Microfluidic Diffusional Sizing (MDS) Measurements of Secretory Neutralizing Antibody Affinity Against SARS-CoV-2.

SARS-CoV-2 has rampantly spread around the globe and continues to cause unprecedented loss through ongoing waves of (re)infection. Increasing our understanding of the protection against infection with SARS-CoV-2 is critical to ending the pandemic. Serological assays have been widely used to assess immune responses, but secretory antibodies, the essential first line of defense, have been studied to only a limited extent. Of particular interest and importance are neutralizing antibodies, which block the binding of the spike protein of SARS-CoV-2 to the human receptor angiotensin-converting enzyme-2 (ACE2) and thus are essential for immune defense. Here, we employed Microfluidic Diffusional Sizing (MDS), an immobilization-free technology, to characterize neutralizing antibody affinity to SARS-CoV-2 spike receptor-binding domain (RBD) and spike trimer in saliva. Affinity measurement was obtained through a contrived sample and buffer using recombinant SARS-CoV-2 RBD and monoclonal antibody. Limited saliva samples demonstrated that MDS applies to saliva neutralizing antibody measurement. The ability to disrupt a complex of ACE2-Fc and spike trimer is shown. Using a quantitative assay on the patient sample, we determined the affinity and binding site concentration of the neutralizing antibodies.

The inhibitor protein IF1 from mammalian mitochondria inhibits ATP hydrolysis but not ATP synthesis by the ATP synthase complex.

The hydrolytic activity of the ATP synthase in bovine mitochondria is inhibited by a protein called IF1, but bovine IF1 has no effect on the synthetic activity of the bovine enzyme in mitochondrial vesicles in the presence of a proton motive force. In contrast, it has been suggested based on indirect observations that human IFI inhibits both the hydrolytic and synthetic activities of the human ATP synthase and that the activity of human IF1 is regulated by the phosphorylation of Ser-14 of mature IF1. Here, we have made both human and bovine IF1 which are 81 and 84 amino acids long, respectively, and identical in 71.4% of their amino acids and have investigated their inhibitory effects on the hydrolytic and synthetic activities of ATP synthase in bovine submitochondrial particles. Over a wide range of conditions, including physiological conditions, both human and bovine IF1 are potent inhibitors of ATP hydrolysis, with no effect on ATP synthesis. Also, substitution of Ser-14 with phosphomimetic aspartic and glutamic acids had no effect on inhibitory properties, and Ser-14 is not conserved throughout mammals. Therefore, it is unlikely that the inhibitory activity of mammalian IF1 is regulated by phosphorylation of this residue.

Sodium channel-inhibiting drugs and cancer-specific survival: a population-based study of electronic primary care data.

OBJECTIVES: Antiepileptic and antiarrhythmic drugs inhibit voltage-gated sodium (Na+) channels (VGSCs), and preclinical studies show that these medications reduce tumour growth, invasion and metastasis. We investigated the association between VGSC inhibitor use and survival in patients with breast, bowel and prostate cancer. DESIGN: Retrospective cohort study. SETTING: Individual electronic primary healthcare records extracted from the Clinical Practice Research Datalink. PARTICIPANTS: Records for 132 996 patients with a diagnosis of breast, bowel or prostate cancer. OUTCOME MEASURES: Adjusted Cox proportional hazards regression was used to analyse cancer-specific survival associated with exposure to VGSC inhibitors. Exposure to non-VGSC-inhibiting antiepileptic medication and other non-VGSC blockers were also considered. Drug exposure was treated as a time-varying covariate to account for immortal time bias. RESULTS: During 1 002 225 person-years of follow-up, there were 42 037 cancer-specific deaths. 53 724 (40.4%) patients with cancer had at least one prescription for a VGSC inhibitor of interest. Increased risk of cancer-specific mortality was associated with exposure to this group of drugs (HR 1.59, 95% CI 1.56 to 1.63, p<0.001). This applied to VGSC-inhibiting tricyclic antidepressants (HR 1.61, 95% CI 1.50 to 1.65, p<0.001), local anaesthetics (HR 1.49, 95% CI 1.43 to 1.55, p<0.001) and anticonvulsants (HR 1.40, 95% CI 1.34 to 1.48, p<0.001) and persisted in sensitivity analyses. In contrast, exposure to VGSC-inhibiting class 1c and 1d antiarrhythmics was associated with significantly improved cancer-specific survival (HR 0.75, 95% CI 0.64 to 0.88, p<0.001 and HR 0.54, 95% CI 0.33 to 0.88, p=0.01, respectively). CONCLUSIONS: Association between VGSC inhibitor use and mortality in patients with cancer varies according to indication. Exposure to VGSC-inhibiting antiarrhythmics, but not anticonvulsants, supports findings from preclinical data, with improved survival. However, additional confounding factors may underlie these associations, highlighting the need for further study.

Continuation of Opioid Therapy at Transitions of Care in Critically Ill Patients.

PURPOSE: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation. METHODS: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge). RESULTS: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively). CONCLUSIONS: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.

Exploring the Impact of Primary Care Physician Burnout and Well-Being on Patient Care: A Focus Group Study.

OBJECTIVES: The aims of the study were (1) to explore whether primary care physicians (general practitioners [GPs]) perceive burnout and well-being to impact on the quality and safety of patient care and (2) to determine potential mechanisms behind these associations. METHOD: Five focus groups with 25 practicing GPs were conducted in England, either in the participants' practice or in a private meeting room outside of their workplace.An interview schedule with prompts was followed with questions asking how participants perceive GP burnout and poor well-being could impact on patient care delivery. Audio recordings were transcribed verbatim and analyzed using thematic analysis. RESULTS: General practitioners believed that poor well-being and burnout affect the quality of care patients receive through reducing doctors' abilities to empathize, to display positive attitudes and listening skills, and by increasing the number of inappropriate referrals made. Participants also voiced that burnout and poor well-being can have negative consequences for patient safety, through a variety of mechanisms including reduced cognitive functioning and decision-making abilities, a lack of headspace, and fatigue. Furthermore, it was suggested that the relationship between well-being/burnout and mistakes is likely to be circular. CONCLUSIONS: Further research is needed to ascertain the validity of these perceptions. If found, physicians, healthcare organizations, and policy makers should examine how they can improve physician well-being and prevent burnout, because this may be a route to ensure high-quality and safe patient care.

The experiences of, and need for, palliative care for people with motor neurone disease and their informal caregivers: A qualitative systematic review.

BACKGROUND: Despite being a terminal neurodegenerative disease, the role of palliative care is less recognised for motor neurone disease than for other life-limiting conditions. Understanding the experiences of, and need for, palliative care for patients and carers is key to configuring optimal policy and healthcare services. AIM: To explore the experiences of, and need for, palliative care of people with motor neurone disease and their informal carers across the disease trajectory. DESIGN: A systematic review of qualitative research conducted using Thematic Synthesis - PROSPERO registration CRD42017075311. DATA SOURCES: Four electronic databases were searched (MEDLINE, CINAHL, PsycINFO, Social Science Citation Index) using terms for motor neurone disease, amyotrophic lateral sclerosis, palliative care, and qualitative research, from inception to November 2018. Included papers were data extracted and assessed for quality. RESULTS: A total of 41 papers were included, representing the experiences of 358 people with motor neurone disease and 369 caregivers. Analytical themes were developed detailing patients' and carers' experiences of living with motor neurone disease and of palliative care through its trajectory including response to diagnosis, maintaining control, decision-making during deterioration, engaging with professionals, planning for end-of-life care, bereavement. CONCLUSION: The review identified a considerable literature exploring the care needs of people with motor neurone disease and their carers; however, descriptions of palliative care were associated with the last days of life. Across the disease trajectory, clear points were identified where palliative care input could enhance patient and carer experience of the disease, particularly at times of significant physical change.

Extrinsic conditions influence the self-association and structure of IF1, the regulatory protein of mitochondrial ATP synthase.

The endogenous inhibitor of ATP synthase in mitochondria, called IF1, conserves cellular energy when the proton-motive force collapses by inhibiting ATP hydrolysis. Around neutrality, the 84-amino-acid bovine IF1 is thought to self-assemble into active dimers and, under alkaline conditions, into inactive tetramers and higher oligomers. Dimerization is mediated by formation of an antiparallel α-helical coiled-coil involving residues 44-84. The inhibitory region of each monomer from residues 1-46 is largely α-helical in crystals, but disordered in solution. The formation of the inhibited enzyme complex requires the hydrolysis of two ATP molecules, and in the complex the disordered region from residues 8-13 is extended and is followed by an α-helix from residues 14-18 and a longer α-helix from residue 21, which continues unbroken into the coiled-coil region. From residues 21-46, the long α-helix binds to other α-helices in the C-terminal region of predominantly one of the ß-subunits in the most closed of the three catalytic interfaces. The definition of the factors that influence the self-association of IF1 is a key to understanding the regulation of its inhibitory properties. Therefore, we investigated the influence of pH and salt-types on the self-association of bovine IF1 and the folding of its unfolded region. We identified the equilibrium between dimers and tetramers as a potential central factor in the in vivo modulation of the inhibitory activity and suggest that the intrinsically disordered region makes its inhibitory potency exquisitely sensitive and responsive to physiological changes that influence the capability of mitochondria to make ATP.

Association of GP wellbeing and burnout with patient safety in UK primary care: a cross-sectional survey.

BACKGROUND: GPs have particularly high levels of burnout and poor wellbeing. Although both are associated with poorer safety outcomes within secondary care, there have been no quantitative studies investigating this within primary care. Furthermore, little is known about how occupational demands, burnout and wellbeing, and patient safety are all associated. AIM: To investigate whether occupational variables (demands and support) are associated with patient safety outcomes in general practice through their influence on GP burnout and wellbeing. DESIGN AND SETTING: Cross-sectional survey in the UK between March 2016 and August 2017. METHOD: A total of 232 practising GPs completed an online or paper survey measuring burnout, wellbeing, occupational demands and support, and patient safety. RESULTS: In all, 93.8% of GPs were classed as likely to be suffering from a minor psychiatric disorder, 94.7% as suffering from mild (22.0%) or severe (72.7%) exhaustion, and 86.8% as having mild (37.9%) or severe (48.9%) disengagement. Structural equation modelling (SEM) analyses showed that spending a higher number of hours on administrative tasks and on call, and feeling less supported in their practice, was associated with lower wellbeing, which in turn was associated with a higher likelihood of having reported a near miss in the previous 3 months. A higher number of hours spent on administrative tasks, a higher number of patients seen per day, and feeling less supported were associated with higher burnout levels, which in turn was associated with worse perceptions of safety. CONCLUSION: To improve patient safety within general practice changes could be made at both practice and individual levels to promote a healthier work environment for staff and patients.

SWATted away: the challenging experience of setting up a programme of SWATs in paediatric trials.

BACKGROUND: Randomised controlled trials are considered the best method for determining the effectiveness and safety of health interventions. Trials involving children are essential to ensure that treatments are safe and effective. However, many trials, in both adult and paediatric populations, do not achieve recruitment targets and/or maintain retention of participants, which can lead to a reduction in the internal and external validity of the results. Identifying ways of improving trial efficiency are important in order to increase the successful completion of trials. MAIN BODY: A 'Study Within A Trial' (SWAT) is a self-contained study embedded within an ongoing trial, which aims to establish evidence to improve the management and delivery of trials in healthcare. Increasing numbers of SWATs have been undertaken in recent years yet very few within paediatric trials. Herein, we describe some of the challenges with undertaking a programme of SWATs within paediatric clinical trials in the UK. The TRECA (TRials Engagement in Children and Adolescents) study involves developing multimedia websites for use within paediatric trials to provide recruitment information to children, young people and their families about the clinical trial. Challenges encountered included governance issues such as host trial approval processes and sharing of anonymised data, funding issues for host trials, internet quality and accessibility within the healthcare setting, and ethical concerns associated with SWAT methodology. We believe the ethical concerns are more pronounced in the paediatric setting, perhaps because of the fewer SWATs undertaken in these settings or that a more cautious, risk-averse approach to undertaking research with children is taken. CONCLUSION: SWATs are becoming increasingly common to provide an evidence base for methods to improve trial efficiency. However, we encountered a number of unanticipated challenges to embedding TRECA that have not been previously reported within the scientific literature. We believe that, if these issues were addressed through wider promotion and explanation of undertaking SWATs involving all key stakeholders, as well as by exploration of alternative funding models for SWATs, this would enable more streamlined, appropriate and timely processes for SWATs and a stronger evidence base for what works to increase trial efficiency. TRIAL REGISTRATION: The TRECA study is registered on ISRCTN, ID 73136092 . Registered on 24 August 2016.

Supporting children and young people when making decisions about joining clinical trials: qualitative study to inform multimedia website development.

OBJECTIVES: To understand stakeholders' views regarding the content and design of paediatric clinical trial multimedia websites. To describe how this knowledge informed the development of the multimedia websites. DESIGN: Qualitative study comprising two rounds of interviews or focus groups, with thematic analysis of interview transcripts. PARTICIPANTS: Sixty-two people (21 children and young people with long-term health conditions, 24 parents and 17 professionals). SETTING: One UK children's hospital and one UK Young Persons' Advisory Group. RESULTS: When asked what was important in deciding whether to join a trial, children, young people and parents prioritised information about what participation would involve, what the trial was testing, potential benefits and risks of participation and knowing they could leave the trial if they later changed their minds. Young people and parents trusted trial teams to follow regulatory and quality requirements and therefore did not think such information was a priority for the websites, although logos of trusted organisations could lend credibility. Professionals largely concurred with these views. Children and young people advised on the importance of designing the multimedia website to ensure its appearance, tone and wording suited the intended audience and on using animated characters to facilitate children's engagement. CONCLUSIONS: Our study provides insights into the information that families value when deciding about healthcare trial participation. It provides guidance on the design of information resources to appeal to children and young people, while also being acceptable to parents and professionals who are often gatekeepers of children's access to information. Our findings will be of use to others developing similar multimedia websites. We report specific information needs and new visual preferences that are not usually addressed in printed trial information. Our work illustrates what qualitative research and participatory design practices can contribute to the development of information resources more generally. TRIAL REGISTRATION NUMBER: ISRCTN73136092; Pre-results.

More than one-third of systematic reviews did not fully report the adverse events outcome.

OBJECTIVES: The aim of the study was to assess the risk for adverse events reporting bias in systematic reviews of health care interventions registered to PROSPERO. STUDY DESIGN AND SETTING: This study was a retrospective cohort study. Systematic review protocols in PROSPERO were screened and included if they focused on a health care intervention and listed an adverse event as either a primary or secondary outcome. The included systematic reviews were assessed to determine the completeness of reporting for the adverse event outcomes. Any discrepancies in reporting between protocol and review were recorded. RESULTS: Of 1,376 protocols for systematic reviews sifted, only 524 (38%) listed adverse events outcomes. One hundred eighty-six protocols were published in 2017 and 2018, of which 146 were included in our analysis. Among the included systematic reviews, 65% (95/146) fully reported the adverse event outcomes as intended by the protocol, 8% (12/146) entirely excluded the adverse event outcome, and the remaining 27% (39/146) either partially reported or changed the adverse event outcomes. CONCLUSION: Sixty-two percent of reviews did not mention adverse events in their protocol, and 35% of PROSPERO-registered systematic reviews had discrepant outcome reporting between the protocol and publication. The findings suggest a need for the encouraged use of harms reporting guidelines and further research into adverse events reporting bias.

Safety netting for primary care: evidence from a literature review.

BACKGROUND: Ensuring patient safety is vital in primary care. One mechanism to increase patient safety is through a practice known as safety netting. Safety netting is widely recommended in national guidelines; however, a variety of definitions exist with no consensus on when safety netting should be used and what advice or actions it should contain. AIM: This study aimed to identify different definitions of safety netting to provide conceptual clarity and propose a common approach to safety netting in primary care. DESIGN AND SETTING: Literature review and evidence synthesis of international articles relating to safety netting in primary care. METHOD: An electronic database and grey-literature search was conducted using terms around the theme of safety netting with broad inclusion criteria. RESULTS: A total of 47 studies were included in the review. Safety netting was defined as a consultation technique to communicate uncertainty, provide patient information on red-flag symptoms, and plan for future appointments to ensure timely re-assessment of a patient's condition. Safety-netting advice may include information on the natural history of the illness, advice on worrying symptoms to look out for, and specific information on how and when to seek help. In addition to advice within the consultation, safety netting includes follow-up of investigations and hospital referrals. Safety netting was considered to be particularly important when consulting with children, the acutely unwell, patients with multimorbidity, and those with mental health problems. CONCLUSION: Safety netting is more than solely the communication of uncertainty within a consultation. It should include plans for follow-up as well as important administrative aspects, such as the communication of test results and management of hospital letters.

User testing digital, multimedia information to inform children, adolescents and their parents about healthcare trials.

Digital, multimedia information resources (MMIs) containing text, video, animation and pictures are a promising alternative to written participant information materials designed to inform children, adolescents and parents about healthcare trials, but little research has tested whether they are fit for purpose. This study employed a consecutive groups design and user testing questionnaire to assess whether participants were able to find and understand key information in multimedia resources. Two rounds of testing were completed. In each round, seven children aged 7-11 tested the MMI with a parent; six adolescents aged 12-17 and seven parents tested the MMI independently. After round 1, the resources were revised based on participant scores, behaviour and feedback. Round 1 identified problems with 2/10 information items (length of trial and use of insulin pump); only 3/20 participants could locate all information items without difficulty. After revisions, 14/20 participants scored a clear round. Information comprehension was high: 96% understood in round 1 and 99% in round 2. Participant feedback on the multimedia resources was positive, although presentation preferences varied. User testing was employed successfully with children, adolescents and parents to identify issues with, and improve, multimedia resources developed to inform potential healthcare trial participants.

"The more you know, the more you realise it is really challenging to do": Tensions and uncertainties in person-centred support for people with long-term conditions.

OBJECTIVE: To identify and examine tensions and uncertainties in person-centred approaches to self-management support - approaches that take patients seriously as moral agents and orient support to enable them to live (and die) well on their own terms. METHODS: Interviews with 26 UK clinicians about working with people with diabetes or Parkinson's disease, conducted within a broader interdisciplinary project on self-management support. The analysis reported here was informed by philosophical reasoning and discussions with stakeholders. RESULTS: Person-centred approaches require clinicians to balance tensions between the many things that can matter in life, and their own and each patient's perspectives on these. Clinicians must ensure that their supportive efforts do not inadvertently disempower people. When attending to someone's particular circumstances and perspectives, they sometimes face intractable uncertainties, including about what is most important to the person and what, realistically, the person can or could do and achieve. The kinds of professional judgement that person-centred working necessitates are not always acknowledged and supported. CONCLUSION: Practical and ethical tensions are inherent in person-centred support and need to be better understood and addressed. PRACTICE IMPLICATIONS: Professional development and service improvement initiatives should recognise these tensions and uncertainties and support clinicians to navigate them well.

What can patients tell us about the quality and safety of hospital care? Findings from a UK multicentre survey study.

BACKGROUND: Patient safety measurement remains a global challenge. Patients are an important but neglected source of learning; however, little is known about what patients can add to our understanding of safety. We sought to understand the incidence and nature of patient-reported safety concerns in hospital. METHODS: Feedback about the experience of safety within hospital was gathered from 2471 inpatients as part of a multicentre, waitlist cluster randomised controlled trial of an intervention, undertaken within 33 wards across three English NHS Trusts, between May 2013 and September 2014. Patient volunteers, supported by researchers, developed a classification framework of patient-reported safety concerns from a random sample of 231 reports. All reports were then classified using the patient-developed categories. Following this, all patient-reported safety concerns underwent a two-stage clinical review process for identification of patient safety incidents. RESULTS: Of the 2471 inpatients recruited, 579 provided 1155 patient-reported incident reports. 14 categories were developed for classification of reports, with communication the most frequently occurring (22%), followed by staffing issues (13%) and problems with the care environment (12%). 406 of the total 1155 patient incident reports (35%) were classified by clinicians as a patient safety incident according to the standard definition. 1 in 10 patients (264 patients) identified a patient safety incident, with medication errors the most frequently reported incident. CONCLUSIONS: Our findings suggest that patients can provide insight about safety that complements existing patient safety measurement, with a frequency of reported patient safety incidents that is similar to those obtained via case note review. However, patients provide a unique perspective about hospital safety which differs from and adds to current definitions of patient safety incidents. TRIAL REGISTRATION NUMBER: ISRCTN07689702; pre-results.

Strategies to improve general practitioner well-being: findings from a focus group study.

Background: Primary care physicians are particularly prone to high levels of burnout and poor well-being. Despite this, no qualitative studies have specifically investigated the best ways to improve well-being and prevent burnout in primary care physicians. Previous interventions within primary care have been person-oriented and mainly focused on mindfulness, but there has been no prior research on whether general practitioners (GPs) deem this to be the best approach. Objectives: To explore strategies that could improve GP well-being and reduce or prevent burnout, based on GP perceptions of the workplace factors that affect their levels of well-being and burnout. Methods: Five focus groups were conducted, with 25 GPs (locums, salaried, trainees, and partners) in the UK, between September 2015 and February 2016. Focus groups took place in GP practices and private meeting rooms. Discussions were centered on the workplace factors that they perceived to influence their well-being, along with strategies that they use either personally, or as a practice, to try and prevent burnout. Furthermore, strategies that could feasibly be implemented by individuals and practices to improve well-being, as well as changes that are needed by groups or organizations that are external to their practice (e.g., the government) to improve the working conditions, were explored. Thematic analysis was conducted on the transcripts. Results: Based on the contributors to burnout and workplace well-being that the participants identified, the following feasible strategies were suggested: compulsory daily coffee breaks, increasing self- and organizational awareness of the risks of burnout and mentoring or buddy systems. System-level organizational changes were voiced as vital, however, to improve the well-being of all primary care physicians. Increasing resources seemed to be the ideal solution, to allow for more administrative staff and GPs. Conclusion: These strategies merit further consideration by researchers, physicians, healthcare organizations and policy makers both in the UK and beyond. Failure to do so may result in healthcare staff becoming even more burntout, potentially leading to a loss of doctors from the workforce.

Patient-reported safety incidents as a new source of patient safety data: an exploratory comparative study in an acute hospital in England.

Objectives To compare a new co-designed, patient incident reporting tool with three established methods of detecting patient safety incidents and identify if the same incidents are recorded across methods. Method Trained research staff collected data from inpatients in nine wards in one university teaching hospital during their stay. Those classified as patient safety incidents were retained. We then searched for patient safety incidents in the corresponding patient case notes, staff incident reports and reports to the Patient Advice and Liaison Service specific to the study wards. Results In the nine wards, 329 patients were recruited to the study, of which 77 provided 155 patient reports. From these, 68 patient safety incidents were identified. Eight of these were also identified from case note review, five were also identified in incident reports, and two were also found in the records of a local Patient Advice and Liaison Service. Reports of patients covered a range of events from their immediate environment, involving different health professionals and spanning the entire spectrum of care. Conclusion Patient safety incidents reported by patients are unlikely to be found through other established methods of incident detection. When hospitalized patients are asked about their care, they can provide a unique perspective on patient safety. Co-designed, real-time reporting could be a helpful addition to existing methods of gathering patient safety intelligence.

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain: A randomized trial (ATLAS).

OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients. METHODS: An economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure-the Northwick Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions.

Developing and evaluating multimedia information resources to improve engagement of children, adolescents, and their parents with trials (TRECA study): Study protocol for a series of linked randomised controlled trials.

BACKGROUND: Randomised controlled trials are widely established as the best method for testing health interventions whilst minimising bias. However, recruitment and subsequent retention of children and adolescents in healthcare trials is challenging. Participant information sheets are often lengthy and difficult to read and understand. Presenting key information using multimedia may help to overcome these limitations and better support young people and their parents in deciding whether to participate in a clinical trial. METHODS: The TRECA (TRials Engagement in Children and Adolescents) study has two phases. The first phase involves a qualitative study with children and adolescents and their parents to inform the development of multimedia information resources and iterative user testing to refine the resources. The second phase will embed the use of the multimedia information resources into six host trials in the United Kingdom. Patients and parents approached to participate in the host trials will be randomly allocated to either use the multimedia information resource in conjunction with standard participant information sheets, the multimedia information resource alone, or the standard participant information sheets alone. The primary outcome will be the effect of the multimedia information resources on recruitment into trials. Other outcomes measured include the effect of multimedia information resources on retention of participants into the host trials and the impact on family members' decision-making processes, when compared to standard participant information sheets alone. DISCUSSION: This study will inform whether multimedia information resources, when developed using participatory design principles, are able to increase recruitment and retention of children and adolescents into trials. There is also the potential for patients to make better informed decisions through the use of multimedia information resources. The multimedia information resources also have the potential to assist with providing information on other healthcare decisions outside of clinical trials. TRIAL REGISTRATION: ISRCTN registry: ISRCTN73136092 (doi: 10.1186/ISRCTN73136092 ). Registered on 24 August 2016.