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.

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.

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.

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.

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.

Implementing electronic records in NHS secondary care organizations in England: policy and progress since 1998.

Background: A number of different policies have aimed to introduce electronic records into National Health Service (NHS) secondary care organizations in England over recent years. There has been little formal attempt to explore the overall impact of these policies (as opposed to evaluations of individual initiatives) and how they have developed and progressed over time. Sources of data: National NHS IT policy documents and evaluations of national NHS IT policy between 1998 and 2015. Areas of agreement: There has been limited progress in implementing integrated electronic records in secondary organizations since 1998. Areas of controversy: The management and execution of NHS IT policy has been poor, with over ambitious aims contributing to the limited success. Growing points: Detailed guidance on how to implement electronic records in secondary care organizations is required. The ambitions of current policy should be revisited. Areas timely for developing further research: Research exploring the costs and benefits of different approaches to introducing electronic records is needed.

We need to talk about purpose: a critical interpretive synthesis of health and social care professionals' approaches to self-management support for people with long-term conditions.

BACKGROUND: Health policies internationally advocate 'support for self-management', but it is not clear how the promise of the concept can be fulfilled. OBJECTIVE: To synthesize research into professional practitioners' perspectives, practices and experiences to help inform a reconceptualization of support for self-management. DESIGN: Critical interpretive synthesis using systematic searches of literature published 2000-2014. FINDINGS: We summarized key insights from 164 relevant papers in an annotated bibliography. The literature illustrates striking variations in approaches to support for self-management and interpretations of associated concepts. We focused particularly on the somewhat neglected question of the purpose of support. We suggest that this can illuminate and explain important differences between narrower and broader approaches. Narrower approaches support people to manage their condition(s) well in terms of disease control. This purpose can underpin more hierarchical practitioner-patient communication and more limited views of patient empowerment. It is often associated with experiences of failure and frustration. Broader approaches support people to manage well with their condition(s). They can keep work on disease control in perspective as attention focuses on what matters to people and how they can be supported to shape their own lives. Broader approaches are currently less evident in practice. DISCUSSION AND CONCLUSION: Broader approaches seem necessary to fulfil the promise of support for self-management, especially for patient empowerment. A commitment to enable people to live well with long-term conditions could provide a coherent basis for the forms and outcomes of support that policies aspire to. The implications of such a commitment need further attention.

"Was that a success or not a success?": a qualitative study of health professionals' perspectives on support for people with long-term conditions.

BACKGROUND: Support for self-management (SSM) is a prominent strand of health policy internationally, particularly for primary care. It is often discussed and evaluated in terms of patients' knowledge, skills and confidence, health-related behaviours, disease control or risk reduction, and service use and costs. However, these goals are limited, both as guides to professional practice and as indicators of its quality. In order to better understand what it means to support self-management well, we examined health professionals' views of success in their work with people with long-term conditions. This study formed part of a broader project to develop a conceptual account of SSM that can reflect and promote good practice. METHODS: Semi-structured individual interviews (n = 26) and subsequent group discussions (n = 5 groups, 30 participants) with diverse health professionals working with people with diabetes and/or Parkinson's disease in NHS services in London, northern England or Scotland. The interviews explored examples of more and less successful work, ways of defining success, and ideas about what facilitates success in practice. Subsequent group discussions considered the practical implications of different accounts of SSM. Interviews and group discussions were audio-recorded, transcribed and analysed thematically. RESULTS: Participants identified a wide range of interlinked aspects or elements of success relating to: health, wellbeing and quality of life; how well people (can) manage; and professional-patient relationships. They also mentioned a number of considerations that have important implications for assessing the quality of their own performance. These considerations in part reflect variations in what matters and what is realistically achievable for particular people, in particular situations and at particular times, as well as the complexity of questions of attribution. CONCLUSIONS: A nuanced assessment of the quality of support for self-management requires attention to the responsiveness of professional practice to a wide, complex range of personal and situational states, as well as actions and interactions over time. A narrow focus on particular indicators can lead to insensitive or even perverse judgements and perhaps counterproductive effects. More open, critical discussions about both success and the assessment of quality are needed to facilitate good professional practice and service improvement initiatives.

Exploring the implementation of an electronic record into a maternity unit: a qualitative study using Normalisation Process Theory.

BACKGROUND: To explore the benefits, barriers and disadvantages of implementing an electronic record system (ERS). The extent that the system has become 'normalised' into routine practice was also explored. METHODS: Qualitative semi-structured interviews were conducted with 19 members of NHS staff who represented a variety of staff groups (doctors, midwives of different grades, health care assistants) and wards within a maternity unit at a NHS teaching hospital. Interviews were conducted during the first year of the phased implementation of ERS and were analysed thematically. The four mechanisms of Normalisation Process Theory (NPT) (coherence, cognitive participation, collective action and reflexive monitoring) were adapted for use within the study and provided a theoretical framework to interpret the study's findings. RESULTS: Coherence (participants' understanding of why the ERS has been implemented) was mixed - whilst those involved in ERS implementation anticipated advantages such as improved access to information; the majority were unclear why the ERS was introduced. Participants' willingness to engage with and invest time into the ERS (cognitive participation) depended on the amount of training and support they received and their willingness to change from paper to electronic records. Collective action (the extent the ERS was used) may be influenced by whether participants perceived there to be benefits associated with the system. Whilst some individuals reported benefits such as improved legibility of records, others felt benefits were yet to emerge. The parallel use of paper and the lack of integration of electronic systems within and between the trust and other healthcare organisations hindered ERS use. When appraising the ERS (reflexive monitoring) participants perceived the system to negatively impact the patient-clinician relationship, time and patient safety. CONCLUSIONS: Despite expectations that the ERS would have a number of advantages, its implementation was perceived to have a range of disadvantages and only a limited number of 'clinical benefits'. The study highlights the complexity of implementing electronic systems and the associated longevity before they can become 'embedded' into routine practice. Through the identification of barriers to the employment of electronic systems this process could be streamlined with the avoidance of any potential detriment to clinical services.

Smokeless Tobacco Supply Chain in South Asia: A Comparative Analysis Using the WHO Framework Convention on Tobacco Control.

INTRODUCTION: Most South Asian countries are signatories to the WHO Framework Convention for Tobacco Control (FCTC). However, there is little information on the extent to which FCTC standards are effectively implemented for controlling smokeless tobacco (SLT)-used by over 250 million people in the region. We assessed the feasibility of a novel approach based on interviewing the key actors of SLT supply chain and analyzing its findings using standards set by FCTC. METHODS: Using a snowball-sampling technique, we interviewed point-of-sale vendors, wholesale retailers, manufacturers, raw-tobacco retailers, and farmers involved in the supply chain of SLT in Bangladesh, Nepal, and Pakistan. Using a structured-questionnaire, participants were asked about their customer profiles; product types; marketing practices; suppliers; profit margins, awareness and adherence to legislation. RESULTS: We recruited 72% (130/180) of all supply chain actors approached. Findings indicate several loopholes in the existing taxation, regulatory, and inspection systems. A significant proportion of smuggled and counterfeit SLT products are available in the market. Most SLT products are sold without recommended warnings, information on their ingredients, and manufacturers' details. There appear to be no restrictions on sale of SLT products to minors. On the other hand, there are also several incentives built-in the supply chain that makes tobacco farming, SLT manufacturing, and its sale a profitable business. CONCLUSIONS: Our novel approach to study SLT control was successful in identifying and interviewing actors involved in its supply chain. The analysis using FCTC could provide valuable information to policy makers and enable them to effectively regulate SLT products.

The patient reporting and action for a safe environment (PRASE) intervention: a feasibility study.

BACKGROUND: There is growing interest in the role of patients in improving patient safety. One such role is providing feedback on the safety of their care. Here we describe the development and feasibility testing of an intervention that collects patient feedback on patient safety, brings together staff to consider this feedback and to plan improvement strategies. We address two research questions: i) to explore the feasibility of the process of systematically collecting feedback from patients about the safety of care as part of the PRASE intervention; and, ii) to explore the feasibility and acceptability of the PRASE intervention for staff, and to understand more about how staff use the patient feedback for service improvement. METHOD: We conducted a feasibility study using a wait-list controlled design across six wards within an acute teaching hospital. Intervention wards were asked to participate in two cycles of the PRASE (Patient Reporting & Action for a Safe Environment) intervention across a six-month period. Participants were patients on participating wards. To explore the acceptability of the intervention for staff, observations of action planning meetings, interviews with a lead person for the intervention on each ward and recorded researcher reflections were analysed thematically and synthesised. RESULTS: Recruitment of patients using computer tablets at their bedside was straightforward, with the majority of patients willing and able to provide feedback. Randomisation of the intervention was acceptable to staff, with no evidence of differential response rates between intervention and control groups. In general, ward staff were positive about the use of patient feedback for service improvement and were able to use the feedback as a basis for action planning, although engagement with the process was variable. Gathering a multidisciplinary team together for action planning was found to be challenging, and implementing action plans was sometimes hindered by the need to co-ordinate action across multiple services. DISCUSSION: The PRASE intervention was found to be acceptable to staff and patients. However, before proceeding to a full cluster randomised controlled trial, the intervention requires adaptation to account for the difficulties in implementing action plans within three months, the need for a facilitator to support the action planning meetings, and the provision of training and senior management support for participating ward teams. CONCLUSIONS: The PRASE intervention represents a promising method for the systematic collection of patient feedback about the safety of hospital care.

Alexander Technique Lessons or Acupuncture Sessions for Persons With Chronic Neck Pain: A Randomized Trial.

BACKGROUND: Management of chronic neck pain may benefit from additional active self-care-oriented approaches. OBJECTIVE: To evaluate clinical effectiveness of Alexander Technique lessons or acupuncture versus usual care for persons with chronic, nonspecific neck pain. DESIGN: Three-group randomized, controlled trial. (Current Controlled Trials: ISRCTN15186354). SETTING: U.K. primary care. PARTICIPANTS: Persons with neck pain lasting at least 3 months, a score of at least 28% on the Northwick Park Questionnaire (NPQ) for neck pain and associated disability, and no serious underlying pathology. INTERVENTION: 12 acupuncture sessions or 20 one-to-one Alexander lessons (both 600 minutes total) plus usual care versus usual care alone. MEASUREMENTS: NPQ score (primary outcome) at 0, 3, 6, and 12 months (primary end point) and Chronic Pain Self-Efficacy Scale score, quality of life, and adverse events (secondary outcomes). RESULTS: 517 patients were recruited, and the median duration of neck pain was 6 years. Mean attendance was 10 acupuncture sessions and 14 Alexander lessons. Between-group reductions in NPQ score at 12 months versus usual care were 3.92 percentage points for acupuncture (95% CI, 0.97 to 6.87 percentage points) (P = 0.009) and 3.79 percentage points for Alexander lessons (CI, 0.91 to 6.66 percentage points) (P = 0.010). The 12-month reductions in NPQ score from baseline were 32% for acupuncture and 31% for Alexander lessons. Participant self-efficacy improved for both interventions versus usual care at 6 months (P < 0.001) and was significantly associated (P < 0.001) with 12-month NPQ score reductions (acupuncture, 3.34 percentage points [CI, 2.31 to 4.38 percentage points]; Alexander lessons, 3.33 percentage points [CI, 2.22 to 4.44 percentage points]). No reported serious adverse events were considered probably or definitely related to either intervention. LIMITATION: Practitioners belonged to the 2 main U.K.-based professional associations, which may limit generalizability of the findings. CONCLUSION: Acupuncture sessions and Alexander Technique lessons both led to significant reductions in neck pain and associated disability compared with usual care at 12 months. Enhanced self-efficacy may partially explain why longer-term benefits were sustained. PRIMARY FUNDING SOURCE: Arthritis Research UK.

The impact of electronic records on patient safety: a qualitative study.

BACKGROUND: Our aim was to explore NHS staff perceptions and experiences of the impact on patient safety of introducing a maternity system. METHODS: Qualitative semi-structured interviews were conducted with 19 members of NHS staff who represented a variety of staff groups (doctors, midwives, health care assistants), staff grades (consultant and midwife grades) and wards within a maternity unit. Participants represented a single maternity unit at a NHS teaching hospital in the North of England. Interviews were conducted during the first 12 months of the system being implemented and were analysed thematically. RESULTS: Participants perceived there to be an elevated risk to patient safety during the system's implementation. The perceived risks were attributed to a range of social and technical factors. For example, poor system design and human error which resulted in an increased potential for missing information and inputting error. CONCLUSIONS: The first 12 months of introducing the maternity system was perceived to and in some cases had already caused actual risk to patient safety. Trusts throughout the NHS are facing increasing pressure to become paperless and should be aware of the  potential adverse impacts on patient safety that can occur when introducing electronic systems. Given the potential for increased risk identified, recommendations for further research and for NHS trusts introducing electronic systems are proposed.

Lost in hospital: a qualitative interview study that explores the perceptions of NHS inpatients who spent time on clinically inappropriate hospital wards.

BACKGROUND: Prior research suggests that the placement of patients on clinically inappropriate hospital wards may increase the risk of experiencing patient safety issues. OBJECTIVE: To explore patients' perspectives of the quality and safety of the care received during their inpatient stay on a clinically inappropriate hospital ward. DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS AND SETTING: Nineteen patients who had spent time on at least one clinically inappropriate ward during their hospital stay at a large NHS teaching hospital in England. RESULTS: Patients would prefer to be treated on the correct specialty ward, but it is generally accepted that this may not be possible. When patients are placed on inappropriate wards, they may lack a sense of belonging. Participants commented on potential failings in communication, medical staff availability, nurses' knowledge and the resources available, each of which may contribute to unsafe care. CONCLUSIONS: Patients generally acknowledge the need for placement on inappropriate wards due to demand for inpatient beds, but may report dissatisfaction in terms of preference and belonging. Importantly, patients recount issues resulting from this placement that may compromise their safety. Hospital managers should be encouraged to appreciate this insight and potential threat to safe practice and where possible avoid inappropriate ward transfers and admissions. Where such admissions are unavoidable, staff should take action to address the gaps in safety of care that have been identified.

Arrangement of subunits in intact mammalian mitochondrial ATP synthase determined by cryo-EM.

Mitochondrial ATP synthase is responsible for the synthesis of ATP, a universal energy currency in cells. Whereas X-ray crystallography has revealed the structure of the soluble region of the complex and the membrane-intrinsic c-subunits, little is known about the structure of the six other proteins (a, b, f, A6L, e, and g) that comprise the membrane-bound region of the complex in animal mitochondria. Here, we present the structure of intact bovine mitochondrial ATP synthase at ∼18 Šresolution by electron cryomicroscopy of single particles in amorphous ice. The map reveals that the a-subunit and c(8)-ring of the complex interact with a small contact area and that the b-subunit spans the membrane without contacting the c(8)-ring. The e- and g-subunits extend from the a-subunit density distal to the c(8)-ring. The map was calculated from images of a preparation of the enzyme solubilized with the detergent dodecyl maltoside, which is visible in electron cryomicroscopy maps. The structure shows that the micelle surrounding the complex is curved. The observed bend in the micelle of the detergent-solubilized complex is consistent with previous electron tomography experiments and suggests that monomers of ATP synthase are sufficient to produce curvature in lipid bilayers.

Implementing electronic patient record systems (EPRs) into England's acute, mental health and community care trusts: a mixed methods study.

BACKGROUND: Our aim was to explore the approaches to and the challenges and benefits of implementing Electronic Patient Record systems (EPRs) into NHS acute, mental health and community care hospitals throughout England. METHODS: A mixed methods approach was adopted that comprised an online survey (n = 59) and semi-structured telephone interviews (n = 8) with chief information officers (or heads of EPR projects) at NHS trusts throughout England. Survey analysis was descriptive, whilst the qualitative interviews were analysed thematically. RESULTS: A range of devices and approaches to implementing EPRs were described with 32 % of survey respondents utilising a best of breed approach. Interviewees' perceived and expected benefits of implementing an EPR included efficiency, availability and accessibility of clinical information, and patient safety. Key challenges to EPR implementation were securing clinician involvement, difficulties posed by government and national policy and limited availability of financial and human resources. CONCLUSIONS: There was no single approach regarding the approaches taken to implementing EPRs among participating English NHS trusts, with various benefits and challenges cited. Policymakers and researchers need to provide clearer guidance for trusts at various stages of implementation ensuring intelligence is shared across England's NHS trusts.

Assessing quality of life with incontinence.

This article reports on an evaluation of commonly recommended questionnaires to measure symptom severity and quality of life in women with urinary incontinence. Three questionnaires outperform the others and a robust assessment concludes that the International Consultation of Incontinence Questionnaire is the most practical tool for the busy practitioner.

An evaluative review of questionnaires recommended for the assessment of quality of life and symptom severity in women with urinary incontinence.

AIMS AND OBJECTIVES: To provide an up-to-date assessment of the quality of commonly recommended questionnaires for measuring symptom severity and quality of life in women with urinary incontinence and also to consider their application to practice. BACKGROUND: Urinary incontinence is a common problem for women. In addition to various physical symptoms, there is a known effect on quality of life. Psychometrically robust questionnaires are reported to be the best way to measure an individual's perceptions of symptom severity and quality of life, and a number of different ones are recommended for use in international and national guidance, which can be confusing for clinicians. Moreover, there are concerns over the applicability of some of these instruments in clinical practice. DESIGN: An evaluative review was carried out examining selected questionnaires measuring symptom severity and/or quality of life. METHODS: Selection of questionnaires for inclusion in the review was based on the recommendations of evidence-based guidance, followed by systematic scrutiny of the characteristics of the individual recommended questionnaires. RESULTS: Thirteen questionnaires were included in the review, of which three appeared to 'outperform' the remainder in terms of their psychometric properties and other characteristics. CONCLUSIONS: This review provides the most up-to-date and comprehensive analysis of the quality and applicability of the included questionnaires and offers the practitioner advice on which to select for use in practice. RELEVANCE TO CLINICAL PRACTICE: This review aims to help the practitioner choose a questionnaire based on a sound evaluation of the quality of the questionnaire and its applicability to the clinical setting.

Could breaks reduce general practitioner burnout and improve safety? A daily diary study.

BACKGROUND: Rates of burnout are currently at record high levels, and GPs experience higher burnout than many other specialties. Organisational interventions may reduce burnout, but few studies have investigated these in primary care. AIM: The current study investigated whether breaks, both with and without social interactions, were associated with burnout and patient safety perceptions in GPs. DESIGN: A within-subjects, interval contingent, quantitative daily diary design. SETTING: UK GP practices. METHOD: Participants completed questionnaires at baseline measuring demographic variables, burnout and patient safety perceptions. They then completed a questionnaire in the evening each day for a week which captured whether they had taken a break that day, whether it involved a positive social interaction, burnout (comprising subscales of disengagement and exhaustion), positive and negative affect and patient safety perceptions. The data were analysed using hierarchical linear modelling to assess same-day and next-day associations. RESULTS: We included 241 responses from 58 GPs for analysis. Taking at least one break (involving any or no social interactions) was associated with lower disengagement that day and lower exhaustion the next day. Taking at least one break involving a positive interaction was associated with 1) lower disengagement, exhaustion, overall burnout and negative affect on the same day, as well as higher positive affect and improved perceptions of patient safety, and 2) lower exhaustion and improved patient safety perceptions on the next day. CONCLUSION: Organizing daily team or practice breaks where staff can socialise may help to reduce burnout and improve perceptions of patient safety.

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.