Design Considerations for Factorial Adaptive Multi-Arm Multi-Stage (FAST) Clinical Trials

Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs can be categorized into several overarching design groups, including adaptive designs (AD) and multi-arm (MA) designs. Factorial clinical trials designs represent an additional group of designs which can provide increased efficiency relative to fixed, traditional designs. In this work, we explore design choices associated with Factorial Adaptive Multi-Arm Multi-Stage (FAST) designs, which represent the combination of factorial and MAMS designs. This category of trial can potentially offer benefits similar to both MAMS and factorial designs. This work is motivated by a proposed clinical trial under development

A Scoping Review of Strategies for the Prevention of Hip Fracture in Elderly Nursing Home Residents

Elderly nursing home residents are at increased risk of hip fracture; however, the efficacy of fracture prevention strategies in this population is unclear.We performed a scoping review of randomized controlled trials of interventions tested in the long-term care (LTC) setting, examining hip fracture outcomes.We searched for citations in 6 respective electronic searches, supplemented by hand searches. Two reviewers independently reviewed all citations and full-text papers; consensus was achieved on final inclusion. Data was abstracted in duplicate.We reviewed 22,349 abstracts or citations and 949 full-text papers. Data from 20 trials were included: 7--vitamin D (n = 12,875 participants), 2--sunlight exposure (n = 522), 1--alendronate (n = 327), 1--fluoride (n = 460), 4--exercise or multimodal interventions (n = 8,165), and 5--hip protectors (n = 2,594). Vitamin D, particularly vitamin D(3) > or = 800 IU orally daily, reduced hip fracture risk. Hip protectors reduced hip fractures in included studies, although a recent large study not meeting inclusion criteria was negative. Fluoride and sunlight exposure did not significantly reduce hip fractures. Falls were reduced in three studies of exercise or multimodal interventions, with one study suggesting reduced hip fractures in a secondary analysis. A staff education and risk assessment strategy did not significantly reduce falls or hip fractures. In a study underpowered for fracture outcomes, alendronate did not significantly reduce hip fractures in LTC.The intervention with the strongest evidence for reduction of hip fractures in LTC is Vitamin D supplementation; more research on other interventions is needed

Depression and anxiety symptoms post-stroke/TIA:prevalence and associations in cross-sectional data from a regional stroke registry

BACKGROUND: Mood disorders are commonly seen in those with cerebrovascular disease. Literature to-date has tended to focus on depression and on patients with stroke, with relatively little known about post-stroke anxiety or mood disorder in those with transient ischaemic attack (TIA). We aimed to describe prevalence of depression and anxiety symptoms in stroke and TIA cohorts and to explore association with clinical and socio-demographic factors. METHODS: We used a city wide primary care stroke registry (Glasgow Local Enhanced Service for Stroke - LES). All community dwelling stroke-survivors were included. We described cross-sectional prevalence of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Data on clinical and demographic details was collected and univariable and multivariable analyses performed to describe associations with HADS scores. We examined those with a diagnosis of 'stroke' and 'TIA' as separate cohorts. RESULTS: From 13,283 potentially eligible stroke patients in the registry, we had full HADS data on 4,079. Of the 3,584 potentially eligible TIA patients, we had full HADS data on 1,247 patients. Across the stroke cohort, 1181 (29%) had HADS anxiety scores suggestive of probable or possible anxiety; 993 (24%) for depression. For TIA patients, 361 (29%) had anxiety and 254 (21%) had depression. Independent predictors of both depression and anxiety symptoms were female sex, younger age and higher socioeconomic deprivation score (all p < 0.001). CONCLUSION: Using HADS, we found a high prevalence of anxiety and depression symptoms in a community-based cohort of patients with cerebrovascular disease

Research activity and the association with mortality.

INTRODUCTION: The aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes. METHODS: National Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated. RESULTS: Low mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855-2,843], 5.9 patients/bed [2.7-9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864-1,357] p<0.0001, 2.6 patients/bed [1.7-3.5] p<0.0169) or, high (n = 42, 930 £/bed [683-1,177] p = 0.0001, 1.8 patients/bed [1.4-2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033-1.068] p<0.0001, recruitment 1.069 [1.052-1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024-1.055] p<0.0001, recruitment 1.085 [1.070-1.100] p<0.0001). CONCLUSIONS: Research active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors

The effect of modifiable risk factors on geographic mortality differentials: a modelling study

Background Australian mortality rates are higher in regional and remote areas than in major cities. The degree to which this is driven by variation in modifiable risk factors is unknown. Methods We applied a risk prediction equation incorporating smoking, cholesterol and blood pressure to a national, population based survey to project all-causes mortality risk by geographic region. We then modelled life expectancies at different levels of mortality risk by geographic region using a risk percentiles model. Finally we set high values of each risk factor to a target level and modelled the subsequent shift in the population to lower levels of mortality risk and longer life expectancy. Results Survival is poorer in both Inner Regional and Outer Regional/Remote areas compared to Major Cities for men and women at both high and low levels of predicted mortality risk. For men smoking, high cholesterol and high systolic blood pressure were each associated with the mortality difference between Major Cities and Outer Regional/Remote areas--accounting for 21.4%, 20.3% and 7.7% of the difference respectively. For women smoking and high cholesterol accounted for 29.4% and 24.0% of the difference respectively but high blood pressure did not contribute to the observed mortality differences. The three risk factors taken together accounted for 45.4% (men) and 35.6% (women) of the mortality difference. The contribution of risk factors to the corresponding differences for inner regional areas was smaller, with only high cholesterol and smoking contributing to the difference in men-- accounting for 8.8% and 6.3% respectively-- and only smoking contributing to the difference in women--accounting for 12.3%. Conclusions These results suggest that health intervention programs aimed at smoking, blood pressure and total cholesterol could have a substantial impact on mortality inequities for Outer Regional/Remote areas. Background: Australian mortality rates are higher in regional and remote areas than in major cities. The degree to which this is driven by variation in modifiable risk factors is unknown. Methods. We applied a risk prediction equation incorporating smoking, cholesterol and blood pressure to a national, population based survey to project all-causes mortality risk by geographic region. We then modelled life expectancies at different levels of mortality risk by geographic region using a risk percentiles model. Finally we set high values of each risk factor to a target level and modelled the subsequent shift in the population to lower levels of mortality risk and longer life expectancy. Results: Survival is poorer in both Inner Regional and Outer Regional/Remote areas compared to Major Cities for men and women at both high and low levels of predicted mortality risk. For men smoking, high cholesterol and high systolic blood pressure were each associated with the mortality difference between Major Cities and Outer Regional/Remote areas - accounting for 21.4%, 20.3% and 7.7% of the difference respectively. For women smoking and high cholesterol accounted for 29.4% and 24.0% of the difference respectively but high blood pressure did not contribute to the observed mortality differences. The three risk factors taken together accounted for 45.4% (men) and 35.6% (women) of the mortality difference. The contribution of risk factors to the corresponding differences for inner regional areas was smaller, with only high cholesterol and smoking contributing to the difference in men - accounting for 8.8% and 6.3% respectively - and only smoking contributing to the difference in women - accounting for 12.3%. Conclusions: These results suggest that health intervention programs aimed at smoking, blood pressure and total cholesterol could have a substantial impact on mortality inequities for Outer Regional/Remote areas

Scoping review of patient- and family-oriented outcomes and measures for chronic pediatric disease.

Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatric diseases similar to IEM in etiology or manifestations and in complexity of management; (ii) reported patient- and/or family-oriented outcomes; and (iii) measured these outcomes using self-administered tools.We developed a comprehensive review protocol and implemented an electronic search strategy to identify relevant citations in Medline, EMBASE, DARE and Cochrane. Two reviewers applied pre-specified criteria to titles/abstracts using a liberal accelerated approach. Articles eligible for full-text review were screened by two independent reviewers with discrepancies resolved by consensus. One researcher abstracted data on study characteristics, patient- and family-oriented outcomes, and self-administered measures. Data were validated by a second researcher.4,118 citations were screened with 304 articles included. Across all included reports, the most-represented diseases were diabetes (35%), cerebral palsy (23%) and epilepsy (18%). We identified 43 unique patient- and family-oriented outcomes from among five emergent domains, with mental health outcomes appearing most frequently. The studies reported the use of 405 independent self-administered measures of these outcomes.Patient- and family-oriented research investigating chronic pediatric diseases emphasizes mental health and appears to be relatively well-developed in the diabetes literature. Future research can build on this foundation while identifying additional outcomes that are priorities for patients and families

Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction

Introduction Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups

VR Touch - Toolkit : Skapandet av ett nytt VR-verktyg för användandet av haptisk feedback och visualisering

Denna undersökning belyser varför beröring är ett viktigt sinne för att stärka VR-upplevelser. Genom att använda beröring som metod för att utforska fysiska egenskaper har vi skapat endigital gestaltning som demonstrerar hur denna unika förmåga kan användas. Denna undersökning har bidragit till skapandet av ett nytt verktyg för framtida utveckling av VR-upplevelser, vilket har öppnat upp möjligheter att använda beröring som huvudmekanik. Genom att kombinera haptisk feedback och visualisering av händer och omgivning kan vi utforska och interagera med VR-spel på ett nytt och spännande sätt.This study highlights why the sense of touch is important for enhancing VR experiences. By using touch as a method to explore physical properties, we have created a digital representation that demonstrates how this unique ability can be utilized. This study has contributed to the development of a new developer tool for future VR experience design, which has opened up possibilities for incorporating the sense of touch as a main mechanic. By combining haptic feedback and visualization of hands and the environment, we can explore and interact with VR games in a new and exciting way

VR Touch - Toolkit : Skapandet av ett nytt VR-verktyg för användandet av haptisk feedback och visualisering

Denna undersökning belyser varför beröring är ett viktigt sinne för att stärka VR-upplevelser. Genom att använda beröring som metod för att utforska fysiska egenskaper har vi skapat endigital gestaltning som demonstrerar hur denna unika förmåga kan användas. Denna undersökning har bidragit till skapandet av ett nytt verktyg för framtida utveckling av VR-upplevelser, vilket har öppnat upp möjligheter att använda beröring som huvudmekanik. Genom att kombinera haptisk feedback och visualisering av händer och omgivning kan vi utforska och interagera med VR-spel på ett nytt och spännande sätt.This study highlights why the sense of touch is important for enhancing VR experiences. By using touch as a method to explore physical properties, we have created a digital representation that demonstrates how this unique ability can be utilized. This study has contributed to the development of a new developer tool for future VR experience design, which has opened up possibilities for incorporating the sense of touch as a main mechanic. By combining haptic feedback and visualization of hands and the environment, we can explore and interact with VR games in a new and exciting way

ConocoPhillips Sweeny IGCC/CCS Project

Under its Industrial Carbon Capture and Sequestration (ICCS) Program, the United States (U.S.) Department of Energy (DOE) selected ConocoPhillips Company (ConocoPhillips) to receive funding through the American Recovery and Reinvestment Act (ARRA) of 2009 for the proposed Sweeny Integrated Gasification Combined Cycle (IGCC)/Carbon Capture and Storage (CCS) Project (Project) to be located in Brazoria County, Texas. Under the program, the DOE is partnering with industry to demonstrate the commercial viability and operational readiness of technologies that would capture carbon dioxide (CO{sub 2}) emissions from industrial sources and either sequester those emissions, or beneficially reuse them. The primary objective of the proposed Project was to demonstrate the efficacy of advanced technologies that capture CO{sub 2} from a large industrial source and store the CO{sub 2} in underground formations, while achieving a successful business venture for the entity (entities) involved. The Project would capture 85% of the CO{sub 2} produced from a petroleum coke (petcoke) fed, 703 MWnet (1,000 MWgross) IGCC power plant, using the ConocoPhillips (COP) proprietary and commercially proven E-Gas{trademark} gasification technology, at the existing 247,000 barrel per day COP Sweeny Refinery. In addition, a number of other commercially available technologies would be integrated into a conventional IGCC Plant in a unique, efficient, and reliable design that would capture CO{sub 2}. The primary destination for the CO{sub 2} would be a depleted natural gas field suitable for CO{sub 2} storage ('Storage Facility'). COP would also develop commercial options to sell a portion of the IGCC Plant's CO{sub 2} output to the growing Gulf Coast enhanced oil recovery (EOR) market. The IGCC Plant would produce electric power for sale in the Electric Reliability Council of Texas Houston Zone. The existing refinery effluent water would be treated and reused to fulfill all process water needs. The DOE ICCS program adopts a two-phase approach. During the 7-month Phase 1 period, ConocoPhillips further defined the Project by advancing the preliminary design, permits, and contracts. In addition, ConocoPhillips was developing a Phase 2 renewal application to seek continued DOE funding for the Project's design, construction, and early operations. The DOE and ConocoPhillips entered into a Phase1 Cooperative Agreement (DOE Award Number DE-FE0001859) on November 16, 2009, agreeing to share cost on a 50/50 basis during the Phase 1 period, with a DOE budget of $2,989,174. On April 7, 2010, ConocoPhillips informed the DOE that it would not participate in Phase 2 of the DOE ICCS program. The company believes that enabling legislation and regulations at both the federal and state levels will not be approved and implemented in time to make a final investment decision such that the Project would be substantially constructed by September 30, 2015, the end of the AARA funding period. Considering current price assumptions, the Project would not generate investment level returns. ConocoPhillips elected not to submit a Phase 2 renewal application, which was due on April 16, 2010. This Final Scientific/Technical Report provides an overview of the Project, including highlights and benefits of the proposed carbon capture and storage project scope, sites, and technologies. It also summarizes the work accomplishments during the Phase 1 period from November 16, 2009 to June 16, 2010. Due to ConocoPhillips decision not to submit the Phase 2 renewal application and not to enter into related agreements, certain information regarding the proposed CO{sub 2} storage facility cannot be publicly reported due to confidentiality agreements