Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice

Six mechanisms behind carer wellbeing effects: A qualitative study of healthcare delivery

YesHealth and care services for patients may improve or harm the wellbeing of their family carers. Formal consideration of these effects (also known as spillovers) in decision-making is advocated, but, to date, little is known about how they occur. This paper presents the first empirical study to determine the mechanisms by which health and care services affect family carers' wellbeing. The study focused on three major health conditions: dementia, stroke, and mental health. Focus groups and interviews were conducted with 49 purposefully sampled care professionals and family carers in the UK between December 2016 and September 2017. Transcripts were coded and analysed thematically, using descriptive accounts and an explanatory account. The analysis generated six over-arching mechanisms by which health and care services affect family carers' wellbeing, through: (i) information (degree to which service delivery informs and trains family carers); (ii) management of care (shifts of responsibility for care between formal and family sectors); (iii) patient outcomes (services changing patient outcomes); (iv) alienation (feelings of alienation or inclusion created by service delivery); (v) compliance (barriers to patients complying and engaging with services); and (vi) timing or location (changes in the timing or location of services). Each mechanism was associated with sub-themes relating to both positive and negative spillovers on the family carers. The six mechanisms can be summarised with the mnemonic ‘IMPACT’. The IMPACT mechanisms may be useful in designing and evaluating services to optimise the wellbeing of carers as well as patients.Hareth Al-Janabi is funded by a National Institute for Health Research (NIHR) Career Development Fellowship (CDF-2015-08-025) for this research project. Mel Calvert is partially funded by the NIHR Birmingham Biomedical Research Centre and the NIHR Surgical Reconstruction and Microbiology Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. This paper presents independent research funded by the National Institute for Health Research (NIHR)

Recent Advances in Printed Capacitive Sensors

In this review paper, we summarize the latest advances in the field of capacitive sensors fabricated by printing techniques. We first explain the main technologies used in printed electronics, pointing out their features and uses, and discuss their advantages and drawbacks. Then, we review the main types of capacitive sensors manufactured with different materials and techniques from physical to chemical detection, detailing the main substrates and additives utilized, as well as the measured ranges. The paper concludes with a short notice on status and perspectives in the field.H2020-MSCA-IF-2017-794885-SELFSEN

Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China

© 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239

Quality of Type 2 Diabetes Management in the States of The Co-Operation Council for the Arab States of the Gulf: A Systematic Review

Type 2 diabetes mellitus is a growing, worldwide public health concern. Recent growth has been particularly dramatic in the states of The Co-operation Council for the Arab States of the Gulf (GCC), and these and other developing economies are at particular risk. We aimed to systematically review the quality of control of type 2 diabetes in the GCC, and the nature and efficacy of interventions. We identified 27 published studies for review. Studies were identified by systematic database searches. Medline and Embase were searched separately (via Dialog and Ovid, respectively; 1950 to July 2010 (Medline), and 1947 to July 2010 (Embase)) on 15/07/2009. The search was updated on 08/07/2010. Terms such as diabetes mellitus, non-insulin-dependent, hyperglycemia, hypertension, hyperlipidemia and Gulf States were used. Our search also included scanning reference lists, contacting experts and hand-searching key journals. Studies were judged against pre-determined inclusion/exclusion criteria, and where suitable for inclusion, data extraction/quality assessment was achieved using a specifically-designed tool. All studies wherein glycaemic-, blood pressure- and/or lipid- control were investigated (clinical and/or process outcomes) were eligible for inclusion. No limitations on publication type, publication status, study design or language of publication were imposed. We found the extent of control to be sub-optimal and relatively poor. Assessment of the efficacy of interventions was difficult due to lack of data, but suggestive that more widespread and controlled trial of secondary prevention strategies may have beneficial outcomes. We found no record of audited implementation of primary preventative strategies and anticipate that controlled trial of such strategies would also be useful

Effects of hyaluronan on carrageenan-induced synovitis in rat TMJ

Nitric oxide is one of many proinflammatory mediators that are involved in temporomandibular joint (TMJ) inflammatory disorder and is synthesized by inducible nitric oxide synthase (iNOS). iNOS is transcriptionally regulated by nuclear factor-κB (NF-κB) in cases of inflammation, proliferation, and apoptosis. It has also been reported that nitric oxide is positively regulated by carrageenan and negatively regulated by hyaluronan in the knee joint. The aim of this study was to histologically evaluate how inflammation and cell proliferation of the synovial membrane are affected by the exogenous administration of carrageenan and hyaluronan in the rat TMJ by investigating iNOS, NF-κB, and anti proliferating cell nuclear antigen (PCNA) immunoreactivity. As results, immunoreactive cells to iNOS, NF-κB, and PCNA were normally localized only in the synovial membrane of wild type TMJs. The numbers of immunoreactive cells were extensively larger in the carrageenan-injected synovial membranes exhibiting excessive folding, and smaller in the hyaluronan-injected synovial membranes showing a few folds. These results indicate that a carrageenan injection induced inflammation and cell proliferation especially in the synovial membrane and that hyaluronan relieved the inflammation by decreasing inflammatory molecules in the synovial membrane

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Pharmacy Care and Adherence to Primary and Secondary Prevention Cardiovascular Medication- A systematic review of studies

Objective To determine if pharmacy service intervention can lead to enhanced adherence to primary and secondary cardiovascular medication and to identify features of interventions that have been found to be effective and feasible. Methods A systematic search of studies related to pharmacy service interventions on adherence and outcomes of cardiovascular diseases was performed using the following databases: PubMed Central UK, PubMed, Cochrane Library, CINHAL, PsycINFO, EMBASE, International Pharmaceutical Abstracts and Google Scholar for the period from 1 January 1990 to 19 November 2013. Trials were included if they were randomised control trials, studies delivered in hospital or community settings, and studies in English language. A hand search of relevant citations was also performed. Key findings Forty-two studies were identified of which 26 had a statistically significant effect on adherence and twenty-seven had a significant effect on clinical outcomes of cardiovascular disease. The interventions included mainly patient education, collaboration between healthcare professionals, use of electronic devices and combined interventions. The interventions were found to be complex and included multiple components. Patient contact with a pharmacist was frequent and thus the interventions may be difficult to adapt to daily practice. Evidence-based data for pharmacy services remain weak but clearly pharmacists can have an impact through face-to-face patient education and telephone consultations. Further research is needed to evaluate the use of a motivational interview in the counselling session of a pharmacist and also to establish the continuity of pharmacy care in primary/secondary setting. Self-reported adherence was the most widely used measure. The acceptable threshold remained 80% among the cardiac population. Conclusion Pharmacist interventions have been shown to be successful in enhancing adherence to cardiovascular medication and improving outcomes of cardiovascular diseases. Whilst pharmacists play a fundamental role in primary and secondary prevention strategies, further randomised controlled trials combining patient education with behaviour change are likely to reap further benefit in medication adherence

Regional seismic wave propagation (Lg and Sn) and Pn attenuation in the Arabian Plate and surrounding regions

An edited version of this paper was published by Blackwell Publishing. Copyright 2004, Blackwell Publishing. See also: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-246X.2004.02246.x; http://atlas.geo.cornell.edu/MiddleEastNorthAfrica/publications/Al-Damegh2004.htmContinuous recordings of 17 broadband and short period digital seismic stations from a newly established seismological network in Saudi Arabia, along with digital recordings from the broadband stations of the GSN, MEDNET, GEOFON, a temporary array in Saudi Arabia, and a temporary short period stations in Oman, were analyzed to study the lithospheric structure of the Arabian plate and surrounding regions. The Arabian plate is surrounded by a variety of types of plate boundaries: continental collision (Zagros belt and Bitlis suture), continental transform (Dead Sea fault system), young sea floor spreading (Red Sea and Gulf of Aden), and oceanic transform (Owen fracture zone). Also, there are many intraplate Cenozoic processes such as volcanic eruptions, faulting, and folding that are taking place. We used this massive waveform database of more than 6200 regional seismogram to map zones of blockage, inefficient, and efficient propagation of the Lg and Sn phases in the Middle East and East Africa. We observed Lg blockage across the Bitlis suture and Zagros fold and thrust belt, corresponding to the boundary between the Arabian and Eurasian plates. This is probably due to a major lateral change in the Lg crustal wave-guide. We also observed inefficient Lg propagation along the Oman mountains. Blockage and inefficient Sn propagation is observed along and for a considerable distance to the east of the Dead Sea fault system and in the northern portion of the Arabian plate (south of the Bitlis suture). These mapped zones of high Sn attenuation, moreover, closely coincide with extensive Neogene and Quaternary volcanic activity. We have also carefully mapped the boundaries of the Sn blockage within the Turkish and Iranian plateaus. Furthermore, we observed Sn blockage across the Owen fracture zone and across some segments of the Red Sea. These regions of high Sn attenuation most probably have anomalously hot and possibly thin lithospheric mantle (i.e., mantle lid). A surprising result is the efficient propagation of Sn across a segment of the Red Sea; an indication that active sea floor spreading is not continuous along the axis of the Red Sea. We also investigated the attenuation of Pn phase (QPn) for 1-2 Hz along the Red Sea, Dead Sea fault system, within the Arabian shield, and in the Arabian platform. Consistent with the Sn attenuation, we observed low QPn values of 22 and 15 along the western coast of the Arabian plate and along the Dead Sea fault system, respectively, for a frequency of 1.5 Hz. Higher QPn values on the order of 400 were observed within the Arabian shield and platform for the same frequency. Our results based on Sn and Pn observations along the western and northern portions of the Arabian plate imply the presence of a major anomalously hot and thinned lithosphere in these regions that may be caused by the extensive upper mantle anomaly that appears to span most of east Africa and western Arabia

How do MNC R&amp;D laboratory roles affect employee international assignments?

Research and development (R&#38;D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&#38;D laboratories in which these employees work on the international assignments they undertake. We categorise R&#38;D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&#38;D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&#38;D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto