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Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice.
To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions.
Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18–65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment.
From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI − €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI −€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI − €2075 to €41 931).
Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
Declaration of interest
Six of the 16 authors have received royalties or fees for RO DBT. R.J.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from NIHR. T.R.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd and a grant outside the submitted work from the Medical Research Council. He was codirector of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two current directors of Radically Open Ltd. H.O’M. reports personal fees from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.C.R. provides RO DBT supervision through S C Rushbrook Ltd. I.T.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M.St. reports personal fees from British Isles DBT Training, Stanton Psychological Services Ltd, and Taylor & Francis Ltd. M.Sw. reports personal fees from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis Ltd. B.W. was codirector of Radically Open Ltd between November 2014 and February 2015.
Sample preparation techniques for radiocarbon analysis of dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) in freshwater, as well as CO2 and CH4 in gas mixtures are presented. Focused efforts have been on developing a robust and low-background wet oxidation extraction method for DOC in freshwater, following routine methods developed for stable carbon isotope analysis and adapted for radiocarbon (14C) analysis. DIC (by acidification) and DOC (by wet oxidation) are converted to CO2 in pre-baked septum-fitted borosilicate bottles, where the resulting CO2 is extracted from the dissolved and headspace portions on a low-flow He-carrier flow-through system interfaced to a vacuum extraction line. A peripheral CH4 extraction line interfaces to the flow line to separate CH4 from environmental samples following the methods of Pack et al. 2015. High sample throughput and low blanks are achievable with this method. DIC and DOC blanks are consistently <0.7 pMC, while CO2 and CH4 blanks are typically <0.1 pMC.
Haughton crater in the Canadian Arctic has been extensively used as a Mars (and lunar) analogue over the past 20 years. Here we report on small scale, dark, semi-seasonal slope streaks formed by melt water flowing down the crater walls that we observed during the Mars Society-sponsored M160 expedition to the F-MARS facility on the NW rim of the crater. The streaks are formed by biofilms colonizing snow melt flowing from semi-permanent snow patches in Haughton crater on Devon Island and elsewhere in the Canadian Arctic. These features superficially resemble the dark slope streaks and recurring slope lineae (RSL) observed on Mars and may serve as analogues for wet models for their formation and a contrast with dry formation models. Their significance to astrobiology and planetary science is three-fold: (1) as examples of dark recurring streaks known to be associated with water they provide a benchmark to compare with Martian slope streaks and RSL. (2) The melt streaks may have potential as astrobiological analogues for wet models of slope streaks and RSL. (3) They are natural laboratories to study planetary protection issues associated with robotic and astronaut exploration of potential water-related slope features on Mars.
Paragonimiasis, human lung fluke disease, is a foodborne anthropozoonosis caused by the trematodes assigned to Paragonimus and is regarded by the World Health Organization as a Neglected Tropical Disease (NTD). The life cycle of this medically important parasite centres on a complex freshwater biological community that includes two intermediate hosts: a mollusc and a decapod, usually a brachyuran. Although there is a perception that the biology, symptoms, diagnosis and treatment of Paragonimus is well understood, in reality, this is not the case, especially in Africa. Much remains unknown concerning the life-cycle of the parasite, its transmission, the current epidemiology of the disease, diagnosis and the effectiveness of treatment. Furthermore, cases of paragonimiasis may be misdiagnosed as resistant tuberculosis (TB) because of the similar pulmonary symptoms and no remission after anti TB therapy. The endemic foci of human paragonimiasis in Africa have been reported mainly in the forest zones of Upper Guinea (Liberia, Guinea and Ivory Coast) and Lower Guinea (Nigeria, Cameroon, Equatorial Guinea and Gabon). Despite the perceived medical importance of paragonimiasis, relatively little attention has been paid to this NTD since its discovery in Africa in the 1960s. This review focuses on the current understanding of the life cycle and transmission of Paragonimus in Africa, discusses its diagnosis and public health importance and highlights many outstanding gaps in the knowledge that still exist for this NTD.
Breast milk is the only source of the essential amino acid tryptophan (TRP) in breast-fed infants. Low levels of TRP could have implications for infant neurodevelopment. The objectives of the present study were to compare the relationship of TRP and its neuroactive pathway metabolites kynurenine (Kyn) and kynurenic acid (KynA) in preterm and term expressed breast milk (EBM) in the first 14 d following birth, and the relationship of TRP metabolism to maternal stress and immune status. A total of twenty-four mothers were recruited from Cork University Maternity Hospital: twelve term (>38 weeks) and twelve preterm (<35 weeks). EBM samples were collected on days 7 and 14. Free TRP, Kyn and KynA were measured using HPLC, total TRP using MS, cytokines using the Meso Scale Discovery (MSD) assay system, and cortisol using a cortisol ELISA kit. Although total TRP was higher in preterm EBM in comparison with term EBM (P < 0·05), free TRP levels were lower (P < 0·05). Kyn, KynA and the Kyn:TRP ratio increased significantly in term EBM from day 7 to day 14 (P < 0·05), but not in preterm EBM. TNF-α, IL-6 and IL-8 were higher in day 7 preterm and term EBM in comparison with day 14. There were no significant differences between term and preterm EBM cortisol levels. Increased availability of total TRP, lower levels of free TRP and alterations in the temporal dynamics of TRP metabolism in preterm compared with term EBM, coupled with higher EBM inflammatory markers on day 7, may have implications for the neurological development of exclusively breast-fed preterm infants.
The Danjon Astrolabe at the Naval Observatory has been traditionally used to determine Universal Time and improve the systematic accuracy of star positions. During the past year, it has been used to determine latitude and longitude at remotely scattered sites for geodetic purposes. Operating this instrument away from the Observatory necessitated a mobile support and timing system rugged enough to operate dependably in ever changing, and sometimes harsh, environmental conditions.
This paper describes the performance of the astrolabe timing and data acquisition system, gives engineering design considerations, and describes the equipment and instrumentation.
In June 2016, the United Kingdom shocked the world by voting to leave the European Union. As this book reveals, the historic vote for Brexit marked the culmination of trends in domestic politics and in the UK's relationship with the EU that have been building over many years. Drawing on a wealth of survey evidence collected over more than ten years, this book explains why most people decided to ignore much of the national and international community and vote for Brexit. Drawing on past research on voting in major referendums in Europe and elsewhere, a team of leading academic experts analyse changes in the UK's party system that were catalysts for the referendum vote, including the rise of the UK Independence Party (UKIP), the dynamics of public opinion during an unforgettable and divisive referendum campaign, the factors that influenced how people voted and the likely economic and political impact of this historic decision.