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COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalised patients is critical as the pandemic progresses. This observational cohort study aimed to characterise the independent associations between the clinical outcomes of hospitalised patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, UK between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling. The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Scale <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality. These important data will aid clinical risk stratification and provide direction for further research.
A recent editorial claimed that the 2014 National Institute for Health and Care Excellence (NICE) guideline on psychosis and schizophrenia, unlike its equivalent 2013 Scottish Intercollegiate Guidelines Network (SIGN) guideline, is biased towards psychosocial treatments and against drug treatments. In this paper we underline that the NICE and SIGN guidelines recommend similar interventions, but that the NICE guideline has more rigorous methodology. Our analysis suggests that the authors of the editorial appear to have succumbed to bias themselves.
Insomnia disorder is common and often co-morbid with mental health conditions. Cognitive behavioural therapy (CBT) for insomnia is effective, but is rarely implemented as a discrete treatment. The aim of this study was to evaluate the effectiveness of brief CBT groups for insomnia compared to treatment as usual (TAU) for insomnia delivered by mental health practitioners in a primary-care mental health service.
A total of 239 participants were randomized to either a five-session CBT group or to TAU. Assessments of sleep and of symptoms of depression and anxiety were carried out at baseline, post-treatment and at 20 weeks. Primary outcome was sleep efficiency post-treatment.
Group CBT participants had better sleep outcomes post-treatment than those receiving TAU [sleep efficiency standardized mean difference 0.63, 95% confidence interval (CI) 0.34–0.92]. The effect at 20 weeks was smaller with a wide confidence interval (0.27, 95% CI −0.03 to 0.56). There were no important differences between groups at either follow-up period in symptoms of anxiety or depression.
Dedicated CBT group treatment for insomnia improves sleep more than treating sleep as an adjunct to other mental health treatment.
The past two decades have seen a great improvement in the care of people with Prader–Willi syndrome (PWS), particularly with regard to control of diet and behaviour management. Has this affected mortality rates or thrown up new issues regarding premature ageing or dementia? We investigated two aspects of ageing in people with PWS: (1) an estimate of mortality over 9 years in a cohort of people with PWS, originally recruited in 1998–2000; and (2) premature ageing or dementia in people aged ⩾40 years.
(1) A follow-up of the population-based 1998–2000 cohort to investigate the subsequent mortality rate; and (2) the recruitment and structured assessment of all members of the Prader–Willi Syndrome Association UK (PWSA-UK) aged ⩾40 years who agreed to participate.
Follow-up of the population-based 1998–2000 cohort gave a mortality rate of at least 7/62 over 9 years (1.25% per annum; 20 untraced), age at death was between 13 and 59 years. Twenty-six members of the PWSA-UK aged ⩾40 years were recruited, 18 of whom had a genetic diagnosis (gd) of PWS. Twenty-two (14 gd) showed no evidence of dementia. Four, with possible symptoms, are described in more detail; all are female, of maternal uniparental disomy (mUPD) genetic subtype, or have a disomic region, and all have a long history of psychotic illness.
The mortality rate in people with PWS seems to be declining. The subgroup of people with PWS due to UPD or disomic region with female gender and a history of psychosis may be at risk of early onset dementia.
People with Prader–Willi syndrome (PWS), a genetically defined developmental disorder, are at increased risk of developing psychotic illness. This is particularly the case for those with a genetic subtype of PWS called maternal uniparental disomy (mUPD), where rates of psychosis are more than 60% by early adult life. Little is known about the long-term course of their disorder.
Individuals who had had episodes of psychosis or were at increased risk of developing psychosis due to their genetic subtype and had taken part in a previous study were contacted. Ten people were untraceable or deceased, leaving a total of 38 potential participants. Of these, 28 agreed to take part in a follow-up interview or complete a questionnaire about their mental health and medication. This represented 20/35 (57.1%) people from the original study who had had psychosis and 8/13 (61.5%) people who were at risk due to their genetic subtype. They were thought to be representative of those groups as a whole based on IQ and number of episodes of psychosis.
Two individuals had had recurrent episodes of psychosis while all others remained well. There were no new-onset cases of psychosis in those at risk. Individuals with PWS remained on high levels of psychiatric medication throughout the follow-up period.
Recurrent episodes of psychosis may be rare in people with PWS once stability has been achieved in the management of their illness. We speculate that this may be due to the protective influence of medication.
Economic analyses of cholera immunization programmes require estimates of the costs of cholera. The Diseases of the Most Impoverished programme measured the public, provider, and patient costs of culture-confirmed cholera in four study sites with endemic cholera using a combination of hospital- and community-based studies. Families with culture-proven cases were surveyed at home 7 and 14 days after confirmation of illness. Public costs were measured at local health facilities using a micro-costing methodology. Hospital-based studies found that the costs of severe cholera were US$32 and US$47 in Matlab and Beira. Community-based studies in North Jakarta and Kolkata found that cholera cases cost between US$28 and US$206, depending on hospitalization. Patients' cost of illness as a percentage of average monthly income were 21% and 65% for hospitalized cases in Kolkata and North Jakarta, respectively. This burden on families is not captured by studies that adopt a provider perspective.
Xasta flies appear to segregate five types of gametes in unequal numbers, namely two which contain both or neither of the chromosomes affected by the translocation and inversions, two further classes which contain one affected and one unaffected chromosome, and finally the remainder which have an unbalanced chromosomal content. These conditions are necessary to fit the results observed in crosses involving the Xasta stock. Xasta exhibits balanced polymorphism under crowded conditions and this may be due to the production of toxic substances by Xa larvae which delay the development of wild type-larvae.
Growth rate is an important performance indicator in pig production and therefore influences profitability. There is also evidence that faster growing pigs have superior tenderness (MLC, 1989), possibly linked to faster muscle protein deposition through the activity and expression of proteolytic enzymes. Slow growth could also result in higher boar taint levels in entire male pigs because they will be older and sexually more mature at slaughter (MLC, 1989). The current project was therefore undertaken to investigate the effect of variations in growth rate on tenderness and boar taint.
Egg-laying patterns and egg production in Heteraxine heterocerca from the gills and Benedenia seriolae from the skin of Japanese yellowtail Seriola quinqueradiata in Japan were investigated in vivo. Eggs were collected every 3 h from sexually mature H. heterocerca and B. seriolae infecting 3 S. quinqueradiata kept individually over 3 consecutive days and exposed to alternating periods of illumination and darkness (LD 12:12; light on 06.00, light off 18.00) and maintained at 23·8±0·1°C and 35 ppt salinity. A well-defined egg-laying rhythm was demonstrated for H. heterocerca while B. seriolae was shown to release eggs continuously. A total of 114 000 H. heterocerca eggs was collected and of these, 45·4 (42·5–49·9)% were collected during the first 3 h period following dark at 18.00 h. A total of 662 857 B. seriolae eggs was collected and these were distributed over each 3 h period ranging from 11·1 to 14·1% of the daily egg output. All eggs extracted from the uterus of each H. heterocerca were joined together forming an ‘egg-string’. The contrasting egg-laying patterns of H. heterocerca and B. seriolae suggest that each species makes use of a different infection strategy to infect the same host species, S. quinqueradiata.
Psychotic illness is strongly associated with the maternal uniparental disomy (mUPD) genetic subtype of Prader–Willi syndrome (PWS), but not the deletion subtype (delPWS). This study investigates the clinical features of psychiatric illness associated with PWS. We consider possible genetic and other mechanisms that may be responsible for the development of psychotic illness, predominantly in those with mUPD.
The study sample comprised 119 individuals with genetically confirmed PWS, of whom 46 had a history of psychiatric illness. A detailed clinical and family psychiatric history was obtained from these 46 using the PAS-ADD, OPCRIT, Family History and Life Events Questionnaires.
Individuals with mUPD had a higher rate of psychiatric illness than those with delPWS (22/34 v. 24/85, p<0.001). The profile of psychiatric illness in both genetic subtypes resembled an atypical affective disorder with or without psychotic symptoms. Those with delPWS were more likely to have developed a non-psychotic depressive illness (p=0.005) and those with mUPD a bipolar disorder with psychotic symptoms (p=0.00005). Individuals with delPWS and psychotic illness had an increased family history of affective disorder. This was confined exclusively to their mothers.
Psychiatric illness in PWS is predominately affective with atypical features. The prevalence and possibly the severity of illness are greater in those with mUPD. We present a ‘two-hit’ hypothesis, involving imprinted genes on chromosome 15, for the development of affective psychosis in people with PWS, regardless of genetic subtype.
Boar taint is a major meat-quality defect in pigs and is due to excessive accumulation of skatole and androstenone in adipose tissue. The present work investigated the relationship between carcass weight, levels of skatole and androstenone in adipose tissue, and expression of the hepatic androstenone-metabolising enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), in 22 entire male and 22 entire female crossbred pigs (Large White (40%) × Landrace (40%) × Duroc (20%)). Animals of each gender were divided into two subgroups (11 pigs in each subgroup): (i) conventional weight (carcass weight 59 to 77 kg) and (ii) heavy weight (carcass weight 84 to 95 kg). No relationship between carcass weight and adipose tissue skatole level was found for entire male pigs (r2 = 0.013, P > 0.05). There was a significant negative relationship between carcass weight and expression of the hepatic 3β-HSD protein (r2 = 0.502, P < 0.001) and a significant negative relationship between 3β-HSD protein expression and androstenone level in adipose tissue (r2 = 0.24, P < 0.05) in entire males. No relationship was found between carcass weight and 3β-HSD protein expression in female pigs (r2 = 0.001, P > 0.05). 3β-HSD expression was 59% higher in conventional-weight male pigs when compared with heavy-weight animals (P < 0.05) and 36% higher in heavy-weight females when compared with heavy-weight males (P < 0.05). It is concluded that an increase in slaughter weight of entire commercial crossbred Large White pigs is accompanied by inhibition of expression of the hepatic 3β-HSD protein, which might result in a reduced rate of hepatic androstenone clearance with its subsequent accumulation in adipose tissue. It is suggested that regulation of pig hepatic 3β-HSD expression is under the control of sex hormones.
A main aim of modern pig production is to reduce nitrogen excretion to the environment, capturing more of the dietary protein in saleable meat. One way to achieve this is to reduce dietary protein level but this is likely to increase fat deposition, especially in late-developing fat depots. Meat quality will also be affected and these effects will all be influenced by breed type. This study compared three nutritional strategies differing in dietary protein provision in terms of their effects on growth and fat deposition.
A reduced protein diet (RPD) is known to increase the level of intramuscular lipid in pig meat with a smaller effect on the amount of subcutaneous adipose tissue. This might be due to tissue-specific activation of the expression of lipogenic enzymes by the RPD. The present study investigated the effect of a RPD, containing palm kernel oil, soyabean oil or palm oil on the activity and expression of one of the major lipogenic enzymes, stearoyl-CoA desaturase (SCD) and on the level of total lipids and the fatty acid composition of muscle and subcutaneous adipose tissue in pigs. The RPD significantly increased SCD protein expression and activity in muscle but not in subcutaneous adipose tissue. The level of MUFA and total fatty acids in muscle was also elevated when the RPD was fed, with only small changes in subcutaneous adipose tissue. A positive significant correlation between SCD protein expression and total fatty acids in muscle was found. The results suggest that an increase in intramuscular but not subcutaneous adipose tissue fatty acids under the influence of a RPD is related to tissue-specific activation of SCD expression. It is suggested that the SCD isoform spectra in pig subcutaneous adipose tissue and muscle might be different.
Boar taint is a major meat quality defect, which affects about 10% of entire male pigs. It is due to an excessive accumulation of skatole and androstenone in adipose tissue. One of the reasons for accumulation of these compounds is a low rate of their metabolism. Androstenone is metabolised in liver via the enzyme 3-beta-hydroxysteroid dehydrogenase (HSD). This enzyme is well characterised in the testis, where it participates in the synthesis of steroids, while its properties in liver are unknown. The aim of the present study was to characterise and compare properties of HSD from pig liver versus pig testis when metabolising androstenone.
Boar taint is off-odours in cooked pork from uncastrated male pigs. It is caused by an excessive accumulation of skatole and androstenone in backfat. Accumulation of skatole is due to a low expression and activity of hepatic enzyme CYP2E1. The mechanism of androstenone accumulation is not clear. It could be due to low activity and expression of 3ß-hydroxysteroid dehydrogenase (HSD), an enzyme metabolising androstenone in liver. On the basis of our previous in vivo experiments with castrated animals we suggest that accumulation of skatole is regulated by androstenone. Castrated pigs manifest lower levels of skatole and androstenone and higher CYP2E1 expression. We hypothesise that high levels of androstenone inhibits CYP2E1 expression and hence, reduces the rate of hepatic skatole metabolism. The aims of the present study were (i) to investigate the expression of androstenone-metabolising enzyme HSD in liver of pigs with high and low skatole and androstenone deposition; (ii) to investigate the effect of androstenone on expression of the skatole-metabolising enzyme CYP2E1 in vitro (in cell culture).
Phylogenetic relationships within the Capsalidae (Monogenea) were examined using large subunit ribosomal DNA sequences from 17 capsalid species (representing 7 genera, 5 subfamilies), 2 outgroup taxa (Monocotylidae) plus Udonella caligorum (Udonellidae). Trees were constructed using maximum likelihood, minimum evolution and maximum parsimony algorithms. An initial tree, generated from sequences 315 bases long, suggests that Capsalinae, Encotyllabinae, Entobdellinae and Trochopodinae are monophyletic, but that Benedeniinae is paraphyletic. Analyses indicate that Neobenedenia, currently in the Benedeniinae, should perhaps be placed in a separate subfamily. An additional analysis was made which omitted 3 capsalid taxa (for which only short sequences were available) and all outgroup taxa because of alignment difficulties. Sequence length increased to 693 bases and good branch support was achieved. The Benedeniinae was again paraphyletic. Higher-level classification of the Capsalidae, evolution of the Entobdellinae and issues of species identity in Neobenedenia are discussed.
Skatole is formed as a result of bacterial degradation of tryptophan in the rumen of cattle and sheep, and the hindgut of pigs. It accumulates in fat where it is an important component of boar taint in pigs (Claus et al, 1994), and with branched chain fatty acids, has been implicated as a contributor to the strong flavour characteristic of sheepmeat (Young et al, 1997). This study examines the role of breed, diet and age on skatole deposition in the fat and perception of beef flavour.
Background. Prader-Willi syndrome (PWS) is a genetic disorder resulting in obesity, short stature, cryptorchidism, learning disabilities (mental retardation) and severe neonatal hypotonia. Associated with the syndrome are a number of behaviours that are sufficiently distinctive that the syndrome is considered to have a specific ‘behavioural phenotype’.
Methods. Through multiple sources we attempted to identify all people with PWS living in one region in the UK. This cohort was augmented by people with PWS from other regions, and a contrast group of people with learning disabilities of varied aetiologies. The main carers were interviewed, using structured and semi-structured interview schedules, to establish the presence and severity of specific behaviours, and PWS diagnostic criteria. The intellectual functioning and attainments of all were determined. Blood samples were obtained for genetic diagnosis from all consenting participants.
Results. Although excessive eating was recognized as a potentially severe problem in those with PWS, it was almost universally controlled by food restriction, and therefore not seen as a ‘problem behaviour’. Those with PWS differed from a learning disabled group of other aetiologies in the prevalence rates of skin picking, temper tantrums, compulsive behaviours and mood fluctuations, and also in the profile of their adaptive behaviours.
Conclusions. The study confirms the distinct behavioural phenotype of PWS. Specific behaviours occurred significantly more frequently in PWS, compared with an age and BMI matched learning disabled comparison group. A factor analysis of the behaviours involved resulted in three factors that we hypothesized to be independent, and to arise from different mechanisms.