Cost-Effectiveness of Collaborative Care for Depression in UK Primary Care: Economic Evaluation of a Randomised Controlled Trial (CADET)

Background: Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking. Aims: To assess the cost-effectiveness of collaborative care in a UK primary care setting. Methods: An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane. Results: The collaborative care intervention had a mean cost of £272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: –0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of £270.72 (95% CI: –202.98, 886.04), and resulted in an estimated mean cost per QALY of £14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual. Conclusion: Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting

Crystal or Glass? Chemical and Crystallographic Factors in the Amorphization of Molecular Materials

YesThe creation of long-lived amorphous phases has potential applications in numerous fields; for example, the instability of the amorphous phase leads to higher solubility of pharmaceutical phases, often leading to higher bioavailability. The rate of recrystallization of an amorphous phase poses a significant limitation to the application of many such phases; however, understanding the energetic and structural factors that control the stability of molecular amorphous phases is limited by empirical classifications based on thermal analysis used to identify materials. From a set of molecularly related benzanilides, examples of all three classes have been identified, allowing use of crystal structural analysis, Raman spectroscopy, and energetic calculations to determine the structural factors playing a role in the different stabilities. While the behavior of most systems reflects the relative energy of the crystalline phase to the amorphous phase, kinetic factors based on whether a NH···O=C hydrogen bond is present in the crystalline phase play a key role in stabilizing the amorphous phase as the loss of this bond reduces the conversion rate. In contrast, systems without this bond display fast recrystallization due to the greater structural similarity between the amorphous and crystalline phases

Integration of water, sanitation, and hygiene for the prevention and control of neglected tropical diseases: a rationale for inter-sectoral collaboration.

Improvements of water, sanitation, and hygiene (WASH) infrastructure and appropriate health-seeking behavior are necessary for achieving sustained control, elimination, or eradication of many neglected tropical diseases (NTDs). Indeed, the global strategies to fight NTDs include provision of WASH, but few programs have specific WASH targets and approaches. Collaboration between disease control programs and stakeholders in WASH is a critical next step. A group of stakeholders from the NTD control, child health, and WASH sectors convened in late 2012 to discuss opportunities for, and barriers to, collaboration. The group agreed on a common vision, namely "Disease-free communities that have adequate and equitable access to water and sanitation, and that practice good hygiene." Four key areas of collaboration were identified, including (i) advocacy, policy, and communication; (ii) capacity building and training; (iii) mapping, data collection, and monitoring; and (iv) research. We discuss strategic opportunities and ways forward for enhanced collaboration between the WASH and the NTD sectors

Isostructurality of quinoxaline crystal phases: The interplay of weak hydrogen bonds and halogen bonding

YesTailoring the physical properties of molecular crystals though the construction of solid solutions requires the existence of isostructural crystals. Simple substitutions of a given molecular framework can give a range of different crystal structures. A set of quinoxaline derivatives, C8H4N2(C6H4X)2,Q3,3′X2, has been investigated (X = F, Cl, Br, I and Me) where kinetic factors generated a set of isostructural crystals for the lighter halogens (F, Cl, Br) alone. Computational analysis shows that the stabilising interactions are maximal for Cl, while DSC studies demonstrate the existence of more stable polymorphs for both F and Br containing systems. Steric factors appear to have a lower contribution than the balance of weaker hydrogen and halogen bonding shown by the Me and I containing systems displaying different packing driven by CH⋯N/CH⋯π bonds and I⋯I bonds respectively

Insights into the effects of sex and tissue location on the evolution of adipocyte dysfunction in an ovine model of polycystic ovary syndrome (PCOS).

Adipose tissue dysfunction is one of the features of Polycystic Ovary Syndrome (PCOS) with dysregulated adipogenesis, altered functional pathways and increased inflammation. It is increasingly clear that there are also male correlates of the hormonal and metabolic features of PCOS. We hypothesised that the effects of adipose tissue dysfunction are not sex-specific but rather fat depot-specific and independent of obesity. We used a clinically realistic ovine model of PCOS where pregnant sheep are injected with 100mg of testosterone propionate twice weekly from day 62 to day 102 of gestation. We studied control and prenatally androgenised (PA) female and male offspring during adolescence and weight-matched control and PA female sheep during adulthood. We examined subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and in adult female sheep bone marrow adipose tissue (BMAT). Adipogenesis related gene expression in SAT was similar in adolescent female and male controls and the reduction in adipogenesis related gene expression by PA in female adipose tissue was not observed in males. Differences in expression of genes associated with adipose tissue function in adolescence in SAT driven by PA were found in both sexes. In adulthood, the changes seen in adolescent females were absent or reversed but there was an increase in inflammatory markers that was weight independent. In addition, BMAT showed increased inflammatory markers. Adipose dysfunction evolves with time and is focussed on SAT rather than VAT and is generally sex-specific although there are also effects of prenatal androgenisation on male SAT. In female adults, the inflammation seen in SAT is also present in BMAT and the development of blood cells in an inflammatory environment may have systemic implications

Rust expression browser: an open source database for simultaneous analysis of host and pathogen gene expression profiles with expVIP

BackgroundTranscriptomics is being increasingly applied to generate new insight into the interactions between plants and their pathogens. For the wheat yellow (stripe) rust pathogen (Puccinia striiformis f. sp. tritici, Pst) RNA-based sequencing (RNA-Seq) has proved particularly valuable, overcoming the barriers associated with its obligate biotrophic nature. This includes the application of RNA-Seq approaches to study Pst and wheat gene expression dynamics over time and the Pst population composition through the use of a novel RNA-Seq based surveillance approach called "field pathogenomics". As a dual RNA-Seq approach, the field pathogenomics technique also provides gene expression data from the host, giving new insight into host responses. However, this has created a wealth of data for interrogation.ResultsHere, we used the field pathogenomics approach to generate 538 new RNA-Seq datasets from Pst-infected field wheat samples, doubling the amount of transcriptomics data available for this important pathosystem. We then analysed these datasets alongside 66 RNA-Seq datasets from four Pst infection time-courses and 420 Pst-infected plant field and laboratory samples that were publicly available. A database of gene expression values for Pst and wheat was generated for each of these 1024 RNA-Seq datasets and incorporated into the development of the rust expression browser (http://www.rust-expression.com). This enables for the first time simultaneous 'point-and-click' access to gene expression profiles for Pst and its wheat host and represents the largest database of processed RNA-Seq datasets available for any of the three Puccinia wheat rust pathogens. We also demonstrated the utility of the browser through investigation of expression of putative Pst virulence genes over time and examined the host plants response to Pst infection.ConclusionsThe rust expression browser offers immense value to the wider community, facilitating data sharing and transparency and the underlying database can be continually expanded as more datasets become publicly available

Discovering Transcription Factor Binding Sites in Highly Repetitive Regions of Genomes with Multi-Read Analysis of ChIP-Seq Data

Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is rapidly replacing chromatin immunoprecipitation combined with genome-wide tiling array analysis (ChIP-chip) as the preferred approach for mapping transcription-factor binding sites and chromatin modifications. The state of the art for analyzing ChIP-seq data relies on using only reads that map uniquely to a relevant reference genome (uni-reads). This can lead to the omission of up to 30% of alignable reads. We describe a general approach for utilizing reads that map to multiple locations on the reference genome (multi-reads). Our approach is based on allocating multi-reads as fractional counts using a weighted alignment scheme. Using human STAT1 and mouse GATA1 ChIP-seq datasets, we illustrate that incorporation of multi-reads significantly increases sequencing depths, leads to detection of novel peaks that are not otherwise identifiable with uni-reads, and improves detection of peaks in mappable regions. We investigate various genome-wide characteristics of peaks detected only by utilization of multi-reads via computational experiments. Overall, peaks from multi-read analysis have similar characteristics to peaks that are identified by uni-reads except that the majority of them reside in segmental duplications. We further validate a number of GATA1 multi-read only peaks by independent quantitative real-time ChIP analysis and identify novel target genes of GATA1. These computational and experimental results establish that multi-reads can be of critical importance for studying transcription factor binding in highly repetitive regions of genomes with ChIP-seq experiments

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS: New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS: Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION: Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING: Cancer Research UK

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy.

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