Early phase cell therapy trials face many barriers to successful, timely completion. To optimise the conduct of a planned clinical trial of mesenchymal stem cell (MSC) therapy for chronic stroke, we sought patient and physician views on possible barriers and enablers that may influence their participation.
Semistructured interview study.
Patients were recruited from three rehabilitation centres in Ontario, Canada; physicians were recruited from across Canada through snowball sampling.
Thirteen chronic stroke patients (patients who had experienced a stroke at least 3 months prior; 10 male, 3 female) and 15 physicians (stroke physiatrists; 9 male, 6 female) participated in our interview study. Data adequacy was reached after 13 patient interviews and 13 physician interviews.
Interview guides and directed content analysis were based on the Theoretical Domains Framework (TDF). Interviews were coded, and relevant themes were identified.
Most patients were optimistic about participating in an MSC therapy clinical trial, and many expressed interest in participating, even if it was a randomised controlled trial with the possibility of being allocated to a placebo group. However, the method of administration of cells (intravascular preferred to intracerebral) and goal of the trial (efficacy preferred to safety) may influence their intention to participate. All physicians expressed interest in screening for the trial, though many stated they were less motivated to contribute to a safety trial. Physicians also identified several time-related barriers and the need for resources to ensure feasibility.
This novel application of the TDF helped identify key potential barriers and enablers prior to conducting a clinical trial of MSC therapy for stroke. This will be used to refine the design and conduct of our trial. A similar approach may be adopted by other investigators considering early phase cell therapy trials.
To synthesise international evidence for demand, use and outcomes of primary care out-of-hours health services (OOHS).
Systematic scoping review.
CINAHL; Medline; PsyARTICLES; PsycINFO; SocINDEX; and Embase from 1995 to 2019.
English language studies in UK or similar international settings, focused on services in or directly impacting primary care.
105 studies included: 54% from mainland Europe/Republic of Ireland; 37% from UK. Most focused on general practitioner-led out-of-hours cooperatives. Evidence for increasing patient demand over time was weak due to data heterogeneity, infrequent reporting of population denominators and little adjustment for population sociodemographics. There was consistent evidence of higher OOHS use in the evening compared with overnight, at weekends and by certain groups (children aged 65, women, those from socioeconomically deprived areas, with chronic diseases or mental health problems). Contact with OOHS was driven by problems perceived as urgent by patients. Respiratory, musculoskeletal, skin and abdominal symptoms were the most common reasons for contact in adults; fever and gastrointestinal symptoms were the most common in the under-5s. Frequent users of daytime services were also frequent OOHS users; difficulty accessing daytime services was also associated with OOHS use. There is some evidence to suggest that OOHS colocated in emergency departments (ED) can reduce demand in EDs.
Policy changes have impacted on OOHS over the past two decades. While there are generalisable lessons, a lack of comparable data makes it difficult to judge how demand has changed over time. Agreement on collection of OOHS data would allow robust comparisons within and across countries and across new models of care. Future developments in OOHS should also pay more attention to the relationship with daytime primary care and other services.
To determine the clinical effectiveness and safety of the Orve + wrap® thermal blanket.
Inadvertent perioperative hypothermia is a common problem in postanaesthetic care units and can have significant effects on patients’ postoperative morbidity. Despite its commercial availability, there is no clinical evidence on the effectiveness of Orve + wrap®.
A single centre prospective, open‐label, noninferiority randomised controlled trial.
Postoperative hypothermic (35.0–35.9°C) patients who had undergone elective surgery were randomised to receive either Orve + wrap® or Forced Air Warming during their PACU stay. Patient temperatures were recorded every 10 min using zero‐heat‐flux thermometry. This study is reported using CONSORT Extension checklist for noninferiority and equivalence trials.
Between December 2016–October 2018, 129 patients were randomised to receive either Orve + wrap® blanket (n = 65, 50.3%) or Forced Air Warming (n = 64, 49.7%). The mean 60‐min postoperative temperature of patients receiving Orve + wrap® blanket was 36.2 and 36.3°C for the patients receiving Forced Air Warming. The predefined noninferiority margin of a mean difference in temperature of 0.3°C was not reached between the groups at 60 min. Additionally, there were no statistical differences between adverse event rates across these groups.
In the context of this study, warming patients with the Orve + wrap® was noninferior to Forced Air Warming. There were comparable rates of associated postoperative consequences of warming (shivering, hypotension, arrhythmias or surgical site infections), between the groups.
The Orve + wrap® potentially provides an alternative warming method to Forced Air Warming for patients requiring short‐term postoperative warming. However, there are still a number of unknowns regarding the Orve + wrap® performance and further exploration is required.
Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID.
We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome – chronic HCV prevalence in PWID – is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a ‘virtual cohort’ of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes.
Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.
Services are being encouraged to provide postdiagnostic treatment to those with dementia but the availability of evidence-based interventions following diagnosis has not kept pace with increase in demand. To address this need, the Journeying through Dementia (JtD) intervention was created. A randomised controlled trial (RCT), based on a pilot study, is in progress.
The RCT is a pragmatic, two-arm, parallel group trial designed to test the clinical and cost-effectiveness of JtD compared with usual care. Recruitment will be through NHS services, third sector organisations and Join Dementia Research. The sample size is 486 randomised (243 to usual care and 243 to the intervention usual care). Participants can choose to ask a friend or relative (supporter) to become involved in the study. The primary outcome measure for participants is Dementia-Related Quality of Life (DEMQOL), collected at baseline and at 8 months’ postrandomisation. Secondary outcome measures will be collected from participants and supporters at those visits. Participants will also be followed up at 12 months’ postrandomisation with a reduced set of measures. A process evaluation will be conducted through qualitative and fidelity substudies. Analyses will compare the two arms of the trial on an intention to treat as allocated basis. The primary analyses will compare the mean DEMQOL scores of the participants at 8 months between the two study arms. A cost-effectiveness analysis will consider the incremental cost per Quality Adjusted Life Years of the intervention compared with usual care. Qualitative and fidelity substudies will be analysed through framework analysis and fidelity assessment tools respectively.
REC and HRA approval were obtained. A Data Monitoring and Ethics Committee has been constituted. Dissemination will be via publications, conferences and social media. Intervention materials will be made open access.
Compelling evidence supports multiple benefits of physical activity (PA) even in small bursts. Less than 50% of Americans achieve recommended PA levels, lower still for individuals living with chronic illness or disease.
The purpose of this study was to develop and evaluate the feasibility and preliminary effects of 3‐min follow‐along video scenarios to promote brief episodes of low–moderate levels of PA among individuals with chronic diseases.
Guided by our previous studies and self‐efficacy theory, the program (WellMe in 3© for Patients) was modeled after another program developed for healthcare staff. An advisory panel and a health and fitness expert guided the creation of twelve 3‐min video scenarios that included two individuals living with chronic illness and a fitness leader who guided the PA scenarios and how to adapt them based on limitations. The 12 scenarios included 3 min of aerobic activities, stretching, or balance. Preliminary pilot effects were measured among 39 patients living with chronic conditions for one month. Standardized instruments were used to measure PA levels, PA self‐efficacy (SE), and quality of life (QoL); usability and satisfaction were assessed using researcher‐developed tools. Descriptive and inferential statistics were used to evaluate change over time.
Twelve video scenarios were created tailored to persons with chronic illness. Thirty‐nine participants piloted the program, reporting an average of two chronic conditions. Baseline QoL scores were lower than normative data, self‐efficacy scores were low‐to‐moderate, and PA levels were very low. Participants averaged using one video per day. 62% of participants provided complete self‐reported pre‐ and post‐QoL and SE data and 41% provided pre‐ and post‐PA (accelerometer) data. Significant improvements were found for general health and energy scores, and trends were found for self‐efficacy scores. PA levels were highly variable with nonsignificant increases from baseline. Effect sizes were low–moderate for several measures. About 79% of participants rated program “Very good”; all recommended the program.
Physical activity has multiple health benefits for all people including those living with chronic conditions. Even short bouts of physical activity have health benefits. A program of 3‐min follow‐along PA videoclips for individuals living with chronic disease holds promise for clinicians and researchers.
The rapid increase in apartment construction in Australia has raised concerns about the impacts of poorly designed and located buildings on resident health and well-being. While apartment design policies exist, their content varies across jurisdictions and evidence on their impact on health and well-being is lacking. This cross-sectional observational study (2017–2021) aims to generate empirical evidence to guide policy decisions on apartment development and help to create healthy, equitable higher-density communities. Objectives include to benchmark the implementation of health-promoting apartment design requirements and to identify associations between requirements and resident health and well-being outcomes.
Eligible buildings in three Australian cities with different apartment design guidelines will be stratified by area disadvantage and randomly selected (~n=99). Building architects, developers and local governments will be approached to provide endorsed development plans from which apartment and building design features will be extracted. Additional data collection includes a resident survey (~n=1000) to assess environmental stressors and health and well-being impacts and outcomes, and geographic information systems measures of the neighbourhood. The study has 85% power to detect a difference of 0.5 SD in the primary outcome of mental well-being (Warwick-Edinburgh Mental Well-being Scale) at a 5% level of significance. Analyses will compare policy compliance and health-promoting design features between cities and area disadvantage groups. Regression models will test whether higher policy compliance (overall and by design theme) is associated with better health and well-being, and the relative contribution of the neighbourhood context.
Human Research Ethics Committees of RMIT University (CHEAN B 21146-10/17) and the University of Western Australia (RA/4/1/8735) approved the study protocol. In addition to academic publications, the collaboration will develop specific health-promoting indicators to embed into the monitoring of apartment design policy implementation and impact, and co-design research dissemination materials to facilitate uptake by decision makers.
To develop and psychometrically test the needs of children questionnaire (NCQ), a new instrument to measure school‐aged children's self‐reported psychosocial physical and emotional needs in paediatric wards.
This is an instrument development study based on recommendations for developing a reliable and valid questionnaire.
The NCQ was developed over three phases between February 2013–April 2017 and included item generation; content adequacy assessment; questionnaire administration; factor analysis; internal consistency assessment and construct validity. Psychometric properties were assessed after 193 school‐aged children completed the needs of children's questionnaire in four paediatric areas in Australia and New Zealand.
The development and validation of the NCQ over two countries resulted in a 16‐item, four‐category tool to measure the self‐reported importance and fulfilment of school‐aged children's needs in hospital. Cronbach's alpha for the combined samples was 0.93.
The NCQ bridges a gap to measure the level of importance and fulfilment of school‐aged children's self‐reported needs in hospital. Future testing and validation is needed in other paediatric areas and countries.
The 16‐item NCQ is a valid measure to evaluate if the quality of care delivered and received in hospital is in line with what children self‐report as important and required and to date indicates good usability and utility. Child self‐reports are essential to inform healthcare delivery, policy, research and theory development from a child and family‐centred care lens that honours the United Nations Convention on the Rights of the Child and the best interests of the child.
To estimate the association between (1) visual impairment (VI) and (2) eye disease and 6-year mortality risk within a cohort of elderly Kenyan people.
The baseline of the Nakuru Posterior Segment Eye Disease Study was formed from a population-based survey of 4318 participants aged ≥50 years, enrolled in 2007–2008. Ophthalmic and anthropometric examinations were undertaken on all participants at baseline, and a questionnaire was administered, including medical and ophthalmic history. Participants were retraced in 2013–2014 for a second examination. Vital status was recorded for all participants through information from community members. Cumulative incidence of mortality, and its relationship with baseline VI and types of eye disease was estimated. Inverse probability weighting was used to adjust for non-participation.
Cumulative incidence of mortality in relation to VI level at baseline.
Of the baseline sample, 2170 (50%) were re-examined at follow-up and 407 (10%) were known to have died (adjusted risk of 11.9% over 6 years). Compared to those with normal vision (visual acuity (VA) ≥6/12, risk=9.7%), the 6-year mortality risk was higher among people with VI (
Visual acuity was related to 6-year mortality risk in this cohort of elderly Kenyan people, potentially because both VI and mortality are related to ageing and risk factors for NCD.
Low quality of life is common in cancer survivors. Increasing physical activity, improving diet, supporting psychological well-being and weight loss can improve quality of life in several cancers and may limit relapse. The aim of the randomised controlled trial outlined in this protocol is to examine whether a digital intervention (Renewed), with or without human support, can improve quality of life in cancer survivors. Renewed provides support for increasing physical activity, managing difficult emotions, eating a healthier diet and weight management.
A randomised controlled trial is being conducted comparing usual care, access to Renewed or access to Renewed with brief human support. Cancer survivors who have had colorectal, breast or prostate cancer will be identified and invited through general practice searches and mail-outs. Participants are asked to complete baseline measures immediately after screening and will then be randomised to a study group; this is all completed on the Renewed website. The primary outcome is quality of life measured by the European Organization for Research and Treatment of Cancer QLQ-c30. Secondary outcomes include anxiety and depression, fear of cancer recurrence, general well-being, enablement and items relating to costs for a health economics analysis. Process measures include perceptions of human support, intervention usage and satisfaction, and adherence to behavioural changes. Qualitative process evaluations will be conducted with patients and healthcare staff providing support.
The trial has been approved by the NHS Research Ethics Committee (Reference 18/NW/0013). The results of this trial will be published in peer-reviewed journals and through conference presentations.
Emergency intubation of children with abnormal respiratory or cardiac physiology is a high-risk procedure and associated with a high incidence of adverse events including hypoxemia. Successful emergency intubation is dependent on inter-related patient and operator factors. Preoxygenation has been used to maximise oxygen reserves in the patient and to prolong the safe apnoeic time during the intubation phase. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) prolongs the safe apnoeic window for a safe intubation during elective intubation. We designed a clinical trial to test the hypothesis that THRIVE reduces the frequency of adverse and hypoxemic events during emergency intubation in children and to test the hypothesis that this treatment is cost-effective compared with standard care.
The Kids THRIVE trial is a multicentre randomised controlled trial performed in participating emergency departments and paediatric intensive care units. 960 infants and children aged 0–16 years requiring emergency intubation for all reasons will be enrolled and allocated to THRIVE or control in a 1:1 allocation with stratification by site, age (7 years) and operator (junior and senior). Children allocated to THRIVE will receive weight appropriate transnasal flow rates with 100% oxygen, whereas children in the control arm will not receive any transnasal oxygen insufflation. The primary outcomes are defined as follows: (1) hypoxemic event during the intubation phase defined as SpO2
Ethics approval for the protocol and consent process has been obtained (HREC/16/QRCH/81). The trial has been actively recruiting since May 2017. The study findings will be submitted for publication in a peer-reviewed journal.
Efforts are needed to reduce gendered inequities and improve health and well-being for women. Patient-centred care (PCC), an approach that informs and engages patients in their own health, is positively associated with improved care delivery, experiences and outcomes. This study aimed to describe how PCC for women (PCCW) has been conceptualised in research.
We conducted a theoretical rapid review of PCCW in four health conditions. We searched MEDLINE, EMBASE, CINAHL, SCOPUS, Cochrane Library and Joanna Briggs index for English-language articles published from January 2008 to February 2018 inclusive that investigated PCC and involved at least 50% women aged 18 or older. We analysed findings using a six-domain PCC framework, and reported findings with summary statistics and narrative descriptions.
After screening 2872 unique search results, we reviewed 51 full-text articles, and included 14 (five family planning, three preventive care, four depression, one cardiovascular disease and one rehabilitation). Studies varied in how they assessed PCC. None examined all six PCC framework domains; least evaluated domains were addressing emotions, managing uncertainty and enabling self-management. Seven studies that investigated PCC outcomes found a positive association with appropriate health service use, disease remission, health self-efficacy and satisfaction with care. Differing views about PCC between patients and physicians, physician PCC attitudes and geographic affluence influenced PCC. No studies evaluated the influence of patient characteristics or tested interventions to support PCCW.
There is a paucity of research that has explored or evaluated PCCW in the conditions of interest. We excluded many studies because they arbitrarily labelled many topics as PCC, or simply concluded that PCC was needed. More research is needed to fully conceptualise and describe PCCW across different characteristics and conditions, and to test interventions that improve PCCW. Policies and incentives may also be needed to stimulate greater awareness and delivery of PCCW.
To explore the acceptability of peer mentoring for people with a traumatic brain injury (TBI) in New Zealand.
This is a qualitative descriptive study exploring the experiences reported by mentees and mentors taking part in a feasibility study of peer mentoring. Interviews with five mentees and six mentors were carried out. Data were analysed using conventional content analysis.
The first mentoring session took place predischarge from the rehabilitation unit. The remaining five sessions took place in mentees’ homes or community as preferred.
Twelve people with TBI took part: six mentees (with moderate to severe TBI; aged 18–46) paired with six mentors (moderate to severe TBI >12 months previously; aged 21–59). Pairing occurred before mentee discharge from postacute inpatient brain injury rehabilitation. Mentors had been discharged from rehabilitation following a TBI between 1 and 5 years previously.
The peer mentoring programme consisted of up to six face-to-face sessions between a mentee and a mentor over a 6-month period. The sessions focused on building rapport, exploring hopes for and supporting participation after discharge through further meetings and supported community activities.
Data were synthesised into one overarching theme: making sense of recovery. This occurred through the sharing of experiences and stories; was pivotal to the mentoring relationship; and appeared to benefit both mentees and mentors. Mentors were perceived as valued experts because of their personal experience of injury and recovery, and could provide support in ways that were different from that provided by clinicians or family members. Mentors required support to manage the uncertainties inherent in the role.
The insight mentors developed through their own lived experience established them as a trusted and credible source of hope and support for people re-engaging in the community post-TBI. These findings indicate the potential for mentoring to result in positive outcomes.