An Economic Evaluation Supported by Qualitative Data About the Patient Concerns Inventory (PCI) versus Standard Treatment Pathway in the Management of Patients with Head and Neck Cancer.

Background The head and neck cancer (HNC) Patient Concerns Inventory (PCI) is a condition-specific prompt list that allows patients to raise concerns to cancer consultants that otherwise might be overlooked. Objective This is the first economic evaluation of the PCI in patients with HNC investigating the costs and effects to the health service of not prioritising certain treatment pathways in addition to the primary cancer pathway. Additional costs can be accrued due to delayed referral to other appropriate services, e.g. hospital dentist. Economic evidence could influence future policy direction in this area globally. Methods Alongside a 3-year clustered randomised controlled trial, an economic evaluation was undertaken with Client Service Receipt Inventory data collected at three different time points (baseline and 6 and 12 months post-baseline). Patients were identified by a multidisciplinary team at the trial clinics. This economic analysis compared the PCI intervention versus the non-PCI treatment pathway. A deterministic and probabilistic sensitivity analysis was conducted to investigate the cost per quality-adjusted life-year (QALY) gain of the PCI versus non-PCI intervention treatment pathways. Qualitative data were also collected from seven consultants to triangulate findings from the economic evaluation. Results The analysis used data from 191 patients (66% of the full trial sample). The PCI inventory was low cost, at just over £13 per participant. The PCI intervention was cost effective and also cost saving, with an incremental cost difference of £295.91 over the 12-month follow-up period. The QALY values were higher in the PCI intervention strategy, with a value of 0.79, whereas the non-PCI group had a value of 0.76, thus the PCI intervention was dominant. The sensitivity analysis showed that, at a willingness-to-pay threshold of £20,000 per QALY gained, the probability of being cost effective was 0.85 (95% confidence interval [CI] 0.80–0.83). Qualitative results showed that consultants using the PCI reported an enhanced awareness of patients’ overall post-treatment needs. Discussion The PCI provided an effective means to conduct clinical consultations by avoiding unnecessary healthcare costs and focussing on aspects of care most important to patients. The cost per QALY gain was within the National Institute for Health and Care Excellence guideline threshold. The economic evaluation showed that the PCI intervention strategy was dominant and therefore cost saving to the national health service (NHS) and was more effective in terms of treatment. Conclusion The PCI appears to be a low-cost intervention that generates a cost-effective benefit to patients from a NHS perspective if rolled out as part of routine care. Qualitative evidence has shown that the use of the PCI is supported by consultants in routine practice. Trial Registration Clinical Trials Identifier: NCT03086629

Moisture transport by Atlantic tropical cyclones onto the North American continent

Tropical Cyclones (TCs) are an important source of freshwater for the North American continent. Many studies have tried to estimate this contribution by identifying TC-induced precipitation events, but few have explicitly diagnosed the moisture fluxes across continental boundaries. We design a set of attribution schemes to isolate the column-integrated moisture fluxes that are directly associated with TCs and to quantify the flux onto the North American Continent due to TCs. Averaged over the 2004–2012 hurricane seasons and integrated over the western, southern and eastern coasts of North America, the seven schemes attribute 7 to 18 % (mean 14 %) of total net onshore flux to Atlantic TCs. A reduced contribution of 10 % (range 9 to 11 %) was found for the 1980–2003 period, though only two schemes could be applied to this earlier period. Over the whole 1980–2012 period, a further 8 % (range 6 to 9 % from two schemes) was attributed to East Pacific TCs, resulting in a total TC contribution of 19 % (range 17 to 22 %) to the ocean-to-land moisture transport onto the North American continent between May and November. Analysis of the attribution uncertainties suggests that incorporating details of individual TC size and shape adds limited value to a fixed radius approach and TC positional errors in the ERA-Interim reanalysis do not affect the results significantly, but biases in peak wind speeds and TC sizes may lead to underestimates of moisture transport. The interannual variability does not appear to be strongly related to the El Nino-Southern Oscillation phenomenon

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

A deeply branching thermophilic bacterium with an ancient acetyl-CoA pathway dominates a subsurface ecosystem

<div><p>A nearly complete genome sequence of <em>Candidatus</em> ‘Acetothermum autotrophicum’, a presently uncultivated bacterium in candidate division OP1, was revealed by metagenomic analysis of a subsurface thermophilic microbial mat community. Phylogenetic analysis based on the concatenated sequences of proteins common among 367 prokaryotes suggests that <em>Ca.</em> ‘A. autotrophicum’ is one of the earliest diverging bacterial lineages. It possesses a folate-dependent Wood-Ljungdahl (acetyl-CoA) pathway of CO₂ fixation, is predicted to have an acetogenic lifestyle, and possesses the newly discovered archaeal-autotrophic type of bifunctional fructose 1,6-bisphosphate aldolase/phosphatase. A phylogenetic analysis of the core gene cluster of the acethyl-CoA pathway, shared by acetogens, methanogens, some sulfur- and iron-reducers and dechlorinators, supports the hypothesis that the core gene cluster of <em>Ca.</em> ‘A. autotrophicum’ is a particularly ancient bacterial pathway. The habitat, physiology and phylogenetic position of <em>Ca.</em> ‘A. autotrophicum’ support the view that the first bacterial and archaeal lineages were H₂-dependent acetogens and methanogenes living in hydrothermal environments.</p> </div

Esophageal Squamous Cell Carcinoma with Marked Eosinophil Infiltration

We report a case of esophageal squamous cell carcinoma (SCC) with marked eosinophil infiltration which was identified postoperatively in the esophageal wall in areas not surrounding the SCC. The eosinophil infiltration was seen in the submucosa, muscle and adventitia, but not in the mucosa. Eosinophilic esophagitis (EoE) is a pathological condition defined as eosinophil infiltration within the esophageal mucosa. Eosinophil infiltration at the invasion front of esophageal SCC is termed tumor-associated tissue eosinophilia (TATE). However, the eosinophil infiltration in this case may be pathologically different from both EoE and TATE. To our knowledge, this is the first report of esophageal SCC with eosinophil infiltration

Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial

BACKGROUND: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0-1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. FINDINGS: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6-69·3) with olaparib and 64·5 months (63·4-68·7) with placebo. Median overall survival was 51·7 months (95% CI 41·5-59·1) with olaparib and 38·8 months (31·4-48·6) with placebo (hazard ratio 0·74 [95% CI 0·54-1·00]; p=0·054), unadjusted for the 38% of patients in the placebo group who received subsequent PARP inhibitor therapy. The most common grade 3 or worse treatment-emergent adverse event was anaemia (which occurred in 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in the placebo group). Serious treatment-emergent adverse events were reported in 50 (26%) of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo. Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the 195 patients receiving olaparib, six of which were judged to be treatment-related (attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]). INTERPRETATION: Olaparib provided a median overall survival benefit of 12·9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients. FUNDING: AstraZeneca and Merck

High genetic diversity in a potentially vulnerable tropical tree species despite extreme habitat loss

10.1371/journal.pone.0082632PLoS ONE812-POLN

Uteroplacental bleeding disorders during pregnancy: do missing paternal characteristics influence risk?

BACKGROUND: Several studies have assessed the risks of uteroplacental bleeding disorders in relation to maternal characteristics. The association between uteroplacental bleeding disorders and paternal characteristics, however, has received considerably less attention. Data on paternal demographics, notably race and age, from birth certificate data are becoming increasingly incomplete in recent years. This pattern of increasingly underreporting of paternal demographic data led us to speculate that pregnancies for which paternal characteristics are partially or completely missing may be associated with increased risk for uteroplacental bleeding disorders. The objective of this study is to examine the association between placenta previa and placental abruption and missing paternal age and race. METHODS: A retrospective cohort study using U.S. linked birth/infant death data from 1995 through 2001 (n = 26,336,549) was performed. Risks of placenta previa and placental abruption among: (i) pregnancies with complete paternal age and race data; (ii) paternal age only missing; (iii) paternal race only missing; and (iv) both paternal age and race missing, were evaluated. Relative risk (RR) with 95% confidence interval (CI) for placenta previa and placental abruption by missing paternal characteristics were derived after adjusting for confounders. RESULTS: Adjusted RR for placental abruption were 1.30 (95% CI 1.24, 1.37), 1.00 (95% CI 0.95, 1.05), and 1.08 (95% CI 1.06, 1.10) among pregnancies with "paternal age only", "paternal race only", and "both paternal age and race" missing, respectively. The increased risk of placental abruption among the "paternal age only missing" category is partly explained by increased risks among whites aged 20–29 years, and among blacks aged ≥30 years. However, no clear patterns in the associations between missing paternal characteristics and placenta previa were evident. CONCLUSION: Missing paternal characteristics are associated with increased risk of placental abruption, likely mediated through low socio-economic conditions

A mammalian functional-genetic approach to characterizing cancer therapeutics

Supplementary information is available online at http://www.nature.com/naturechemicalbiology/. Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/.Identifying mechanisms of drug action remains a fundamental impediment to the development and effective use of chemotherapeutics. Here we describe an RNA interference (RNAi)–based strategy to characterize small-molecule function in mammalian cells. By examining the response of cells expressing short hairpin RNAs (shRNAs) to a diverse selection of chemotherapeutics, we could generate a functional shRNA signature that was able to accurately group drugs into established biochemical modes of action. This, in turn, provided a diversely sampled reference set for high-resolution prediction of mechanisms of action for poorly characterized small molecules. We could further reduce the predictive shRNA target set to as few as eight genes and, by using a newly derived probability-based nearest-neighbors approach, could extend the predictive power of this shRNA set to characterize additional drug categories. Thus, a focused shRNA phenotypic signature can provide a highly sensitive and tractable approach for characterizing new anticancer drugs.National Institute of Mental Health (U.S.) (grant RO1 CA128803-03)American Association for Cancer ResearchMassachusetts Institute of Technology. Dept. of BiologyNational Cancer Institute (U.S.). Integrative Cancer Biology Program (grant 1-U54-CA112967