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1.  Proceedings of the 14th annual conference of INEBRIA 
Holloway, Aisha S. | Ferguson, Jennifer | Landale, Sarah | Cariola, Laura | Newbury-Birch, Dorothy | Flynn, Amy | Knight, John R. | Sherritt, Lon | Harris, Sion K. | O’Donnell, Amy J. | Kaner, Eileen | Hanratty, Barbara | Loree, Amy M. | Yonkers, Kimberly A. | Ondersma, Steven J. | Gilstead-Hayden, Kate | Martino, Steve | Adam, Angeline | Schwartz, Robert P. | Wu, Li-Tzy | Subramaniam, Geetha | Sharma, Gaurav | McNeely, Jennifer | Berman, Anne H. | Kolaas, Karoline | Petersén, Elisabeth | Bendtsen, Preben | Hedman, Erik | Linderoth, Catharina | Müssener, Ulrika | Sinadinovic, Kristina | Spak, Fredrik | Gremyr, Ida | Thurang, Anna | Mitchell, Ann M. | Finnell, Deborah | Savage, Christine L. | Mahmoud, Khadejah F. | Riordan, Benjamin C. | Conner, Tamlin S. | Flett, Jayde A. M. | Scarf, Damian | McRee, Bonnie | Vendetti, Janice | Gallucci, Karen Steinberg | Robaina, Kate | Clark, Brendan J. | Jones, Jacqueline | Reed, Kathryne D. | Hodapp, Rachel M. | Douglas, Ivor | Burnham, Ellen L. | Aagaard, Laura | Cook, Paul F. | Harris, Brett R. | Yu, Jiang | Wolff, Margaret | Rogers, Meighan | Barbosa, Carolina | Wedehase, Brendan J. | Dunlap, Laura J. | Mitchell, Shannon G. | Dusek, Kristi A. | Gryczynski, Jan | Kirk, Arethusa S. | Oros, Marla T. | Hosler, Colleen | O’Grady, Kevin E. | Brown, Barry S. | Angus, Colin | Sherborne, Sidney | Gillespie, Duncan | Meier, Petra | Brennan, Alan | de Vargas, Divane | Soares, Janaina | Castelblanco, Donna | Doran, Kelly M. | Wittman, Ian | Shelley, Donna | Rotrosen, John | Gelberg, Lillian | Edelman, E. Jennifer | Maisto, Stephen A. | Hansen, Nathan B. | Cutter, Christopher J. | Deng, Yanhong | Dziura, James | Fiellin, Lynn E. | O’Connor, Patrick G. | Bedimo, Roger | Gibert, Cynthia | Marconi, Vincent C. | Rimland, David | Rodriguez-Barradas, Maria C. | Simberkoff, Michael S. | Justice, Amy C. | Bryant, Kendall J. | Fiellin, David A. | Giles, Emma L. | Coulton, Simon | Deluca, Paolo | Drummond, Colin | Howel, Denise | McColl, Elaine | McGovern, Ruth | Scott, Stephanie | Stamp, Elaine | Sumnall, Harry | Vale, Luke | Alabani, Viviana | Atkinson, Amanda | Boniface, Sadie | Frankham, Jo | Gilvarry, Eilish | Hendrie, Nadine | Howe, Nicola | McGeechan, Grant J. | Ramsey, Amy | Stanley, Grant | Clephane, Justine | Gardiner, David | Holmes, John | Martin, Neil | Shevills, Colin | Soutar, Melanie | Chi, Felicia W. | Weisner, Constance | Ross, Thekla B. | Mertens, Jennifer | Sterling, Stacy A. | Shorter, Gillian W. | Heather, Nick | Bray, Jeremy | Cohen, Hildie A. | McPherson, Tracy L. | Adam, Cyrille | López-Pelayo, Hugo | Gual, Antoni | Segura-Garcia, Lidia | Colom, Joan | Ornelas, India J. | Doyle, Suzanne | Donovan, Dennis | Duran, Bonnie | Torres, Vanessa | Gaume, Jacques | Grazioli, Véronique | Fortini, Cristiana | Paroz, Sophie | Bertholet, Nicolas | Daeppen, Jean-Bernard | Satterfield, Jason M. | Gregorich, Steven | Alvarado, Nicholas J. | Muñoz, Ricardo | Kulieva, Gozel | Vijayaraghavan, Maya | Adam, Angéline | Cunningham, John A. | Díaz, Estela | Palacio-Vieira, Jorge | Godinho, Alexandra | Kushir, Vladyslav | O’Brien, Kimberly H. M. | Aguinaldo, Laika D. | Sellers, Christina M. | Spirito, Anthony | Chang, Grace | Blake-Lamb, Tiffany | LaFave, Lea R. Ayers | Thies, Kathleen M. | Pepin, Amy L. | Sprangers, Kara E. | Bradley, Martha | Jorgensen, Shasta | Catano, Nico A. | Murray, Adelaide R. | Schachter, Deborah | Andersen, Ronald M. | Rey, Guillermina Natera | Vahidi, Mani | Rico, Melvin W. | Baumeister, Sebastian E. | Johansson, Magnus | Sinadinovic, Christina | Hermansson, Ulric | Andreasson, Sven | O’Grady, Megan A. | Kapoor, Sandeep | Akkari, Cherine | Bernal, Camila | Pappacena, Kristen | Morley, Jeanne | Auerbach, Mark | Neighbors, Charles J. | Kwon, Nancy | Conigliaro, Joseph | Morgenstern, Jon | Magill, Molly | Apodaca, Timothy R. | Borsari, Brian | Hoadley, Ariel | Scott Tonigan, J. | Moyers, Theresa | Fitzgerald, Niamh M. | Schölin, Lisa | Barticevic, Nicolas | Zuzulich, Soledad | Poblete, Fernando | Norambuena, Pablo | Sacco, Paul | Ting, Laura | Beaulieu, Michele | Wallace, Paul George | Andrews, Matthew | Daley, Kate | Shenker, Don | Gallagher, Louise | Watson, Rod | Weaver, Tim | Bruguera, Pol | Oliveras, Clara | Gavotti, Carolina | Barrio, Pablo | Braddick, Fleur | Miquel, Laia | Suárez, Montse | Bruguera, Carla | Brown, Richard L. | Capell, Julie Whelan | Paul Moberg, D. | Maslowsky, Julie | Saunders, Laura A. | McCormack, Ryan P. | Scheidell, Joy | Gonzalez, Mirelis | Bauroth, Sabrina | Liu, Weiwei | Lindsay, Dawn L. | Lincoln, Piper | Hagle, Holly | Wallhed Finn, Sara | Hammarberg, Anders | Andréasson, Sven | King, Sarah E. | Vargo, Rachael | Kameg, Brayden N. | Acquavita, Shauna P. | Van Loon, Ruth Anne | Smith, Rachel | Brehm, Bonnie J. | Diers, Tiffiny | Kim, Karissa | Barker, Andrea | Jones, Ashley L. | Skinner, Asheley C. | Hinman, Agatha | Svikis, Dace S. | Thacker, Casey L. | Resnicow, Ken | Beatty, Jessica R. | Janisse, James | Puder, Karoline | Bakshi, Ann-Sofie | Milward, Joanna M. | Kimergard, Andreas | Garnett, Claire V. | Crane, David | Brown, Jamie | West, Robert | Michie, Susan | Rosendahl, Ingvar | Andersson, Claes | Gajecki, Mikael | Blankers, Matthijs | Donoghue, Kim | Lynch, Ellen | Maconochie, Ian | Phillips, Ceri | Pockett, Rhys | Phillips, Tom | Patton, R. | Russell, Ian | Strang, John | Stewart, Maureen T. | Quinn, Amity E. | Brolin, Mary | Evans, Brooke | Horgan, Constance M. | Liu, Junqing | McCree, Fern | Kanovsky, Doug | Oberlander, Tyler | Zhang, Huan | Hamlin, Ben | Saunders, Robert | Barton, Mary B. | Scholle, Sarah H. | Santora, Patricia | Bhatt, Chirag | Ahmed, Kazi | Hodgkin, Dominic | Gao, Wenwu | Merrick, Elizabeth L. | Drebing, Charles E. | Larson, Mary Jo | Sharma, Monica | Petry, Nancy M. | Saitz, Richard | Weisner, Constance M. | Young-Wolff, Kelly C. | Lu, Wendy Y. | Blosnich, John R. | Lehavot, Keren | Glass, Joseph E. | Williams, Emily C. | Bensley, Kara M. | Chan, Gary | Dombrowski, Julie | Fortney, John | Rubinsky, Anna D. | Lapham, Gwen T. | Forray, Ariadna | Olmstead, Todd A. | Gilstad-Hayden, Kathryn | Kershaw, Trace | Dillon, Pamela | Weaver, Michael F. | Grekin, Emily R. | Ellis, Jennifer D. | McGoron, Lucy | McGoron, Lucy
doi:10.1186/s13722-017-0087-8
PMCID: PMC5606215
2.  Advice given by NHS Direct in Wales: do deprived patients get more urgent decisions? Study of routine data 
Background
In the UK, National Health Service Direct Wales (NHSDW) uses computerised decision support software to advise patients on appropriate care. However, the effect of deprivation on the advice given is not known. We aimed to estimate the effect of deprivation on advice given by nurses in NHSDW adjusting for confounding variables.
Methods
We included 400 000 calls to NHSDW between January 2002 and June 2004. We used logistic regression to model the effect of deprivation on advice given by nurses in response to calls seeking advice or information. We analysed two outcomes: receiving advice to phone 999 emergency care rather than to seek other care and receiving advice to seek care face to face rather than self-care.
Results
After adjustment for covariates, an increase in deprivation from one-fifth of the distribution to the next fifth increased by 13% the probability that those calling for advice rather than information received advice to phone 999 (OR 1.127; 95% CI from 1.113 to 1.143). Deprivation increased the corresponding probability of being advised to seek care face to face rather than self-care by 5% (OR 1.049; 95% CI from 1.041 to 1.058) within advice calls and by 3% (OR 1.034; 95% CI from 1.022 to 1.047) within information calls.
Conclusions
Deprivation increased the chance of receiving more urgent advice, particularly advice to call 999. While our dataset may underestimate the ‘need’ of deprived patients, it yields no evidence of major inequity in advice given to these patients.
doi:10.1136/jech-2017-208978
PMCID: PMC5561357  PMID: 28733459
telemedicine; hotlines; health services needs and demand; poverty areas; socioeconomic factors; vulnerable populations
3.  Amplification mode differs along the length of the mouse cochlea as revealed by connexin 26 deletion from specific gap junctions 
Scientific Reports  2017;7:5185.
The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters’ cells (DCs) and pillar cells (PCs), coupled by gap-junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving-voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses. However, the Cx26 cKO desensitizes mid-high-frequency DPOAEs and active BM responses and sensitizes low-mid-frequency neural excitation. This functional segregation may indicate that the flexible, apical turn cochlear partition facilitates transfer of OHC displacements (isotonic forces) for cochlear amplification and neural excitation. DC and PC Cx26 expression is essential for cochlear amplification in the stiff basal turn, possibly through maintaining cochlear partition mechanical impedance, thereby ensuring effective transfer of OHC isometric forces.
doi:10.1038/s41598-017-04279-3
PMCID: PMC5507891  PMID: 28701711
4.  The nature, characteristics and associations of care home staff stress and wellbeing: a national survey 
BMC Nursing  2017;16:22.
Background
The majority of residents in care homes in the United Kingdom are living with dementia or significant memory problems. Caring in this setting can be difficult and stressful for care staff who work long hours, have little opportunity for training, are poorly paid and yet subject to high expectation. This may affect their mental and physical wellbeing, cause high rates of staff turnover and absenteeism, and affect the quality of care they provide. The main objective of this survey was to explore the nature, characteristics and associations of stress in care home staff.
Methods
Staff working in a stratified random sample of care homes within Wales completed measures covering: general health and wellbeing (SF-12); stress (Work Stress Inventory); job content (Karasek Job Content); approach to, and experience of, working with people living with dementia (Approaches to Dementia Questionnaire; and Experience of Working with Dementia Patients); and Productivity and Health Status (SPS-6). Multiple linear regressions explored the effects of home and staff characteristics on carers.
Results
212 staff from 72 care homes completed questionnaires. Staff from nursing homes experienced more work stress than those from residential homes (difference 0.30; 95% confidence interval (CI) from 0.10 to 0.51; P < 0.01), and were more likely to report that their health reduced their ability to work (difference -4.77; CI -7.80 to -1.73; P < 0.01). Psychological demands on nurses were higher than on other staff (difference = 1.57; CI 0.03 to 3.10; P < 0.05). A positive approach to dementia was more evident in those trained in dementia care (difference 8.54; CI 2.31 to 14.76; P < 0.01), and in staff working in local authority homes than in the private sector (difference 7.75; CI 2.56 to 12.94; P < 0.01).
Conclusions
Our study highlights the importance of dementia training in care homes, with a particular need in the private sector. An effective intervention to reduce stress in health and social care staff is required, especially in nursing and larger care homes, and for nursing staff.
Trial registration
ISRCTN registry: ISRCTN80487202. Registered 24 July 2013
doi:10.1186/s12912-017-0216-4
PMCID: PMC5422906
Care home; Dementia; Care staff; Stress; Wellbeing; Job content; Job satisfaction; Productivity
5.  The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: A randomised controlled trial 
PLoS Medicine  2017;14(3):e1002269.
Background
Cognitive stimulation therapy (CST) is a well-established group psychosocial intervention for people with dementia. There is evidence that home-based programmes of cognitive stimulation delivered by family caregivers may benefit both the person and the caregiver. However, no previous studies have evaluated caregiver-delivered CST. This study aimed to evaluate the effectiveness of a home-based, caregiver-led individual cognitive stimulation therapy (iCST) program in (i) improving cognition and quality of life (QoL) for the person with dementia and (ii) mental and physical health (well-being) for the caregiver.
Methods and findings
A single-blind, pragmatic randomised controlled trial (RCT) was conducted at eight study sites across the United Kingdom. The intervention and blinded assessment of outcomes were conducted in participants’ homes. Three hundred fifty-six people with mild to moderate dementia and their caregivers were recruited from memory services and community mental health teams (CMHTs).
Participants were randomly assigned to iCST (75, 30-min sessions) or treatment as usual (TAU) control over 25 wk. iCST sessions consisted of themed activities designed to be mentally stimulating and enjoyable. Caregivers delivering iCST received training and support from an unblind researcher.
Primary outcomes were cognition (Alzheimer’s Disease Assessment Scale–cognitive [ADAS-Cog]) and self-reported QoL (Quality of Life Alzheimer’s Disease [QoL-AD]) for the person with dementia and general health status (Short Form-12 health survey [SF-12]) for the caregiver. Secondary outcomes included quality of the caregiving relationship from the perspectives of the person and of the caregiver (Quality of the Carer Patient Relationship Scale) and health-related QoL (European Quality of Life–5 Dimensions [EQ-5D]) for the caregiver.
Intention to treat (ITT) analyses were conducted. At the post-test (26 wk), there were no differences between the iCST and TAU groups in the outcomes of cognition (mean difference [MD] = −0.55, 95% CI −2.00–0.90; p = 0.45) and self-reported QoL (MD = −0.02, 95% CI −1.22–0.82; p = 0.97) for people with dementia, or caregivers’ general health status (MD = 0.13, 95% CI −1.65–1.91; p = 0.89). However, people with dementia receiving iCST rated the relationship with their caregiver more positively (MD = 1.77, 95% CI 0.26–3.28; p = 0.02), and iCST improved QoL for caregivers (EQ-5D, MD = 0.06, 95% CI 0.02–0.10; p = 0.01). Forty percent (72/180) of dyads allocated to iCST completed at least two sessions per week, with 22% (39/180) completing no sessions at all. Study limitations include low adherence to the intervention.
Conclusions
There was no evidence that iCST has an effect on cognition or QoL for people with dementia. However, participating in iCST appeared to enhance the quality of the caregiving relationship and caregivers’ QoL.
Trial registration
The iCST trial is registered with the ISRCTN registry (identified ISRCTN 65945963, URL: DOI 10.1186/ISRCTN65945963).
In a randomized controlled trial, Martin Orrell and colleagues investigate the impact of individual cognitive stimulation therapy (iCST) on cognition, quality of life, caregiver health, and family relationships for people with dementia.
Author summary
Why was this study done?
Cognitive stimulation therapy (CST) is a structured group activity programme for people with dementia that has been shown to improve quality of life (QOL) and cognition.
This therapy is recommended by organisations such as the Alzheimer’s Disease International (ADI) and the UK National Institute for Health and Care Excellence.
Although CST is becoming more widely available both in the UK and internationally, some people may not have access to groups because groups are not available near their home, they are not able to get to centres offering groups because of transport, health, or mobility problems, or they would prefer not to do group activities.
This study aimed to look at the potential use and benefits of an adapted version of CST called individual CST (iCST) delivered by a family carer or friend at the person with dementia’s home for 30 min ideally two or three times a week.
What did the researchers do and find?
The research team produced the iCST programme (including a manual, activity workbook, and materials such as maps and dominoes) in collaboration with people with dementia, carers, health care professionals, and experts.
In a randomised controlled trial (RCT), 356 pairs of people with dementia and carers were split between two groups; 180 pairs received iCST, and 176 pairs continued with activities, treatments, and services offered as part of usual care but did not receive iCST, to test whether iCST benefits cognition and QOL for people with dementia and mental and physical health for carers.
The study found that people with dementia receiving iCST did not benefit in terms of cognition or QOL, and neither was there evidence to suggest iCST improved carers’ mental or physical health.
However, people with dementia in the iCST group reported better relationship quality with their family carer at 26 wk, and carers delivering iCST had better QOL at 26 wk.
What do these findings mean?
We did not find that iCST improves cognition or QOL for people with dementia.
Given that iCST appears to have a positive effect on the caregiving relationship and carer well-being, the programme might be a useful part of personally tailored home care packages.
doi:10.1371/journal.pmed.1002269
PMCID: PMC5369684  PMID: 28350796
7.  A connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics 
Nature Communications  2017;8:14530.
Accelerated age-related hearing loss disrupts high-frequency hearing in inbred CD-1 mice. The p.Ala88Val (A88V) mutation in the gene coding for the gap-junction protein connexin30 (Cx30) protects the cochlear basal turn of adult CD-1Cx30A88V/A88V mice from degeneration and rescues hearing. Here we report that the passive compliance of the cochlear partition and active frequency tuning of the basilar membrane are enhanced in the cochleae of CD-1Cx30A88V/A88V compared to CBA/J mice with sensitive high-frequency hearing, suggesting that gap junctions contribute to passive cochlear mechanics and energy distribution in the active cochlea. Surprisingly, the endocochlear potential that drives mechanoelectrical transduction currents in outer hair cells and hence cochlear amplification is greatly reduced in CD-1Cx30A88V/A88V mice. Yet, the saturating amplitudes of cochlear microphonic potentials in CD-1Cx30A88V/A88V and CBA/J mice are comparable. Although not conclusive, these results are compatible with the proposal that transmembrane potentials, determined mainly by extracellular potentials, drive somatic electromotility of outer hair cells.
A point mutation in the gap-junction protein connexin 30 stops early onset age-related hearing loss. Here, the authors show that gap junctions contribute to cochlear micromechanics and that cochlear amplification is likely controlled by extracellular potentials in vicinity of the cochlear sensory cells.
doi:10.1038/ncomms14530
PMCID: PMC5321796  PMID: 28220769
8.  Rapid analgesia for prehospital hip disruption (RAPID): protocol for feasibility study of randomised controlled trial 
Background
Adequate pain relief at the point of injury and during transport to hospital is a major challenge in all acute traumas, especially for those with hip fractures, whose injuries are difficult to immobilise and whose long-term outcomes may be adversely affected by administration of opiate analgesics. Fascia iliaca compartment block (FICB) is a procedure routinely undertaken by doctors and nurses in the emergency department for patients with hip fracture but not yet evaluated for use by paramedics at the scene of emergency calls.
In this feasibility study, we aim to test whether FICB administered by paramedics at the scene of participants’ hip fractures is feasible, safe and acceptable. This will enable us to decide whether to proceed to a fully powered, multi-centre pragmatic randomised trial to evaluate whether the procedure is effective for patients and worthwhile for the NHS.
Methods/design
In this study, we propose to recruit ten paramedics in an urban area of South Wales. We will train them to carry out FICB when they attend patients with hip fracture. We will randomly allocate eligible patients to FICB or usual care using audited scratch cards. We will follow up participants to assess measurability of key outcomes including quality of life, pain scores, adverse events, length of stay in hospital, acceptability to patients and compliance of paramedics. We will assess whether the findings meet specified feasibility criteria and, if so, plan a full trial.
Discussion
This study will enable us to recommend whether to undertake a definitive trial of FICB by paramedics for hip fracture.
Trial registration
ISRCTN60065373
doi:10.1186/s40814-016-0115-6
PMCID: PMC5282771  PMID: 28163926
Paramedic; Hip fracture; Fractured neck of femur; Analgesia; Prehospital; Pain
9.  Peer support and reminiscence therapy for people with dementia and their family carers: a factorial pragmatic randomised trial 
Objective
The objective of this study was to evaluate peer support and reminiscence therapy, separately and together, in comparison with usual care for people with dementia and their family carers.
Design
Factorial pragmatic randomised trial, analysed by treatment allocated, was used for this study.
Setting
The trial ran in Community settings in England.
Participants
People with dementia and their family carers were the participants.
Interventions
Treatment as usual (TAU) plus one of the following: one-to-one peer support to family carers from experienced carers (Carer Supporter Programme; CSP), group reminiscence therapy (Remembering Yesterday, Caring Today; RYCT) for people with dementia and carers, both or neither.
Main outcome measures
Primary outcomes included health-related quality of life (SF-12) for carers and quality of life (QoL-AD) for people with dementia; secondary outcomes included quality of relationship for carers and people with dementia; both were collected by blinded assessors at baseline, 5 and 12 months (primary end point).
Results
Of 291 pairs recruited, we randomised 145 (50%) to CSP (71% uptake) and 194 (67%) to RYCT (61% uptake). CSP and RYCT, separately or together, were not effective in improving primary outcomes or most secondary outcomes. For CSP versus ‘no CSP’, adjusted difference in means was 0.52 points on the SF-12 (95% CI −1.28 to 2.32) and −0.08 points on the QoL-AD (95% CI −1.70 to 1.56). For RYCT versus ‘no RYCT’, the difference was 0.10 points on the SF-12 (95% CI −1.72 to 1.93) and 0.51 points on the QoL-AD (95% CI −1.17 to 2.08). However, carers reported better relationships with the people with dementia (difference 1.11, 95% CI 0.00 to 2.21, p=0.05). Comparison of combined intervention with TAU, and of intervention received, suggested differential impacts for carers and persons with dementia.
Conclusions
There is no evidence from the trial that either peer support or reminiscence is effective in improving the quality of life.
Trial registration number
ISRCTN37956201; Results.
doi:10.1136/jnnp-2016-313736
PMCID: PMC5099314  PMID: 27521377
10.  What can we learn from trial decliners about improving recruitment? Qualitative study 
Trials  2016;17:494.
Background
Trials increasingly experience problems in recruiting participants. Understanding the causes of poor recruitment is critical to developing solutions. We interviewed people who had declined a trial of an innovative psychological therapy for depression (REFRAMED) about their response to the trial invitation, in order to understand their decision and identify ways to improve recruitment.
Methods
Of 214 people who declined the trial, 35 (16 %) gave permission to be contacted about a qualitative study to explore their decision. Analysis of transcripts of semi-structured interviews was informed by grounded theory.
Results
We interviewed 20 informants: 14 women and six men, aged 18 to 77 years. Many interviewees had prior experience of research participation and positive views of the trial. Interviewees’ decision making resembled a four-stage sequential process; in each stage they either decided not to participate in the trial or progressed to the next stage. In stage 1, interviewees assessed the invitation in the context of their experiences and attitudes; we term those who opted out at this stage ‘prior decliners’ as they had an established position of declining trials. In stage 2, interviewees assessed their own eligibility; those who judged themselves ineligible and opted out at this stage are termed ‘self-excluders’. In stage 3, interviewees assessed their need for the trial therapy and potential to benefit; we term those who decided they did not need the trial therapy and opted out at this stage ‘treatment decliners’. In stage 4, interviewees deliberated the benefits and costs of trial participation; those who opted out after judging that disadvantages outweighed advantages are termed ‘trial decliners’. Across all stages, most individuals declined because they judged themselves ineligible or not in need of the trial therapy. While ‘prior decliners’ are unlikely to respond to any trial recruitment initiative, the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials or a personal stance.
Conclusions
To improve recruitment in similar trials, the most successful interventions are likely to address patients’ assessments of their eligibility and their potential to benefit from the trial treatment, rather than reducing trial burden.
Trial registration
International Standard Randomised Controlled Trial Number: ISRCTN85784627. Registration date 10 August 2011.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1626-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-016-1626-4
PMCID: PMC5062905  PMID: 27733181
Randomised controlled trials; Non-participation; Depression; Qualitative research; Recruitment
11.  REMCARE: Pragmatic Multi-Centre Randomised Trial of Reminiscence Groups for People with Dementia and their Family Carers: Effectiveness and Economic Analysis 
PLoS ONE  2016;11(4):e0152843.
Background
Joint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and cost-effectiveness of joint reminiscence groups as compared to usual care.
Methods
This multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person's home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5)were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both.
Results
The intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions—only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group.
Conclusions
This trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions.
Trial Registration
ISRCTN Registry ISRCTN42430123
doi:10.1371/journal.pone.0152843
PMCID: PMC4836678  PMID: 27093052
12.  Costs, effects and implementation of routine data emergency admission risk prediction models in primary care for patients with, or at risk of, chronic conditions: a systematic review protocol 
BMJ Open  2016;6(3):e009653.
Introduction
Emergency admission risk prediction models are increasingly used to identify patients, typically with one or more chronic conditions, for proactive management in primary care to avoid admissions, save costs and improve patient experience.
Aim
To identify and review the published evidence on the costs, effects and implementation of emergency admission risk prediction models in primary care for patients with, or at risk of, chronic conditions.
Methods
We shall search for studies of healthcare interventions using routine data-generated emergency admission risk models. We shall report: the effects on emergency admissions and health costs; clinician and patient views; and implementation findings. We shall search ASSIA, CINAHL, the Cochrane Library, HMIC, ISI Web of Science, MEDLINE and Scopus from 2005, review references in and citations of included articles, search key journals and contact experts. Study selection, data extraction and quality assessment will be performed by two independent reviewers.
Ethics and dissemination
No ethical permissions are required for this study using published data. Findings will be disseminated widely, including publication in a peer-reviewed journal and through conferences in primary and emergency care and chronic conditions. We judge our results will help a wide audience including primary care practitioners and commissioners, and policymakers.
Trial registration number
CRD42015016874; Pre-results.
doi:10.1136/bmjopen-2015-009653
PMCID: PMC4785313  PMID: 26932140
PRIMARY CARE; Risk management < HEALTH SERVICES ADMINISTRATION & MANAGEMENT; PREVENTIVE MEDICINE; EPIDEMIOLOGY
13.  Community occupational therapy for people with dementia and family carers (COTiD-UK) versus treatment as usual (Valuing Active Life in Dementia [VALID] programme): study protocol for a randomised controlled trial 
Trials  2016;17:65.
Background
A community-based occupational therapy intervention for people with mild to moderate dementia and their family carers (Community Occupational Therapy in Dementia (COTiD)) was found clinically and cost effective in the Netherlands but not in Germany. This highlights the need to adapt and implement complex interventions to specific national contexts. The current trial aims to evaluate the United Kingdom-adapted occupational therapy intervention for people with mild to moderate dementia and their family carers living in the community (COTiD-UK) compared with treatment as usual.
Methods/Design
This study is a multi-centre, parallel-group, pragmatic randomised trial with internal pilot. We aim to allocate 480 pairs, with each pair comprising a person with mild to moderate dementia and a family carer, who provides at least 4 hours of practical support per week, at random between COTiD-UK and treatment as usual. We shall assess participants at baseline, 12 and 26 weeks, and by telephone at 52 and 78 weeks (first 40 % of recruits only) after randomisation. The primary outcome measure is the Bristol Activities of Daily Living Scale (BADLS) at 26 weeks. Secondary outcome measures will include quality of life, mood, and resource use. To assess intervention delivery, and client experience, we shall collect qualitative data via audio recordings of COTiD-UK sessions and conduct semi-structured interviews with pairs and occupational therapists.
Discussion
COTiD-UK is an evidence-based person-centred intervention that reflects the current priority to enable people with dementia to remain in their own homes by improving their capabilities whilst reducing carer burden. If COTiD-UK is clinically and cost effective, this has major implications for the future delivery of dementia services across the UK.
Trial registration
Current Controlled Trials ISRCTN10748953
Date of registration: 18 September 2014.
doi:10.1186/s13063-015-1150-y
PMCID: PMC4739339  PMID: 26841799
Occupational therapy; Dementia; Caregiver; Community; Psychosocial; Activities of daily living; Social participation; Quality of life; Cost-effectiveness
14.  Alleviating staff stress in care homes for people with dementia: protocol for stepped-wedge cluster randomised trial to evaluate a web-based Mindfulness- Stress Reduction course 
BMC Psychiatry  2015;15:317.
Background
There has been continuing change in the nature of care homes in the UK with 80 % of residents now living with some form of dementia or memory problem. Caring in this environment can be complex, challenging and stressful for staff; this can affect the quality of care provided to residents, lead to staff strain and burnout, and increase sickness, absence and turnover rates. It is therefore important to find interventions to increase the wellbeing of staff that will not only benefit staff themselves but also residents and care providers. Mindfulness training is known to be effective in treating a variety of physical and mental health conditions.
Methods and design
The study uses mixed methods centred on a stepped-wedge cluster randomised trial. Thirty care homes in Wales are implementing a brief web-based mindfulness training course, starting in random sequence. Four to ten consenting staff from each facility undertake the course and complete validated questionnaires at baseline and after eight and 20 weeks. We shall also interview a stratified sample of ten trained staff and analyse the transcripts thematically. The primary outcome is stress; secondary outcomes include job satisfaction, attitudes towards residents and sickness absence rates.
Discussion
With increasing numbers of people living with dementia in care homes and causing stress in their carers, it is important to evaluate support strategies for staff. Mindfulness-based therapies may be of potential benefit and need detailed examination.
Trial registration
ISRCTN registry. ISRCTN80487202. Registered 24 July 2013.
doi:10.1186/s12888-015-0703-7
PMCID: PMC4687382  PMID: 26691663
Dementia; Challenging behaviour; Care homes; Care staff; Stress; Mindfulness; Stepped-wedge cluster randomised trial
15.  Systematic Review and Meta-Regression of Factors Affecting Midline Incisional Hernia Rates: Analysis of 14 618 Patients 
PLoS ONE  2015;10(9):e0138745.
Background
The incidence of incisional hernias (IHs) following midline abdominal incisions is difficult to estimate. Furthermore recent analyses have reported inconsistent findings on the superiority of absorbable versus non-absorbable sutures.
Objective
To estimate the mean IH rate following midline laparotomy from the published literature, to identify variables that predict IH rates and to analyse whether the type of suture (absorbable versus non-absorbable) affects IH rates.
Methods
We undertook a systematic review according to PRISMA guidelines. We sought randomised trials and observational studies including patients undergoing midline incisions with standard suture closure. Papers describing two or more arms suitable for inclusion had data abstracted independently for each arm.
Results
Fifty-six papers, describing 83 separate groups comprising 14 618 patients, met the inclusion criteria. The prevalence of IHs after midline incision was 12.8% (range: 0 to 35.6%) at a weighted mean of 23.7 months. The estimated risk of undergoing IH repair after midline laparotomy was 5.2%. Two meta-regression analyses (A and B) each identified seven characteristics associated with increased IH rate: one patient variable (higher age), two surgical variables (surgery for AAA and either surgery for obesity surgery (model A) or using an upper midline incision (model B)), two inclusion criteria (including patients with previous laparotomies and those with previous IHs), and two circumstantial variables (later year of publication and specifying an exact significance level). There was no significant difference in IH rate between absorbable and non-absorbable sutures either alone or in conjunction with either regression analysis.
Conclusions
The IH rate estimated by pooling the published literature is 12.8% after about two years. Seven factors account for the large variation in IH rates across groups. However there is no evidence that suture type has an intrinsic effect on IH rates.
doi:10.1371/journal.pone.0138745
PMCID: PMC4577082  PMID: 26389785
16.  Development and validation of a new disease severity index: the Inflammatory Bowel Disease Index (IBDEX) 
Frontline Gastroenterology  2014;6(3):161-168.
Objective
To develop, validate and apply a generic clinical severity index applicable to all adult patients with inflammatory bowel disease (IBD).
Design
A review of the literature and an expert focus group consultation were carried out in order to draw out relevant items from existing literature. The new index was called the IBD Index (IBDEX). Standard psychometric analysis was carried out. The construct validity was assessed against biochemical markers, clinical and endoscopic indices. The new index was completed again within 6 weeks to check responsiveness and reproducibility.
Results
IBDEX was used to assess 255 adult patients with IBD (125 with Crohn’s disease and 130 with ulcerative colitis), and 64 patients were re-evaluated within 6 weeks. It had good internal consistency (Cronbach's α=0.79) and correlated very well with the Harvey Bradshaw Index (r=0.94), the Simple Clinical Colitis Activity Index (r=0.92), the Mayo Clinic Index (r=0.87) and the Simple Endoscopic Score (r=0.76), all with p values <0.05. IBDEX had a moderate but positive correlation with C reactive protein (r=0.51) and erythrocyte sedimentation rate (r=0.36) p values both <0.05. The test–retest reliability was good (intraclass correlation coefficient 0.97) and responsiveness ratio was 2.27.
Conclusions
IBDEX is the first properly validated Clinical Disease Severity Index in IBD. Our results showed that it is valid, reliable and reproducible and has the potential to be used in clinical practice.
doi:10.1136/flgastro-2014-100530
PMCID: PMC5369573
INFLAMMATORY BOWEL DISEASE; CROHN'S DISEASE; CROHN'S COLITIS; ULCERATIVE COLITIS
17.  Linked randomised controlled trials of face-to-face and electronic brief intervention methods to prevent alcohol related harm in young people aged 14–17 years presenting to Emergency Departments (SIPS junior) 
BMC Public Health  2015;15:345.
Background
Alcohol is a major global threat to public health. Although the main burden of chronic alcohol-related disease is in adults, its foundations often lie in adolescence. Alcohol consumption and related harm increase steeply from the age of 12 until 20 years. Several trials focusing upon young people have reported significant positive effects of brief interventions on a range of alcohol consumption outcomes. A recent review of reviews also suggests that electronic brief interventions (eBIs) using internet and smartphone technologies may markedly reduce alcohol consumption compared with minimal or no intervention controls.
Interventions that target non-drinking youth are known to delay the onset of drinking behaviours. Web based alcohol interventions for adolescents also demonstrate significantly greater reductions in consumption and harm among ‘high-risk’ drinkers; however changes in risk status at follow-up for non-drinkers or low-risk drinkers have not been assessed in controlled trials of brief alcohol interventions.
Design and methods
The study design comprises two linked randomised controlled trials to evaluate the effectiveness and cost-effectiveness of two intervention strategies compared with screening alone. One trial will focus on high-risk adolescent drinkers attending Emergency Departments (Eds) and the other will focus on those identified as low-risk drinkers or abstinent from alcohol but attending the same ED.
Our primary (null) hypothesis is similar for both trials: Personalised Feedback and Brief Advice (PFBA) and Personalised Feedback plus electronic Brief Intervention (eBI) are no more effective than screening alone in alcohol consumed at 12 months after randomisation as measured by the Time-Line Follow-Back 28-day version. Our secondary (null) hypothesis relating to economics states that PFBA and eBI are no more cost-effective than screening alone.
In total 1,500 participants will be recruited into the trials, 750 high-risk drinkers and 750 low-risk drinkers or abstainers. Participants will be randomised with equal probability, stratified by centre, to either a screening only control group or one of the two interventions: single session of PFBA or eBI. All participants will be eligible to receive treatment as usual in addition to any trial intervention. Individual participants will be followed up at 6 and 12 months after randomisation.
Discussion
The protocol represents an ambitious innovative programme of work addressing alcohol use in the adolescent population.
Trial registration
ISRCTN45300218. Registered 5th July 2014.
doi:10.1186/s12889-015-1679-4
PMCID: PMC4394590  PMID: 25886178
Adolescents; SBI; eBI; Emergency Department
18.  A novel mechanism of cochlear excitation during simultaneous stimulation and pressure relief through the round window 
The round window (RW) membrane provides pressure relief when the cochlea is excited by sound. Here, we report measurements of cochlear function from guinea pigs when the cochlea was stimulated at acoustic frequencies by movements of a miniature magnet which partially occluded the RW. Maximum cochlear sensitivity, corresponding to subnanometre magnet displacements at neural thresholds, was observed for frequencies around 20 kHz, which is similar to that for acoustic stimulation. Neural response latencies to acoustic and RW stimulation were similar and taken to indicate that both means of stimulation resulted in the generation of conventional travelling waves along the cochlear partition. It was concluded that the relatively high impedance of the ossicles, as seen from the cochlea, enabled the region of the RW not occluded by the magnet, to act as a pressure shunt during RW stimulation. We propose that travelling waves, similar to those owing to acoustic far-field pressure changes, are driven by a jet-like, near-field component of a complex pressure field, which is generated by the magnetically vibrated RW. Outcomes of research described here are theoretical and practical design principles for the development of new types of hearing aids, which use near-field, RW excitation of the cochlea.
doi:10.1098/rsif.2013.1120
PMCID: PMC3928943  PMID: 24501274
cochlear round window; guinea pig cochlea; cochlear excitation; active middle ear prosthesis; implantable hearing aid; near-field excitation
19.  Cost-effectiveness of steroid (methylprednisolone) injections versus anaesthetic alone for the treatment of Morton’s neuroma: economic evaluation alongside a randomised controlled trial (MortISE trial) 
Background
Morton’s neuroma is a common foot condition affecting health-related quality of life. Though its management frequently includes steroid injections, evidence of cost-effectiveness is sparse. So, we aimed to evaluate whether steroid injection is cost-effective in treating Morton’s neuroma compared with anaesthetic injection alone.
Methods
We undertook incremental cost-effectiveness and cost-utility analyses from the perspective of the National Health Service, alongside a patient-blinded pragmatic randomised trial in hospital-based orthopaedic outpatient clinics in Edinburgh, UK. Of the original randomised sample of 131 participants with Morton’s neuroma (including 67 controls), economic analysis focused on 109 (including 55 controls). Both groups received injections guided by ultrasound. We estimated the incremental cost per point improvement in the area under the curve of the Foot Health Thermometer (FHT-AUC) until three months after injection. We also conducted cost-utility analyses using European Quality of life-5 Dimensions–3 Levels (EQ-5D-3L), enhanced by the Foot Health Thermometer (FHT), to estimate utility and thus quality-adjusted life years (QALYs).
Results
The unit cost of an ultrasound-guided steroid injection was £149. Over the three months of follow-up, the mean cost of National Health Service resources was £280 for intervention participants and £202 for control participants – a difference of £79 [bootstrapped 95% confidence interval (CI): £18 to £152]. The corresponding estimated incremental cost-effectiveness ratio was £32 per point improvement in the FHT-AUC (bootstrapped 95% CI: £7 to £100). If decision makers value improvement of one point at £100 (the upper limit of this CI), there is 97.5% probability that steroid injection is cost-effective. As EQ-5D-3L seems unresponsive to changes in foot health, we based secondary cost-utility analysis on the FHT-enhanced EQ-5D. This estimated the corresponding incremental cost-effectiveness ratio as £6,400 per QALY. Over the recommended UK threshold, ranging from £20,000 to £30,000 per QALY, there is 80%-85% probability that steroid injection is cost-effective.
Conclusions
Steroid injections are effective and cost-effective in relieving foot pain measured by the FHT for three months. However, cost-utility analysis was initially inconclusive because the EQ-5D-3L is less responsive than the FHT to changes in foot health. By using the FHT to enhance the EQ-5D, we inferred that injections yield good value in cost per QALY.
Trial registration
Current Controlled Trials ISRCTN13668166
doi:10.1186/s13047-015-0064-y
PMCID: PMC4347553  PMID: 25737743
Morton’s neuroma; Interdigital plantar nerves; Methylprednisolone; Steroid injection; Foot health; Cost-effectiveness analysis; Cost-utility analysis; Quality-adjusted life years
20.  Modifications in Wheelchair Propulsion Technique with Speed 
Objective
Repetitive loading of the upper limb joints during manual wheelchair (WC) propulsion (WCP) has been identified as a factor that contributes to shoulder pain, leading to loss of independence and decreased quality of life. The purpose of this study was to determine how individual manual WC users with paraplegia modify propulsion mechanics to accommodate expected increases in reaction forces (RFs) generated at the pushrim with self-selected increases in WCP speed.
Methods
Upper extremity kinematics and pushrim RFs were measured for 40 experienced manual WC users with paraplegia while propelling on a stationary ergometer at self-selected free and fast propulsion speeds. Upper extremity kinematics and kinetics were compared within subject between propulsion speeds. Between group and within-subject differences were determined (α = 0.05).
Results
Increased propulsion speed was accompanied by increases in RF magnitude (22 of 40, >10 N) and shoulder net joint moment (NJM, 15 of 40, >10 Nm) and decreases in pushrim contact duration. Within-subject comparison indicated that 27% of participants modified their WCP mechanics with increases in speed by regulating RF orientation relative to the upper extremity segments.
Conclusions
Reorientation of the RF relative to the upper extremity segments can be used as an effective strategy for mitigating rotational demands (NJM) imposed on the shoulder at increased propulsion speeds. Identification of propulsion strategies that individuals can use to effectively accommodate for increases in RFs is an important step toward preserving musculoskeletal health of the shoulder and improving health-related quality of life.
doi:10.3389/fbioe.2015.00171
PMCID: PMC4620433  PMID: 26579513
biomechanics; spinal cord injury; shoulder pain; wheelchair; rehabilitation; propulsion; joint kinetics; upper extremity
21.  Support and Assessment for Fall Emergency Referrals (SAFER 1): Cluster Randomised Trial of Computerised Clinical Decision Support for Paramedics 
PLoS ONE  2014;9(9):e106436.
Objective
To evaluate effectiveness, safety and cost-effectiveness of Computerised Clinical Decision Support (CCDS) for paramedics attending older people who fall.
Design
Cluster trial randomised by paramedic; modelling.
Setting
13 ambulance stations in two UK emergency ambulance services.
Participants
42 of 409 eligible paramedics, who attended 779 older patients for a reported fall.
Interventions
Intervention paramedics received CCDS on Tablet computers to guide patient care. Control paramedics provided care as usual. One service had already installed electronic data capture.
Main Outcome Measures
Effectiveness: patients referred to falls service, patient reported quality of life and satisfaction, processes of care.
Safety
Further emergency contacts or death within one month.
Cost-Effectiveness
Costs and quality of life. We used findings from published Community Falls Prevention Trial to model cost-effectiveness.
Results
17 intervention paramedics used CCDS for 54 (12.4%) of 436 participants. They referred 42 (9.6%) to falls services, compared with 17 (5.0%) of 343 participants seen by 19 control paramedics [Odds ratio (OR) 2.04, 95% CI 1.12 to 3.72]. No adverse events were related to the intervention. Non-significant differences between groups included: subsequent emergency contacts (34.6% versus 29.1%; OR 1.27, 95% CI 0.93 to 1.72); quality of life (mean SF12 differences: MCS −0.74, 95% CI −2.83 to +1.28; PCS −0.13, 95% CI −1.65 to +1.39) and non-conveyance (42.0% versus 36.7%; OR 1.13, 95% CI 0.84 to 1.52). However ambulance job cycle time was 8.9 minutes longer for intervention patients (95% CI 2.3 to 15.3). Average net cost of implementing CCDS was £208 per patient with existing electronic data capture, and £308 without. Modelling estimated cost per quality-adjusted life-year at £15,000 with existing electronic data capture; and £22,200 without.
Conclusions
Intervention paramedics referred twice as many participants to falls services with no difference in safety. CCDS is potentially cost-effective, especially with existing electronic data capture.
Trial Registration
ISRCTN Register ISRCTN10538608
doi:10.1371/journal.pone.0106436
PMCID: PMC4162545  PMID: 25216281
22.  Medication Monitoring in a Nurse-Led Respiratory Outpatient Clinic: Pragmatic Randomised Trial of the West Wales Adverse Drug Reaction Profile 
PLoS ONE  2014;9(5):e96682.
Objective
To assess the clinical effect of medication monitoring using the West Wales Adverse Drug Reaction (ADR) Profile for Respiratory Medicine.
Design
Single-site parallel-arm pragmatic trial using stratified randomisation.
Setting
Nurse-led respiratory outpatient clinic in general hospital in South Wales.
Participants
54 patients with chronic respiratory disease receiving bronchodilators, corticosteroids or leukotriene receptor antagonists.
Intervention
Following initial observation of usual nursing care, we allocated participants at random to receive at follow up: either the West Wales ADR Profile for Respiratory Medicine in addition to usual care (‘intervention arm’ with 26 participants); or usual care alone (‘control arm’ with 28 participants).
Main Outcome Measures
Problems reported and actions taken.
Results
We followed up all randomised participants, and analysed data in accordance with treatment allocated. The increase in numbers of problems per participant identified at follow up was significantly higher in the intervention arm, where the median increase was 20.5 [inter-quartile range (IQR) 13–26], while that in the control arm was −1 [−3 to +2] [Mann-Whitney U test: z = 6.28, p<0.001]. The increase in numbers of actions per participant taken at follow up was also significantly higher in the intervention arm, where the median increase was 2.5 [1]–[4] while that in the control arm was 0 [−1.75 to +1] [Mann-Whitney U test: z = 4.40, p<0.001].
Conclusion
When added to usual nursing care, the West Wales ADR Profile identified more problems and prompted more nursing actions. Our ADR Profile warrants further investigation as a strategy to optimise medication management.
Trial Registration
Controlled-trials.com ISRCTN10386209
doi:10.1371/journal.pone.0096682
PMCID: PMC4010491  PMID: 24798210
23.  Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT) 
BMJ Open  2014;4(4):e005091.
Introduction
Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC.
Methods and analysis
Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants’ scores, analysed by Cox regression. Secondary outcome measures include: the CCQ—an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures—EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants’ views on therapies for acute severe UC and healthcare professionals’ views on the two drugs and their administration.
Ethics and dissemination
The Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals.
Trial registration number
ISRCTN: 22663589; EudraCT number: 2008-001968-36
doi:10.1136/bmjopen-2014-005091
PMCID: PMC4010821  PMID: 24785401
Ulcerative colitis; Acute severe; Steroid refractory; Ciclosporin; Infliximab; Randomised controlled trial
24.  Mindfulness-Based Cognitive Therapy for Preventing Relapse in Recurrent Depression: A Randomized Dismantling Trial 
Objective: We compared mindfulness-based cognitive therapy (MBCT) with both cognitive psychological education (CPE) and treatment as usual (TAU) in preventing relapse to major depressive disorder (MDD) in people currently in remission following at least 3 previous episodes. Method: A randomized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU, CPE plus TAU, and TAU alone, and data were analyzed for the 255 (93%; MBCT = 99, CPE = 103, TAU = 53) retained to follow-up. MBCT was delivered in accordance with its published manual, modified to address suicidal cognitions; CPE was modeled on MBCT, but without training in meditation. Both treatments were delivered through 8 weekly classes. Results: Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up, hazard ratio for MBCT vs. CPE = 0.88, 95% CI [0.58, 1.35]; for MBCT vs. TAU = 0.69, 95% CI [0.42, 1.12]. However, severity of childhood trauma affected relapse, hazard ratio for increase of 1 standard deviation = 1.26 (95% CI [1.05, 1.50]), and significantly interacted with allocated treatment. Among participants above median severity, the hazard ratio was 0.61, 95% CI [0.34, 1.09], for MBCT vs. CPE, and 0.43, 95% CI [0.22, 0.87], for MBCT vs. TAU. For those below median severity, there were no such differences between treatment groups. Conclusion: MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma, but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression.
doi:10.1037/a0035036
PMCID: PMC3964149  PMID: 24294837
mindfulness-based cognitive therapy; major depression; relapse prevention; suicidality; childhood trauma
25.  Paramedic-supplied ‘Take Home’ Naloxone: protocol for cluster randomised feasibility study 
BMJ Open  2014;4(3):e004712.
Introduction
‘Take Home’ Naloxone (THN) kits for use by peers in the event of an opioid overdose may reduce further overdose and deaths, but distribution through Drugs Services may not reach those at highest risk. Attendance by paramedics at emergency calls for patients who have suffered an overdose presents an opportunity to distribute THN kits. In this feasibility study we will assess the acceptability of this intervention, and gather data to inform definitive trial planning.
Methods and analysis
Cluster randomised trial with staggered allocation of paramedics (clusters) to groups. We will invite paramedics in an urban area of south Wales, UK to take part. We will randomly allocate those that accept to training sessions during the first 4 months of the trial. Patients attended by paramedics who have been trained and issued THN kits will fall into the intervention group. Patients attended by paramedics following usual practice (until they receive their training and THN kits) will fall into the control group. We will gather data about processes and outcomes of care: numbers of patients eligible for intervention, offered and accepted THN, attended emergency department, suffered further overdose, died within 3 months and about follow-up rates: numbers of patients consented, completed (postal or telephone) questionnaire. We will gather qualitative data about acceptability to patients and paramedics through interviews and focus groups.
Ethics and dissemination
Ethical approval for this study was granted on 7 December 2011, by South East Wales Research Ethics Committee, Panel C. Results of this study will be reported through peer-reviewed scientific journals, conference presentations and internal organisational report. We will also seek to report our findings through local and national substance misuse networks and publications.
Trial registration number
ISRCTN98216498.
doi:10.1136/bmjopen-2013-004712
PMCID: PMC3963087  PMID: 24650810
Accident & Emergency Medicine; Public Health

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