Guidance Notes for commercial offices: Safe return to work during COVID-19

This report explores multiple strategies and control measures for preventing or limiting the transmission of the SARS-CoV-2 virus in indoor office workplaces. It has been commissioned by Savile Row Projects Ltd to ensure that, in collaboration with its clients and supply chain, its work on the design, installation and operation of office interiors is executed in light of what is known about the disease. The background study on which this report is based focuses on three areas of advice: clinical, behavioural and built environment

Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders

Inherited methylation disorders are a group of rarely reported, probably largely underdiagnosed disorders affecting transmethylation processes in the metabolic pathway between methionine and homocysteine. These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. This paper provides the first consensus recommendations for the diagnosis and management of methylation disorders. Following search of the literature and evaluation according to the SIGN-methodology of all reported patients with methylation defects, graded recommendations are provided in a structured way comprising diagnosis (clinical presentation, biochemical abnormalities, differential diagnosis, newborn screening, prenatal diagnosis), therapy and follow-up. Methylation disorders predominantly affect the liver, central nervous system and muscles, but clinical presentation can vary considerably between and within disorders. Although isolated hypermethioninemia is the biochemical hallmark of this group of disorders, it is not always present, especially in early infancy. Plasma S-adenosylmethionine and S-adenosylhomocysteine are key metabolites for the biochemical clarification of isolated hypermethioninemia. Mild hyperhomocysteinemia can be present in all methylation disorders. Methylation disorders do not qualify as primary targets of newborn screening. A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. S-adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. Recommendations given in this article are based on general principles and in practice should be adjusted individually according to patient's age, severity of the disease, clinical and laboratory findings

Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders

Purpose: Liver transplantation (LTx) is performed in individuals with urea cycle disorders when medical management (MM) insufficiently prevents the occurrence of hyperammonemic events. However, there is a paucity of systematic analyses on the effects of LTx on health-related outcome parameters compared to individuals with comparable severity who are medically managed. Methods: We investigated the effects of LTx and MM on validated health-related outcome parameters, including the metabolic disease course, linear growth, and neurocognitive outcomes. Individuals were stratified into “severe” and “attenuated” categories based on the genotype-specific and validated in vitro enzyme activity. Results: LTx enabled metabolic stability by prevention of further hyperammonemic events after transplantation and was associated with a more favorable growth outcome compared with individuals remaining under MM. However, neurocognitive outcome in individuals with LTx did not differ from the medically managed counterparts as reflected by the frequency of motor abnormality and cognitive standard deviation score at last observation. Conclusion: Whereas LTx enabled metabolic stability without further need of protein restriction or nitrogen-scavenging therapy and was associated with a more favorable growth outcome, LTx—as currently performed—was not associated with improved neurocognitive outcomes compared with long-term MM in the investigated urea cycle disorders.</p

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early

Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs

Degenerative endplate changes of the lumbosacral spine: Dynamic contrast-enhanced MRI profiles related to age, sex, and spinal level

Purpose To investigate differences in perfusion profiles between degenerative endplate marrow changes and normal vertebral marrow in relation to spinal level, age, and sex with dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Materials and Methods Ninety-two consecutive patients referred for evaluation of low back pain or sciatica, without history of malignant or chronic disease, underwent conventional and DCE MRI of the lumbosacral spine. Fifty-two of them demonstrated degenerative endplate marrow changes. Regions of interest were placed on sites of normal marrow (group A) and degenerative changes (group B) on subtracted images. Fitted time-intensity curves (fTICs) were generated and evaluated for curve pattern. Both groups were stratified into upper (L1-L2) and lower (L3-I1) levels, males and females younger or older than 50 years. Perfusion parameters were calculated and statistically compared for both groups and subgroups. Receiver operator curve (ROC) analysis was also performed. Results Two fTIC patterns were identified. Perfusion parameters of degenerative changes and normal marrow differed significantly, even when groups were stratified for spinal level, age, and sex (P &lt; 0.05). A time to peak value &gt;108 seconds was characteristic for degenerative changes with sensitivity 69.5% and specificity 84.6%. Conclusion DCE MRI profiles of degenerative endplate marrow changes of the lumbosacral spine differ significantly from normal marrow regardless of spinal level, age, or sex. Copyright © 2011 Wiley-Liss, Inc

The social invisibility of mental health: understanding social exclusion through place & space

Background Mental health is considered the Cinderella of any healthcare system. There is a European target that the 5% of the healthcare service budget goes to mental health and most countries have reached that target. Yet, this might not be enough to cover the inequity between health and mental health provision. Aim ‘The social invisibility of mental health facilities’ is a multi-disciplinary, innovative, research-through-arts project, involving a School of Architecture, a Division of Psychiatry and a School of Art. The aim is to detect if there are elements demonstrating inequality demonstrated from place and space related to the facility provision. Methods It compares healthcare vs mental health facilities of the same catchment area, raising awareness of inequalities between the two and the social exclusion of mentally ill people through a visual, multimedia perspective. It juxtaposes (mental) healthcare facilities in terms of access, condition and status compared to their surroundings. The exhibits were created from both art and architectural schools postgraduate students. The exhibition took place close to Bentham’s auto-icon, the designer of Panopticon custodial facility, demonstrating inverse links between his Panopticon, and the concealment/invisibility that NIMBYism produces towards the mentally ill that resulted in their exclusion, within deprived, under-funded, isolated facilities “in the community”. Conclusions The exhibition with the satellite actions, such as the mapping of the facilities and the picture-rich book demonstrated the under-budgeting of mental health facilities and their stigmatization as expressed by the centrality of locations and the overall projected image of the building exteriors. This outlined the path for integrated, transdisciplinary research in the future involving architecture, arts and psychiatry