Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

OBJECTIVES: It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage. METHODS: Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142). RESULTS: A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated. DISCUSSION: Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.

COpenhagen Neuroplastic TRaining Against Contractures in Toddlers (CONTRACT): protocol of an open-label randomised clinical trial with blinded assessment for prevention of contractures in infants with high risk of cerebral palsy.

INTRODUCTION: Contractures are frequent causes of reduced mobility in children with cerebral palsy (CP) already at the age of 2-3 years. Reduced muscle use and muscle growth have been suggested as key factors in the development of contractures, suggesting that effective early prevention may have to involve stimuli that can facilitate muscle growth before the age of 1 year. The present study protocol was developed to assess the effectiveness of an early multicomponent intervention, CONTRACT, involving family-oriented and supervised home-based training, diet and electrical muscle stimulation directed at facilitating muscle growth and thus reduce the risk of contractures in children at high risk of CP compared with standard care. METHODS AND ANALYSIS: A two-group, parallel, open-label randomised clinical trial with blinded assessment (n=50) will be conducted. Infants diagnosed with CP or designated at high risk of CP based on abnormal neuroimaging or absent fidgety movement determined as part of General Movement Assessment, age 9-17 weeks corrected age (CA) will be recruited. A balanced 1:1 randomisation will be made by a computer. The intervention will last for 6 months aiming to support parents in providing daily individualised, goal-directed activities and primarily in lower legs that may stimulate their child to move more and increase muscle growth. Guidance and education of the parents regarding the nutritional benefits of docosahexaenic acid (DHA) and vitamin D for the developing brain and muscle growth will be provided. Infants will receive DHA drops as nutritional supplements and neuromuscular stimulation to facilitate muscle growth. The control group will receive standard care as offered by their local hospital or community. Outcome measures will be taken at 9, 12, 18, 24, 36 and 48 months CA. Primary and secondary outcome measure will be lower leg muscle volume and stiffness of the triceps surae musculotendinous unit together with infant motor profile, respectively. ETHICS AND DISSEMINATION: Full approval from the local ethics committee, Danish Committee System on Health Research Ethics, Region H (H-19041562). Experimental procedures conform with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT04250454. EXPECTED RECRUITMENT PERIOD: 1 January 2021-1 January 2025.

Finger orthoses for management of joint hypermobility disorders: Relative effects on hand function and cognitive load.

BACKGROUND: Joint hypermobility refers to joints that move beyond their normal limits. Individuals with hypermobility of the fingers experience difficulties in activities of daily living. Finger orthoses are available for managing hypermobility of the fingers, but their effectiveness has received little attention in scholarly literature. OBJECTIVES: To determine if use of custom fit finger orthoses leads to improvements in time needed to perform standardised hand function tests, and attentional demand required to perform these tests, in individuals with joint hypermobility syndrome, Hypermobile Ehlers-Danlos syndrome or Classical Ehlers-Danlos syndrome. STUDY DESIGN: Repeated-measures study. METHODS: Fourteen participants performed three different hand function tests (target box and block test, writing and picking up coins), with and without their finger orthoses. Time to complete each test was recorded as a measure of functional performance. Brain activity was recorded in the pre-frontal cortices as a measure of attentional demand. RESULTS: Functional performance significantly improved for all but one test (picking up coins with non-dominant hand) when participants wore finger orthoses (p < 0.05). Activity in the pre-frontal cortex was lower when using the orthosis to perform the coin test (dominant hand; p < 0.05). No differences were observed in other tests (p > 0.05). CONCLUSIONS: Results suggested that finger orthoses improved hand function and provided limited evidence to suggest that they may also affect attentional demand. While the limited sample does not provide conclusive evidence supporting the use of finger orthosis in this clinical population, results warrant further investigation in large scale longitudinal studies or randomised controlled trials.

Safety of High-Volume Plasmapheresis in Children With Acute Liver Failure.

OBJECTIVES: Paediatric acute liver failure (P-ALF) is a rare condition and is associated with a high mortality rate. Management of P-ALF aims to stabilise vital organ functions and to remove circulating toxins and provide vital plasma factors that are lacking. High-volume plasmapheresis (HVP) removes protein-bound substances and improves survival in adult ALF. It is unknown if this effect can be extrapolated to P-ALF. The aim of this study is to report the safety and feasibility of HVP in P-ALF. METHODS: Children with P-ALF were offered HVP if bilirubin was higher than 200 µmol/L or if the aetiology was toxic hepatitis. HVP was performed with fresh frozen plasma corresponding to 10% of the body weight on a minimum of 3 consecutive days. Diagnostics, biochemical and clinical data during HVP as well as outcome data after 3 months were collected from 2012 to 2019 and retrospectively analysed. RESULTS: Sixteen children were treated by HVP and completed at least one series of three treatment sessions with HVP. The only complication seen was an increase in pH > 7.55 in three children within the first 12 hours and was corrected with hydrochloric acid. No bleeding or septic episodes were noted during HVP. Eight children survived without liver transplantation, two survived after successful grafting and a total of six children died. The liver injury unit score between survivors with their own liver and the rest, the two groups was significantly different (P = 0.005). CONCLUSION: HVP with fresh frozen plasma is feasible and well tolerated in children with P-ALF. No serious adverse events and no procedure-related mortality were observed.

[Malignant pertussis in a three-week-old girl].

Whooping cough is an infectious disease caused by Bordetella pertussis. Particularly children under the age of six months can be severely affected by the infection. Severe leukocytosis may lead to thrombosis and pulmonary hypertension and eventually circulatory failure and death. This a case report of a three-week-old girl with malignant pertussis, who due to respiratory insufficiency was mechanically ventilated, and her severe leucocytosis was treated with exchange blood transfusion. Whooping cough may partially be prevented with efficient vaccination programmes.

The Efficacy of Intermittent Long-term Bell Boot Application for the Correction of Muscle Asymmetry in Equine Subjects.

It has been proposed that manipulating proprioceptive signals of the equine distal limb as part of a rehabilitation process in cases of musculoskeletal pain or neurologic deficits can be used to correct postural control and restore normal motor programs. This trial has examined the effect of treatment with a light-weight and loose-fitting bell boot (82 g) on an imbalance of muscle gluteus superficialis function in horses as measured using acoustic myography (AMG). Eight horses were trained over a 60-minute period every 3 days for 6 weeks, a protocol based on preliminary findings. Acoustic myography measurements, recording the coordination, spatial and temporal summation of muscle contractions, were made at the start (baseline) and at the finish (week 6) after a warmup period and following a set procedure of physical activity. Walking, trotting, and cantering during a left-hand circle at the start of the trial revealed a slight but significant asymmetry between the left and right hind limb muscle, which improved successfully after 6 weeks of proprioception training. Data for the right-hand circle, which revealed no significant asymmetry, during walk, trot, and canter at the start, showed no change after 6 weeks of training at the walk and trot but developed an imbalance during cantering, the result of overcompensation. This study demonstrates that functional musculoskeletal asymmetry measured during periods of activity can not only be accurately detected using AMG but it also reveals an association between the program of proprioceptive training adopted and an improvement in muscular imbalance.

Paediatric intensive care is feasible in a neonatal department.

INTRODUCTION: Intensive care of infants below one year of age has been centralized in a paediatric intensive care unit (PICU) related to the neonatal intensive care unit (NICU) at Rigshospitalet, the University Hospital in Copenhagen in eastern Denmark (approximately 2.5 million inhabitants) since 2002. The aim of this paper was to evaluate the experiences from the PICU. MATERIAL AND METHODS: A descriptive study including data from the 01.01.2002-31.12.2010-period from all the admissions to the PICU for infants below one year of age fulfilling one of two criteria: 1) born preterm and admitted to the department after 40 weeks of gestational age or 2) born at term and admitted to the department at an age -older than 28 days. Data were registered prospectively including information on primary diagnoses at admission, the need for mechanical ventilation and the duration of mechanical ventilation. Mortality was evaluated in the three year-period 2008-2010 by use of the Paediatric Index of Mortality 2 score (PIM2 score). RESULTS: The nine-year period saw 927 admissions to the PICU and 355 infants received mechanical ventilation (median three days). The PIM2 score was 6.7% and the mortality was 6.7% in the period during which PIM2 score was registered. The incidence of mechanical ventilation due to respiratory failure was 0.74/1,000 infants born in the -region. CONCLUSION: The experience from the NICU seems to -compensate for a low volume of infants in the PICU. The -incidence of mechanically ventilated infants due to respiratory disease in eastern Denmark is relatively low. FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant. The study was not registered, as it is an observational study.

The effect of a combination of plant sterol-enriched foods in mildly hypercholesterolemic subjects.

BACKGROUND & AIMS: The purpose of this study was to evaluate the effect of low-fat products enriched with plant sterols in addition to a National Cholesterol Education Program step 1 diet on serum lipids and lipoproteins. METHODS: This study was a double-blind, randomised, placebo-controlled cross-over design with a run-in period and 2 intervention periods, each lasting 4 weeks. A total of 46 mildly hypercholesterolemic subjects (age 50.6+/-9.8) completed the trial. The study products consisted of 20 g low-fat margarine (35% fat) and 250 ml low-fat milk (0.7% fat), in total delivering 2.3g plant sterols/d. RESULTS: Serum total and low-density lipoprotein cholesterol were significantly reduced by 5.5% (p<0.001, 95% CI: 2.5; 8.3) and 7.7% (p=0.001, 95% CI: 3.4; 11.9), respectively, by plant sterol-enriched products compared to placebo. Serum apolipoprotein B was significantly reduced by 4.6% (p<0.05, 95% CI: 1.7; 7.5), and apolipoprotein B/apolipoprotein A-I by 3.4% (p<0.05, 95% CI: 0.1; 6.6) after plant sterol intake compared to the placebo supplement. CONCLUSIONS: A combination of low-fat margarine and milk enriched with plant sterols significantly reduced low-density lipoprotein cholesterol, apolipoprotein B and the ratio of apolipoprotein B to apolipoprotein A-I in mildly hypercholesterolemic subjects, but had no effect on C-reactive protein and lipoprotein (a) concentrations. SPONSORSHIP: Unilever Denmark A/S.

[Criteria validation of the Roland Morris questionnaire. A Danish translation of the international scale for the assessment of functional level in patients with low back pain and sciatica]. / Kriterievalidering af Roland Morris-spørgeskemaet. Et oversat internationalt skema til vurdering af aendringer i funktionsniveau hos patienter med laendesmerter og iskias.

INTRODUCTION: The main concern of patients with low back pain is the functional limitation which the symptoms cause. Therefore it is important to find a valid tool by means of which their functional level can be assessed. The aim of this study was to validate the first Danish translation of the Roland Morris Questionnaire (RMQ), which evaluates the functional level of activity of patients with low back pain and possible sciatica. The RMQ was compared with the functional scale of a Danish functional and pain level questionnaire, The Low Back Pain Rating Scale (RS), and the functional scale (PF) of the SF-36. MATERIAL AND METHODS: Independently, three professionals made a retroversion of the RMQ. Then 135 patients with lumbar disc herniation completed the RMQ, RS and the SF-36. The patients comprised 47% women and 53% men with an average age of 43 years. RESULTS: A significant correlation between the RMQ and the other two questionnaires was found. RMQ-RS; r = 0.89, p < or = 0.001, RMQ-PF (SF-36); r = -0.88 p < or = 0.001. A Chronbach Alpha showed a value of 0.94 (scale 0-1). Differences in scores between the three questionnaires were within the 95% limits of agreement. The average RMQ score was 10% higher than the score of RS and PF (SF-36). CONCLUSION: According to this study the RMQ can be used as a valid tool in the assessment of the functional level of patients with lumbar pain and previous lumbar herniation. Due to the fact that the questionnaire is fast and easy to complete, it is valid, reliable and sensitive and widely used internationally. We recommend the questionnaire to be used as a supplement to the clinical examination both in clinical practice and in research.

Degradation of carbazole, dibenzothiophene, and dibenzofuran at low temperature by Pseudomonas sp. strain C3211.

Pseudomonas sp. strain C3211 was isolated from a temperate climate soil contaminated with creosote. This strain was able to degrade carbazole, dibenzothiophene and dibenzofuran at 10 degrees C with acetone as a co-substrate. When dibenzothiophene was degraded by strain C3211, an orange compound, which absorbed at 472 nm, accumulated in the medium. Degradation of dibenzofuran was followed by accumulation of a yellowish compound, absorbing at 462 nm. The temperature optimum of strain C3211 for degradation of dibenzothiophene and dibenzofuran was at 20 to 21 degrees C, while the maximum temperature for degradation was at 27 degrees C. Both compounds were degraded at 4 degrees C. Degradation at 10 degrees C was faster than degradation at 25 degrees C. This indicates that strain C3211 is adapted to life at low temperatures.