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The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Declaration of interest
F.G. has received honoraria for advisory work and lectures or CME activity support from Roche, BMS, Lundbeck, Otsuka, Janssen and Sunovion, is a collaborator on an NHS Innovations project co-funded by Janssen and has a family member with professional links to Lilly and GSK, including shares. R.M.M. has received honoraria for lectures from Lundbeck, Otsuka, Janssen and Sunovian. M.D.F. has received honoraria for lectures from Janssen and Sunovian. Z.A. has received honoraria for advisory work and lectures from Roche, Sanofi, Lilly and Otsuka. O.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, Biogen, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. D.T. has received funding for lectures and research from Janssen, Otsuka, Servier, Lundbeck, Sunovion.
Eating disorders have the highest mortality rate of mental disorders and a high incidence of morbidity, but if diagnosed and treated promptly individuals can benefit from full recovery. However, there are numerous problems at the healthcare interface (i.e. primary and secondary care) for eating disorders. It is important to examine these to facilitate appropriate, seamless treatment and improve access to specialist care.
To examine the current literature on the experiences and perspectives of those across healthcare interfaces for eating disorders, to include individuals with eating disorders, people close to or caring for those with eating disorders such as family and friends, and health professionals.
To identify relevant papers, a systematic search of electronic databases was conducted. Other methods, including hand-searching, scanning reference lists and internet resources were also used. Papers that met inclusion criteria were analysed using a systematic methodology and synthesised using an interpretative thematic approach.
Sixty-three papers met the inclusion criteria. The methodological quality was relatively good. The included papers were of both qualitative (n = 44) and quantitative studies (n = 24) and were from ten different countries. By synthesising the literature of these papers, three dominant themes were identified, with additional subthemes. These included: ‘the help-seeking process at primary care’; ‘expectations of care and appropriate referrals’ and ‘opposition and collaboration in the treatment of and recovery from eating disorders’.
This review identifies both facilitators and barriers in eating disorder healthcare, from the perspectives of those experiencing the interface first hand. The review provides recommendations for future research and practice.
Patent systems commonly empower courts to order accused or adjudged infringers to refrain from continuing infringing conduct in the future. Some patentees file suit for the primary purpose of obtaining and enforcing an injunction against infringement by a competitor, and even in cases in which the patentee is willing to license an invention to an accused infringer for an agreed price, the indirect monetary value of an injunction against future infringement can dwarf the amount a finder of fact is likely to award as compensation for past infringement. In some of these cases, an injunction, if granted, would impose costs on accused infringers or third parties that go well beyond the more intrinsic value of the patented technology. This chapter explores the theory behind injunctive relief in patent cases, surveys the availability of this remedy in major patent systems, and suggests a general framework for courts to use when deciding whether injunctive relief is appropriate in individual cases.
This chapter describes the current state of, and normative basis for, the law of reasonable royalties among the leading jurisdictions for patent infringement litigation, as well as the principal arguments for and against various practices relating to the calculation of reasonable royalties; and for each of the major issues discussed, the chapter provides one or more recommendations. The chapter’s principal recommendation is that, when applying a “bottom-up” approach to estimating reasonable royalties, courts should replace the Georgia-Pacific factors (and analogous factors used outside the United States) with a smaller list of considerations, specifically (1) calculating the incremental value of the invention and dividing it appropriately between the parties; (2) assessing market evidence, such as comparable licenses; and (3) where feasible and cost justified, using each of these first two considerations as a “check” on the accuracy of the other
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Changing rates of water input can affect both the flow of glaciers and ice sheets and their propensity to crevasse. Here we examine geodetic and seismic observations during two substantial (10–18-times background velocity) rain-induced glacier accelerations at Haupapa/Tasman Glacier, New Zealand. Changes in rain rate result in glacier acceleration and associated uplift, which propagate down-glacier. This pattern of acceleration results in a change to the strain rate field, which correlates with an order of magnitude increase in the apparent seismicity rate and an overall down-glacier migration in located seismicity. After each acceleration event the apparent seismicity rate decreases to below the pre-acceleration rate for 3 days. This suggests that seismic events associated with surface crevasse growth occur early during phases of glacier acceleration due to elevated extensional stresses, and then do not occur again until stresses recover.
Evidence has been slowly accumulating that the urban home gardens of immigrants or transnational migrants in the USA conserve food plant diversity with roots in the developing world. Published species lists for home gardens indicate that, at least at the species level, this diversity is not novel but consists of widely grown, culturally important plant species that are also available through the horticultural trade. In 2018, we returned to the home garden of a Mexican-origin household in Chicago and confirmed the identity of a plant provisionally identified as Jaltomata darcyana during an earlier inventory of the garden. A recently named species of Central America, J. darcyana has not been previously recorded in cultivation. Collection of this species from a Chicago garden suggests that urban gardens may harbor other novel species awaiting documentation by urban ecologists and botanists.
To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.
Memory clinics and dementia services.
Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).
Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.
There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).
There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.
The Transforming Care national plan for England to develop community services and close hospital beds for people with intellectual disabilities and/or autism was published in October 2015 and is due to finish in March 2019. In this editorial the key plan objectives are evaluated, with particular reference to people with intellectual disabilities and/or autism who offend or are at risk of offending. The conclusion is that, to date, the plan has failed to meet its targets to reduce the number of in-patients with intellectual disabilities and/or autism and to invest in community services, and the number of patients in independent sector beds is increasing.
Declaration of interest
The author is employed by Northumberland, Tyne and Wear National Health Service Foundation Trust, however the opinions expressed in this article are the author's own and do not reflect the views of the Trust.
We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.
Let E be a completely regular space, let C* denote the Banach algebra of continuous bounded real-valued functions on E, and let A* denote a Banach subalgebra which contains the constant function 1. Let
The purpose of this note is to discuss some properties of the subsets L(A*) of the ring C of continuous real-valued functions on E. They arose out of an unsuccessful attempt to distinguish C* from its Banach subalgebras.
Here, we examine the influence of small-scale turbulence on the evolution of fronts in the ocean and atmosphere. Specifically, we consider the evolution of an initially balanced density front subject to an imposed viscosity and diffusivity as a simple analogue for small-scale turbulence. At late times, the dominant balance is found to be the quasisteady turbulent thermal wind balance with time evolution due to an advection–diffusion balance in the buoyancy equation. We use the leading-order balance to determine analytical similarity solutions for the spreading of a front and find that the spreading rate is maximum for an intermediate value of the Ekman number, with the spreading resulting from shear dispersion associated with the cross-front flow and vertical diffusion of density. In response to shear dispersion, the front evolves towards a density profile that is nearly linear in the cross-front coordinate. At the edges of the frontal zone, the density field develops large curvature, and these regions are associated with narrow bands of intense vertical velocity.
We consider one misconception of those who currently reject the general validity of radiocarbon (14C) age determinations older than, at most, 10,000 BP. There is an allegation that the presence of 14C reported by accelerator mass spectrometry (AMS) laboratories in their measurements of 14C infinite age (>100,000 years) organics used to define background levels, support their point of view. This article has been written for a general audience, primarily for those who have questions about the validity of these arguments. However, they may not be familiar with the literature relevant to providing a clear response to the claims of these individuals. We conclude that, in our view, of all of the possible explanations for the reports of the presence of 14C in these background samples, the least probable explanation has been advanced by those rejecting the validity of the 14C time scale in excess of, at most, 10,000 BP.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
The landmark US Multimodal Treatment of ADHD (MTA) study established the
benefits of individualised medication titration and optimisation
strategies to improve short- to medium-term outcomes in attention-deficit
hyperactivity disorder (ADHD). This individualised medication management
approach was subsequently incorporated into the National Institute for
Health and Care Excellence (NICE) ADHD Clinical Guidelines (NICE CG78).
However, little is known about clinicians' attitudes towards implementing
these medication management strategies for ADHD in routine care.
To examine National Health Service (NHS) healthcare professionals'
consensus on ADHD medication management strategies.
Using the Delphi method, we examined perceptions on the importance and
feasibility of implementing 103 ADHD treatment statements from sources
including the UK NICE ADHD guidelines and US medication management
Certain recommendations for ADHD medication management were judged as
important and feasible to implement, including a stepwise titration of
stimulant medication. Other recommendations were perceived as important
but not feasible to implement in routine practice, such as weekly clinic
follow-up with the family during titration and collection of follow-up
Many of the key guideline recommendations for ADHD medication management
are viewed by clinicians as important and feasible to implement. However,
some recommendations present significant implementation challenges within
the context of routine NHS clinical care in England.
Outcome measures for mental health services need to adopt a service-user recovery focus.
To develop and validate a 10- and 20-item self-report recovery-focused quality of life outcome measure named Recovering Quality of Life (ReQoL).
Qualitative methods for item development and initial testing, and quantitative methods for item reduction and scale construction were used. Data from >6500 service users were factor analysed and item response theory models employed to inform item selection. The measures were tested for reliability, validity and responsiveness.
ReQoL-10 and ReQoL-20 contain positively and negatively worded items covering seven themes: activity, hope, belonging and relationships, self-perception, well-being, autonomy, and physical health. Both versions achieved acceptable internal consistency, test–retest reliability (>0.85), known-group differences, convergence with related measures, and were responsive over time (standardised response mean (SRM) > 0.4). They performed marginally better than the Short Warwick-Edinburgh Mental Well-being Scale and markedly better than the EQ-5D.
Both versions are appropriate for measuring service-user recovery-focused quality of life outcomes.
Declaration of interest
M.B. and J.Co. were members of the research group that developed the Clinical Outcomes in Routine Evaluation (CORE) outcome measures.