Investigation of the Impact of Wellinks on the Quality of Life and Clinical Outcomes in Patients With Chronic Obstructive Pulmonary Disease: Interventional Research Study.

BACKGROUND: Wellinks is a remote disease management solution that provides novel chronic obstructive pulmonary disease (COPD) care delivery. OBJECTIVE: This study evaluated the satisfaction, engagement, and clinical outcomes of Wellinks participants. This study also investigated the cadence of health coaching for patients with COPD. METHODS: A 24-week interventional study was conducted by Wellinks and the COPD Foundation in 2022. Adults with COPD were recruited by the COPD Foundation in the United States and determined to be eligible if they had phone and internet access, owned a smartphone, and were not currently participating in pulmonary rehabilitation. All study participants provided written informed consent. The Wellinks solution included remote health coaching, pulmonary rehabilitation, and group education; participants were provided the Wellinks app and smart spirometry and pulse oximetry devices. Participants were offered 6 coaching sessions in the first 12 weeks. For the second 12-week period, participants either reduced frequency or discontinued coaching; all other components of the Wellinks solution remained unchanged. The COPD Self-Efficacy Scale, Modified Medical Research Council dyspnea scale, pulmonary function, pulse oximetry, and patient-reported healthcare resource utilization were the clinical outcome measures. Nonclinical outcomes included engagement and satisfaction with Wellinks and net promoter score. RESULTS: In total, 141 adults consented and completed Wellinks onboarding; 84.4% (n=119) of whom remained engaged throughout the 24-week study. Participants had a mean age of 70 (SD 7.8; range 48-88) years, and 55.7% (n=78) were female. Most participants (n=119, 84.4%) completed all 6 coaching sessions during the first 12-week period. Compliance with spirometer and pulse oximeter use was 82.3% and 89.4%, respectively, at week 1 but waned over the study period to 8.5% and 9.2%, respectively, at the end of the study. Participants indicated a high degree of satisfaction with Wellinks, with 95.5% (n=85) and 91% (n=81) of participants indicating that they agreed or strongly agreed that the educational content and health coaching, respectively, were valuable. At the end of the study, the net promoter score was +64 and +55 in the coaching continuation and discontinuation arms, respectively. A significant improvement from baseline to end of the study was observed in the COPD Self-Efficacy Scale total score (P<.001) and domain scores (P<.001 for each domain). In total, 35.1% (n=27) of participants improved by at least 1 category of change on the 5-point Modified Medical Research Council dyspnea scale from baseline to week 24. CONCLUSIONS: This study confirmed the feasibility of using a remote model of care delivery to support people living with COPD. The insights gained in this study have allowed for further refinement and personalization of the Wellinks care model. Findings related to the combined use of technology and personal care delivery should be considered by others developing remote disease management tools. TRIAL REGISTRATION: ClinicalTrials.gov NCT05259280; https://clinicaltrials.gov/ct2/show/NCT05259280.

Information needs of ethnically diverse, vaccine-hesitant parents during decision-making about the HPV vaccine for their adolescent child: a qualitative study.

BACKGROUND: The English schools-based human papillomavirus (HPV) vaccination programme has the potential to eliminate HPV-related cancers if high uptake is achieved. However, unmet information needs among some parents may contribute to persisting lower uptake among minority ethnic groups. Through this study we aimed to understand the information needs of vaccine-hesitant, ethnically diverse parents during decision-making about the HPV vaccine for their adolescent child, to inform the future development of tailored communication materials. METHODS: Recruitment was facilitated thorough healthcare and community organisations within London and the South West of England. Semi-structured interviews took place between April and August 2023. Thematic analysis was undertaken, assisted by NVivo software. RESULTS: Of the 29 parents interviewed, the majority were mothers (79%), belonged to a minority ethnic group (88%), and had an adolescent child unvaccinated against HPV (72%). Five of the interviews were undertaken in the participants' primary language with translation support. Most parents interviewed had limited knowledge about the HPV vaccine and appeared conflicted as to whether vaccines could offer benefits to health. Misunderstanding around the potential of developing serious side-effects (e.g. fertility issues, developing cancer) were factors that could negatively impact decision-making by parents. Stigma associated with the sexual transmissibility of HPV did not always negatively impact decision-making. However, some parents chose not to vaccinate on the basis of perceptions of low risk and a preference to provide education about sexual behaviours to their adolescent child. CONCLUSIONS: Tailoring communication materials to address misunderstandings could support informed decision-making by vaccine hesitant parents for their adolescent children to be vaccinated against HPV. Future communication materials about the HPV vaccine should highlight the benefits of protection against cancer to increase parents' motivation for protect their adolescent child; provide accurate convincing information in relation to the excellent safety profile; and emphasise the importance of providing HPV vaccine at the recommended age, all alongside communicating the universality and commonality of HPV infection. TRIAL REGISTRATION: N/A.

Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

Development of an educational package for the universal human papillomavirus (HPV) vaccination programme: a co-production study with young people and key informants.

BACKGROUND: The English schools-based human papillomavirus (HPV) vaccination programme is routinely offered to all young people aged 12-13 years, to prevent cancers affecting the cervix, vulva, vagina, penis, anus and mouth. Lower uptake among some population groups has been identified, in part, because of unmet information needs among young people. To address these unmet needs we report intervention planning and development processes to co-produce an educational package about the HPV vaccine. METHODS: We used co-production research methodologies and the 'person-based approach' involving the following iterative stages: (i) collating and analysing primary and secondary evidence, including HPV vaccine communication materials, interviews and workshops; (ii) developing guiding principles; (iii) undertaking a behavioural analysis informed by the Behaviour Change Wheel and the Behaviour Change Technique taxonomy; (iv) development of a preliminary logic model; (v) co-production of resources, and; (vi) refinement of resources informed by feedback from young people and key informants. RESULTS: We co-produced EDUCATE, a theory-based educational package, that is designed to be delivered to young people prior to being offered the HPV vaccine to support uptake. Young people and key informants identified the following key issues to include as content: (i) HPV-related information; (ii) how vaccines work; (iii) safety and side-effects of the HPV vaccine; (iii) eligibility for the HPV vaccination programme, and; (iv) preparation of young people to receive the HPV vaccine. A manual for professionals (e.g. immunisation nurses, school staff) delivering the intervention and a PowerPoint presentation, interspersed with five short films, were co-produced with young people and key informants. Following feedback, the content of the EDUCATE package was refined to increase acceptability, engagement, and persuasiveness to the target users. CONCLUSION: Engagement with young people and key informants was integral to the development of our rigorously developed, theory-based intervention to address young people's information needs about the HPV vaccination programme. The acceptability and persuasiveness of the package has been maximised by working closely with young people and key informants to develop the content. An implementation study to examine how the EDUCATE package is implemented in practice and the impact on uptake of the HPV vaccination programme is underway.

In England, young people are offered the human papillomavirus (HPV) vaccine in schools at age 12­13 years to prevent some types of cancer. Some young people have unanswered questions which may stop them getting vaccinated. We report how we developed a lesson about the HPV vaccine jointly with young people and professionals to improve how information about the HPV vaccine is given. First, we reviewed research studies and HPV vaccine information materials designed for young people. Then, we carried out interviews and workshops to ask about the best way to give a lesson and the most important information to include. We worked with creative designers to produce films and animations. Finally, we asked young people and professionals for feedback on the lesson materials. The lesson includes a PowerPoint presentation with five films and guidance for people leading the session. Key topics about the HPV vaccine to be covered were identified by young people. These included information about how vaccines work and ways to improve young people's experience of having the HPV vaccine at school. We made changes to the information in the lesson to ensure that it was relevant to young people. We are now carrying out a study to find out how well the lesson is given and whether it can help more young people get the HPV vaccine if they want it.

International Differences in the Frequency of Chronic Obstructive Pulmonary Disease Exacerbations Reported in Three Clinical Trials.

Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries. Objectives: We investigated whether systematic differences in national exacerbation rates might explain this observed variation. Methods: We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of COPD, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution. Measurements and Main Results: For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was two- to threefold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrollment. Of the 18 countries contributing to all trials, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across trials. Severe exacerbations showed a different rank order internationally. Conclusions: Countries contributing to COPD trials differ consistently in their reporting of healthcare-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.

Development of a multicomponent intervention to increase parental vaccine confidence and young people's access to the universal HPV vaccination programme in England: protocol for a co-design study.

INTRODUCTION: Persistent infection with HPV can result in cancers affecting men and, especially, women. Lower uptake exists by area and different population groups. Increasing parental confidence about, and adolescent access to, the universal HPV vaccination programme may help reduce inequalities in uptake. However, the evidence-base for interventions to address uptake for schools-based HPV vaccination programmes is currently lacking. This study protocol outlines how a multicomponent intervention to address this evidence gap will be codesigned with parents. METHODS AND ANALYSIS: The proposed research will be undertaken in localities covered by two immunisation teams in London and the south-west of England. The 'person-based approach' to intervention development will be followed. In the first phase, an exploratory qualitative study will be undertaken with key stakeholders (n=8) and parents (n=40) who did not provide consent for their adolescent child to be vaccinated. During the interviews, parents' views on ways to improve parental confidence about, and adolescents' access to, HPV vaccination will be sought. The findings will be used to inform the co-design of a preliminary plan for a targeted, multicomponent intervention. In the second phase, at least two parent working groups (n=8) will be convened and will work with creative designers to co-design communication materials aimed at increasing parents' confidence in vaccination. At least two workshops with each parent group will be organised to obtain feedback on the intervention plan and communication materials to ensure they are fit for purpose. These findings will inform a protocol for a future study to test the effectiveness of the intervention at increasing HPV vaccination uptake. ETHICS AND DISSEMINATION: The National Health Services Research Ethics Service and London School of Hygiene & Tropical Medicine Observational / Interventions Research Ethics Committee provided approvals for the study (reference 22/SW/0003 & 26902, respectively). We will work with parent advisory groups to inform our dissemination strategy and co-present our findings (eg, at community events or through social media). We will disseminate our findings with academics and healthcare professionals through webinars and academic conferences, as well as peer-reviewed publications.

Impact of new consent procedures on uptake of the schools-based human papillomavirus (HPV) vaccination programme.

BACKGROUND: Local policy change initiating new consent procedures was introduced during 2017-2018 for the human papillomavirus (HPV) vaccination programme year in two local authorities in the south-west of England. This study aims to assess impact on uptake and inequalities. METHODS: Publicly available aggregate and individual-level routine data were retrieved for the programme years 2015-2016 to 2018-2019. Statistical analyses were undertaken to show: (i) change in uptake in intervention local authorities in comparison to matched local authorities and (ii) change in uptake overall, and by local authority, school type, ethnicity and deprivation. RESULTS: Aggregate data showed uptake in Local Authority One increased from 76.3% to 82.5% in the post-intervention period (risk difference: 6.2% P = 0.17), with a difference-in-differences effect of 11.5% (P = 0.03). There was no evidence for a difference-in-differences effect in Local Authority Two (P = 0.76). Individual-level data showed overall uptake increased post-intervention (risk difference: +1.1%, P = 0.05), and for young women attending school in Local Authority One (risk difference: 2.3%, P < 0.01). No strong evidence for change by school category, ethnic group and deprivation was found. CONCLUSION: Implementation of new consent procedures can improve and overcome trends for decreasing uptake among matched local authorities. However, no evidence for reduction in inequalities was found. IMPLICATIONS AND DISCUSSION: The new consent procedures increased uptake in one of the intervention sites and appeared to overcome trends for decreasing uptake in matched sites. There are issues in relation to the quality of data which require addressing.

Investigation of the Clinical, Radiological and Biological Factors Associated with Disease Progression, Phenotypes and Endotypes of COPD in China (COMPASS): study design, protocol and rationale.

COPD is heterogeneous, and its presentation varies between countries. The major COPD cohort studies have only been performed in Western populations; the disease is not well characterised in other regions. The COMPASS (Investigation of the Clinical, Radiological and Biological Factors, Humanistic and Healthcare Utilisation Burden Associated with Disease Progression, Phenotypes and Endotypes of COPD in China; NCT04853225) is a prospective, 2.5-year-long, multi-centre, longitudinal, observational study with three aims: 1) to characterise stable and exacerbation phenotypes/endotypes in terms of clinical characteristics, blood and sputum biomarkers, lung microbiome and lung imaging; 2) to understand the relevance of markers of COPD disease progression identified in Western cohorts to Chinese patients; and 3) to characterise treatment pathways and healthcare resource utilisation. COMPASS will recruit 2000 participants, of which 1700 will be in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grades I-IV (n=700, 700, 200 and 100, respectively), 180 participants with chronic bronchitis without airflow limitation and 120 never-smoker healthy controls. Study visits will be at baseline, 6, 18 and 30 months and at exacerbation. Assessments include lung function, exacerbation frequency, health status, blood biomarkers and, in a sub-cohort of 400 patients, chest high-resolution computed tomography, additional blood and sputum biomarkers, airway micro-, viral- and myco-biome, and physical activity. COMPASS will establish a unique clinical and biological dataset in a well-characterised cohort of individuals with COPD in China, with a particular focus on milder patients. As the first study of its kind attempting to understand the disease in an Asian setting, it will provide valuable insights into regional and ethnic differences in COPD.

Challenging the obesity paradox: extreme obesity and COPD mortality in the SUMMIT trial.

Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the "obesity paradox". Relationships in less-severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity. We examined the relationship between body mass index (BMI; defined as underweight: <20 kg·m-2, normal: 20-25 kg·m-2, overweight: 25- <30 kg·m-2, obese class I: 30- <35 kg·m-2, class II: 35- <40 kg·m-2 and class III: ≥40 kg·m-2), morbidity, and mortality in the SUMMIT trial population (n=16 485), characterised by moderate COPD and heightened cardiovascular risk with a substantial proportion with class III obesity. The association between BMI category and time to event was modelled via proportional hazards (reference normal weight) adjusted for demographics and cardiorespiratory disease. Consistent with the paradox, underweight individuals demonstrated higher mortality (hazard ratio (HR) 1.31 (95% CI 1.04-1.64)), with lower mortality among overweight (HR 0.62 (95% CI 0.52-0.73)) and obese class I (HR 0.75 (95% CI 0.62-0.90)). However, mortality increased in obese class III (HR 1.36 (95% CI 1.00-1.86)). Death was primarily attributable to cardiovascular causes. Within a large, multinational cohort with moderate COPD and increased cardiovascular risk, the phenomenon of reduced mortality with obesity did not persist at BMI >40 kg·m-2, suggesting that obesity may not remain protective at the extremes in this population.

Secondary analyses to test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new consent policy in the south-west of England.

OBJECTIVES: To test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new policy providing additional opportunities to consent. SETTING: Two local authorities in the south-west of England. PARTICIPANTS: Young women (n=7129) routinely eligible for HPV vaccination aged 12-13 years during the intervention period (2017/2018 to 2018/2019 programme years). INTERVENTIONS: Local policy change that included additional opportunities to provide consent (parental verbal consent and adolescent self-consent). OUTCOMES: Secondary analyses of cross-sectional intervention data were undertaken to examine uptake by: (1) receipt of parental written consent forms and; (2) percentage of unvaccinated young women by stage of implementation. RESULTS: During the intervention period, 6341 (89.0%) eligible young women initiated the HPV vaccination series. Parental written consent forms were less likely to be returned where young women attended alternative education provider settings (p<0.001), belonged to non-white British ethnic groups (p<0.01) or more deprived quintiles (p<0.001). Implementation of parental verbal consent and adolescent self-consent reduced the percentage of unvaccinated young women from 21.3% to 16.5% (risk difference: 4.8%). The effect was greater for young women belonging to the most deprived compared with the least deprived quintile (risk difference: 7.4% vs 2.3%, p<0.001), and for young women classified as Unknown ethnic category compared with white British young women (6.7% vs 4.2%, p<0.001). No difference was found for non-white British young women (5.4%, p<0.21). CONCLUSIONS: Local policy change to consent procedures that allowed parents to consent verbally and adolescents to self-consent overcame some of the barriers to vaccination of young women belonging to families less likely to respond to paper-based methods of gaining consent and at greater risk of developing cervical cancer. TRIAL REGISTRATION NUMBER: 49 086 105.

Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort.

RATIONALE: There are no validated measures of disease activity in COPD. Since "active" disease is expected to have worse outcomes (e.g. mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality. METHODS: We investigated 1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; 2) whether these variables inter-relate; and 3) if any clinical, imaging and/or biological marker measured cross-sectionally at baseline relates to any activity component. RESULTS: Results showed that 1) after 1 year, hospitalisation for COPD, exacerbation frequency, worsening of body mass index, airflow obstruction, dyspnoea and exercise (BODE) index or health status (St George's Respiratory Questionnaire (SGRQ)) and persistence of systemic inflammation were significantly associated with 8-year mortality; 2) at 3 years, the same markers, plus forced expiratory volume in 1 s (FEV1) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; 3) changes in FEV1, inflammatory cytokines and CT emphysema were not inter-related, while the multidimensional indices (BODE and SGRQ) showed modest correlations; and 4) changes in these markers could not be predicted by any baseline cross-sectional measure. CONCLUSIONS: In COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores and FEV1 decline are independent markers of disease activity associated with 8-year all-cause mortality. These disease activity markers are generally independent and not predictable from baseline measurements.

Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review.

Rationale: Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial. Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.Objectives: We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.Methods: A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted. Articles were excluded if study duration was <1 year, <3 spirometric measurements, or <100 subjects per arm. Study design was assessed using the Jadad score. To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.Measurements and Main Results: There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies). The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P < 0.001) in the rate of FEV1 decline compared with the placebo arms. The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.Conclusions: In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline. The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies. Guidelines should be adjusted according to these findings.

Co-production of an educational package for the universal human papillomavirus (HPV) vaccination programme tailored for schools with low uptake: a participatory study protocol.

AIM: To co-produce with young people an educational package about the human papillomavirus (HPV) vaccine that is tailored to increase vaccine uptake in schools and populations with lower uptake. INTRODUCTION: Persistent infection with HPV can result in cancers affecting men and especially women. From September 2019, the English-schools-based HPV vaccination programme was expanded to include young men (in addition to young women) aged 12-13 years. Some young people attending schools with lower uptake of the vaccine have unmet information needs. We hypothesise that mechanisms to address information needs and increase young people's autonomy in consent procedures will result in higher uptake. METHODS AND ANALYSIS: The Medical Research Council's framework for development and evaluation of complex interventions will inform intervention development. Recruitment of young people aged 12-15 years and key stakeholders (National Health Service commissioners, school staff, immunisation nurses and youth workers/practitioners) will be facilitated through existing links with healthcare organisations, schools and youth organisations in areas with lower uptake of the HPV vaccination programme. The proposed research will comprise three phases: (1) a rapid review of adolescent immunisation materials and preliminary qualitative interviews with young people and key stakeholders, (2) theory development and co-production of HPV vaccine communication materials through an iterative process with young people and (iii) testing delivery mechanisms and acceptability of the educational package in four schools with lower uptake. ETHICS AND DISSEMINATION: The University of Bristol's Faculty of Health Sciences and London School of Hygiene and Tropical Medicine's Research Ethics Committees provided approvals for the study. A dissemination event for young people and key stakeholders and webinar with the National Immunisation Network will be organised. The study findings will be published in peer-reviewed journals and presented at conferences. Recommendations for a future larger scale study will be made.

Young women's autonomy and information needs in the schools-based HPV vaccination programme: a qualitative study.

BACKGROUND: Until 2019, the English schools-based human papillomavirus (HPV) vaccination programme was offered to young women (but not young men) aged 12 to 13 years to reduce HPV-related morbidity and mortality. The aim of this study is to explore the extent to which young women were able to exercise autonomy within the HPV vaccination programme. We consider the perspectives of young women, parents and professionals and how this was influenced by the content and form of information provided. METHODS: Recruitment was facilitated through a healthcare organisation, schools and community organisations in a local authority in the south-west of England. Researcher observations of HPV vaccination sessions were carried out in three schools. Semi-structured interviews took place with 53 participants (young women, parents of adolescent children, school staff and immunisation nurses) during the 2017/18 and 2018/19 programme years. Interviews were recorded digitally and transcribed verbatim. Thematic analysis was undertaken, assisted by NVivo software. RESULTS: Young women's active participation and independence within the HPV vaccination programme was constrained by the setting of vaccination and the primacy of parental consent procedures. The authoritarian school structure influenced the degree to which young women were able to actively participate in decisions about the HPV vaccination programme. Young women exercised some power, either to avoid or receive the vaccine, by intercepting parental consent forms and procedures. Reliance on leaflets to communicate information led to unmet information needs for young women and their families. Communication may be improved by healthcare professional advocacy, accessible formats of information, and delivery of educational sessions. CONCLUSIONS: Strategies to improve communication about the HPV vaccine may increase young people's autonomy in consent procedures, clarify young people's rights and responsibilities in relation to their health care services, and result in higher uptake of the HPV vaccination programme. TRIAL REGISTRATION: ISRCTN 49086105 ; Date of registration: 12 January 2018; Prospectively registered.

FEV1 is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations. However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value. Patients and Methods: Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC). The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score. Results: Compared to Q1 (<53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively). In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV1 nor FVC was associated with cardiovascular risk. Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase). Conclusion: Our results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.

Adjudication of cardiovascular events in patients with chronic obstructive pulmonary disease: SUMMIT trial.

BACKGROUND: Adjudicated cause-specific mortality has been used in major trials of chronic obstructive pulmonary disease. However, there is less experience with adjudicated major adverse cardiovascular events as a key efficacy outcome in chronic obstructive pulmonary disease trials. The Study to Understand Mortality and Morbidity in chronic obstructive pulmonary disease trial required a Clinical Endpoint Committee to adjudicate the outcomes of modified major adverse cardiovascular events and cause-specific mortality. METHODS AND RESULTS: A six-member Clinical Endpoint Committee reviewed adverse event and serious adverse event reports included in a list of 204 Medical Dictionary for Regulatory Activities terms. Adverse events were triaged by one Clinical Endpoint Committee member, and then reviewed by three reviewers (round 1). If these three disagreed on the adjudication, the event was discussed by the full committee to reach a consensus (round 2). Among 16,485 participants, 48,105 adverse events were reported, among which 3314 were reviewed by the Clinical Endpoint Committee. After triage, 1827 were adjudicated in round 1; 338 required committee consensus in round 2, yielding 450 myocardial infarctions, strokes, unstable anginas or transient ischaemic attacks. Only 20/1627 (1%) non-serious adverse events were adjudicated as cardiovascular events. Only 45/204 Medical Dictionary for Regulatory Activities terms reviewed yielded cardiovascular events. A total of 430 deaths were adjudicated in round 1 and 631 in round 2, yielding 459 cardiovascular deaths. Adjudication of chest pain and sudden death often required additional information from site investigators. Site assessment of cardiovascular death was moderately specific (501/602 = 83%) but not sensitive (256/459 = 56%). CONCLUSION: A Clinical Endpoint Committee is useful for adjudication of major adverse cardiovascular events in chronic obstructive pulmonary disease trials but requires considerable resources and effort by investigators. This process can be streamlined by reviewing only serious adverse events and filtering by selected Medical Dictionary for Regulatory Activities terms.

Influence of commissioned provider type and deprivation score on uptake of the childhood flu immunization.

BACKGROUND: Since 2015/16 the UK seasonal influenza immunization programme has included children aged 5 and 6 years. In the South West of England school-based providers, GPs or community pharmacies were commissioned to deliver the vaccine depending on the locality. We aimed to assess variation in vaccine uptake in relation to the type of commissioned provider, and levels of socioeconomic deprivation. METHODS: Data from the South West of England (2015-16 season) were analysed using multilevel logistic regression to assess variation in vaccine uptake by type of commissioned provider, allowing for clustering of children within delivery sites. RESULTS: Overall uptake in 5 and 6 year olds was 34.3% (37 555/109 404). Vaccine uptake was highest when commissioned through school-based programmes 50.2% (9983/19 867) and lowest when commissioned through pharmacies, 23.1% (4269/18 479). Delivery through schools resulted in less variation by site and equal uptake across age groups, in contrast to GP and pharmacy delivery for which uptake was lower among 6 year olds. Vaccine uptake decreased with increasing levels of deprivation across all types of commissioned provider. CONCLUSION: School-based programmes achieve the highest and most consistent rates of childhood influenza vaccination. Interventions are still needed to promote more equitable uptake of the childhood influenza vaccine.

Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England.

Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaDB) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.