the LUMC and registered with ClinicalTrials.gov, NCT01271127.

Determinants of virulence of influenza A virus.

Influenza A viruses cause yearly seasonal epidemics and occasional global pandemics in humans. In the last century, four human influenza A virus pandemics have occurred. Occasionally, influenza A viruses that circulate in other species cross the species barrier and infect humans. Virus reassortment (i.e. mixing of gene segments of multiple viruses) and the accumulation of mutations contribute to the emergence of new influenza A virus variants. Fortunately, most of these variants do not have the ability to spread among humans and subsequently cause a pandemic. In this review, we focus on the threat of animal influenza A viruses which have shown the ability to infect humans. In addition, genetic factors which could alter the virulence of influenza A viruses are discussed. The identification and characterisation of these factors may provide insights into genetic traits which change virulence and help us to understand which genetic determinants are of importance for the pandemic potential of animal influenza A viruses.

ST-segment elevation associated with allergic reaction to echocardiographic contrast agent administration.

We report a case of an allergic reaction after the administration of an echocardiographic contrast agent which resulted in ST-segment elevation. Hypersensitivity and allergic reactions are known causes of acute cardiovascular events. However, only limited reports are available which suggest the exact mechanism of the occurrence of angina or myocardial infarction during severe allergic reactions. In our case, through invasive imaging (coronary angiography and IVUS) we have shown for the first time a transient coronary spasm in the absence of intra-coronary thrombus and only minimal neointimal hyperplasia.

Myocardial bridging: what have we learned in the past and will new diagnostic modalities provide new insights?

The clinical significance of myocardial bridging has been a subject of discussion and controversy since the introduction of coronary arteriography (CAG) in the early 1960s. More recently computed tomography coronary angiography (CTCA) has made it possible to visualise the overlying muscular bands and appears to have a higher sensitivity for detecting myocardial bridging than CAG. Combining CTCA with invasive techniques such as CAG should make it possible to improve our understanding of the pathophysiology of myocardial bridging and to provide answers to hitherto unresolved questions. This paper critically reviews the outcomes of previous studies and defines remaining questions that should be answered to optimise the management of the presumably fast growing number of patients in whom a diagnosis of myocardial bridging has been made.

Coronary calcium score in COVID-19 survivors: Association with cardiac injury and cardiac function after 6 weeks.

Aims: Cardiac manifestations are common in COVID-19, often elevated serum troponin levels or myocardial dysfunction on trans-thoracic echocardiography (TTE) is observed. Both parameters are associated with increased in-hospital mortality. Possibly, subclinical coronary atherosclerosis plays a role, of which severity can be assessed by calculating the coronary artery calcium (CAC) score. This study aims to determine the relation between coronary atherosclerosis and cardiac manifestations in COVID-19 survivors. Methods: This study was conducted at the Leiden University Medical Center. All patients admitted for COVID-19 were included and scheduled for a 6-week follow-up visit with trans-thoracic echocardiography (TTE). CAC was assessed according to an ordinal score on non-gated, non-contrast enhanced computed tomography of the chest. Patients with and without CAC were compared on cardiac injury as reflected by elevated serum troponin levels and impaired cardiac function assessed through TTE. Results: In total, 146 patients were included. Mean age was 62 years and 62 % of the patients were male. During admission, patients with CAC showed significantly higher levels of troponin (19 ng/L vs 10 ng/L; p < 0.01). Overall, mild echocardiographic abnormalities were seen; 12 % showed reduced left ventricular function (left ventricular ejection fraction of <50 %) and 14 % reduced right ventricular function (tricuspid annular planar systolic excursion ≤17 mm). Following multivariable adjustments, there was no significant relation between CAC and myocardial function at 6 weeks. Conclusion: The present study shows that coronary atherosclerosis is associated with cardiac injury in COVID-19 survivors. However, no significant relation with impaired cardiac function was demonstrated.

Spawning migrations of the endemic Labeobarbus (Cyprinidae, Teleostei) species of Lake Tana, Ethiopia: status and threats.

The reproductive biology of the only known intact species flock of large cyprinids, the 16 Labeobarbus species of Lake Tana (Ethiopia), has been extensively studied for the past two decades. Seven species of Labeobarbus are known to migrate >50 km upstream into tributary rivers for spawning during the rainy season (July to October), whereas eight other species are absent from these rivers and probably developed a new strategy of lacustrine spawning (macro-spatial segregation). One species (L. intermedius) probably spawns in the lake as well as in the rivers. Between the early 1990s and 2000s, the riverine spawners showed a decline of 75% in both biomass and number in both fishery independent surveys and in commercial catches. Reproductive migration makes fishes vulnerable to fisheries and other threats like habitat modifications. Lacustrine spawners are probably more resilient as they are not known to form spawning aggregations that can easily be exploited by fishermen. In addition, upstream rivers and catchments around Lake Tana are highly degraded by erosion and recently subjected to intensive habitat modification for irrigation and hydroelectric power generation. This article reviews results of field studies on the Labeobarbus spawning migration from Lake Tana to spawning rivers, giving emphasis on segregation and homing. It also summarizes existing and emerging threats which form potential causes for the decline of the migratory Labeobarbus species. Knowledge gaps on the reproductive biology are identified for further investigation.

Transmural ischemia visualized using routine Chest CTA.

Chest computed tomography (CT) is not routinely used for the diagnosis of myocardial infarction. However, there have been some reports of patients undergoing chest CT for other indications in which ultimately MI was diagnosed due to the presence of areas of myocardial hypoperfusion. The authors present the case of a 60-years old male who is referred due to acute chest pain radiating between the scapulae. Thoracic computed tomography angiography to rule out an aortic dissection revealed an occlusion of the left anterior descending coronary artery with an area of relative hypoperfusion. Hence, the present case demonstrates how using routine thoracic computed tomography angiography, transmural ischemia can be visualized in the setting of an acute myocardial infarction. It should make clinicians aware of the fact it may be beneficial to look for myocardial perfusion abnormalities when assessing chest CT's.

Myocardial function in COVID-19 patients after hospital discharge: a descriptive study comparing the first and second 'wave' patients.

In hospitalized COVID-19 patients, myocardial injury and echocardiographic abnormalities have been described. The present study investigates cardiac function in COVID-19 patients 6 weeks post-discharge and evaluates its relation to New York Heart Association (NYHA) class. Furthermore cardiac function post-discharge between the first and second wave COVID-19 patients was compared. We evaluated 146 patients at the outpatient clinic of the Leiden University Medical Centre. NYHA class of II or higher was reported by 53% of patients. Transthoracic echocardiography was used to assess cardiac function. Overall, in 27% of patients reduced left ventricular (LV) ejection fraction was observed and in 29% of patients LV global longitudinal strain was impaired (> - 16%). However no differences were observed in these parameters reflecting LV function between the first and second wave patients. Right ventricular (RV) dysfunction as assessed by tricuspid annular systolic planar excursion (< 17 mm) was present in 14% of patients, this was also not different between the first and second wave patients (15% vs. 12%; p = 0.63); similar results were found for RV fraction area change and RV strain. Reduced LV and RV function were not associated with NYHA class. In COVID-19 patients at 6 weeks post-discharge, mild abnormalities in cardiac function were found. However these were not related to NYHA class and there was no difference in cardiac function between the first and second wave patients. Long term symptoms post-COVID might therefore not be explained by mildly abnormal cardiac function.

Neck pain with radiculopathy: A systematic review of classification systems.

BACKGROUND: Disparities in eligibility criteria for cervical radiculopathy (CR) in clinical trials have been acknowledged previously. The increasing use of CR related neck pain classification systems to inform eligibility criteria in clinical trials warrants evaluation. OBJECTIVE: To evaluate existing neck pain classification systems for CR. DESIGN: Systematic review and critical appraisal, reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. METHODS: Database searches were performed from inception until 31/7/2020. Neck pain classification systems containing CR as a component were included. Methodological quality of each classification system was assessed using seven measurement property domains and scored using a framework developed by Buchbinder and colleagues. Classification criteria for CR from classification systems assessed as moderate or good quality were narratively synthesised using inductive content analysis which consisted of selecting unit of analysis, open coding, grouping and categorisation. RESULTS: Out of 19,975 references, 14,893 remained after elimination of duplicates with 17 articles reporting 11 classification systems included. Five moderate and one good quality classification systems were identified. Nine classification criteria for CR were derived, including dermatomal sensory deficit, positive Spurling's test, positive upper limb tension test. CONCLUSION: All classification systems had methodological limitations with Childs et al. (2008) classification system identified as good quality and most clinically useful. Future studies should investigate the reliability of Childs et al. (2008) classification system as it has the potential to further strengthen its methodological quality and clinical utility. The nine derived classification criteria can inform eligibility criteria in future trials.

Diagnostic ultrasound in patients with shoulder pain: An inter-examiner agreement and reliability study among Dutch physical therapists.

STUDY DESIGN: A cross-sectional inter-examiner agreement and reliability study among physical therapists in primary care. BACKGROUND: musculoskeletal ultrasound (MSU) is frequently used by physical therapists to improve specific diagnosis in patients with shoulder pain, especially for the diagnosis rotator cuff tendinopathy (RCT) including tears. OBJECTIVES: To estimate the inter-examiner agreement and reliability in physical therapists using MSU for patients with shoulder pain. METHODS: Physical therapists performed diagnostic MSU in 62 patients with shoulder pain. Both physical therapists were blinded to each other's results and patients were not informed about the test results. We calculated the overall inter-examiner agreement, specific positive and negative inter-examiner agreement, and inter-examiner reliability (Cohen's Kappa's). RESULTS: Overall agreement for detecting RC ruptures ranged from 61.7% to 85.5% and from 43.9% to 91.4% for specific positive agreement. The specific negative agreement was lower with values ranging from 44.4% to 79.1% for RC ruptures. Overall agreement for other pathology than ruptures related to SAPS, ranged from 72.6% to 93.6% and from 77.3% to 96% for specific positive agreement. The specific negative agreement was lower with values ranging from 44.4% to 79.1% for RC ruptures and 52.5%-83.3% for other pathology than ruptures related to SAPS. Reliability values varied from substantial for any thickness ruptures to moderate for partial thickness ruptures and fair for full thickness tears. Moreover, reliability was fair for cuff tendinopathy. The reliability for AC arthritis and no pathology found was fair and moderate. There was substantial agreement for the calcifying tendinopathy. CONCLUSIONS: Physical therapists using MSU agree on the diagnosis of cuff tendinopathy and on the presence of RCT in primary care, but agree less on the absence of pathology.

Association of environmental surface contamination with hand hygiene and infections in nursing homes: a prospective cohort study.

BACKGROUND: Little is known about the presence of infections in nursing home residents, the causative micro-organisms, how hand hygiene (HH) influences the presence of infections in residents, and the extent to which environmental contamination is associated with the incidence of infection among residents. AIMS: To establish if environmental contamination can be used as an indicator for HH compliance, and if environmental contamination is associated with the incidence of infection. METHODS: Environmental surface samples (ESS) were collected in an exploratory study as part of a HH intervention in 60 nursing homes. ESS results from three distinct surfaces (nurses' station, communal toilet and residents' shared living area) were compared with nurses' HH compliance and the incidence of infection among residents. Real-time polymerase chain reaction assays were used to detect norovirus genogroup I and II, rhinovirus and Escherichia coli. HH compliance was measured by direct observation. The incidence of infection was registered weekly. FINDINGS: Rhinovirus (nurses' station: 41%; toilet: 14%; living area: 29%), norovirus (nurses' station: 18%; toilet: 12%; living area: 16%) and E. coli (nurses' station: 14%; toilet: 58%; living area: 54%) were detected. No significant (P<0.05) associations were found between HH compliance and the presence of micro-organisms. An association was found between E. coli contamination and the incidence of disease in general (P=0.04). No other associations were found between micro-organisms and the incidence of disease. CONCLUSION: Rhinovirus, norovirus and E. coli were detected on surfaces in nursing homes. No convincing associations were found between environmental contamination and HH compliance or the incidence of disease. This study provides reference data about surface contamination.