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OBJECTIVE: To establish an international core set of patient-reported outcomes (PROs) selected by both patients and healthcare providers (HCPs) from the United States (US), Europe, and Asia. SUMMARY BACKGROUND DATA: PROs are increasingly recognized in pancreatic cancer studies. There is no consensus on which of the many available PROs are most important. METHODS: A multicenter Delphi study among patients with pancreatic cancer (curative- and palliative-setting) and HCPs in 6 pancreatic centers in the US (Baltimore, Boston), Europe (Amsterdam, Verona), and Asia (Mumbai, Seoul) was performed. In round 1, participants rated the importance of 56 PROs on a 1 to 9 Likert scale. PROs rated as very important (scores 7-9) by the majority (≥80%) of curative- and/or palliative-patients as well as HCPs were included in the core set. PROs not fulfilling these criteria were presented again in round 2, together with feedback on individual and group ratings. Remaining PROs were ranked based on the importance ratings. RESULTS: In total 731 patients and HCPs were invited, 501 completed round 1, and 420 completed both rounds. This included 204 patients in curative-setting, 74 patients in palliative-setting, and 142 HCPs. After 2 rounds, 8 PROs were included in the core set: general quality of life, general health, physical ability, ability to work/do usual activities, fear of recurrence, satisfaction with services/care organization, abdominal complaints, and relationship with partner/family. CONCLUSIONS: This international Delphi study among patients and HCPs established a core set of PROs in pancreatic cancer, which should facilitate the design of future pancreatic cancer trials and outcomes research.

The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community’s massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of 10 separate disease maps and sources of experimental data focused on SARS-CoV-2/COVID-19 pathophysiology. By applying our systematic approach, we were able to predict the synergistic effect of specific drug pairs, such as Remdesivir and Thioguanosine or Nelfinavir and Raloxifene, on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.

Background Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. Methods/design PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. Discussion The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. Trial registration ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

The lipid kinase phosphoinositide 3-kinase γ (PI3Kγ) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3Kγ, we discovered a series of azaisoindolinones as selective, brain penetrant inhibitors of PI3Kγ. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy in murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.

Objective This study aims to identify patients with oesophageal cancer's level of distress, type of problems, and wish for referral prior to treatment. To identify the clinical relevance of patients with oesophageal cancer's level of distress and type of problems, we build models to predict elevated distress, wish for referral, and overall survival. Methods We implemented the Distress Thermometer and Problem List in daily clinical practice. A score of ≥5 on the Distress Thermometer reflected elevated distress. We first created an initial model including predictors based on the literature. We then added predictors to the initial model to create an extended model based on the sample data. We used the ‘least absolute shrinkage and selection operator’ to define our final model. Results We obtained data from 187 patients (47.9%, of 390 eligible patients with oesophageal cancer) which were similar to non-respondents in their demographic and clinical characteristics. One-hundred thirteen (60%) patients reported elevated distress. The five most frequently reported problems were as follows: eating, tension, weight change, fatigue, and pain. Most patients did not have a wish for referral. Predictors for elevated distress were as follows: being female, total number of practical, emotional, and physical problems, pain, and fatigue. For referral, we identified age, the total number of emotional problems, the level of distress, and fear. The level of distress added prognostic information in a model to predict overall survival. Conclusions Patients with oesophageal cancer report elevated distress and a myriad of problems yet do not have an explicit wish for referral prior to receiving their medical treatment plan. Copyright © 2016 John Wiley & Sons, Ltd.

Aim To determine the completeness of reporting of patient-reported outcomes (PROs) of head and neck cancer (HNC) and thyroid cancer randomised-controlled trials (RCTs) and identify PRO measures used. Methods A systematic literature search was conducted for HNC and thyroid cancer RCTs with PRO end-points (January 2004–June 2015). Two investigators independently extracted data, assessed adherence to the International Society for Quality of Life Research (ISOQOL) PRO reporting standards and concordance between hypotheses and PRO measures used. Data were entered into the Patient-Reported Outcomes Measurements Over Time in Oncology (PROMOTION) Registry. Results Sixty-six RCTs were included, 56 (85%) HNC and 10 (15%) thyroid cancer. Twenty-two (33%) included a primary and 44 (67%) included a secondary PRO end-point. A total of 40 unique PRO measures were used. Adherence to the ISOQOL PRO reporting standards was higher for RCTs with primary PRO end-points than for secondary PRO end-points: (mean adherence of 43% and 29% respectively). Completeness of PRO reporting did not improve with time: r = .13, p = .31. ISOQOL checklist items poorly reported included: PRO hypothesis (reported for eight RCTs, 12%), justification chosen of PRO measures (n = 16, 24%), rates of missing PRO data (n = 19, 29%), and generalisability of results (n = 12, 18%). Encouragingly, PROs were identified in 55 RCT abstracts (83%) and PRO results interpreted for 30 RCTs (45%). Conclusions Reporting of PRO end-points was more comprehensive in RCTs with primary rather than secondary PRO end-points. Improvement is needed in the transparent reporting of PRO studies, particularly regarding data collection, analyses and generalisability of PRO results.

We developed a web-based question prompt sheet (QPS) to support information provision of health-related quality of life (HRQL) topics after oesophageal cancer surgery. The QPS was evaluated and updated in three consecutive studies. In Study 1, eight patients were guided in using the QPS. Feasibility was assessed by cognitive walkthrough, questionnaire and interview. We obtained 430 notes (217 negative, 213 positive) of patients' actions and or remarks, and 91 suggestions. With minor support, most patients were able to use the QPS. In Study 2, forty patients independently used and appraised a modified version of the QPS by questionnaire. All patients deemed the QPS to be usable and useful. In Study 3, 21 patients and three surgeons used the QPS in clinical practice. Clinical feasibility was assessed by the number of QPS sent to the researcher/surgeon. Patients and surgeons were surveyed and the follow-up consultation was audio-recorded. Surgeons were additionally interviewed. Twenty/fourteen patients sent their QPS to the researcher/surgeon. Five QPSs were read by the consultation surgeon. Patients considered the QPS usable and useful. Surgeons considered the QPS of added value and helpful in informing patients, but currently not clinically feasible due to increased consultation time.

Objective The aim of this study was to examine the effect of spiritual interventions on quality of life of cancer patients. Methods We conducted our search on June 6, 2014 in Medline, PsycINFO, Embase, and PubMed. All clinical trials were included that compared standard care with a spiritual intervention that addressed existential themes using a narrative approach. Study quality was evaluated by the Cochrane Risk of Bias Tool. Results A total of 4972 studies were identified, of which 14 clinical trials (2050 patients) met the inclusion criteria, and 12 trials (1878 patients) were included in the meta-analysis. The overall risk of bias was high. When combined, all studies showed a moderate effect (d) 0.50 (95% CI = 0.20–0.79) 0–2 weeks after the intervention on overall quality of life in favor of the spiritual interventions. Meta-analysis at 3–6 months after the intervention showed a small insignificant effect (0.14, 95% CI = −0.08 to 0.35). Subgroup analysis including only the western studies showed a small effect of 0.17 (95% CI = 0.05–0.29). Including only studies that met the allocation concealment criteria showed an insignificant effect of 0.14 (95% CI = −0.05 to 0.33). Conclusions Directly after the intervention, spiritual interventions had a moderate beneficial effect in terms of improving quality of life of cancer patients compared with that of a control group. No evidence was found that the interventions maintained this effect up to 3–6 months after the intervention. Further research is needed to understand how spiritual interventions could contribute to a long-term effect of increasing or maintaining quality of life. Copyright © 2015 John Wiley & Sons, Ltd.

BACKGROUND The main objectives of this study were to identify the number of randomized controlled trials (RCTs) including a patient-reported outcome (PRO) endpoint across a wide range of cancer specialties and to evaluate the completeness of PRO reporting according to the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. METHODS RCTs with a PRO endpoint that had been performed across several cancer specialties and published between 2004 and 2013 were considered. Studies were evaluated on the basis of previously defined criteria, including the CONSORT PRO extension and the Cochrane Collaboration's tool for assessing the risk of bias of RCTs. Analyses were also conducted by the type of PRO endpoint (primary vs secondary) and by the cancer disease site. RESULTS A total of 56,696 potentially eligible records were scrutinized, and 557 RCTs with a PRO evaluation, enrolling 254,677 patients overall, were identified. PROs were most frequently used in RCTs of breast (n = 123), lung (n = 85), and colorectal cancer (n = 66). Overall, PROs were secondary endpoints in 421 RCTs (76%). Four of 6 evaluated CONSORT PRO items were documented in less than 50% of the RCTs. The level of reporting was higher in RCTs with a PRO as a primary endpoint. The presence of a supplementary report was the only statistically significant factor associated with greater completeness of reporting for both RCTs with PROs as primary endpoints (β = .19, P = .001) and RCTs with PROs as secondary endpoints (β = .30, P < .001). CONCLUSIONS Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute to revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting. Cancer 2015;121:3335–3342. © 2015 American Cancer Society.

In our efforts to develop novel small-molecule inhibitors for the treatment of influenza, we utilized molecular modeling and the X-ray crystal structure of the PB2 subunit of the influenza polymerase to optimize a series of acyclic β-amino acid inhibitors, highlighted by compound 4. Compound 4 showed good oral exposure in both rat and mouse. More importantly, it showed strong potency versus multiple influenza-A strains, including pandemic 2009 H1N1 and avian H5N1 strains and showed a strong efficacy profile in a mouse influenza model even when treatment was initiated 48 h after infection. Compound 4 offers good oral bioavailability with great potential for the treatment of both pandemic and seasonal influenza.

Aim: The aim for this study is to investigate the methodological quality and potential impact on clinical decision making of patient reported outcome (PRO) assessment in randomised controlled trials (RCTs) in the gynecological cancer sites. Methods: A systematic review identified RCTs published between January 2004 and June 2012. Relevant studies were evaluated using a pre-determined extraction form which included: 1) Trial demographics and clinical and PRO characteristics; 2) level of PRO reporting; 3) Bias, assessed using the Cochrane Risk of Bias tool. All studies were additionally analysed in relation to their relevance in supporting clinical decision making. Results: Fifty RCTs enrolling 24991 patients were identified. In eight RCTs (16%) a PRO was the primary endpoint. Twenty-one studies (42%) were carried out in a multi-national context. Where statistically significant PRO differences between treatments were found, it related in most cases to both symptoms and domains other than symptoms (n=17, 57%). The majority of studies (n=42, 84%) did not mention the mode of administration nor the methods of collecting PRO data. Statistical approaches for dealing with missing data were only explicitly mentioned in 9 RCTs (18%). Sixteen RCTs (32%) were considered to be of high-quality and thus able to inform clinical decision making. Higher-quality PRO studies were generally associated with RCTs that were at a low risk of bias. Conclusion: This study showed that RCTs with PROs were generally well designed and conducted. In a third the information was very informative to fully understand the pros and cons of PROs treatment decision-making.

Purpose To (1) assess the quality of studies evaluating Health-Related Quality of Life (HRQL) after potentially curative treatment for esophageal cancer, and (2) to identify high-quality studies that provide robust HRQL results. Methods A systematic literature search is to identify studies evaluating HRQL with a validated multidimensional patient-reported outcome measure. Study quality focused on study design, risk of bias, HRQL outcome reporting, and additional issues of reporting and methodology. A study was deemed high-quality if criteria for robust study methodology and robust HRQL outcome reporting were met. Results Six RCTs, 12 cohort studies, 13 case-series, and 31 cross-sectional studies were identified. Overall risk of bias was high. Reporting of HRQL concept (e.g., a priori hypothesis), methodology (e.g., reasons for missing data), and interpretation (e.g., clinical significance) was often absent or unclear. Additional issues of reporting (e.g., unclear treatment descriptions) and methodology (e.g., no control for multiple testing) were identified. Four studies (6 %) met the criteria for robust study methodology, and 26 studies (42 %) met the criteria for robust HRQL outcome reporting. We identified three high-quality studies (5 %)— two RCTs and one case-series—capable of providing robust results. Conclusions Current evidence is restricted in its ability to inform practice on HRQL after potentially curative treatment for esophageal cancer.

We report a clustering of public human protein kinase structures based on the conformations of two structural elements, the activation segment and the C-helix, revealing three discrete clusters. One cluster includes kinases in catalytically active conformations. Each of the other clusters contains a distinct inactive conformation. Typically, kinases adopt at most one of the inactive conformations in available X-ray structures, implying that one of the conformations is preferred for many kinases. The classification is consistent with selectivity profiles of several well-characterized kinase inhibitors. We show further that inhibitor selectivity profiles guide kinase classification. For example, selective inhibition of lck among src-family kinases by imatinib (Gleevec) suggests that the relative stabilities of inactive conformations of lck are different from other src-family kinases. We report the X-ray structure of the lck/imatinib complex, confirming that the conformation adopted by lck is distinct from other structurally-characterized src-family kinases and instead resembles kinases abl1 and kit in complex with imatinib. Our classification creates new paths for designing small-molecule inhibitors. Proteins 2008. © 2007 Wiley-Liss, Inc.

VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m 7 GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a K D (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC 50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC 50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection.

Health-related quality of life (HRQOL) and other patient-reported outcomes (PROs) are crucial for a comprehensive evaluation of treatment effectiveness. A systematic review of randomized controlled trials (RCTs) with a PRO endpoint conducted in patients with leukemia and myelodysplastic syndromes (MDS) was performed. Eligible studies were evaluated independently, according to a pre-defined coding scheme, by two reviewers. Thirteen RCTs, enrolling overall 3380 patients were identified. There were four RCTs involving acute myeloid leukemia patients (AML), one with acute lymphoid leukemia (ALL), five with chronic lymphocytic leukemia (CLL) and three with MDS. Six RCTs accurately documented PRO methodology assessment and were thus considered likely to robustly inform clinical decision-making. Of these, three RCTs dealt with AML, two with CLL, one with MDS. A growing number of RCTs in leukemia and MDS have included a PRO component in recent years. Inclusion of PROs in RCTs is feasible and can provide unique information to facilitate clinical decision-making.

Soft rubber foams like poly(ethylene-co-vinyl acetate) (EVA) are industrially applied in a broad range of products, including sports gear, insulation materials and drug delivery systems. In contrast to glassy polymers, few studies in literature concern the foaming of soft rubbers using supercritical carbon dioxide. In this study, open microporous matrices of EVA have been formed with CO2. Prior to the foam expansion, sorption and swelling isotherms of CO2 in EVA have been measured and the obtained isotherms have been correlated using the Sanchez–Lacombe equation of state. Additionally, a pressure-independent diffusion coefficient of CO2 in EVA has been obtained from these experiments. The microporous foams have been formed by a pressure quench of the CO2-swollen polymer matrix. Sorption pressure as well as temperature and decompression times appear to determine the pore size and bulk density of the foam. These parameters allow for a control of the foam structure of EVA rubbers.

In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C., Leong, M. A., and Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.

BackgroundTo determine the net clinical benefit of a new treatment strategy, information on both survival and patient-reported outcomes (PROs) is required. However, to make an adequately informed decision, PRO evidence should be of sufficiently high quality.ObjectiveTo investigate the methodological quality of PRO reporting in randomised controlled trials (RCTs) in patients with brain tumours, and to assess the proportion of studies that should impact clinical decision-making.MethodsWe conducted a systematic literature search in several databases covering January 2004 to March 2012. We selected relevant RCTs and retrieved the following data: (1) basic trial demographics and PRO characteristics, (2) quality of PRO reporting and (3) risk of bias. Studies that should impact clinical decision-making based on their methodological robustness were analysed systematically.ResultsWe identified 14 RCTs, representing over 3000 glioma patients. Only two RCTs (14%) satisfied sufficiently many key methodological criteria to provide high-quality PRO evidence, and should therefore impact clinical decision-making. Important methodological limitations in other studies were lack of reporting of the extent (43%) and reasons (86%) of missing data and statistical approaches to handle this (71%). PRO results were not interpreted in 79% of the studies and clinical significance was not discussed in 86%. Studies with high-quality PRO evidence generally showed lower risk of bias.ConclusionsInvestigators involved in brain tumour research should pay special attention to methodological challenges identified in current work. The level of PRO reporting should continue to improve in order to facilitate a critical appraisal of study results.

Background There is no consensus among patients and healthcare professionals (HCPs) on the topics that need to be addressed after oesophageal cancer surgery. The aim of this study was to identify these topics, using a two-round Delphi survey. Methods In round 1, patients and HCPs (surgeons, dieticians, nurses) were invited to rate the importance of 49 topics. The proportion of panellists that considered a topic to be of low, moderate or high importance was then calculated for each of these two groups. Based on these proportions and the i.q.r., topics were categorized as: ‘consensus to be included’, ‘consensus to be excluded’ and ‘no consensus’. Only topics in the first category were included in the second round. In round 2, panellists were provided with individual and group feedback. To be included in the final list, topics had to meet criteria for consensus and stability. Results There were 108 patients and 77 HCPs in the round 2 analyses. In general, patients and HCPs considered the same topics important. The final list included 23 topics and revealed that it was most important to address: cancer removed/lymph nodes, the new oesophagus, eating and drinking, surgery, alarming new complaints and the recovery period. Conclusion The study provides surgeons with a list of topics selected by patients and HCPs that may be addressed systematically at the initial follow-up consultation after oesophageal cancer surgery.

The purpose of the study is to (1) estimate the direction, clinical relevance, and duration of health-related quality-of-life (HRQL) change in the first year following esophageal cancer surgery and (2) to assess the robustness of the estimates by subgroup and sensitivity analyses, and an exploration of publication bias. A systematic literature search in MEDLINE, EMBASE, CINAHL, PsychINFO, and CENTRAL to identify randomized and non-randomized studies was performed. We compared the baseline HRQL data with 3-, 6-, 9-, or 12-month follow-ups to estimate the magnitude and duration of HRQL change. These estimates were then classified as trivial, small, medium, or large. Primary outcomes were role functioning, eating, and fatigue. Secondary outcomes were physical and social functioning, dysphagia, pain, and coughing problems. We conducted subgroup analysis for open surgery, open surgery preceded by neoadjuvant therapy, and minimally invasive surgery. Sensitivity analyses assessed the influence of study design, transformation/imputation of the data, and HRQL questionnaire used. We included the data from 15 studies to estimate the change in 28 HRQL outcomes after esophageal cancer surgery. The main analysis showed that patients' social functioning deteriorated. Symptoms of fatigue, pain, and coughing problems increased. These changes lasted for 9-12 months, although some symptoms persisted beyond the first year after surgery. For many other HRQL outcomes, estimates were only robust after subgroup or sensitivity analyses (e.g., role and physical functioning), or remained too heterogeneous to interpret (e.g., eating and dysphagia). Patients will experience a clinically relevant and long-lasting deterioration in HRQL after esophageal cancer surgery. However, for many HRQL outcomes, more and better quality evidence is needed.

BackgroundSynthesis of patient-reported outcome (PRO) data is hindered by the range of available PRO measures (PROMs) composed of multiple scales and single items with differing terminology and content. The use of core outcome sets, an agreed minimum set of outcomes to be measured and reported in all trials of a specific condition, may improve this issue but methods to select core PRO domains from the many available PROMs are lacking. This study examines existing PROMs and describes methods to identify health domains to inform the development of a core outcome set, illustrated with an example.MethodsSystematic literature searches identified validated PROMs from studies evaluating radical treatment for oesophageal cancer. PROM scale/single item names were recorded verbatim and the frequency of similar names/scales documented. PROM contents (scale components/single items) were examined for conceptual meaning by an expert clinician and methodologist and categorised into health domains. A patient advocate independently checked this categorisation.ResultsSearches identified 21 generic and disease-specific PROMs containing 116 scales and 32 single items with 94 different verbatim names. Identical names for scales were repeatedly used (for example, ‘physical function’ in six different measures) and others were similar (overlapping face validity) although component items were not always comparable. Based on methodological, clinical and patient expertise, 606 individual items were categorised into 32 health domains.ConclusionThis study outlines a methodology for identifying candidate PRO domains from existing PROMs to inform a core outcome set to use in clinical trials.

Delphi methods are common in the development of core sets with panels including patients and healthcare professionals (HCPs) as important key stakeholders. Individuals are provided with feedback between survey rounds but methods for considering different stakeholders' views are lacking. This study explored the influence of randomised stakeholder feedback on responses. In a survey to develop a core set for oesophageal cancer surgery, 185 patients and 126 HCPs rated 67 items on a scale of 1: not essential to 9: absolutely essential (Round 1). Feedback on each item was provided in Round 2 with participants randomly allocated to 1) patients receiving own-group feedback, 2) patients receiving both patient and HCP feedback, 3) HCPs receiving both patient and HCP feedback and 4) HCPs receiving own-group feedback. "Important" items were defined using a predetermined cut-off (rated 7-9 by >70% of participants). Ratings were summarised as mean scores and differences between randomised groups compared. 147 patients and 107 HCPs completed Round 2. Patients receiving only own-group feedback rated more items as important (Group 1: 20 important items versus Group 2: 18 important items). However, HCPs receiving both-group feedback rated more items as important (Group 3: 21 important items versus Group 4: 16 important items). For individual items, the difference in mean scores between randomised groups was small, although there was a trend for HCPs ratings to be influenced by patient feedback. Evidence suggests panel composition and the feedback provided may influence results. Researchers should carefully consider these methodological factors when designing a Delphi study.

Methods Systematic literature searches (MEDLINE, Embase, PsycINFO and CINAHL) identified articles reporting HRQL data after curative treatments for oesophageal cancer from validated patient-completed questionnaires. The most frequently used instruments were examined (EORTC QLQ-C30, QLQ-OES24, QLQ-OES18, SF-36 & FACT-E). Outcome reporting bias was explored by examining which of the instrument’s scales and single items were documented in the methods and the results of papers, with each article checked by two independent reviewers.

Background Patient-reported outcomes (PROs) are amongst the most relevant outcome measures in pancreatic cancer care and research. However, it is unknown which out of the numerous PROs are most important to patients and health care professionals (HCPs) in this setting. The aim of this study was to identify a core set of PROs to be incorporated in a nationwide prospective multidisciplinary pancreatic cancer registry. Patients and methods We performed a two-round Delphi survey among 150 patients diagnosed with pancreatic or periampullary cancer (treated either with curative intent or in palliative setting) and 78 HCPs (surgeons, medical oncologists, gastroenterologists, radiotherapists, nurses, and dietitians) in The Netherlands. In round 1, participants were invited to rate the importance of 53 PROs, which were extracted from 17 different PRO measures and grouped into global domains, on a 1–9 Likert scale. PROs rated as very important (score 7–9) by the majority (≥80%) of curative and/or palliative patients as well as HCPs were considered sufficiently important to be incorporated in the core set. PROs not fulfilling these criteria in round 1 were presented again to the participants in round 2 along with individual and group feedback. Results A total of 97 patients (94%) in curative-intent setting, 38 patients (81%) in palliative setting and 73 HCPs (94%) completed both rounds 1 and 2. After the first round, 7 PROs were included in the core set: general quality of life, general health, physical ability, satisfaction with caregivers, satisfaction with services and care organisation, coping and defecation. After the second round, 10 additional PROs were added: appetite, ability to work/do usual activities, medication use, weight changes, fatigue, negative feelings, positive feelings, fear of recurrence, relationship with partner/family, and pancreatic enzyme replacement therapy use. Conclusion This study provides a core set of PROs selected by patients and HCPs, which may be incorporated in pancreatic cancer care and research. Validation outside the Dutch context is recommended for generalisation and use in international studies.

The effects of oil content and droplet size distributions of dilute oil-in-water emulsions on release of four esters with different hydrophobicities were studied under in vivo, static headspace, and artificial throat conditions. The effect of oil content on orthonasal and retronasal perceived intensity of ethyl hexanoate was studied using a seven-person panel. With increasing oil content and with a higher hydrophobicity of the aroma compound, a stronger decrease in aroma release was found. This effect was stronger under static headspace conditions than under in vivo and artificial throat conditions, and the sensory intensity of ethyl hexanoate was perceived stronger orthonasally than retronasally. The lowest effective oil content was determined for all systems. Of the compounds tested, droplet size distribution only influenced the in vivo release of geranyl acetate. The artificial throat results correlated well with in vivo release, giving support to the assumption that a thin layer of liquid remaining in the throat after swallowing determines aroma release.

Background: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. Methods: Subjects were 313 male and female outpatients at 5 centers with aDSM-III-Rdiagnosis of schizophrenia or schizoaffective disorder. In a 3X2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. Results: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. Conclusions: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

The prevalence and course of alcohol and drug use were examined in a longitudinal, retrospective study of 100 schizophrenic outpatients. During the 18 month study period, problem substance use (abuse and dependence) was not associated with differential attrition from outpatient treatment. Thirty to forty percent of subjects were using drugs or alcohol during any evaluation period. The overall level of substance use and problem use of alcohol, marijuana, and other drugs remained stable, while problem use of cocaine and multiple substances increased over time. Problem substance use was associated with lower functional status and the detrimental effect of problem substance use appeared to increase with time. These findings underscore the need to address substance use problems in the context of outpatient schizophrenia treatment.

Objective: Given the poor prognosis of esophageal cancer and the impact of surgery on health-related quality of life (HRQL), addressing patients' postoperative information needs is important. This study aimed to examine (1) the content and type of patients' information needs and (2) patient perceived facilitators and barriers to patient participation. Methods: Interviews were conducted with 20 purposefully selected esophageal cancer patients. Open and structured questions were alternated. The transcribed interviews were analysed inductively and deductively, using MAXqda. Results: Patients' post-operative information needs concerned HRQL, medical care and prognosis, covering several sub-domains. Different types of needs were identified, e.g., requests for information about cause, course and self-management. Barriers to patient participation mostly reflected beliefs and skills, and could be categorized into agenda and communication barriers. Facilitators of patient participation reflected physician, patient and interaction characteristics, companion support and pre-visit preparation. Many patients saw merit in pre-visit preparation interventions; few endorsed skill-building interventions. Conclusion: This study listed the postoperative information needs of esophageal cancer patients. Moreover, it gained insight into patient-perceived barriers and facilitators of patient participation. Practice implications: The findings demonstrate what information physicians should have available and informs interventions to support patients in meeting their information needs. (C) 2011 Elsevier Ireland Ltd. All rights reserved