Newark, New York

National Emergency Bariatric Surgery Audit

The National Emergency Bariatric Surgery Audit (NEBSA) is an observational study aimed at investigating the incidence, management, and outcomes of complications following bariatric surgery in the United Kingdom. The detailed description of the protocol includes the following components: Patient Recruitment and Data Collection: Patients will be identified in hospitals across the UK where they present for an unplanned intervention to treat a complication related to or following bariatric surgery. Data on demographics, surgical history, site and type of index bariatric surgery, comorbidities, complications, treatments, and outcomes will be collected through a combination of electronic health records and manual data extraction. Quality Assurance Plan: Data checks will be performed to ensure range, completeness and consistency with other data fields in the registry. Data entry is restricted in most fields of the data form to ensure conformity of the entries and facilitate analysis. Sample Size Assessment: This is a prospective observational study, so a sample size assessment is not required. Data collection will continue for a six month period per centre then analysed to report any statistically significant findings. Plan for Missing Data: Missing data is reported back to the collaborating sites to complete. Statistical Analysis Plan: The Shapiro-Wilk test will be used to check variables for Gaussian distribution. Basic demographics will be presented as absolute numbers of participants with the respective percentage per group or as parameter mean and standard deviation or median and range, depending on distribution. For comparisons of interval-scaled variables, unpaired t tests will be performed. Nonparametric between-group testing will be undertaken with 2-tailed Mann-Whitney U tests. Additionally, the chi-square test or Fisher exact test will be applied to nominal scale data. Multivariable linear regression be performed for differences among baseline demographics. Analyses will be performed in RStudio with significance defined with p < 0.05. The NEBSA will provide valuable insights into the prevalence, management, and outcomes of complications following bariatric surgery in the UK. By comparing different management strategies and their impact on patient outcomes, this study aims to identify best practices for emergency bariatric care, ultimately improving patient outcomes and overall healthcare quality. Another important aim is analysing the effect of patient demographics, and engagement with NHS specialised weight loss services on the choice of route for bariatric surgery.

Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms

In this prospective multicentre case-control study, the investigators will recruit a total of 518 patients. These will be divided into the following groups: 1. Cancer group (n=259): Patients with treatment naive, histopathology confirmed OSCC. 2. Control group (n=259): Patients who have undergone or are undergoing an upper gastrointestinal (GI) endoscopy as part of their investigation for upper GI symptoms and are found to have either - (i) A normal upper GI tract or (ii) Benign upper GI disease. Eligible and willing participants will be asked to provide two breath samples by exhaling into single-use breath collection bags. Using a custom designed gas sampling pump, the breath VOCs will be transferred onto thermal desorption (TD) tubes at a controlled flow rate. When the participants' breath sampling is complete, room air (Blank) samples will be taken onto additional TD tubes using the same process. Once collected, the TD tubes will be transported to Imperial College London (The Hanna lab), where they will be analysed.

Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers

EVEREST-HN 1: EVolution of a patiEnt-REported Symptom-based Risk Stratification sySTem

The EVEREST-HN pathway should be based on a comprehensive understanding of existing HNC diagnostic pathways and what patients and clinicians value in these. The language used within the EVEREST pathway needs to be accessible and optimal to elicit appropriate information.

Axillary Management in Breast Cancer Patients with Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease. Aim: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years. Methods: Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio. Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node). Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years. Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years. Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness. Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years. Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated. Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

SCOOT: Sample Collection for DART

The results from this study will be linked with the data from the DART study (also collecting data through the Lung Health Check programme) to develop new ways of using computer technology (artificial intelligence) to improve lung health care. The studies use computer programs (called 'algorithms') which can be trained to analyse medical samples. Once developed, these algorithms can be used to support doctors by increasing their speed and accuracy of diagnosing issues.

ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis

Darbepoetin in Neonatal Encephalopathy Trial

Birth asphyxia related brain injury occurs in 2.6 (95% CI 2.5 to 2.8) per 1000 live births in the UK and is the most common cause of death and neurodisability in term babies. The economic burden to the treasury on support costs of neurodisability from neonatal encephalopathy is massive (£4 billion per year). In addition, birth asphyxia related (obstetric) claims accounted for almost half of the NHS litigation expenses in 2016/17 (approx. £2 billion), increasing by 15% from the previous year. It has been reported that the NHS cost to meet the complex life-long care needs of babies born with brain damage could be soon over £20m per child, and this situation is unsustainable to the NHS.The UK Government has recently (October 2016) announced that reducing birth asphyxia related costs is a priority area for the Government. The only effective treatment for neonatal encephalopathy is whole-body cooling, with an estimated saving of £100 million per annum to the UK economy, since its introduction as standard therapy in the NHS in 2007. Cooling therapy has substantially improved the outcomes of babies with neonatal encephalopathy in the past decade. However, unacceptably high rate of adverse outcomes are still seen in cooled babies with moderate or severe neonatal encephalopathy : death 28% (range 24-38); cognitive impairment 24% (range 21-25); cerebral palsy 22% (range 13-28); epilepsy 19% (range 15-24); cortical visual impairment 6% (range 1-10), with combined death or moderate/severe disability 48% (range 44- 53), and hence better treatments and further optimisation of cooling therapy is required. Additionally, cooling provides a window of opportunity for therapeutic interventions that may arrest or reduce secondary brain injury and it is unclear whether it provides protection from a sub-acute chronic injury that may have occurred during the antenatal period. A key roadblock in clinical translation of over fifteen highly effective neuroprotective treatments in animal models is the long delay between the intervention and outcome assessments in neonatal encephalopathy . i.e., the earliest age at which neurodevelopmental outcome can be accurately assessed is 18 months. Hence, despite having several highly effective treatments in animal models, no further neuroprotective drugs in neonatal encephalopathy have been introduced into the NHS in the past ten years. Erythropoietin (Epo) is a widely used drug for treating anaemia in various age groups, including newborn infants. Several recent reviews have highlighted Epo as one of the most promising therapies to augment hypothermic neuroprotection. Epo has both acute effects (anti-inflammatory, anti-excitotoxic, anti-oxidant, and anti-apoptotic) and regenerative effects (neurogenesis, angiogenesis, and oligodendrogenesis) essential for the repair of injury and normal neurodevelopment in animal models. Of the long list of highly effective drugs in animal models of neonatal encephalopathy and early clinical studies, Epo is the most promising. It is the only drug with a long therapeutic window, is widely available, inexpensive, and can be easily administered on a once-a-day dosing schedule. It has been extensively evaluated in large randomised controlled trials for anaemia of prematurity and has a proven safety profile in newborn infants. Due to the regenerative effects and the longer therapeutic window provided by Epo, there is potential to impact the chronic injury caused to an antenatally compromised foetus. Although earlier studies have shown benefit with Epo, the time of initiation and duration of treatment remains uncertain. Moreover, recently published High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial which administered high dose Epo (1000u/kg/day) within 24 hours of birth and continued until 7 days of age failed to demonstrate the neuroprotective effect of erythropoietin in moderate and severe encephalopathy as an adjuvant to therapeutic hypothermia. This result suggest the exposure of the drug during the therapeutic hypothermia may not be beneficial due to an overlap in the neuroprotective mechanism. Perhaps a prolonged exposure of Epo following therapeutic hypothermia might be beneficial. Another erythropoiesis stimulating agent is Darbepoetin (Darbe) with dual erythropoietic and potential neuroprotective effects. Darbe is an ideal candidate to augment hypothermic neuroprotection as it is a long-acting erythropoiesis stimulating agent, allowing prolonged exposure with less dosing. In preclinical study in rats, darbepoetin alfa crossed the blood brain barrier and remained stable up to 24 hours. Neuroprotective effects of darbepoetin were demonstrated following the contusion injury and hemorrhage in rats. The DANCE study (Darbepoetin Administered to Neonates undergoing Cooling for Encephalopathy) randomised 30 term infants with moderate to severe neonatal encephalopathy to placebo (n=10), 2 μg/kg Darbe (n=10) or 10 μg/kg Darbe (n=10). At 2 and 10 μg/kg Darbe, t1/2 was 24 and 32 hours. A dose of 10 μg/kg dose achieved an AUC in the neuroprotective range and a terminal t1/2 of 53.4 hours when compared to the 2 μg/kg dose. No side effects attributable to Darbe were reported. In another feasibility and safety trial, infants with mild encephalopathy were randomised to receive Darbepoetin 10 μg/kg single dose within 24 hours and found the drug to be safe with no reported adverse events. The EDEN trial is a 2 arm randomised control trial and aims to examine the physiological effects of Darbepoetin alfa (Darbe) therapy on proton magnetic resonance spectroscopy thalamic N-acetylaspartate (NAA) level in babies with neonatal encephalopathy undergoing cooling therapy. After informed parental consent, a total of 150 babies with HIE (aged <24 hours) undergoing therapeutic hypothermia will be randomised to one of the following groups - Arm 1:Darbepoetin Alpha (10 mcg/kg) IV x2 doses following cooling therapy. - Arm 2: Cooling only (usual care) Babies recruited will have electroencephalography (EEG), MR imaging and spectroscopy will be performed at 1 to 2 weeks of age to examine the brain injury. The neurological outcomes will be assessed between 18 to 22 months of age. The trial duration will be 4 years, consisting of a 4 week start up period, 24 month recruitment period, a 18 month follow-up period, and 5 months for data analysis and write up.

CARESSES Testing and Evaluation Phases

The objective of the "Culture-Aware Robots and Environmental Sensor Systems for Elderly Support' (CARESSES) project is to build culturally competent robots that are able to re-configure their way of acting and speaking when offering a service to a person they are assisting, and match his / her culture, customs and etiquette. This study will test and evaluate robots that have been configured to provide a culturally-competent care to older adults residing in care homes. It is hypothesised that by introducing robots, which are more sensitive to the user's needs and able to adapt to his / her cultural background, the CARESSES' innovative solution will offer a safe, reliable and intuitive system that fosters independence and autonomy, improves quality of life of older adults, and also reduces informal carer's burden. The methodology adopted to develop this culturally competent solution is based on the principles of Transcultural Nursing, specifically on Hofstede's Cultural dimensions theory (for describing general cultural characteristics at national level) and on Papadopoulos, Tilki and Taylor's model of cultural competence. At the heart of the CARESSES software is a cultural knowledge base (CKB) that stores all the required information about the user and his / her cultural background. CKB was developed using the guidelines provided by the experts in Transcultural Nursing, who identified through field observations differences and similarities between individuals within three cultural groups (i.e. White-English, Indian and Japanese) in order to avoid as much as possible stereotyping and to provide suggestions regarding how likely culturally-specific behaviours are valid for an individual belonging to the cultural group. The study will employ a mixed method (qualitative and quantitative) single-blind, controlled before-and-after experimental design with two testing sites (UK and Japan), in which participants will either be purposefully allocated to an experimental arm (who will receive and be assisted by the CARESSES robot), control arm 1 (who will receive and be assisted by the control CARESSES robot) or control arm 2 (who will receive care as usual). Between and within subjects comparisons will be used to evaluate whether and how the assistance of a CARESSES Pepper robot improves health and well-being related outcomes among care home residents and their informal carers. Eligible older adults from three cultural groups (White-English, Indian and Japanese) will be recruited from the UK-based (White-English and Indian cultural backgrounds only) and Japanese-based testing sites. Additionally, the participants will be requested to nominate up to three informal carers of their choice who will also be invited to take part in the study, but to a different degree. After the recruitment, the participants from both sites will then be purposefully allocated to either an experimental arm (UK site: n=10; Japan site: n=5) that will adopt the CARESSES robot, or to a control arm 1 (UK site: n=10; Japan site: n=5) that will adopt the CARESSES control robot, or to control arm 2 (UK site: n=10; Japan site n=5). In the UK site, each of the arms will include five participants who primarily identify themselves with the White-English culture, and five participants who primarily identify themselves with the Indian culture. In the Japan site, three arms will only include participants who primarily identify themselves with the Japanese culture. The participants allocated to the control arm 2 will engage in testing first, followed by the control arm 1 and then the experimental arm. Testing will occur on two participants at any one time in the UK site, and on one participant in the Japan site. Each participant will adopt a Pepper robot over a period of two weeks. Prior to commencing the full-scale study, a pre-trial feasibility pilot will be conducted aimed at assessing the feasibility and acceptability of the screening, recruitment and evaluation procedures, as well as identifying and tackling any technical issues associated with the implementation of the CARESSES robot within a care home. One resident, who primarily identifies himself / herself with the White-English culture and one informal carer will be invited to take part in the pilot study. The evaluation procedure will take place in a condensed format across one week (9 hours) rather than two weeks (18 hours) as during the full-scale study.

Tenecteplase in Wake-up Ischaemic Stroke Trial

Background: One in five strokes occur during sleep, but patients with "wake-up" stroke are not given thrombolytic therapy because time of stroke onset is unknown. On-going trials are testing alteplase, and use MRI techniques for selection of patients. Tenecteplase has many pharmacological advantages over alteplase: greater fibrin specificity, very rapid action, longer half-life, and single bolus administration. In addition, patient selection based on MRI findings risks excluding many patients that might otherwise benefit. TWIST will test tenecteplase and will not use MRI techniques for selection of patients. Plain CT and CT angiography (if possible) will be performed before randomisation, and CT perfusion will be performed at selected centres, as part of a sub-study. Study design: TWIST is an international, multi-centre, randomised, open-label, blinded-endpoint trial of tenecteplase for acute ischaemic 'wake-up' stroke. Study questions: 1. Can tenecteplase given <4.5 hours of awakening improve functional outcome at 3 months? 2. Can findings on cerebral plain CT and CT angiography (and CT perfusion, at selected centres) identify patients who benefit from such treatment, compared to other patients? Patients eligible for treatment who are able to receive tenecteplase within 4.5 hours of waking, will be randomly allocated to treatment with tenecteplase in addition to best standard treatment, versus best standard treatment. Randomisation and treatment: Central randomisation (over the internet) to tenecteplase 0.25 mg/mg i.v. (maximum dose 25 mg) plus best medical treatment vs. best medical treatment alone. Imaging: All patients will undergo CT and CT angiography (CTA, if possible) before randomisation and on day 2. CT perfusion (CTP) will be performed at selected centres, as part of a sub-study. Follow-up and primary effect variable: Centralised follow-up via telephone or mail at 3 months. The primary effect variable is functional outcome (modified Rankin Scale score). Study size and centers: 600 patients from centers in Norway, Sweden, Denmark, Finland, Estonia, Latvia, Lithuania, United Kingdom, Switzerland and New Zealand.