Academic literature on the topic 'Conference of Local Medical Committees'

IntroductionHip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse.Methods and analysisThe iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60.Ethics and disseminationiHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals.Trial registration numberDRKS00013644; Pre-results

IntroductionPeople with severe mental illness (SMI) die on average 10–20 years earlier than the general population. Most of these deaths are due to physical health conditions. The aim of this cross-sectional study is to determine the prevalence of physical health conditions and their associations with health-risk behaviours, health-related quality of life and various demographic, behavioural, cognitive, psychological and social variables in people with SMI attending specialist mental health facilities in South Asia.Methods and analysisWe will conduct a survey of patients with SMI attending specialist mental health facilities in Bangladesh, India and Pakistan (n=4500). Diagnosis of SMI will be confirmed using the Mini-international neuropsychiatric interview V.6.0. We will collect information about physical health and related health-risk behaviours (WHO STEPwise approach to Surveillance (STEPS)); severity of common mental disorders (Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder scale (GAD-7)) and health-related quality of life (EQ-5D-5L). We will measure blood pressure, height, weight and waist circumference according to WHO guidelines. We will also measure glycated haemoglobin, lipid profile, thyroid function, liver function, creatinine and haemoglobin. Prevalence rates of physical health conditions and health-risk behaviours will be presented and compared with the WHO STEPS survey findings in the general population. Regression analyses will explore the association between health-risk behaviours, mental and physical health conditions.Ethics and disseminationThe study has been approved by the ethics committees of the Department of Health Sciences University of York (UK), Centre for Injury Prevention and Rehabilitation (Bangladesh), Health Ministry Screening Committee and Indian Council of Medical Research (India) and National Bioethics Committee (Pakistan). Findings will be disseminated in peer-reviewed articles, in local and international conferences and as reports for policymakers and stakeholders in the countries involved.Trial registration numberISRCTN88485933; 3 June 2019.

IntroductionConcurrent chemoradiotherapy with conventional fractionation has been acknowledged as one of the standard treatments for locally advanced non-small cell lung cancer (NSCLC). The radiotherapy dose of 60 Gy is far from enough for local tumour control. Due to this fact, hypofractionated radiotherapy can shorten the total treatment duration, partially counteract the accelerated repopulation of tumour cells and deliver a higher biological effective dose, it has been increasingly used for NSCLC. In theory, concurrent hypofractionated chemoradiotherapy can result in an enhanced curative effect. To date, the vast majority of radiotherapy prescriptions assign a uniform radiotherapy dose to all patients. However this kind of uniform radiotherapy prescription may lead to two consequences: excess damage to normal tissues for large tumours and insufficient dose for small tumours. Our study aims to evaluate whether delivering individualised radiotherapy dose is feasible using intensity-modulated radiotherapy.Methods and analysisOur study of individualised radiotherapy is a multicenter phase II trial. From April 2019, a total of 30 patients from three Chinese centres, with a proven histological or cytological diagnosis of inoperable NSCLC, will be recruited. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 69 Gy is reached. The primary end point is feasibility, with response rates, progression-free survival and overall survival as secondary end points. The concurrent chemotherapy regimen will be docetaxel plus lobaplatin.Ethics and disseminationThe study has been approved by medical ethics committees from three research centres. The trial is conducted in accordance with the Declaration of Helsinki.The trial results will be disseminated through academic conference presentations and peer-reviewed publications.Trial registration numberNCT03606239

IntroductionThis research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the ‘Kihon Check List’, study 2 the ‘Cognitive Function instrument’ and EuroQol-5 Dimension (EQ-5D) and study 3 the ‘Cognitive Function instrument’ and EQ-5D as well as the ‘Frail Kenshin’ health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies.Methods and analysisBaseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression.ConclusionThis project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention.Ethics and disseminationAll studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan’s ‘Ethical Guidelines for Medical and Health Research Involving Human Subjects’. All findings will be disseminated at conferences and published in peer-reviewed journals.Trial registration numberUMIN000023283.

IntroductionPrimary healthcare professionals will increasingly be required to manage and optimise their treatment for patients with dementia. With DementiaNet, we aim to reduce the burden of dementia on healthcare services and society through implementation and facilitation of integrated network-based care with increased dementia expertise. DementiaNet is designed as a stepwise approach including clinical leadership, quality improvement cycles and interprofessional training, which are tailor-made to the local context. For example, the composition of the network and improvement goals are tailored to the local context and availability. Here, we describe the linked evaluation study which aims to provide insight in effectiveness, process and mechanism of the DementiaNet approach through an innovative evaluation design.Methods and analysisWe designed a longitudinal, mixed methods, multiple case study. Study population consists of two levels: (i) local DementiaNet networks of primary care professionals and (ii) patients and informal caregivers who receive care from these networks. At the start and after 12 and 24 months, quantitative data are collected for each network on: level of network maturity, quality of care indicators and outcomes reported by informal caregivers of dementia patients. We assess changes in networks over time and the association with quality of care and informal caregiver-reported outcomes. Throughout the study, logs about each network are registered. Additionally, semi-structured interviews with network members and informal caregivers will provide insight in experiences and opinions regarding effects and mechanisms through which changes in quantitative outcomes are effectuated. Rich narratives will be constructed about the development of the local networks using collected data.Ethics and disseminationThe study protocol was reviewed by the local medical ethics committee; formal judgement was not required (protocol number: 2015–2053). The findings of this study will be disseminated through peer-reviewed publications, conference presentations and presentations for healthcare professionals where appropriate.

Abstract Background Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas (NHL). PTCL accounts for approximately 10% of all NHL cases in the US and Europe, and may be as high as 24% in Asia. The most common frontline treatment of PTCL is anthracycline-based chemotherapy with CHOP or CHOP-like regimens which do not produce durable remissions in the majority of subtypes, including ALK+ systemic anaplastic large cell lymphoma (sALCL) with high International Prognostic Index (IPI) scores. Brentuximab vedotin is an antibody-drug conjugate directed against CD30 currently approved for the treatment of relapsed or refractory sALCL with demonstrated antitumor activity in frontline PTCL. A phase 1 trial combining brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone (CHP [CHOP without vincristine to eliminate additive neurotoxicity]) as frontline treatment of PTCL demonstrated estimated 5-year progression-free survival (PFS) and overall survival (OS) rates of 52% and 79% (Fanale 2018). Based on the encouraging activity and manageable safety profile of the combination, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin in combination with CHP (A+CHP) versus standard CHOP for the treatment of patients (pts) with PTCL (ClinicalTrials.gov No. NCT01777152). Here we report the blinded, pooled analyses per investigator of the ECHELON-2 trial. Methods ECHELON-2 is a phase 3, randomized, double-blind, active-controlled, multicenter study. Adults with newly diagnosed CD30+ (≥10% of neoplastic cells by local review) PTCL were enrolled. Pts with ALK+ sALCL were required to have an IPI ≥2. The primary endpoint of ECHELON-2 is PFS per an independent review facility. Pts were randomized 1:1 to receive 21-day cycles of either CHOP or A+CHP for 6 to 8 cycles. Consolidative SCT or radiotherapy was permitted at the investigator's discretion after end of treatment. Results A total of 452 pts across 17 countries were randomized between January 2013 and November 2016 in Europe (44%), North America (29%), and other (26%) regions including Asia and Australia. The median age was 58 years (range, 18-85) and 63% were male. Most pts were white (62%) or Asian (22%). Most pts entering the study had an ECOG performance status of 0 or 1 (39% each) and the remaining 22% of pts had a performance status of 2. Most pts had advanced-stage disease (Stage III [27%] or IV [53%]) at diagnosis and 78% had IPI scores ≥2 (2 [34%], 3 [29%], 4 [12%]. 5 [3%]). PTCL subtypes included sALCL (316 pts [70%]: ALK+ 98 pts [22%]; ALK- 218 pts [48%]), PTCL - not otherwise specified (72 pts [16%]), angioimmunoblastic T-cell lymphoma (54 pts [12%]), adult T-cell leukemia/lymphoma (7 pts [2%]), and enteropathy-associated T-cell lymphoma (3 pts [1%]). Of the 452 randomized pts, 449 received at least 1 dose of study treatment and all pts had either completed (82%) or discontinued treatment as of April 2017. Treatment was discontinued for adverse events (AEs) (7%), progressive disease (7%), investigator decision (2%), and patient decision (2%). Preliminary results by investigator assessment, show an overall blinded pooled objective response rate (ORR) following completion of the frontline treatment of 79% (95% CI: 75.4-83.1) with 64% achieving a complete response (CR) (95% CI: 59.1-68.2). With a median follow-up of 35.2 mos, the 3-year PFS and OS for all pts were 52.9% (95% CI: 47.7-57.7) and 73.1% (95% CI: 68.3-77.2). The incidence of AEs was consistent with the known safety profiles of brentuximab vedotin and CHOP chemotherapy, including the AE of interest, peripheral sensory neuropathy (43%). Grade 3 or higher AEs reported in ≥10% of pts were neutropenia (33%), febrile neutropenia (17%), and anemia (12%). Conclusions ECHELON-2 is the largest prospective, randomized, double-blind study to compare the efficacy and safety of standard CHOP with an alternative regimen that includes a CD30-targeted agent in frontline treatment of sALCL and other CD30+ PTCLs. Blinded pooled data from ECHELON-2 show that the treatment was well tolerated with encouraging 3-year PFS and OS rates. The primary analysis by treatment regimen will be unblinded prior to the meeting and presented at the conference. Disclosures Horwitz: Seattle Genetics: Consultancy, Research Funding; Aileron Therapeutics: Consultancy, Research Funding; Innate Pharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Corvus: Consultancy; Mundipharma: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Trillium: Consultancy; Celgene: Consultancy, Research Funding; Portola: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Spectrum: Research Funding; Kyowa-Hakka-Kirin: Consultancy, Research Funding. O'Connor:Seattle Genetics: Research Funding; Celgene: Research Funding; ADC Therapeutics: Research Funding. Pro:kiowa: Honoraria; Takeda Pharmaceuticals: Honoraria, Other: Travel expenses; Seattle Genetics: Consultancy, Other: Travel expenses, Research Funding; portola: Honoraria. Illidge:Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria. Fanale:Amgen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Merck & Co: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding. Advani:Agensys: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board, Research Funding; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board; Merck: Research Funding; Janssen: Research Funding; Autolus: Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board; Celgene: Research Funding; Kyowa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board; Regeneron: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Research Funding; Kura: Research Funding; Celgene: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board, Research Funding; Gilead/Kite: Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board; Cell Medica: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board; Millenium: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board, Research Funding; Forty Seven Inc.: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board. Bartlett:KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ImaginAB: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck & Co: Research Funding; Immune Design: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Affimed: Research Funding; Celgene: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Novartis: Research Funding; Bristol-Meyers Squibb: Research Funding; Millennium: Research Funding. Christensen:Seattle Genetics: Research Funding. Morschhauser:Janssen: Other: Scientific Lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Domingo-Domenech:Affimed: Research Funding. Rossi:Novartis: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Travel expenses; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Mundipharma: Honoraria; Sandoz: Honoraria; Seattle Genetics: Research Funding; Alexion: Other: Travel expenses. Feldman:Portola: Research Funding; Celgene: Speakers Bureau; Pharmacyclics: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; KITE: Speakers Bureau; Johnson and Johnson: Speakers Bureau; Janssen: Speakers Bureau. Lennard:Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding. Belada:Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Illés:Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Tobinai:Zenyaku Kogyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; SERVIER: Research Funding; Abbvie: Research Funding; GlaxoSmithKline: Research Funding; Takeda: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; HUYA Bioscience International: Consultancy, Honoraria; Chugai Pharma: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Tsukasaki:Celgene: Honoraria; Eisai: Research Funding; Chugai Pharma: Honoraria, Research Funding; HUYA: Consultancy, Research Funding; Ono Pharma: Consultancy; Daiich-Sankyo: Consultancy; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Shustov:Seattle Genetics: Research Funding. Hüttmann:Roche: Other: Travel expenses; Celgene: Other: Travel expenses. Savage:Verastem: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Servier: Consultancy. Yuen:Seattle Genetics: Research Funding. Zinzani:MSD: Honoraria, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hua:Takeda Pharmaceuticals International Co.: Employment. Little:Takeda Pharmaceuticals: Employment. Rao:Seattle Genetics: Employment, Equity Ownership. Woolery:Seattle Genetics: Employment, Equity Ownership. Manley:Seattle Genetics: Employment, Equity Ownership. Trümper:Seattle Genetics: Research Funding.

Background: Tisagenlecleucel (Tisagen) and Axicabtagene Ciloleucel (Axicel) CD19 CAR T-cell products are licensed in the UK for adults with relapsed/refractory high-grade B-cell Non-Hodgkin's lymphoma (B-NHL). Infection rates for the first 30 days post CAR T range from 23% (Hill et al, Blood 2018) to 42% (Park et al, Clin Infect Dis 2018) with a predominance of early bacterial infections. Infection etiology is multifactorial, including pre-existing immunosuppression, poor marrow reserve, concomitant disease, delayed cytopenias and lymphodepletion. CRS has been shown to be an independent risk factor and associated treatment (Tocilizumab, steroids) may contribute. Risk assessment is limited by heterogenous cohorts in published reports and practice variations in use of prophylactic antibiotics and intravenous immunoglobulin (IVIG). To determine incidence and outcome of infection with licensed CAR T-cell products, we conducted a retrospective review at UCLH, London, UK. Methods: Electronic medical records were used to collect data on patients treated with Tisagen/Axicel from May 2019 to July 2020. Infections at ≤28 days and >28days following infusion were recorded. Infections were defined as a positive microbiological/virology result in conjunction with clinical symptoms. Invasive fungal infections were classified according to revised EORTC criteria. Infections were graded as severe (requiring systemic treatment) or life threatening (hypotension/organ support). Results: Sixty adults with B-NHL received Tisagen (n=19) or Axicel (n=41). Patients did not receive prophylactic antibiotics. IVIG was given for hypogammaglobulinaemia with recurrent infections (n=4). Within 28 days of infusion, 44 episodes of infection occurred in 28 patients (47%). Post day 28 (range 29-452), 19 episodes occurred in 9 patients (15%). Severe (n=9) and life-threatening (n=7) infection occurred in 15% and 12% of patients respectively, with two infections resulting or contributing to death (3.3%). Infections were bacterial (56%), respiratory viral (24%), other viral (14%) and fungal (6%). Six (10%) developed viral reactivations; CMV (n=1), BK virus in blood or urine (n=2), HHV6 (n=1) or AdV (n=2). PCR proven JC virus causing progressive multifocal leukoencephalopathy was reported in 1 patient at day 116. Only one late COVID-19 infection occurred despite the program remaining operational throughout lockdown. There was no association between early infection and CRS severity (p=0.43), or use (p=0.94) and dose of Tocilizumab (p=0.54). With regard to pre-treatment variables, advanced disease at time of infusion (≥stage 3) was associated with higher risk of any infection (OR 4.2, 95% CI 1.3- 13.4, p=0.016) and lines of prior therapy (≥3) with higher risk of early infection (OR 3.0, 95% CI 1.0-8.9, p=0.048). Steroid treatment was associated with a higher risk of early (and overall) infection (OR 3.0. 95% CI 1.0-8.6, p=0.048). A diagnosis of ICANS was associated with infection beyond day 30 (p=0.021). In multivariate analyses, steroid use (p=0.03) and ≥3 lines of prior therapy (p=0.021) were associated with infection ≤28 days of infusion. Steroid use (p= 0.049) and stage pre infusion (p=0.023) were associated with higher risk of any infection. Conclusion: In this real world analysis of B-NHL patients treated with Tisagen or Axicel, 47% developed early infection at ≤28 days. Severe or life-threatening infection occurred in 27% of patients. Multivariate analysis confirms significant association with (1) steroid exposure (2) ≥stage 3 disease and (3) ≥3 lines of previous therapy. There was no overt association with Tocilizumab use or CRS severity. Unlike other centers, our cohort did not receive prophylactic antibiotics or IVIG. Patients with advanced disease are high risk for CRS, ICANS and infectious complications. Risk modification strategies include bridging optimization to reduce disease burden pre CAR T with infectious prophylaxis from referral until at least 3-6 months post-infusion. In this analysis, steroids represent a significant risk and efforts should be made to wean doses swiftly. The use of steroid sparing agents such as Anakinra may be important (clinical trial results awaited). In ≥ stage 3 disease or heavily pre-treated patients, there may be a role for prophylactic antibiotics but this should be explored within a clinical study with consideration of local antimicrobial resistance patterns. Disclosures Neill: Novartis: Other: Funded attendance at academic conferences; Celgene: Other: Funded attendance at academic conferences. Townsend:Roche, Gilead: Consultancy, Honoraria. Ardeshna:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi, Genzyme, AstraZeneca: Speakers Bureau; University College London (UCL)/UCL Hospitals (UCLH) Biomedical Research Unit: Other: Supported by this organisation. Cwynarski:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Peggs:Autolus: Consultancy. Roddie:Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria. O'Reilly:Gilead: Honoraria; Novartis: Honoraria, Other: Travel support.

IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.

In many low-income and 'fragile' states, citizens' committees are elected to co-manage basic social services. However, the effects of such committees on service delivery, and the way they are influenced by local contexts, remain understudied. This thesis seeks to fill these gaps by examining the case of the health facility committees in Burundi and South Kivu between 2011 and 2014. It relies on original health facility and committee surveys, household surveys, nested interviews and focus groups, and interviews with key informants. The thesis firstly explores how the committees came about. It then looks at the questions, What makes them get involved in decisions at their health facility? and, How do measures designed to improve committee functioning lead to changes in service delivery, if at all? Mixed-methods work finds that chief nurses largely dominate the health facilities, and the committees appear to be both the product of recent political and administrative changes and a façade of community governance. The work's randomised controlled trial tests the idea that this inefficiency arises from an 'institutional knowledge gap': the committee members and nurses do not know the committee's (official) functioning. An information session has strengthened the committees and led to changes in health facility management in South Kivu, but not in Burundi. This difference seems to come from dissimilar management structures and people's relationships to service providers. The intervention has had no effect on service provision. The remaining chapters report on additional interventions in Burundi, which theory and qualitative research suggest might improve the effects of the knowledge intervention: trust-building between nurses and committee, information about health facility performance, and increased interaction between local leaders and committees. These are either ineffective or have unintended consequences. Overall, the thesis nuances the promises of social accountability mechanisms and stresses the importance of power relationships within basic social services.

Despite the availability of numerous models for knowledge translation into practice and policy, research uptake remains low in resource-limited countries. This study was aimed at developing a model to facilitate research uptake in healthcare practice and policy development. The study used a two-phase exploratory sequential approach (QUAL→QUAN). Qualitative data were collected through semi-structured interviews with a total of 21 participants, categorised as researchers (6), frontline workers/practitioners (7), programme/policy managers (4), and directors/senior managers (4) from government, private sector and academic institutions of higher learning (universities and colleges). Quantitative data were collected through an online cross-sectional survey, administered to 212 respondents who conducted research studies in the Mpumalanga Province between 2014 to 2019. The most significant findings seem to be lack of awareness of research findings and champions to lead engagements among research stakeholders on research uptake. In addition, the research has established a failure by researchers to align public health research projects to existing local contexts and available resources. Conversely, there is a growing propensity of using informal research without consideration of data quality issues. It was further observed that establishing and sustaining beneficial collaboration between all research stakeholders is required to promote effective research uptake for practice and policy development. The survey results established a total of 13 components: four individual factors (support, experience, motivation & time factor); four organisational factors (research agenda, funding, resources & partnerships), and five research characteristics factors (gatekeeping, local research committees, accessibility of evidence, quality of evidence & critical appraisal skills). However, the Spearman’s correlation coefficient revealed that of the 13 factors, only six factors had a significant positive correlation with research uptake, namely: support, experience, motivation, time factor, resources, and critical appraisal skills. Consequently, a model for institutionalising research uptake is proposed. The roles of local research committees have been clarified, and a logical framework has been incorporated with pathways and channels of engagements to enable successful implementation of the research uptake model.
Health Studies
Ph. D. (Public Health)

This chapter illustrates how the local standoff was broken in the last three months of 1974. At a central party work conference in mid-October, Wang Hongwen and Zhang Chunqiao, ranking central leaders associated with the radical group that had supported Mao Zedong in launching the Cultural Revolution, harshly criticized the crackdown against May 16 elements in Jiangsu Province. This was part of their drive to push military officers out of revolutionary committees in the wake of Lin Biao's purge. It was also due to their perception that the crackdowns were part of a military effort to persecute genuine rebel groups who had spearheaded the mass movements that they had sponsored back in 1967. The veteran cadres who now headed Jiangsu immediately relayed these instructions to party committees across the province, because it helped them push out lingering army control over civilian administration. In December of 1974, Shao Wen was transferred far away from Feng County. However, the new county leaders seemed indifferent to Paolian's grievances against Liansi. This is the primary reason why, after these leaders were later attacked by Liansi at the end of 1975 and early 1976, Paolian did not actively defend them. The chapter then looks at the death of Mao and considers the final major campaign to rid leading bodies across China of individuals who had risen into positions as a result of their earlier factional activity.

The Syrian conflict stands as the most brutally violent conflict of the twenty-first century. Yet it also witnessed an unprecedented blossoming of nonviolent civil action. During the early months of the unarmed uprising that began in March 2011, a network of local grass-roots committees formed to coordinate and sustain nonviolent street demonstrations; citizen journalists documented events; and communities mobilized to provide medical relief. As the Assad regime responded to dissent with repression and the opposition took up arms, a multidimensional war and humanitarian catastrophe propelled new forms of civil action, including rescue services and the building of institutions of self-governance and service provision in rebel-controlled areas. Syrian civil action groups were not more successful than the international community in bringing an end to the war. Yet they played important roles in alleviating some of the effects of violence, monitoring human rights violations, and even shaping the behavior of armed groups.

For the past ten years, heterogeneous networks wired and wireless had tended to integrate seamlessly, offering effective and reliable service for medical operations. One of the problems encountered by network practitioners is the seamless integration of network components into healthcare delivery. As a multiplexing hospital model, the implementation certainly presents some challenges. The major technical and performance issues involve are as following. The operating parameters should keep aligned to the Quality of Service (QoS) requirement throughout simulation. Bandwidth utilisation of wireless networking is a challenging issue for real-time multimedia transmission. IEEE 802.11 provides relatively lower data rate than wired networks, thus the developer tends to adopt a more compromised solution: either reduce the file size or compress the image packets. Communication performance that varies constantly with the impact of signal strength, traffic load and interference. As stated radio signal senses as a curve and attenuates greatly while metallic object and microwave exist within the active range. To ensure devices do not interfere with other electronic equipments (e.g. heart monitors), assert wireless spectrum has to be managed appropriately. This research paper aims to develop a generic hospital network scenarios using Wireless Local Area Network (WLAN) over OPNET Simulation, to evaluate the performance of the integrated network scenario for Intensive Care Units (ICU). This research makes use of computer simulation and discusses various aspects of the network design, so as to discover the performance behaviour pertaining to effect of traffic type, traffic load and network size. In the ICU scenario, the performance of video conference degrades with network size, thus, a QoS-enabled device is recommended to reduce the packet delay and data loss. IEEE 802.11a suits in hospital environment because it mitigates interference on the 2.4GHz band where most wireless devices operate. Experiment examines the effect of signal strength in WLAN. It is convinced that -88dBm is the best signal strength threshold. Although 802.11a generates slightly lower throughput than 802.11g, this issues can be addressed by placing more APs in the service area. It is convinced that 802.11a suits the hospital environments, because it mitigates interference on the popular 2.4GHz band where most wireless devices operate. It is important for medical devices which require future upgrade and Bluetooth deployment.