Falsification of home rapid antigen lateral flow tests during the COVID-19 pandemic.

During the COVID-19 pandemic, lateral flow tests (LFTs) were used to regulate access to work, education, social activities, and travel. However, falsification of home LFT results was a concern. Falsification of test results during an ongoing pandemic is a sensitive issue. Consequently, respondents may not answer truthfully to questions about LFT falsification behaviours (FBs) when asked directly. Indirect questioning techniques such as the Extended Crosswise model (ECWM) can provide more reliable prevalence estimates of sensitive behaviors than direct questioning. Here we report the prevalence of LFT FBs in a representative sample in England (n = 1577) using direct questioning (DQ) and the ECWM. We examine the role of demographic and psychological variables as predictors of LFT FBs. We show that the prevalence estimates of the FBs in the DQ condition were significantly lower than the ECWM estimates, e.g., reporting a negative result without conducting a test: 5.7% DQ vs 18.4% ECWM. Moral norms, subjective norms, anticipated regret, perception of risk to self, and trust in government predicted some of the FBs. Indirect questioning techniques can help provide more realistic and higher quality data about compliance with behavioural regulations to government and public health agencies.

Information provision and decision-making in the treatment of abdominal aortic aneurysm: A qualitative study of patient experience.

INTRODUCTION: Shared decision making (SDM) refers to patients and health care professionals working together to reach a decision about treatment/care. In abdominal aortic aneurysm (AAA) treatment options are influenced by patients' clinical characteristics, their preferences, and potential trade-offs between alternative interventions. This is a prime example of where SDM is essential to ensure the right decision is made for the right patient, yet we have little understanding of what happens in practice. This study explored patient experiences to understand SDM practice in AAA surgery. METHODS: We used a qualitative approach to describe, and identify improvements to, current treatment decision making in abdominal aortic aneurysm (AAA) surgery. Two groups of patients were interviewed: those at the point of discussing treatment options (with corresponding digitally recorded consultation data) and following surgical intervention from one hospital. Framework analysis was used. RESULTS: Fifteen patients were interviewed, seven at the point of discussing treatment options and eight following surgical intervention. Timing, format and sources of information, verbal framing of interventions and level of patient engagement were key themes. Four areas for improvement were identified: earlier provision and more detailed written information along with signposting to quality on-line information; both intervention options, risks, benefits, and consequences, were not always discussed; some clinicians were somewhat directive in the decision-making process; and patients' treatment values/preferences were not explored-the only example was in one of the eight recorded consultations. Patients could feel overwhelmed by the information and decision and fearful of the impending surgery. CONCLUSIONS: More emphasis should be placed on the provision of full information and the exploration of patient values and preferences for treatment. Clinician training and support for patients, including decision aids, could facilitate the decision-making process. Providing written information earlier and guidance on reliable on-line resources would benefits patients and their families.

Assessing the unmet needs of patients with advanced cancer treated by biological and precision therapies: protocol for TARGET, a mixed methods study.

INTRODUCTION: Biological and precision therapies are increasingly used in cancer treatment. Although they may improve survival, they are also associated with various-and unique-adverse effects, which can be long lasting. Little is known about the experiences of people treated with these therapies. Moreover, their supportive care needs have not been fully explored. Consequently, it is unclear whether existing instruments adequately capture the unmet needs of these patients. The TARGET study seeks to address these evidence gaps by exploring the needs of people treated with these therapies with the aim of developing an unmet needs assessment instrument for patients on biological and precision therapies. METHODS AND ANALYSIS: The TARGET study will adopt a multi-methods design involving four Workstreams (1) a systematic review to identify, describe and assess existing unmet needs instruments in advanced cancer; (2) qualitative interviews with patients on biological and precision therapies, and their healthcare professionals, to explore experiences and care needs; (3) development and piloting of a new (or adapted) unmet needs questionnaire (based on the findings of Workstream 1 and Workstream 2) designed to capture the supportive care needs of these patients; and finally, (4) a large-scale patient survey using the new (or modified) questionnaire to determine (a) the psychometric properties of the questionnaire, and (b) the prevalence of unmet needs in these patients. Based on the broad activity of biological and precision therapies, the following cancers will be included: breast, lung, ovarian, colorectal, renal and malignant melanoma. ETHICS AND DISSEMINATION: This study was approved by National Health Service (NHS) Heath Research Authority Northeast Tyne and Wear South Research Ethics Committee (REC ref: 21/NE/0028). Dissemination of the research findings will take several formats to reach different audiences, including patients, healthcare professionals and researchers.

Using the precaution adoption process model to understand decision-making about the COVID-19 booster vaccine in England.

BACKGROUND: COVID-19 continues to pose a threat to public health. Booster vaccine programmes are critical to maintain population-level immunity. Stage theory models of health behaviour can help our understanding of vaccine decision-making in the context of perceived threats of COVID-19. PURPOSE: To use the Precaution Adoption Process Model (PAPM) to understand decision-making about the COVID-19 booster vaccine (CBV) in England. METHODS: An online, cross-sectional survey informed by the PAPM, the extended Theory of Planned Behaviour and Health Belief Model administered to people over the age of 50 residing in England, UK in October 2021. A multivariate, multinomial logistic regression model was used to examine associations with the different stages of CBV decision-making. RESULTS: Of the total 2,004 participants: 135 (6.7%) were unengaged with the CBV programme; 262 (13.1%) were undecided as to whether to have a CBV; 31 (1.5%) had decided not to have a CBV; 1,415 (70.6%) had decided to have a CBV; and 161 (8.0%) had already had their CBV. Being unengaged was positively associated with beliefs in their immune system to protect against COVID-19, being employed, and low household income; and negatively associated with CBV knowledge, a positive COVID-19 vaccine experience, subjective norms, anticipated regret of not having a CBV, and higher academic qualifications. Being undecided was positively associated with beliefs in their immune system and having previously received the Oxford/AstraZeneca (as opposed to Pfizer/BioNTech) vaccine; and negatively associated with CBV knowledge, positive attitudes regarding CBV, a positive COVID-19 vaccine experience, anticipated regret of not having a CBV, white British ethnicity, and living in East Midlands (vs London). CONCLUSIONS: Public health interventions promoting CBV may improve uptake through tailored messaging directed towards the specific decision stage relating to having a COVID-19 booster.

Safety and impact of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome: protocol for a multicentre, open-label, prospective, single-arm study.

INTRODUCTION: Atypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disease caused by excessive activation of part of the immune system called complement. Eculizumab is an effective treatment, controlling aHUS in 90% of patients. Due to the risk of relapse, lifelong treatment is currently recommended. Eculizumab treatment is not without problems, foremost being the risk of severe meningococcal infection, the burden of biweekly intravenous injections and the high cost.This paper describes the design of the Stopping Eculizumab Treatment Safely in aHUS trial that aims to establish whether a safety monitoring protocol, including the reintroduction of eculizumab for those who relapse, could be a safe, alternative treatment strategy for patients with aHUS. METHODS AND ANALYSIS: This is a multicentre, non-randomised, open-label study of eculizumab withdrawal with continuous monitoring of thrombotic microangiopathy-related serious adverse events using the Bayes factor single-arm design. 30 patients will be recruited to withdraw from eculizumab and have regular blood and urine tests for 24 months, to monitor for disease activity. If relapse occurs, treatment will be restarted within 24 hours of presentation. 20 patients will remain on treatment and complete health economic questionnaires only. An embedded qualitative study will explore the views of participants. ETHICS AND DISSEMINATION: A favourable ethical opinion and approval was obtained from the North East-Tyne & Wear South Research Ethics Committee. Outcomes will be disseminated via peer-reviewed articles and conference presentations. TRIAL REGISTRATION NUMBER: EudraCT number: 2017-003916-37 and ISRCTN number: ISRCTN17503205.

Shared medical appointments in English primary care for long-term conditions: a qualitative study of the views and experiences of patients, primary care staff and other stakeholders.

BACKGROUND: Shared medical appointments (SMAs) or group consultations have been promoted in primary care to improve workload pressures, resource-use efficiency and patient self-management of long-term conditions (LTCs). However, few studies have explored stakeholders' perspectives of this novel care delivery model in the English NHS context, particularly patients' views and experiences of SMAs. METHOD: Semi-structured interviews were used to explore the perspectives of stakeholders (21 patients, 17 primary care staff, 2 commissioners and 2 SMA training providers) with and without SMA experience from a range of geographical and socio-economic backgrounds in the North East and North Cumbrian region of England. Thematic analysis was conducted to examine perceptions around impact on patient care and outcomes and barriers and facilitators to implementation. RESULTS: Three main themes were identified: 'Value of sharing', 'Appropriateness of group setting', 'Implementation processes'. Patients experiences and perceptions of SMAs were largely positive yet several reported reservations about sharing personal information, particularly in close-knit communities where the risk of breaching confidentiality was perceived to be greater. SMAs were considered by patients and staff to be inappropriate for certain personal conditions or for some patient groups. Staff reported difficulties engaging sufficient numbers of patients to make them viable and having the resources to plan and set them up in practice. Whilst patients and staff anticipated that SMAs could deliver high quality care more efficiently than 1:1 appointments, none of the practices had evaluated the impact SMAs had on patient health outcomes or staff time. CONCLUSION: Stakeholder experiences of SMA use in English primary care are largely similar to those reported in other countries. However, several important cultural barriers were identified in this setting. Further work is needed to better understand how patient and staff perceptions, experiences and engagement with SMAs change with regular use over time. Concerns regarding staff capacity, additional resource requirements and numbers of eligible patients per practice suggest SMAs may only be feasible in some smaller practices if facilitated by primary care networks. Further mixed-method evaluations of SMAs are needed to inform the evidence base regarding the effectiveness, efficiency and feasibility of SMAs long-term and subsequently their wider roll-out in English primary care.

A comparison of seasonal influenza and novel Covid-19 vaccine intentions: A cross-sectional survey of vaccine hesitant adults in England during the 2020 pandemic.

We compared intention to receive the seasonal influenza vaccine with a prospective coronavirus (COVID-19) vaccine among undecided or COVID-19 vaccine hesitant individuals to better understand the underlying differences and similarities in factors associated with vaccine intention. We delivered a cross-sectional online survey in October-November 2020. We included psychological constructs and sociodemographic variables informed by theory. We conducted pairwise comparisons and multiple linear regression models to explore associations between vaccine intention and psychological constructs. We recruited 1,660 participants, where 47.6% responded that they would likely receive the influenza vaccine, 31.0% that they would probably not accept the vaccination and 21.4% were unsure. In relation to the prospective COVID-19 vaccine, 39.0% responded that they would likely receive the vaccination, 23.7% that they would probably not accept the vaccination and 37.3% were unsure. Unique factors positively associated with COVID-19 vaccine intention were: perceived knowledge sufficiency about vaccine safety, beliefs about vaccine safety, and living in an area of low deprivation. The only unique factor positively associated with influenza intention was past influenza behavior. The strongest common predictors positively associated with intention were: favorable vaccine attitudes, the anticipated regret they may feel following infection if they were not to receive a vaccine, and the expectation from family or friends to accept the vaccine. Despite overall similarities in those factors associated with vaccination intention, we identified unique influences on intention. This additional insight will help support the planning and tailoring of future immunizations programmes for the respective viruses.

Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

BACKGROUND: Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. DESIGN: Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. SETTING: Eight UK NHS secondary care sites. PARTICIPANTS: A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. INTERVENTIONS: A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. MAIN OUTCOME MEASURES: The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. RESULTS: Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. LIMITATIONS: This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. CONCLUSIONS: This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. RECOMMENDATIONS FOR RESEARCH: Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. TRIAL REGISTRATION: This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

Women with recurrent urine infections often require preventative treatment to reduce the frequency of infection episodes. Daily low-dose antibiotic medication is a guideline-recommended treatment option for these women. There is increasing concern globally regarding antibiotic-resistant infections, which has led researchers to look at alternative treatments. This trial was conducted to find out whether or not taking an alternative treatment that is not an antibiotic [i.e. methenamine hippurate (Hiprex^®; Mylan NV, Canonsburg, PA, USA)] was as effective as the standard daily low-dose antibiotics. A total of 240 women from across the UK took part in the trial. They were divided equally into two groups; half of the women were given methenamine hippurate and the other half were given standard low-dose antibiotics. Both treatments were prescribed to be taken every day for 1 year. To make a fair comparison, people were put into the two groups at random using a computer program. Aspects of the trial that could be improved were identified through telephone interviews with patients and recruiting staff. Feedback from these telephone interviews helped to ensure the successful conduct of the trial. Patients were followed up for 18 months, comprising the 12 months when they were taking treatment and a 6-month follow-up phase after they had finished treatment. We found that the non-antibiotic option of methenamine hippurate was no worse than the current standard treatment of daily antibiotics in preventing urinary tract infection episodes in adult women. For both treatments, patients expressed high levels of satisfaction. One advantage of the methenamine hippurate treatment was that infecting bacteria were slightly less likely to develop resistance to antibiotics. We also evaluated health-care costs of both treatments and found that methenamine hippurate seemed worthwhile to the NHS in the short term, but there was uncertainty over longer-term costs and benefits. These results will help patients with repeated urinary tract infections to decide on treatment options, particularly if they want to avoid prolonged courses of preventative antibiotics.

Health professional and patient views of a novel prognostic test for melanoma: A theoretically informed qualitative study.

OBJECTIVES: Cutaneous melanoma rates are steadily increasing. Up to 20% of patients diagnosed with AJCC Stage I/II melanomas will develop metastatic disease. To date there are no consistently reliable means to accurately identify truly high versus low-risk patient subpopulations. There is hence an urgent need for more accurate prediction of prognosis to determine appropriate clinical management. Validation of a novel prognostic test based on the immunohistochemical expression of two protein biomarkers in the epidermal microenvironment of primary melanomas was undertaken; loss of these biomarkers had previously been shown to be associated with a higher risk of recurrence or metastasis. A parallel qualitative study exploring secondary care health professional and patient views of the test was undertaken and this paper reports the perceived barriers and enablers to its implementation into the melanoma care pathway. METHODS: Qualitative methods were employed drawing upon the Theoretical Domains Framework (TDF) in the exploration and analysis. An inductive-deductive analysis was performed, with all data coded using a thematic then TDF framework. FINDINGS: 20 dermatologists, plastic surgeons, cancer nurse specialists, oncologists and histopathologists participated. Nine TDF domains were relevant to all health professional groups and the 'Skills' and 'Beliefs about Capabilities' domains were relevant only to histopathologists. 'Optimism' and 'Beliefs about consequences' were strong enablers particularly for clinicians. 'Environmental context and resources' (impact on pathology services) and 'Knowledge' (the need for robust evidence about the test reliability) were the main perceived barriers. 19 patients and one carer were interviewed. For the patients eight domains were relevant. ('Knowledge', 'Emotions', 'Beliefs about consequences', 'Social Role and identity', 'Behavioural regulation', 'Memory, attention and decision processes', 'Reinforcement' and 'Skills'). The consequences of the implementation of the test were reassurance about future risk, changes to the follow-up pathway on which there were mixed views, and the need to ensure they maintained self-surveillance (Beliefs about consequences). The test was acceptable to all patient interviewees but the resultant changes to management would need to be supported by mechanisms for fast-track back into the clinic, further information on self-surveillance and clear management plans at the time the result is conveyed (Behavioural regulation). CONCLUSIONS: Health professionals and patients perceived positive consequences-for patients and for health services-of adopting the test. However, its implementation would require exploration of the resource implications for pathology services, psychological support for patients with a high-risk test result and mechanisms to reassure and support patients should the test lead to reduced frequency or duration of follow-up. Exploring implementation at an early stage with health professionals presented challenges related to the provision of specific details of the test and its validation.

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial.

OBJECTIVE: To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics. DESIGN: Multicentre, open label, randomised, non-inferiority trial. SETTING: Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS: Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS: Random assignment (1:1, using permuted blocks of variable length via a web based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. MAIN OUTCOME MEASURE: Absolute difference in incidence of symptomatic, antibiotic treated, urinary tract infections during treatment. A patient and public involvement group predefined the non-inferiority margin as one episode of urinary tract infection per person year. Analyses performed in a modified intention-to-treat population comprised all participants observed for at least six months. RESULTS: Participants were randomly assigned to antibiotic prophylaxis (n=120) or methenamine hippurate (n=120). The modified intention-to-treat analysis comprised 205 (85%) participants (antibiotics, n=102 (85%); methenamine hippurate, n=103 (86%)). Incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.89 episodes per person year (95% confidence interval 0.65 to 1.12) in the antibiotics group and 1.38 (1.05 to 1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90% confidence interval 0.15 to 0.84) confirming non-inferiority. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the methenamine group and most reactions were mild. CONCLUSION: Non-antibiotic prophylactic treatment with methenamine hippurate might be appropriate for women with a history of recurrent episodes of urinary tract infections, informed by patient preferences and antibiotic stewardship initiatives, given the demonstration of non-inferiority to daily antibiotic prophylaxis seen in this trial. TRIAL REGISTRATION: ISRCTN70219762.

Factors associated with vaccine intention in adults living in England who either did not want or had not yet decided to be vaccinated against COVID-19.

Early studies showed that 28-36% of UK adults were unsure or unwilling to be vaccinated against COVID-19. We wanted to identify which socio-demographic, socio-economic, personal health and psychological factors were associated with COVID-19 vaccine intentions (CVI) in adults living in England who did not want, yet to consider, or not sure whether to vaccinate. In October/November 2020, prior to vaccine availability, we surveyed adults stratified by gender, region, and deprivation, with additional purposive sampling of those aged 50 and over and those from an ethnic minority. Two hundred and ten did not want; 407 had yet to consider; and 1,043 were not sure whether to be vaccinated. Factors positively associated with CVI were: favorable vaccine views, trust in institutions associated with vaccine approval, vaccine subjective norms, anticipated regret of not having a vaccine, perceived vaccine benefits, perceived safety knowledge sufficiency, and a history of having an influenza vaccine. Factors negatively associated were: anti-lockdown views, and being a health or social care worker. Whilst showing significant relationships with CVI when analyzed in isolation, neighborhood deprivation and ethnicity did show an independent relationship to intention when all study measures were controlled for. Our findings suggest vaccine promotion focusing on the anticipated regret of not having a vaccine, the benefits of a mass COVID-19 immunization program, and the safety of a vaccine whilst ensuring or engendering trust in those bodies that brand a campaign may be most supportive of COVID-19 vaccine uptake.

Public understanding of COVID-19 antibody testing and test results: A qualitative study conducted in the U.K. early in the pandemic.

BACKGROUND: During the COVID-19 pandemic, antibody testing was proposed by several countries as a surveillance tool to monitor the spread of the virus and potentially to ease restrictions. In the UK, antibody testing originally formed the third pillar of the UK Government's COVID-19 testing programme and was thought to offer hope that those with a positive antibody test result could return to normal life. However, at that time scientists and the public had little understanding of the longevity of COVID-19 antibodies, and whether they provided immunity to reinfection or transmission of the virus. OBJECTIVE: This paper explores the UK public's understanding of COVID-19 testing, perceived test accuracy, the meaning of a positive test result, willingness to adhere to restrictive measures in response to an antibody test result and how they expect other people to respond. METHODS: On-line synchronous focus groups were conducted in April/May 2020 during the first wave of the pandemic and the most stringent period of the COVID-19 restrictive measures. Data were analysed thematically. RESULTS: There was confusion in responses as to whether those with a positive or negative test should return to work and which restrictive measures would apply to them or their household members. Participants raised concerns about the wider public response to positive antibody test results and the adverse behavioural effects. There were worries that antibody tests could create a divided society particularly if those with a positive test result were given greater freedoms or chose to disregard the restrictive measures. CONCLUSION: Should these tests be offered more widely, information should be developed in consultation with the public to ensure clarity and address uncertainty about test results and subsequent behaviours.

Lansoprazole for persistent throat symptoms in secondary care: the TOPPITS RCT.

BACKGROUND: Persistent throat symptoms are commonly attributed to 'laryngopharyngeal reflux'. Despite a limited evidence base, these symptoms are increasingly being treated in primary care with proton pump inhibitors. OBJECTIVE: To assess the value of proton pump inhibitor therapy in patients with persistent throat symptoms. DESIGN: This was a double-blind, placebo-controlled, randomised Phase III trial. SETTING: This was a multicentre UK trial in eight UK ear, nose and throat departments. PARTICIPANTS: A total of 346 participants aged ≥ 18 years with persistent throat symptoms and a Reflux Symptom Index score of ≥ 10, exclusive of the dyspepsia item, were recruited. INTERVENTION: Random allocation (1 : 1 ratio) to either 30 mg of lansoprazole twice daily or matched placebo for 16 weeks. MAIN OUTCOME MEASURE: Symptomatic response (i.e. total Reflux Symptom Index score after 16 weeks of therapy). RESULTS: A total of 1427 patients were screened and 346 were randomised. The mean age was 52 years (standard deviation 13.7 years, range 20-84 years); 150 (43%) participants were male and 196 (57%) were female; 184 (53%) participants had a mild Reflux Symptom Index minus the heartburn/dyspepsia item and 162 (47%) had a severe Reflux Symptom Index minus the heartburn/dyspepsia item. A total of 172 patients were randomised to lansoprazole and 174 were randomised to placebo. MAIN OUTCOMES: A total of 267 participants completed the primary end-point visit (lansoprazole, n = 127; placebo, n = 140), of whom 220 did so between 14 and 20 weeks post randomisation ('compliant' group); 102 received lansoprazole and 118 received placebo. The mean Reflux Symptom Index scores at baseline were similar [lansoprazole 22.0 (standard deviation 8.0), placebo 21.7 (standard deviation 7.1), overall 21.9 (standard deviation 7.5)]. The mean Reflux Symptom Index scores at 16 weeks reduced from baseline in both groups [overall 17.4 (standard deviation 9.9), lansoprazole 17.4 (standard deviation 9.9), placebo 15.6 (standard deviation 9.8)]. Lansoprazole participants had estimated Reflux Symptom Index scores at 16 weeks that were 1.9 points higher (worse) than those of placebo participants (95% confidence interval -0.3 to 4.2; padj = 0.096), adjusted for site and baseline severity. SECONDARY OUTCOMES: Ninety-five (43%) participants achieved a Reflux Symptom Index score in the normal range (< 12) at 16 weeks: 42 (41%) in the lansoprazole group and 53 (45%) in the placebo group. A total of 226 participants completed the end-of-trial follow-up visit (lansoprazole, n = 109; placebo, n = 117), of whom 181 were 'compliant'. The mean Reflux Symptom Index scores at 12 months reduced from baseline in both groups [lansoprazole 16.0 (standard deviation 10.8), placebo 13.6 (standard deviation 9.6), overall 14.7 (standard deviation 10.2)]. A total of 87 (48%) participants achieved a Reflux Symptom Index score in the normal range at 12 months: 33 (40%) in the lansoprazole group and 54 (55%) in the placebo group. Likewise, the Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life total scores and subscales all showed very similar changes in the lansoprazole and placebo cohorts at both 16 weeks and 12 months. LIMITATIONS: Drop-out rate and compliance are issues in pragmatic clinical trials. The Trial Of Proton Pump Inhibitors in Throat Symptoms (TOPPITS) aimed to detect clinically relevant difference with 90% power. The 346 randomised participants reduced to 283 at the primary end point; 267 completed the primary outcome measure, 220 within the protocol time scale. Despite this, the powers to detect the clinically relevant difference in Reflux Symptom Index score at 16 weeks were 82% (compliant comparison) and 89% (pragmatic comparison). The lack of difference between lansoprazole and placebo is generalisable across NHS clinics. CONCLUSIONS: Participants on lansoprazole did not report significantly better outcomes than participants on placebo on any of the three patient-reported outcome tools (Reflux Symptom Index, Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life). This multicentre, pragmatic, powered, definitive Phase III trial found no evidence of benefit for patients by treating persistent throat symptoms with lansoprazole. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38578686 and EudraCT number 2013-004249-17. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 3. See the NIHR Journals Library website for further project information.

BACKGROUND: One of the commonest reasons for patients attending hospital throat or voice clinics is persistent throat symptoms, which include a feeling of a lump in the throat, a cough or a hoarse voice. Over time, more of these patients are being treated with proton pump inhibitors to suppress stomach acid in the belief that stomach acid entering the throat causes the symptoms, but there is little evidence that these medications work. STUDY AIM: The aim of this study is to explore whether or not having a 16-week course of proton pump inhibitors has any impact on throat symptoms. We also tested the usefulness of three different questionnaires in measuring throat symptoms, explored side effects and whether or not patients adhere to treatment, and measured patients' quality of life. METHODS: Patients with persistent (lasting for more than 6 weeks) throat symptoms who agreed to participate were randomised to receive either the proton pump inhibitor lansoprazole or a placebo. Participants took lansoprazole or placebo for 16 weeks. Symptoms and quality of life were measured before patients were randomised and at 4 and 12 months after randomisation. RESULTS: The total number of participants was 346. The mean Reflux Symptom Index outcome score (higher scores meaning worse symptoms) was 22 before the 4-month course of capsules, 16 after 4 months and 15 after 12 months. Participant-reported throat symptoms and quality of life in all participants improved over the 12 months of the study. There was no difference in the symptom improvement experienced by proton pump inhibitor and placebo participants. CONCLUSIONS: This study shows that proton pump inhibitors do not benefit patients with persistent throat symptoms. Future research should focus on other available therapies.

Nurses' and patients' experiences and preferences of the ankle-brachial pressure index and multi-site photoplethysmography for the diagnosis of peripheral arterial disease: A qualitative study.

Peripheral arterial disease is a global health problem, affecting around 20% of people aged over 60 years. Whilst ankle-brachial pressure index (ABPI) is regularly used for diagnosis, it has a number of limitations, which have presented a need for alternative methods of diagnosis. Multi-site photoplethysmography (MPPG) is one such method, but evidence of acceptability of both methods is lacking. This study aims to describe and compare preferences and experiences amongst nurses and patients of ABPI and MPPG use in primary care. We used qualitative research methods in the context of a clinical diagnostic study comparing ABPI with MPPG. Use of ABPI and MPPG by 13 nurses were observed with 51 patients across general practice surgeries in North-East England in 2015/16. Follow-up semi-structured interviews were conducted with 12 nurses and 27 patients. Data were thematically analysed. Two major themes were identified: (1) device preferences; (2) test discomfort and anxiety. There was a compelling preference for MPPG due to ease of use, speed of the test, patient comfort, and perceived device accuracy/objectivity. However some patients struggled to identify a preference, describing ambivalence to medical testing. ABPI was deemed uncomfortable and painful, particularly when the blood pressure cuff was inflated at the lower limbs. There was also evidence of anxiety amongst patients when their foot pulses were not identified using ABPI. Whilst ABPI is a non-invasive and routine procedure it was associated with a number of drawbacks in clinical practice. Nurses required considerable dexterity to employ the test, and it resulted in anxiety amongst some patients. Conversely, MPPG was deemed to be easier and quicker to use, and perceived to be less subjective. Should diagnostic accuracy and cost be comparable to ABPI, then the findings of this study suggest MPPG would be preferable to ABPI for patients as well as nurses.

Peripheral arterial disease diagnosis and management in primary care: a qualitative study.

BACKGROUND: Patients diagnosed with peripheral arterial disease (PAD) are at an increased risk of coronary heart disease, stroke, heart attack, and PAD progression. If diagnosed early, cardiovascular risk factors can be treated and the risk of other cardiovascular diseases can be reduced. There are clear guidelines on PAD diagnosis and management, but little is known about the issues faced in primary care with regards adherence to these, and about the impact of these issues on patients. AIM: To identify the issues for primary care health professionals (HPs) and patients in PAD diagnosis and management, and to explore the impact of these on HPs and PAD patients. DESIGN & SETTING: Qualitative study conducted in a primary care setting in the North East of England. Data was collected between December 2014 and July 2017. METHOD: Semi-structured interviews and focus groups were conducted with PAD register patients (n = 17), practice nurses ([PNs], n = 17), district nurses (DNs], n = 20), tissue viability nurses (n = 21), and GPs (n = 21). RESULTS: HPs' attitudes to PAD, difficulty accessing tests, and patient delays impacted upon diagnosis. Some HPs had a reactive approach to PAD identification. Patients lacked understanding about PAD and some reported a delay consulting their GP after the onset of PAD symptoms. After diagnosis, few were attending for regular GP follow-up. CONCLUSION: Patient education about PAD symptoms and risks, and questioning about exercise tolerance, could address the problem of under-reporting. Annual reviews could provide an opportunity to probe for PAD symptoms and highlight those requiring further investigation. Improved information when PAD is diagnosed and, considering the propensity for patients to tolerate worsening symptoms, the introduction of annual follow-up (at minimum) is warranted.

Understanding frames: A qualitative exploration of standing frame use for young people with cerebral palsy in educational settings.

BACKGROUND: Consensus opinion supports standing frame use as part of postural management for nonambulant young people with cerebral palsy. Most young people with cerebral palsy in the United Kingdom, who use standing frames, use them at nursery or school, rather than at home. In this paper we report professionals' and parents' experiences and views of standing frame use specifically in educational settings. This research was conducted as part of a large mixed methods study to determine the acceptability and inform the design of a future trial of standing frames. METHODS: Qualitative methods were used: focus groups with educational professionals, parents and clinicians (paediatricians, physiotherapists and occupational therapists) were convened. Data were analysed thematically using framework analysis. RESULTS: Five focus groups were conducted. The overarching theme "flexibility" encompassed four subordinate themes: (i) "balancing education and therapy," which described the way education professionals had to juggle different priorities from health professionals within a multi-disciplinary team; (ii) "young people's autonomy," which highlighted participants' belief that standing frame use should be centred on the individual young person and their needs; (iii) "working within logistical boundaries," which demonstrated that "ideal" standing frame use was not always possible due to logistical issues (e.g., staffing and standing frame availability); and (iv) "competence and confidence," which highlighted that educational professionals felt that they lacked the training to confidently position young people in their standing frame. CONCLUSIONS: This paper highlights the complexity of standing frame use in the educational setting. If a standing frame programme is prescribed to be delivered in an educational setting, strong multidisciplinary and interagency communication is essential to balance therapy versus education. Training is required to ensure staff are competent in using the standing frame with the young person understanding their individual requirements. A flexible approach-inclusive of the young person's needs, logistical demands and resource-is necessary.

Should I stay or should I go? A qualitative study exploring participation in a urology clinical trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to identify modifiable factors to improve recruitment in a urology clinical trial of women with recurrent urinary tract infection (rUTI). An embedded qualitative study was conducted with patients and recruiting clinicians in the first 8 months of the trial. We present a matrix of factors influencing how patients make decisions about trial participation. METHODS: This was a qualitative study using telephone interviews. When they were first approached about the trial, women were asked to complete an expression of interest form if they wished to be contacted for an interview. Data were analysed thematically. NVivo 10 software (Qualitative data analysis software. 10th ed: QSR International Pty Ltd; 2012) was used as a management tool. RESULTS: Thirty patients and 11 clinicians were interviewed. Influences on patient participation included the impact of rUTI on quality of life (QoL), understanding of antibiotic resistance, and previous experiences with antibiotics either positive or negative. Very few women who declined the trial agreed to be interviewed. However, some of those who participated had reservations about it. These included the perceived risk of trying a new treatment, trial length, and the burden of participating. One person interviewed left the trial because of repeated infections and difficulties getting general practitioner appointments. CONCLUSIONS: A combination of factors worked to influence women to decide to participate, to remain in, or to leave the trial. A better understanding of how these factors interact and work can assist in the recruitment and retention of individual trial participants.

ALternatives To prophylactic Antibiotics for the treatment of Recurrent urinary tract infection in women (ALTAR): study protocol for a multicentre, pragmatic, patient-randomised, non-inferiority trial.

BACKGROUND: At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the 'gold standard' preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention. DESIGN /METHODS: This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants' and recruiting clinicians' views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study. DISCUSSION: The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a 'Type A' study. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762 . Registered on 31 May 2016.

Standing frames for children with cerebral palsy: a mixed-methods feasibility study.

BACKGROUND: Standing frames are recommended as part of postural management for young people with cerebral palsy (CP) Gross Motor Function Classification System (GMFCS) level IV or V. They may have a variety of benefits, including improving bone mineral density, gastrointestinal function and social participation. The NHS needs to know if these benefits are real, given the cost implications of use and the reported negative effects (e.g. pain). The lack of evidence for the clinical effectiveness of standing frames demonstrates the need for evaluative research. OBJECTIVE(S): The aim of the study was to explore the acceptability of a future trial to determine the clinical effectiveness of standing frames. DESIGN: A sequential mixed-methods design was used. The findings of each stage informed the next stage. We conducted surveys, focus groups and in-depth interviews. PARTICIPANTS: Professionals who work with young people who use standing frames and parents who have a child who uses a standing frame took part in a survey of current standing frame practice (n = 551), a series of focus groups (seven focus groups, 49 participants in total) and a survey of research trial acceptability and feasibility (n = 585). Twelve young people who use a standing frame were interviewed. RESULTS: Standing frames were widely used as part of postural management for young people with CP both in school and at home but more frequently in school, and particularly by young people in primary school. Achieving the prescribed use was not always possible owing to resources, environment and family factors. Participation and activity engagement were important to young people. The majority of participants believed that standing frames research is necessary. Some reported concern that stopping standing frame use for a trial would cause irreversible damage. The maximum amount of time most health professionals and parents would agree to suspend standing frame use would be 12 weeks. LIMITATIONS: Owing to the nature of recruitment, we could not calculate response rates or determine non-response bias. Therefore, participants may not be representative of all standing frame users. CONCLUSIONS: Although parents and professionals who engaged in the qualitative aspect of this research and stakeholders who took part in the design workshops appreciated the lack of clinical evidence, our surveys, qualitative information and PPI demonstrated that most people had strong beliefs regarding the clinical effectiveness of standing frames. However, with key stakeholder engagement and careful planning, a trial would be acceptable. FUTURE WORK: We recommend a carefully planned trial that includes a pilot phase. The trial should evaluate the following question: 'does using a standing frame in school improve patient-reported outcomes of participation (primary outcome), quality of life, subjective well-being, body function and body structure (secondary outcomes) in young children (aged 4-11 years) with CP GMFCS III-V?'. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Parents' Opinions about an Intervention to Manage Repetitive Behaviours in Young Children with Autism Spectrum Disorder: A Qualitative Study.

BACKGROUND: Early intervention for autism spectrum disorder (ASD) tends to focus on enhancing social communication skills. We report data collected via focus group discussions as part of a feasibility and acceptability pilot randomized controlled trial (RCT) about a new parent group intervention to manage restricted and repetitive behaviours (RRB) in young children with ASD. METHODS: The focus groups were led by two independent facilitators and followed a semi-structured topic guide with the aim of considering three key topics: experiences of participating in a RCT, opinions about the intervention and the impact of the intervention on the participants, their children and the family. RESULTS: Fourteen participants attended the focus groups. Most participants reported that they had little knowledge of RRB before attending the intervention and that it had had a positive impact on them, their children and their family. CONCLUSION: The findings support the view that there is an unmet need for a parent-mediated intervention focusing on RRB.