Does the level of mobility on ICU discharge impact post-ICU outcomes? A retrospective analysis.

PURPOSE: Mobilisation is a common intervention in Intensive Care (ICU). However, few studies have explored the relationship between mobility levels and outcomes. This study assessed the association of the level of mobility on ICU discharge with discharge destination from the hospital and hospital length of stay. MATERIALS AND METHODS: A retrospective analysis of data from 522 patients admitted to a single UK general ICU who were ventilated for ≥5 days was performed. The level of mobility was assessed using the Manchester Mobility Score (MMS). Multivariable regression analysed demographic and clinical variables for the independence of association with discharge destination and hospital length of stay. RESULTS: MMS ≥5 on ICU discharge was independently associated with discharge destination and hospital LOS (p < 0.001). Patients achieving MMS ≥5 on ICU discharge were more likely to be discharged home (OR 3.86 95% CI 2.1 to 6.9, p < 0.001), and had an 11.8 day shorter hospital LOS (95% CI -17.6 to -6.1, p < 0.001). CONCLUSIONS: The ability to step transfer to a chair (MMS ≥5) before ICU discharge was independently associated with discharge to usual residence and hospital LOS, irrespective of preadmission morbidity. Increasing the level of patient mobility at ICU discharge should be a key focus of rehabilitation interventions.

Mobilisation in the Intensive Care Unit (ICU) is common practice, however studies to date have not evaluated the impact on acute hospital outcomes.Achieving the ability to step to a chair on ICU discharge is an important rehabilitation milestone, and is associated with a shorter hospital length of stay and being discharged home.Rehabilitation interventions in the ICU should be targeted at progressing patients towards this milestone.

Exploring the application of machine learning to expert evaluation of research impact.

The objective of this study is to investigate the application of machine learning techniques to the large-scale human expert evaluation of the impact of academic research. Using publicly available impact case study data from the UK's Research Excellence Framework (2014), we trained five machine learning models on a range of qualitative and quantitative features, including institution, discipline, narrative style (explicit and implicit), and bibliometric and policy indicators. Our work makes two key contributions. Based on the accuracy metric in predicting high- and low-scoring impact case studies, it shows that machine learning models are able to process information to make decisions that resemble those of expert evaluators. It also provides insights into the characteristics of impact case studies that would be favoured if a machine learning approach was applied for their automated assessment. The results of the experiments showed strong influence of institutional context, selected metrics of narrative style, as well as the uptake of research by policy and academic audiences. Overall, the study demonstrates promise for a shift from descriptive to predictive analysis, but suggests caution around the use of machine learning for the assessment of impact case studies.

Dosimetric Evaluation of Organs at Risk From SAVE Protocol.

PURPOSE: The objective of this work was to evaluate dosimetric characteristics to organs at risk (OARs) from short-course adjuvant vaginal cuff brachytherapy (VCB) in early endometrial cancer compared with standard of care (SOC) in a multi-institutional prospective randomized trial. METHODS AND MATERIALS: SAVE (Short Course Adjuvant Vaginal Brachytherapy in Early Endometrial Cancer Compared to Standard of Care) is a prospective, phase 3, multisite randomized trial in which 108 patients requiring VCB were randomized to an experimental short-course arm (11 Gy × 2 fractions [fx] to surface) and SOC arm. Those randomized to the SOC arm were subdivided into treatment groups based on treating physician discretion as follows: 7 Gy × 3 fx to 5 mm, 5 to 5.5 Gy × 4 fx to 5 mm, and 6 Gy × 5 fx to surface. To evaluate doses to OARs of each SAVE cohort, the rectum, bladder, sigmoid, small bowel, and urethra were contoured on planning computed tomography, and doses to OARs were compared by treatment arm. Absolute doses for each OAR and from each fractionation scheme were converted to 2 Gy equivalent dose (EQD23). Each SOC arm was compared with the experimental arm separately using 1-way analysis of variance, followed by pairwise comparisons using Tukey's honestly significant difference test. RESULTS: The experimental arm had significantly lower doses for rectum, bladder, sigmoid, and urethra compared with the 7 Gy × 3 and 5 to 5.5 Gy × 4 fractionation schemes; however, the experimental arm did not differ from the 6 Gy × 5 fractionation scheme. For small bowel doses, none of the SOC fractionation schemes were statistically different than the experimental. The highest EQD23 doses to the examined OARs were observed to come from the most common dose fractionation scheme of 7 Gy × 3 fx. With a short median follow-up of 1 year, there have been no isolated vaginal recurrences. CONCLUSIONS: Experimental short-course VCB of 11 Gy × 2 fx to the surface provides a comparable biologically effective dose to SOC courses. Experimental short-course VCB was found to reduce or be comparable to D2cc and D0.1cc EQD23 doses to rectum, bladder, sigmoid, small bowel, and urethra critical structures. This may translate into a comparable or lower rate of acute and late adverse effects.

The indispensable role of pharmacy services and medication therapy management in cystic fibrosis.

Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary approach where the pharmacist plays a vital role. The purpose of this manuscript is to serve as a guideline for pharmacists and pharmacy technicians who provide care for PWCF by providing background and current recommendations for the use of cystic fibrosis (CF)-specific medications in both the acute and ambulatory care settings. The article explores current literature surrounding the role of pharmacists and pharmacy technicians, proven pharmacy models to emulate, and pharmacokinetic idiosyncrasies unique to the CF population while also identifying areas of future research. Clinical recommendations for the use of CF-specific medications are broken down by organ system including mechanism of action, adverse events, dosages, and monitoring parameters. The article also includes quick reference tables essential to the acute and chronic medication therapy management of PWCF.

Fundamental challenges in assessing the impact of research infrastructure.

Clinical research infrastructure is one of the unsung heroes of the scientific response to the current COVID-19 pandemic. The extensive, long-term funding into research support structures, skilled people, and technology allowed the United Kingdom research response to move off the starting blocks at pace by utilizing pre-existing platforms. The increasing focus from funders on evaluating the outcomes and impact of research infrastructure investment requires both a reframing and progression of the current models in order to address the contribution of the underlying support infrastructure. The majority of current evaluation/outcome models focus on a "pipeline" approach using a methodology which follows the traditional research funding route with the addition of quantitative metrics. These models fail to embrace the complexity caused by the interplay of previous investment, the coalescing of project outputs from different funders, the underlying infrastructure investment, and the parallel development across different parts of the system. Research infrastructure is the underpinning foundation of a project-driven research system and requires long-term, sustained funding and capital investment to maintain scientific and technological expertise. Therefore, the short-term focus on quantitative metrics that are easy to collect and interpret and that can be assessed in a roughly 5-year funding cycle needs to be addressed. The significant level of investment in research infrastructure necessitates investment to develop bespoke methodologies that develop fit-for-purpose, longer-term/continual approach(es) to evaluation. Real-world research should reflect real-world evaluation and allow for the accrual of a narrative of value indicators that build a picture of the contribution of infrastructure to research outcomes. The linear approach is not fit for purpose, the research endeavour is a complex, twisted road, and the evaluation approach needs to embrace this complexity through the development of realist approaches and the rapidly evolving data ecosystem. This paper sets out methodological challenges and considers the need to develop bespoke methodological approaches to allow a richer assessment of impact, contribution, attribution, and evaluation of research infrastructure. This paper is the beginning of a conversation that invites the community to "take up the mantle" and tackle the complexity of real-world research translation and evaluation.

EVITA 2.0, an updated framework for understanding evidence-based mental health policy agenda-setting: tested and informed by key informant interviews in a multilevel comparative case study.

BACKGROUND: Mental health remains a neglected issue on the global health policy agenda, particularly in low- and middle-income countries (LMIC), and the translation of research evidence into policy and practice is slow. The new EVITA framework was developed to improve mental health evidence uptake and policy agenda-setting in LMICs. In addition, behavioural science methods may be able to support knowledge translation to policy. METHODS: Using a mixed-methods study design, we applied and tested the newly developed EVITA 1.1 framework against three case studies related to South Africa at the district, national and international levels. In-depth interviews with 26 experts were conducted between August and November 2019, transcribed, coded and analysed in NVivo, using iterative categorization. The data were analysed against both the EVITA framework and the MINDSPACE framework for behavioural insights. RESULTS: In our case study comparison, we found that (1) research translation to the policy agenda occurs in a complex, fluid system which includes multiple "research clouds", "policy spheres" and other networks; (2) mental health research policy agenda-setting is based on key individuals and intermediaries and their interrelationships; and (3) key challenges and strategies for successful research to policy agenda impact are known, but are frequently not strategically implemented, such as including all stakeholders to overcome the policy implementation gap. Our data also suggest that behavioural science methods can be strategically applied to support knowledge translation to policy agenda-setting. CONCLUSION: We found that the EVITA framework is useful for understanding and improving mental health research policy interrelationships to support evidence uptake to the policy agenda, and that behavioural science methods are effective support mechanisms. The revised EVITA 2.0 framework therefore includes behavioural insights, for improved mental health policy agenda-setting in LMICs. More research is needed to understand whether EVITA can be applied to other LMICs and to high-income contexts.

Biliary disease and cholecystectomy after initiation of elexacaftor/ivacaftor/tezacaftor in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have an increased risk for gallbladder abnormalities and biliary tract disease, but the reported incidence of these manifestations of CF varies widely in the literature. With the approval of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), increasing numbers of CF patients have been initiated on highly effective cystic fibrosis transmembrane regulator (CFTR) modulator therapy. While elevations in hepatic panel are known potential side effects of CFTR modulators, there have been no published cases of biliary disease or acute cholecystitis attributed to these medications. In this case series, we describe seven patients at two adult CF centers with biliary colic shortly after initiation with ELX/TEZ/IVA, six of whom required cholecystectomy.

From COVID-19 research to vaccine application: why might it take 17 months not 17 years and what are the wider lessons?

It is often said that it takes 17 years to move medical research from bench to bedside. In a coronavirus disease (COVID-19) world, such time-lags feel intolerable. In these extraordinary circumstances could years be made into months? If so, could those lessons be used to accelerate medical research when the crisis eases?To measure time-lags in health and biomedical research as well as to identify ways of reducing them, we developed and published (in 2015) a matrix consisting of overlapping tracks (or stages/phases) in the translation from discovery research to developed products, policies and practice. The matrix aids analysis by highlighting the time and actions required to develop research (and its translation) both (1) along each track and (2) from one track to another, e.g. from the discovery track to the research-in-humans track. We noted four main approaches to reducing time-lags, namely increasing resources, working in parallel, starting or working at risk, and improving processes.Examining these approaches alongside the matrix helps interpret the enormous global effort to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of COVID-19. Rapid progress in the discovery/basic and human research tracks is being made through a combination of large-scale funding, work being conducted in parallel (between different teams globally and through working in overlapping tracks), working at greater (but proportionate) risk to safety than usual, and adopting various new processes. The overlapping work of some of the teams involves continuing animal research whilst entering vaccine candidates into Phase I trials alongside planning their Phase II trials. The additional funding available helps to reduce some of the usual financial risks in moving so quickly. Going forward through the increasingly large human trials for safety, dosage and efficacy, it will be vital to overlap work in parallel in the often challenging public policy and clinical tracks. Thus, regulatory and reimbursement bodies are beginning and preparing rapid action to pull vaccines proving to be safe and effective through to extraordinarily rapid application to the general population. Monitoring the development of a COVID-19 vaccine using the matrix (modified as necessary) could help identify which of the approaches speeding development and deployment could be usefully applied more widely in the future.

Development and Implementation of Clinical Outcome Measures for Automated Collection Within Specialty Pharmacy Practice.

BACKGROUND: Johns Hopkins Specialty Pharmacy Services recognized the need to identify and develop standardized collection methods for clinical outcome measures (COMs) to demonstrate program quality and value to third-party payers, manufacturers, and internal stakeholders. OBJECTIVE: To define specialty COMs and develop a framework for standardized data collection and reporting. METHODS: COMs for specialty pharmacy disease states (cystic fibrosis; hepatitis C; inflammatory conditions in dermatology, gastroenterology and rheumatology; and multiple sclerosis) were identified through a literature search, collaboration with specialty pharmacists, and committee review. Once identified, these measures were distributed to internal and external stakeholders that included specialty clinic team members, drug manufacturers, and third-party payers for input and validation. A standardized process for discrete documentation and data collection of these measures was implemented using case management software, electronic medical record integration, and informatics support. RESULTS: 28 COMs were identified. The various data sources used to collect the COMs were incorporated into an automated virtual dashboard to allow for regular review and sharing with clinicians, leadership, and other key stakeholders. The virtual dashboard included COMs with data derived from electronic medical records (n = 9), patient-reported outcomes based on responses to pharmacist-delivered questions (n = 11), and pharmacist assessment of outcomes (n = 8). The completed virtual dashboard was further refined to allow for reporting of both population and patient-level outcome results on a quarterly basis. CONCLUSIONS: This project describes methods to standardize documentation, data collection, and reporting of clinical outcomes data for multiple specialty conditions in a health system-integrated specialty pharmacy program. Through literature review and stakeholder consultation, a variety of potential COMs were identified for further evaluation of feasibility and value considering documentation and data collection requirements. Incorporation of COMs into a virtual dashboard will help facilitate the evaluation of program effectiveness, quality improvement planning, and sharing with stakeholders. Additional opportunities exist to further standardize COMs across the pharmacy industry to allow for future benchmarking and standardized evaluation of patient care programs. DISCLOSURES: No funding supported the writing of this article. The authors have no relevant conflicts of interest to disclose. This study was presented as a poster presentation at the APhA Annual Meeting, March 2018, Nashville, TN, and as a platform presentation at the Eastern States Conference, May 2018, Hershey, PA.

The EVITA framework for evidence-based mental health policy agenda setting in low- and middle-income countries.

The burden of mental illness is excessive, but many countries lack evidence-based policies to improve practice. Mental health research evidence translation into policymaking is a 'wicked problem', often failing despite a robust evidence base. In a recent systematic review, we identified a gap in frameworks on agenda setting and actionability, and pragmatic, effective tools to guide action to link research and policy are needed. Responding to this gap, we developed the new EVITA 1.1 (EVIdence To Agenda setting) conceptual framework for mental health research-policy interrelationships in low- and middle-income countries (LMICs). We (1) drafted a provisional framework (EVITA 1.0); (2) validated it for specific applicability to mental health; (3) conducted expert in-depth interviews to (a) validate components and mechanisms and (b) assess intelligibility, functionality, relevance, applicability and effectiveness. To guide interview validation, we developed a simple evaluation framework. (4) Using deductive framework analysis, we coded and identified themes and finalized the framework (EVITA 1.1). Theoretical agenda-setting elements were added, as targeting the policy agenda-setting stage was found to lead to greater policy traction. The framework was validated through expert in-depth interviews (n = 13) and revised. EVITA 1.1 consists of six core components [advocacy coalitions, (en)actors, evidence generators, external influences, intermediaries and political context] and four mechanisms (capacity, catalysts, communication/relationship/partnership building and framing). EVITA 1.1 is novel and unique because it very specifically addresses the mental health research-policy process in LMICs and includes policy agenda setting as a novel, effective mechanism. Based on a thorough methodology, and through its specific design and mechanisms, EVITA has the potential to improve the challenging process of research evidence translation into policy and practice in LMICs and to increase the engagement and capacity of mental health researchers, policy agencies/planners, think tanks, NGOs and others within the mental health research-policy interface. Next, EVITA 1.1 will be empirically tested in a case study.

Recurrent early stage endometrial cancer: Patterns of recurrence and results of salvage therapy.

OBJECTIVE: To analyze our institutional experience and oncologic outcomes for salvage treatment for the recurrence of early-stage endometrial cancer patients. METHODS: We included women of all ages diagnosed with FIGO stage I-II, any grade endometrial cancer from 2000 to 2016 at our institutions who were treated with at least a hysterectomy. Recurrences in the pelvis and/or vagina were considered locoregional recurrences (LRR). Overall survival (OS) was assessed using Kaplan-Meier survival analysis. Univariate (UV) and multivariate (MV) Cox proportional hazards modeling was also used. RESULTS: A total of 2691 women were analyzed. The majority had endometrioid histology (91%), stage IA disease (61%), and were grade 1 (57%). With a median follow-up of 6.1 years, the overall rate of recurrence was 7.2%, and the rate of LRR was 3.7%. Women with vaginal-only recurrences had a longer median OS after recurrence (14.0 years) compared to both pelvic (1.2 years) and distant (1.0 year) failures. For women with vaginal-only recurrences, salvage radiotherapy (RT) was the only factor associated with improved OS on MVA (HR 0.1, p = .04). For women with pelvic recurrences, salvage surgery (HR 0.3, p = .01), salvage RT (HR 0.3, p < .01), and salvage chemotherapy (HR 0.4, p = .03) were associated with improved OS. CONCLUSIONS: Failure rates for women with early-stage endometrial cancer are low. Women with vaginal-only recurrences have improved OS compared to pelvic or distant recurrences. Salvage RT appears to be an important factor for treatment of women with vaginal-only recurrences. Aggressive multimodality treatment may be beneficial for women with pelvic recurrences.

Do vaginal recurrence rates differ among adjuvant vaginal brachytherapy regimens in early-stage endometrial cancer?

PURPOSE: We sought to retrospectively examine clinical outcomes for three adjuvant vaginal high-dose-rate (HDR) brachytherapy regimens after hysterectomy for early-stage endometrial cancer. METHODS: Included were women of all ages from two independent hospital systems diagnosed with Stage I-II endometrial cancer of any grade between 2000 and 2016 who underwent hysterectomy followed by adjuvant vaginal cylinder HDR brachytherapy with either 7.0 Gy × 3 fractions prescribed to 0.5 cm vaginal depth, 6.5 Gy × 3 fractions prescribed to 0.5 cm vaginal depth, or 6.0 Gy × 5 fractions prescribed to the vaginal surface. Outcomes included vaginal recurrence (VR), pelvic recurrence, distant recurrence, locoregional recurrence, recurrence-free survival, and overall survival. RESULTS: Of the 348 women, 45 (13%) received 7.0 Gy × 3 fractions, 259 (74%) received 6.5 Gy × 3 fractions, and 44 (13%) received 6.0 Gy × 5 fractions. Women receiving 5-fraction brachytherapy were more likely to be younger with a higher performance status. At a median follow-up of 4.5 years, VR rates were 2.2%, 0.8%, and 4.5%, respectively. Multivariate analysis revealed no significant differences in the risks for VR among brachytherapy regimens. Risks for VR, pelvic recurrence, distant recurrence, locoregional recurrence, recurrence-free survival, and overall survival did not differ between propensity score-matched five- and 3-fraction brachytherapy cohorts. CONCLUSIONS: VR rates after hysterectomy and adjuvant vaginal brachytherapy for early-stage endometrial cancer were low and not significantly different by HDR dose fractionation.

Economic returns to medical research funding.

Following the publication of the final paper in a planned series of four studies estimating the economic returns from biomedical and health research, we reflect on what we have learnt from these types of assessment.

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries.

BACKGROUND: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence-policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). METHODS: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. RESULTS: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out 'agenda-setting', we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. CONCLUSION: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs.

ISRIA statement: ten-point guidelines for an effective process of research impact assessment.

As governments, funding agencies and research organisations worldwide seek to maximise both the financial and non-financial returns on investment in research, the way the research process is organised and funded is becoming increasingly under scrutiny. There are growing demands and aspirations to measure research impact (beyond academic publications), to understand how science works, and to optimise its societal and economic impact. In response, a multidisciplinary practice called research impact assessment is rapidly developing. Given that the practice is still in its formative stage, systematised recommendations or accepted standards for practitioners (such as funders and those responsible for managing research projects) across countries or disciplines to guide research impact assessment are not yet available.In this statement, we propose initial guidelines for a rigorous and effective process of research impact assessment applicable to all research disciplines and oriented towards practice. This statement systematises expert knowledge and practitioner experience from designing and delivering the International School on Research Impact Assessment (ISRIA). It brings together insights from over 450 experts and practitioners from 34 countries, who participated in the school during its 5-year run (from 2013 to 2017) and shares a set of core values from the school's learning programme. These insights are distilled into ten-point guidelines, which relate to (1) context, (2) purpose, (3) stakeholders' needs, (4) stakeholder engagement, (5) conceptual frameworks, (6) methods and data sources, (7) indicators and metrics, (8) ethics and conflicts of interest, (9) communication, and (10) community of practice.The guidelines can help practitioners improve and standardise the process of research impact assessment, but they are by no means exhaustive and require evaluation and continuous improvement. The prima facie effectiveness of the guidelines is based on the systematised expert and practitioner knowledge of the school's faculty and participants derived from their practical experience and research evidence. The current knowledge base has gaps in terms of the geographical and scientific discipline as well as stakeholder coverage and representation. The guidelines can be further strengthened through evaluation and continuous improvement by the global research impact assessment community.

Estimating the returns to United Kingdom publicly funded musculoskeletal disease research in terms of net value of improved health outcomes.

BACKGROUND: Building on an approach applied to cardiovascular and cancer research, we estimated the economic returns from United Kingdom public- and charitable-funded musculoskeletal disease (MSD) research that arise from the net value of the improved health outcomes in the United Kingdom. METHODS: To calculate the economic returns from MSD-related research in the United Kingdom, we estimated (1) the public and charitable expenditure on MSD-related research in the United Kingdom between 1970 and 2013; (2) the net monetary benefit (NMB), derived from the health benefit in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of £25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1994 to 2013; (3) the proportion of NMB attributable to United Kingdom research; and (4) the elapsed time between research funding and health gain. The data collected from these four key elements were used to estimate the internal rate of return (IRR) from MSD-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using a one-way sensitivity analysis. RESULTS: Expressed in 2013 prices, total expenditure on MSD-related research from 1970 to 2013 was £3.5 billion, and for the period used to estimate the rate of return, 1978-1997, was £1.4 billion. Over the period 1994-2013 the key interventions analysed produced 871,000 QALYs with a NMB of £16 billion, allowing for the net NHS costs resulting from them and valuing a QALY at £25,000. The proportion of benefit attributable to United Kingdom research was 30% and the elapsed time between funding and impact of MSD treatments was 16 years. Our best estimate of the IRR from MSD-related research was 7%, which is similar to the 9% for CVD and 10% for cancer research. CONCLUSIONS: Our estimate of the IRR from the net health gain to public and charitable funding of MSD-related research in the United Kingdom is substantial, and justifies the research investments made between 1978 and 1997. We also demonstrated the applicability of the approach previously used in assessing the returns from cardiovascular and cancer research. Inevitably, with a study of this kind, there are a number of important assumptions and caveats that we highlight, and these can inform future research.

Preoperative radiation dose escalation for rectal cancer using a concomitant boost strategy improves tumor downstaging without increasing toxicity: A matched-pair analysis.

PURPOSE: Pathologic complete response to neoadjuvant chemoradiation therapy (CRT) is associated with improved outcomes for patients with locally advanced rectal cancer (LARC). Increased response rates have been reported with higher radiation doses, but these studies often lack long-term outcome and/or toxicity data. We conducted a case-control analysis of patients with LARC who underwent definitive CRT to determine the efficacy and safety of intensified treatment with a concomitant boost (CB) approach. METHODS AND MATERIALS: From 1995 to 2003, a phase 2 protocol examined CRT with 5-fluorouracil and CB radiation therapy (52.5 Gy in 5 weeks) for patients with LARC. Seventy-six protocol patients were matched (case-control approach) for surgery type, tumor (T) stage, and clinical nodal (N) stage with patients who received standard dose (SD) CRT (5-fluorouracil, 45 Gy). A chart review was performed. McNemar's test and Kaplan-Meier analyses were used for statistical analysis. RESULTS: The SD and CB groups did not differ in tumor circumferential involvement and length, but the tumors of CB patients were closer to the anal verge (4.7 vs 5.7 cm; P = .02). Although tumor downstaging was higher in the CB cohort (76% vs 51%; P < .01), pathologic complete response rates did not differ (CB, 17.1% vs SD, 15.8%, P = 1.00). The incidence of grade ≥3 radiation-related toxicities was low and similar in both groups (CB, 10% vs SD, 3%, P = .22). Postoperative (anastomotic leak, wound complications/abscess, bleeding) and late (small bowel obstruction, stricture) complication rates did not differ between the groups (P > .05). The median follow-up was 11.9 years. The 5-year local control rates were higher for CB (100.0%) compared with SD (90.0%) patients (P = .01). CB patients had higher rates of 10-year progression-free survival (71.9% vs 57.6%, P < .01) and overall survival (71.6% vs 62.4%, P = .01) compared with SD patients. CONCLUSIONS: CRT dose escalation for patients with LARC is safe and effective. The improved T-downstaging and local control observed in CB patients should encourage further dose escalation studies.

Bibliometric Analysis of Mental Health Research: 1980--2008.

This article presents the findings of a bibliometric study of mental health research papers published from 1980 to 2008. The aim of this study was to map mental health research in the G20 and other leading countries in order to analyse i) the research productivity of nations; ii) the relative intensity of research; iii) the level of research (clinical or basic); iv) levels of scientific impact; and v) levels of collaboration. This work is the result of a collaboration between Observatoire des sciences et des technologies in Montreal and RAND Europe.

The National Institute for Health Research at 10 Years: An Impact Synthesis: 100 Impact Case Studies.

The National Institute for Health Research (NIHR) funds and supports world-leading clinical and applied health and social care research, as well as research infrastructure in the NHS. Providing £1 billion of funding each year, NIHR aims to: drive the faster translation of new treatments, technologies and diagnostics to improve outcomes for health and care services; promote the wealth of the nation, including via inward investment from the health research community; pull basic science discoveries through into tangible benefits for patients and the public; and provide research evidence to support more effective and cost-effective NHS delivery. To mark its tenth anniversary, the Department of Health commissioned the Policy Research in Science and Medicine unit to consider the question: "What are the ways in which NIHR has benefited the health research landscape in the past ten years?" This study identifies and celebrates 100 examples of positive change resulting from NIHR's support of research. A synthesis of 100 case studies is provided, which highlights the benefits and wider impacts of research, capacity building, and other activities undertaken with NIHR's support since its creation in 2006. The study concludes with a reflection of how the NIHR has transformed R&D in and for the NHS and wider health service, and the people they serve. The study draws together---for the first time---examples of the breadth of NIHR's impacts in a single resource. It will be of interest to healthcare professionals involved in research, academics working in health and social care, and members of the public wishing to understand the value of research in the NHS and the wider health and care system.