Improved insulin sensitivity and body composition, irrespective of macronutrient intake, after a 12 month intervention in adolescents with pre-diabetes; RESIST a randomised control trial

© 2014 Garnett et al..Background: A higher protein to carbohydrate ratio in the diet may potentiate weight loss, improve body composition and cardiometabolic risk, including glucose homeostasis in adults. The aim of this randomised control trial was to determine the efficacy of two structured lifestyle interventions, differing in dietary macronutrient content, on insulin sensitivity and body composition in adolescents. We hypothesised that a moderate-carbohydrate (40-45% of energy), increased-protein (25-30%) diet would be more effective than a high-carbohydrate diet (55-60%), moderate-protein (15%) diet in improving outcomes in obese, insulin resistant adolescents. Methods: Obese 10-17 year olds with either pre-diabetes and/or clinical features of insulin resistance were recruited at two hospitals in Sydney, Australia. At baseline adolescents were prescribed metformin and randomised to one of two energy restricted diets. The intervention included regular contact with the dietician and a supervised physical activity program. Outcomes included insulin sensitivity index measured by an oral glucose tolerance test and body composition measured by dual-energy x-ray absorptiometry at 12 months. Results: Of the 111 adolescents recruited, 85 (77%) completed the intervention. BMI expressed as a percentage of the 95th percentile decreased by 6.8% [95% CI: -8.8 to -4.9], ISI increased by 0.2 [95% CI: 0.06 to 0.39] and percent body fat decreased by 2.4% [95% CI: -3.4 to -1.3]. There were no significant differences in outcomes between diet groups at any time. Conclusion: When treated with metformin and an exercise program, a structured, reduced energy diet, which is either high-carbohydrate or moderate-carbohydrate with increased-protein, can achieve clinically significant improvements in obese adolescents at risk of type 2 diabetes.Link_to_subscribed_fulltex

Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study

<p>Abstract</p> <p>Background</p> <p>Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections.</p> <p>Methods</p> <p>68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded.</p> <p>Results</p> <p>34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome.</p> <p>Conclusion</p> <p>TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.</p

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

British waterborne domestic freight (BWDF) : the waterborne freight alternative to road transport in the UK, and its role in sustainable mobility

Increasingly it has been recognised that there are many problems associated with the over-dependence on road haulage, and that along with the reality of congestion and gridlock on the EU road network, the external costs of road haulage in terms of the pollution roads inflict on society is now considered unsustainable in the long term. In response to this reality, both the EU and UK governments have developed policy advocating a transfer of freight from roads to the more environmentally friendly transport modes of water and rail. In essence this is an investigation and analysis of the economic, environmental and political issues which affect the diversion of freight from roads to water in the 21st century. Packer's 1994 "Roads to water" study examined the prospect of the viability of a significant modal switch from roads to water and highlighted a numbe of issues which he felt would adversley affect modal transfer. This thesis tests a number of these conclusions to see if they are still a barrier to conversion in 2004 as Packer suggested they were ten years earlier. This is achieved by the analysis of six different case studies, where it is felt that the traditional road haulage element could be transferred to water transport. An analysis of the pollution and external costs imposed on society by the road halulage element within these studies has been compared to an alternative BWDF option, and the results clearly show that water, in every case is considerably more environmentally friendly than road. In addition to this, the research has established a number of other results pertaining to these studies. These include the compariosn of the operation costs of both modes, the number of LGV kilometres eradicated by the modal transfer and the reduction of fuel used. The conclusion of this analysis is that, in one year, 33,594 long distance road haulage journeys could be eradicated from UK roads. It also concluded that the distance generated by long distance road haulage would reduce from 6,084,091 kms to 422,837 kms local (short distance) haulage, a reduction of 5,661,254 kms. In addition, 2,055 tonnes of fuel would be reduced to 139 tonnes saving 1,916 tonnes per annum, and road halulage pollution would fall from 9,051 tonnes per annum to 630 tonnes eradicating 8,421 tonnes of land based pollution. In terms of external costs it also concluded that the external costs imposed on society would reduce by £751,520 per annum.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism

<p>Abstract</p> <p>Background/Aims</p> <p>Infants with diabetes insipidus (DI), especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence.</p> <p>Methods</p> <p>A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose). The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott). We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days.</p> <p>Results</p> <p>After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L) <it>vs.</it> only 51% on the old regimen (p = 0.0001). The sodium ranged from 132-154 mmol/L, compared to 120–156 on the old regimen. She was discharged home.</p> <p>Conclusion</p> <p>This practical regimen improved sodium control, parental independence, and allowed discharge home.</p