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Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.
To estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627).
We undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life.
The additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold.
In its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.
Declaration of interest
R.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 the National Institute for Health Research (NIHR). T.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 co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.
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.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Chronic suppurative otitis media is a massive public health problem in numerous low- and middle-income countries. Unfortunately, few low- and middle-income countries can offer surgical therapy.
A six-month long programme in Cambodia focused on training local surgeons in type I tympanoplasty was instigated. Qualitative educational and quantitative surgical outcomes were evaluated in the 12 months following programme completion. A four-month long training programme in mastoidectomy and homograft ossiculoplasty was subsequently implemented, and the preliminary surgical and educational outcomes were reported.
A total of 124 patients underwent tympanoplasty by the locally trained surgeons. Tympanic membrane closure at six weeks post-operation was 88.5 per cent. Pure tone audiometry at three months showed that 80.9 per cent of patients had improved hearing, with a mean gain of 17.1 dB. The trained surgeons reported high confidence in performing tympanoplasty. Early outcomes suggest the local surgeons can perform mastoidectomy and ossiculoplasty as safely as overseas-trained surgeons, with reported surgeon confidence reflecting these positive outcomes.
The training programme has demonstrated success, as measured by surgeon confidence and operative outcomes. This approach can be emulated in other settings to help combat the global burden of chronic suppurative otitis media.
There is convincing evidence that lower socioeconomic position is associated with increased risk of mental disorders. However, the mechanisms involved are not well understood. This study aims to elucidate the causal pathways between socioeconomic position and depression symptoms in South African adults. Two possible causal theories are examined: social causation, which suggests that poor socioeconomic conditions cause mental ill health; and social drift, which suggests that those with poor mental health are more likely to drift into poor socioeconomic circumstances.
The study used longitudinal and cross-sectional observational data on 3904 adults, from a randomised trial carried out in 38 primary health care clinics between 2011 and 2012. Structural equation models and counterfactual mediation analyses were used to examine causal pathways in two directions. First, we examined social causation pathways, with language (a proxy for racial or ethnic category) being treated as an exposure, while education, unemployment, income and depression were treated as sequential mediators and outcomes. Second, social drift was explored with depression treated as a potential influence on health-related quality of life, job loss and, finally, income.
The results suggest that the effects of language on depression at baseline, and on changes in depression during follow-up, were mediated through education and income but not through unemployment. Adverse effects of unemployment and job loss on depression appeared to be mostly mediated through income. The effect of depression on decreasing income appeared to be mediated by job loss.
These results suggest that both social causation and social selection processes operate concurrently. This raises the possibility that people could get trapped in a vicious cycle in which poor socioeconomic conditions lead to depression, which, in turn, can cause further damage to their economic prospects. This study also suggests that modifiable factors such as income, employment and treatable depression are suitable targets for intervention in the short to medium term, while in the longer term reducing inequalities in education will be necessary to address the deeply entrenched inequalities in South Africa.
Contact precautions are a traditional strategy to prevent transmission of methicillin-resistant Staphylococcus aureus (MRSA). Chlorhexidine bathing is increasingly used to decrease MRSA burden and transmission in intensive care units (ICUs). We sought to evaluate a hospital policy change from routine contact precautions for MRSA compared with universal chlorhexidine bathing, without contact precautions. We measured new MRSA acquisition in ICU patients and surveyed for MRSA environmental contamination in common areas and non-MRSA patient rooms before and after the policy change. During the baseline and chlorhexidine bathing periods, the number of patients (453 vs. 417), ICU days (1999 vs. 1703) and MRSA days/1000 ICU days (109 vs. 102) were similar. MRSA acquisition (2/453 vs. 2/457, P = 0·93) and environmental MRSA contamination (9/474 vs. 7/500, P = 0·53) were not significantly different between time periods. There were 58% fewer contact precaution days in the ICU during the chlorhexidine period (241/1993 vs. 102/1730, P < 0·01). We found no evidence that discontinuation of contact precautions for patients with MRSA in conjunction with adoption of daily chlorhexidine bathing in ICUs is associated with increased MRSA acquisition among ICU patients or increased MRSA contamination of ICU fomites. Although underpowered, our findings suggest this strategy, which has the potential to reduce costs and improve patient safety, should be assessed in similar but larger studies.
The biological mechanisms underlying psychiatric diagnoses are not well defined. Clinical diagnosis based on categorical systems exhibit high levels of heterogeneity and co-morbidity. The Research Domain Criteria (RDoC) attempts to reconceptualize psychiatric disorders into transdiagnostic functional dimensional constructs based on neurobiological measures and observable behaviour. By understanding the underlying neurobiology and pathophysiology of the relevant processes, the RDoC aims to advance biomarker development for disease prediction and treatment response. This important evolving dimensional framework must also consider environmental factors. Emerging evidence suggests that gut microbes (microbiome) play a physiological role in brain diseases by modulating neuroimmune, neuroendocrine and neural signalling pathways between the gut and the brain. The integration of the gut microbiome signature as an additional dimensional component of the RDoC may enhance precision psychiatry.
The endothelial glycocalyx layer (EGL) is a macromolecular layer that lines the inner surface of blood vessels. It is believed to serve a number of physiological functions in the microvasculature, including protection of the vessel walls from potentially harmful levels of fluid shear, as a molecular sieve that acts to regulate transendothelial mass transport, and as a transducer of mechanical stress from the vessel lumen. To best fulfil some of its roles, it has been suggested that the EGL redistributes, so that it is thickest at the cell–cell junctions. It has also been suggested that the majority of mechanotransduction occurs through the solid phase of the EGL, rather than via its fluid phase. The difficulties associated with measuring the distribution of the EGL in vivo make these hypotheses difficult to confirm experimentally. Consequently, to gauge the impact of EGL redistribution from a theoretical standpoint, we compute the flow through a porous-lined microvessel, the endothelial surface of which has been informed by confocal microscopy images of a postcapillary venule. Following earlier studies, we model the poroelastohydrodynamics of the EGL using biphasic mixture theory, taking advantage of a recently developed boundary integral representation of these equations to solve the coupled poroelastohydrodynamics using the boundary element method. However, the low permeabilities of the EGL mean that viscous effects are confined to thin layers, thereby also enabling an asymptotic treatment of the dynamics in this limit. In this asymptotic regime, we also consider a two-layer Stokes flow model for the lumen flow to approximate the effect of red blood cells within the lumen. We demonstrate that redistribution of the EGL can have a substantial impact upon microvessel haemodynamics. We also confirm that the bulk of the mechanical stress is indeed carried through the solid phase of the EGL.
Strong recommendations have been made for the periodic developmental surveillance, screening, and evaluation of children with CHD. This supports similar calls for all at-risk children in order to provide timely, structured early developmental intervention that may improve outcomes. The aim of this study was to determine the accuracy of screening for language delay after life-saving therapies using the parent-completed vocabulary screen of the language Development Survey, by comparing screening with the individually administered language scores of the Bayley Scales of Infant and Toddler Development, Third edition.
In total, 310 (92.5%) of 335 eligible term-born children, born between 2004 and 2011, receiving complex cardiac surgery, heart or liver transplantation, or extracorporeal membrane oxygenation in infancy, were assessed at 21.5 (2.8) months of age (lost, 25 (7.5%)), through developmental/rehabilitation centres at six sites as part of the Western Canadian Complex Pediatric Therapies Follow-up Group.
Vocabulary screening delay was defined as scores ⩽15th percentile. Language delay defined as scores >1 SD below the mean was calculated for language composite score, receptive and expressive communication scores of the Bayley-III. Delayed scores for the 310 children were as follows: vocabulary, 144 (46.5%); language composite, 125 (40.3%); receptive communication, 98 (31.6%); and expressive communication, 124 (40%). Sensitivity, specificity, positive predictive values, and negative predictive values of screened vocabulary delay for tested language composite delay were 79.2, 75.7, 68.8, and 84.3%, respectively.
High rates of language delay after life-saving therapies are concerning. Although the screening test appears to over-identify language delay relative to the tested Bayley-III, it may be a useful screening tool for early language development leading to earlier referral for intervention.
The rate at which the poaching of rhinoceroses has escalated since 2010 poses a threat to the long-term persistence of extant rhinoceros populations. The policy response has primarily called for increased investment in military-style enforcement strategies largely based upon simple economic models of rational crime. However, effective solutions will probably require a context-specific, stakeholder-driven mix of top-down and bottom-up mechanisms grounded in theory that represents human behaviour more realistically. Using a problem-oriented approach we illustrate in theory and practice how community-based strategies that explicitly incorporate local values and institutions are a foundation for combating rhinoceros poaching effectively in specific contexts. A case study from Namibia demonstrates how coupling a locally devised rhinoceros monitoring regime with joint-venture tourism partnerships as a legitimate land use can reconcile individual values represented within a diverse stakeholder group and manifests as both formal and informal community enforcement. We suggest a social learning approach as a means by which international, national and regional governance can recognize and promote solutions that may help empower local communities to implement rhinoceros management strategies that align individual values with the long-term health of rhinoceros populations.
Little is known about cause-specific long-term mortality beyond 30 days in pneumonia. We aimed to compare the mortality of patients with hospitalized pneumonia compared to age- and sex-matched controls beyond 30 days. Participants were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study. Hospitalized pneumonia cases were identified from record linkage (ICD-10: J12-J18). For this study we excluded people with hospitalized pneumonia who died within 30 days. Each case identified was matched to four controls and followed up until the end June 2012 (total 15 074 person-years, mean 6·1 years, range 0·08–15·2 years). Cox regression models were constructed to examine the all-cause, respiratory and cardiovascular mortality using date of pneumonia onset as baseline with binary pneumonia status as exposure. A total of 2465 men and women (503 cases, 1962 controls) [mean age (s.d.) 64·5 (8·3) years] were included in the study. Between a 30-day to 1-year period, hazard ratios (HRs) of all-cause and cardiovascular mortality were 7·3 [95% confidence interval (CI) 5·4–9·9] and 5·9 (95% CI 3·5–9·7), respectively (with very few respiratory deaths within the same period) in cases compared to controls after adjusting for age, sex, asthma, smoking status, pack years, systolic and diastolic blood pressure, diabetes, physical activity, waist-to-hip ratio, prevalent cardiovascular and respiratory diseases. All outcomes assessed also showed increased risk of death in cases compared to controls after 1 year; respiratory cause of death being the most significant during that period (HR 16·4, 95% CI 8·9–30·1). Hospitalized pneumonia was associated with increased all-cause and specific-cause mortality beyond 30 days.
Intestinal health is important for maximising the health, welfare, and performance of poultry. In addition, intestinal health issues in poultry can have devastating financial impacts for producers, and food safety concerns for consumers. Until recently, intestinal health issues were seen as a handful of known infectious agents leading to a set of severe and identifiable named diseases. There is however an emerging area which depicts intestinal health as a more complex and multifaceted system than previously known. Recent progress in technology suitable for microbial community analysis has evolved our understanding of the chicken intestinal microbiome. It is now understood that shifts in the composition of microbial communities can occur. These shifts can result in a series of implications, including: disease, welfare, environmental, and food safety concerns. Minor shifts in intestinal microbial balance can result in a wide continuum of disease presentations ranging from severe to mild clinical, subclinical or asymptotic. Differential diagnosis of poultry intestinal health issues may be challenging and is important for applying appropriate treatment options. This review discusses new and emerging topics in broiler chicken intestinal health, with a focus on microbial composition, newly discovered microbial shifts in classical poultry diseases, range in severity of enteric diseases, newly identified organisms in normal intestinal flora, implications of shifts in intestinal microbial communities and diagnosis of emerging intestinal health issues in poultry.
The Murchison Widefield Array is a Square Kilometre Array Precursor. The telescope is located at the Murchison Radio–astronomy Observatory in Western Australia. The MWA consists of 4 096 dipoles arranged into 128 dual polarisation aperture arrays forming a connected element interferometer that cross-correlates signals from all 256 inputs. A hybrid approach to the correlation task is employed, with some processing stages being performed by bespoke hardware, based on Field Programmable Gate Arrays, and others by Graphics Processing Units housed in general purpose rack mounted servers. The correlation capability required is approximately 8 tera floating point operations per second. The MWA has commenced operations and the correlator is generating 8.3 TB day−1 of correlation products, that are subsequently transferred 700 km from the MRO to Perth (WA) in real-time for storage and offline processing. In this paper, we outline the correlator design, signal path, and processing elements and present the data format for the internal and external interfaces.