Association between cannabis potency and mental health in adolescence.

INTRODUCTION: In legal and illegal markets, high-potency cannabis (>10 % delta-9-tetrahydrocannabinol (THC)) is increasingly available. In adult samples higher-potency cannabis has been associated with mental health disorder but no studies have considered associations in adolescence. METHODS: A population-wide study compared no, low and high potency cannabis using adolescents (aged 13-14 years) self-reported symptoms of probable depression, anxiety, and auditory hallucinations. RESULTS: Of the 6672 participants, high-potency cannabis was used by 2.6 % (n=171) and low-potency by 0.6 % (n=38). After adjustment for sociodemographic factors, tobacco and alcohol use, in comparison to participants who had never used cannabis, people who had used high-potency but not low-potency cannabis were more likely to report symptoms of depression (odds ratio 1.59 [95 % confidence interval 1.06, 2.39), anxiety (OR 1.45, 95 % CI 0.96, 2.20), and auditory hallucinations (OR 1.56, 95 % CI 0.98, 2.47). CONCLUSIONS: High-potency cannabis use is associated with an increased risk of probable mental health disorders. Services and programming to minimise drug harms may need to be adapted to pay more attention to cannabis potency.

Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study.

OBJECTIVE: It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN: We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS: 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS: Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.

Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS): a prospective cohort study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment targeting hair follicles and deroofing of skin tunnels are standard HS interventions in some countries but are rarely offered in the UK. OBJECTIVES: To describe current UK HS management pathways and influencing factors to inform the design of future randomized controlled trials (RCTs). METHODS: THESEUS was a nonrandomized 12-month prospective cohort study set in 10 UK hospitals offering five interventions: oral doxycycline 200 mg daily; oral clindamycin and rifampicin both 300 mg twice daily for 10 weeks, extended for longer in some cases; laser treatment targeting hair follicles; deroofing; and conventional surgery. The primary outcome was the combination of clinician-assessed eligibility and participant hypothetical willingness to receive each intervention. The secondary outcomes were the proportion of participants selecting each intervention as their final treatment option; the proportion who switch treatments; treatment fidelity; and attrition rates. THESEUS was prospectively registered on the ISRCTN registry: ISRCTN69985145. RESULTS: The recruitment target of 150 participants was met after 18 months, in July 2021, with two pauses due to the COVID-19 pandemic. Baseline demographics reflected the HS secondary care population: average age 36 years, 81% female, 20% non-White, 64% current or ex-smokers, 86% body mass index ≥ 25, 68% with moderate disease, 19% with severe disease and 13% with mild disease. Laser was the intervention with the highest proportion (69%) of participants eligible and willing to receive treatment, then deroofing (58%), conventional surgery (54%), clindamycin and rifampicin (44%), and doxycycline (37%). Laser was ranked first choice by the greatest proportion of participants (41%). Attrition rates were 11% and 17% after 3 and 6 months, respectively. Concordance with doxycycline was 52% after 3 months due to lack of efficacy, participant choice and adverse effects. Delays with procedural interventions were common, with only 43% and 26% of participants starting laser and deroofing, respectively, after 3 months. Uptake of conventional surgery was too small to characterize the intervention. Switching treatment was uncommon and there were no serious adverse events. CONCLUSIONS: THESEUS has established laser treatment and deroofing for HS in the UK and demonstrated their popularity with patients and clinicians for future RCTs.

Treatment of Hidradenitis Suppurativa Evaluation Study: the THESEUS prospective cohort study.

Background: Hidradenitis suppurativa is a chronic inflammatory skin disease characterised by recurrent inflammatory lesions and skin tunnels in flexural sites such as the axilla. Deroofing of skin tunnels and laser treatment are standard hidradenitis suppurativa interventions in some countries but not yet introduced in the United Kingdom. Objective: To understand current hidradenitis suppurativa management pathways and what influences treatment choices to inform the design of future randomised controlled trials. Design: Prospective 12-month observational cohort study, including five treatment options, with nested qualitative interviews and an end-of-study consensus workshop. Setting: Ten United Kingdom hospitals with recruitment led by dermatology and plastic surgery departments. Participants: Adults with active hidradenitis suppurativa of any severity not adequately controlled by current treatment. Interventions: Oral doxycycline 200 mg once daily; oral clindamycin and rifampicin, both 300 mg twice daily for 10 weeks initially; laser treatment targeting the hair follicle (neodymium-doped yttrium aluminium garnet or alexandrite); deroofing; and conventional surgery. Main outcome measures: Primary outcome was the proportion of participants who are eligible, and hypothetically willing, to use the different treatment options. Secondary outcomes included proportion of participants choosing each of the study interventions, with reasons for their choices; proportion of participants who switched treatments; treatment fidelity; loss to follow-up rates over 12 months; and efficacy outcome estimates to inform outcome measure instrument responsiveness. Results: Between February 2020 and July 2021, 151 participants were recruited, with two pauses due to the COVID-19 pandemic. Follow-up rates were 89% and 83% after 3 and 6 months, decreasing to 70% and 44% at 9 and 12 months, respectively, because pandemic recruitment delays prevented all participants reaching their final review. Baseline demographics included an average age of 36 years, 81% female, 20% black, Asian or Caribbean, 64% current or ex-smokers and 86% with a raised body mass index. Some 69% had moderate disease, 19% severe disease and 13% mild disease. Regarding the study's primary outcome, laser treatment was the intervention with the highest proportion (69%) of participants who were eligible and hypothetically willing to receive treatment, followed by deroofing (58%), conventional surgery (54%), the combination of oral clindamycin and rifampicin (44%) and doxycycline (37%). Considering participant willingness in isolation, laser was ranked first choice by the greatest proportion (41%) of participants. The cohort study and qualitative study demonstrated that participant willingness to receive treatment was strongly influenced by their clinician. Fidelity to oral doxycycline was only 52% after 3 months due to lack of effectiveness, participant preference and adverse effects. Delays receiving procedural interventions were common, with only 43% and 26% of participants commencing laser therapy and deroofing, respectively, after 3 months. Treatment switching was uncommon and there were no serious adverse events. Daily pain score text messages were initiated in 110 participants. Daily responses reduced over time with greatest concordance during the first 14 days. Limitations: It was not possible to characterise conventional surgery due to a low number of participants. Conclusion: The Treatment of Hidradenitis Suppurativa Evaluation Study established deroofing and laser treatment for hidradenitis suppurativa in the United Kingdom and developed a network of 10 sites for subsequent hidradenitis suppurativa randomised controlled trials. Future work: The consensus workshop prioritised laser treatment and deroofing as interventions for future randomised controlled trials, in some cases combined with drug treatment. Trial registration: This trial is registered as ISRCTN69985145. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/64) and is published in full in Health Technology Assessment; Vol. 27, No. 30. See the NIHR Funding and Awards website for further award information.

The Treatment of Hidradenitis Suppurativa Evaluation Study introduced deroofing of skin tunnels and laser treatment for hidradenitis suppurativa and found that these are preferred interventions for future trials compared with oral antibiotics or conventional surgery.

Association of cannabis, cannabidiol and synthetic cannabinoid use with mental health in UK adolescents.

BACKGROUND: Cannabis has been associated with poorer mental health, but little is known of the effect of synthetic cannabinoids or cannabidiol (often referred to as CBD). AIMS: To investigate associations of cannabis, synthetic cannabinoids and cannabidiol with mental health in adolescence. METHOD: We conducted a cross-sectional analysis with 13- to 14-year-old adolescents across England and Wales in 2019-2020. Multilevel logistic regression was used to examine the association of lifetime use of cannabis, synthetic cannabinoids and cannabidiol with self-reported symptoms of probable depression, anxiety, conduct disorder and auditory hallucinations. RESULTS: Of the 6672 adolescents who participated, 5.2% reported using of cannabis, 1.9% reported using cannabidiol and 0.6% reported using synthetic cannabinoids. After correction for multiple testing, adolescents who had used these substances were significantly more likely to report a probable depressive, anxiety or conduct disorder, as well as auditory hallucinations, than those who had not. Adjustment for socioeconomic disadvantage had little effect on associations, but weekly tobacco use resulted in marked attenuation of associations. The association of cannabis use with probable anxiety and depressive disorders was weaker in those who reported using cannabidiol than those who did not. There was little evidence of an interaction between synthetic cannabinoids and cannabidiol. CONCLUSIONS: To our knowledge, this study provides the first general population evidence that synthetic cannabinoids and cannabidiol are associated with probable mental health disorders in adolescence. These associations require replication, ideally with prospective cohorts and stronger study designs.

Changes in incidence and clinical features of inflammatory bowel disease in Cardiff, UK over 50 years: an update for 2005-2016.

INTRODUCTION: Population-based studies of inflammatory bowel disease (IBD) in Cardiff have recorded data back to 1930 for Crohn's disease (CD) and 1968 for ulcerative colitis (UC). This study compares incidence and phenotype for 2005-2016 with past data. METHODS: All new IBD cases resident in the Cardiff at diagnosis were collected retrospectively for the 12-year period 2005-2016, and compared with previous Cardiff data for trends in incidence and phenotype. Overall incidence was age/sex corrected to the UK population. RESULTS: There were 991 new patients: 34% had CD, 5.4% IBD unclassified (IBD-U) and 60.5% had UC. The corrected incidence of CD was 7.7 per 100,000 person years [95% CI 6.9-8.6]. CD incidence is significantly higher than previous Cardiff studies, but the annual percentage change (APC) for 1980-2016 of 0.06; [95%CI -0.02 to 0.14] is not significant, with a previous higher APC for 1953-1980 of 0.18, [95%CI 0.13 to 0.23]. Uncorrected IBD-U incidence was 1.3 per 100,000 person years [95% CI 1.0-1.7]. UC corrected incidence was 14.4 per 100,000 person years [95% CI 13.3-15.6]. Incidence of UC is greater than in previous studies but did not increase during the current 12-year period. CD distribution at diagnosis continues to change as in previous Cardiff studies, with further increase in colonic disease and ileocolonic, (42% L2, 28% L3) and reduction in isolated terminal ileal disease (29% L1). CONCLUSIONS: Incidence of both CD and UC are no longer rising significantly, but the location of CD at diagnosis continues to change with an increase in colonic location.Key messagesWhat is already known? It is unclear whether the incidence of IBD has now plateaued in urbanised nations. Changes in Crohn's disease location are often not reported in incidence studies and terminal ileal disease has usually been reported as the commonest site of diseaseWhat is new here? The incidence of UC and Crohn's is no longer rising in Cardiff UK, but the phenotype has changed progressively over time with a continuing increase in colonic disease location and decrease in isolated terminal ileal diseaseHow can this study help patient care? Understanding that Crohn's colitis is the predominant location has implications for diagnostic tests and implications for treatment optionsIMPACT STATEMENTThis work shows that although IBD incidence is no longer rising, the pattern of Crohn's disease is changing with more colonic disease and less isolated terminal ileal disease.PRACTITIONER RELEVANCE STATEMENTThe changing pattern of Crohn's disease location has implications for diagnostic assessment and treatment of this disease.

Protocol for a feasibility study of a cancer symptom awareness campaign to support the rapid diagnostic centre referral pathway in a socioeconomically deprived area: Targeted Intensive Community-based campaign To Optimise Cancer awareness (TIC-TOC).

INTRODUCTION: Rapid diagnostic centres (RDCs) are being implemented across the UK to accelerate the assessment of vague suspected cancer symptoms. Targeted behavioural interventions are needed to augment RDCs that serve socioeconomically deprived populations who are disproportionately affected by cancer, have lower cancer symptom awareness and are less likely to seek help for cancer symptoms. The aim of this study is to assess the feasibility and acceptability of delivering and evaluating a community-based vague cancer symptom awareness intervention in an area of high socioeconomic deprivation. METHODS AND ANALYSIS: Intervention materials and messages were coproduced with local stakeholders in Cwm Taf Morgannwg, Wales. Cancer champions will be trained to deliver intervention messages and distribute intervention materials using broadcast media (eg, local radio), printed media (eg, branded pharmacy bags, posters, leaflets), social media (eg, Facebook) and attending local community events. A cross-sectional questionnaire will include self-reported patient interval (time between noticing symptoms to contacting the general practitioner), cancer symptom recognition, cancer beliefs and barriers to presentation, awareness of campaign messages, healthcare resource use, generic quality of life and individual and area-level deprivation indicators. Consent rates and proportion of missing data for patient questionnaires (n=189) attending RDCs will be measured. Qualitative interviews and focus groups will assess intervention acceptability and barriers/facilitators to delivery. ETHICS AND DISSEMINATION: Ethical approval for this study was given by the London-West London & GTAC Research Ethics (21/LO/0402). This project will inform a potential future controlled study to assess intervention effectiveness in reducing the patient interval for vague cancer symptoms. The results will be critical to informing national policy and practice regarding behavioural interventions to support RDCs in highly deprived populations.

Health behaviour change among UK adults during the pandemic: findings from the COVID-19 cancer attitudes and behaviours study.

BACKGROUND: COVID-19 related lockdowns may have affected engagement in health behaviours among the UK adult population. This prospective observational study assessed socio-demographic patterning in attempts to change and maintain a range of health behaviours and changes between two time points during the pandemic. METHODS: Adults aged 18 years and over (n = 4,978) were recruited using Dynata (an online market research platform) and the HealthWise Wales platform, supplemented through social media advertising. Online surveys were conducted in August/September 2020 when lockdown restrictions eased in the UK following the first major UK lockdown (survey phase 1) and in February/March 2021 during a further national lockdown (survey phase 2). Measures derived from the Cancer Awareness Measure included self-reported attempts to reduce alcohol consumption, increase fruit/vegetable consumption, increase physical activity, lose weight and reduce/stop smoking. Multivariable logistic regressions were used to assess individual health behaviour change attempts over time, adjusted for age, sex, ethnicity, employment and education. RESULTS: Around half of participants in survey phase 1 reported trying to increase physical activity (n = 2607, 52.4%), increase fruit/vegetables (n = 2445, 49.1%) and lose weight (n = 2413, 48.5%), with 19.0% (n = 948) trying to reduce alcohol consumption among people who drink. Among the 738 participants who smoked, 51.5% (n = 380) were trying to reduce and 27.4% (n = 202) to stop smoking completely. Most behaviour change attempts were more common among women, younger adults and minority ethnic group participants. Efforts to reduce smoking (aOR: 0.98, 95% CI: 0.82-1.17) and stop smoking (aOR: 0.98, 95% CI: 0.80-1.20) did not differ significantly in phase 2 compared to phase 1. Similarly, changes over time in attempts to improve other health behaviours were not statistically significant: physical activity (aOR: 1.07; 95% CI: 0.99-1.16); weight loss (aOR: 0.95; 95% CI: 0.90-1.00); fruit/vegetable intake (aOR: 0.98, 95% CI: 0.91-1.06) and alcohol use (aOR: 1.32, 95% CI: 0.92-1.91). CONCLUSION: A substantial proportion of participants reported attempts to change health behaviours in the initial survey phase. However, the lack of change observed over time indicated that overall motivation to engage in healthy behaviours was sustained among the UK adult population, from a period shortly after the first lockdown toward the end of the second prolonged lockdown.

Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS): protocol for a prospective cohort study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful, inflammatory skin disease with estimates of prevalence in the European population of 1%-2%. Despite being a relatively common condition, the evidence base for management of HS is limited. European and North American management guidelines rely on consensus for many aspects of treatment and within the UK variations in management of HS have been identified. The HS James Lind Alliance Priority Setting Partnership (PSP) published a top 10 list of future HS research priorities including both medical and surgical interventions. The aims of the THESEUS study are to inform the design of future HS randomised controlled trials (RCTs) and to understand how HS treatments are currently used. THESEUS incorporates several HS PSP research priorities, including investigation of oral and surgical treatments. Core outcome domains have been established by the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) and THESEUS is designed to validate instruments to measure the domains. METHODS AND ANALYSIS: The THESEUS study is a prospective observational cohort study. Participants, adults with active HS of any severity, will be asked to select one of five HS treatment options that is appropriate for their HS care. Participants will be allocated to their chosen treatment intervention and followed for a period of up to 12 months. Outcomes will be assessed at 3-monthly intervals using HISTORIC core outcome instruments. Video recordings of the surgical and laser operations will provide informational and training videos for future trials. Nested mixed-methods studies will characterise the interventions in clinical practice, understand facilitators and barriers to recruitment into future HS RCTs and examine patients' and clinicians' perspectives on HS treatment choices. TRIAL REGISTRATION NUMBER: ISRCTN69985145.

Intentions to participate in cervical and colorectal cancer screening during the COVID-19 pandemic: A mixed-methods study.

Worldwide, cancer screening faced significant disruption in 2020 due to the COVID-19 pandemic. If this has led to changes in public attitudes towards screening and reduced intention to participate, there is a risk of long-term adverse impact on cancer outcomes. In this study, we examined previous participation and future intentions to take part in cervical and colorectal cancer (CRC) screening following the first national lockdown in the UK. Overall, 7543 adults were recruited to a cross-sectional online survey in August-September 2020. Logistic regression analyses were used to identify correlates of strong screening intentions among 2319 participants eligible for cervical screening and 2502 eligible for home-based CRC screening. Qualitative interviews were conducted with a sub-sample of 30 participants. Verbatim transcripts were analysed thematically. Of those eligible, 74% of survey participants intended to attend cervical screening and 84% intended to complete home-based CRC screening when next invited. Thirty percent and 19% of the cervical and CRC samples respectively said they were less likely to attend a cancer screening appointment now than before the pandemic. Previous non-participation was the strongest predictor of low intentions for cervical (aOR 26.31, 95% CI: 17.61-39.30) and CRC (aOR 67.68, 95% CI: 33.91-135.06) screening. Interview participants expressed concerns about visiting healthcare settings but were keen to participate when screening programmes resumed. Intentions to participate in future screening were high and strongly associated with previous engagement in both programmes. As screening services recover, it will be important to monitor participation and to ensure people feel safe to attend.

Cancer symptom experience and help-seeking behaviour during the COVID-19 pandemic in the UK: a cross-sectional population survey.

OBJECTIVES: To understand self-reported potential cancer symptom help-seeking behaviours and attitudes during the first 6 months (March-August 2020) of the UK COVID-19 pandemic. DESIGN: UK population-based survey conducted during August and September 2020. Correlates of help-seeking behaviour were modelled using logistic regression in participants reporting potential cancer symptoms during the previous 6 months. Qualitative telephone interviews with a purposeful subsample of participants, analysed thematically. SETTING: Online UK wide survey. PARTICIPANTS: 7543 adults recruited via Cancer Research UK online panel provider (Dynata) and HealthWise Wales (a national register of 'research ready' participants) supplemented with social media (Facebook and Twitter) recruitment. 30 participants were also interviewed. MAIN OUTCOME MEASURES: Survey measures included experiences of 15 potential cancer symptoms, help-seeking behaviour, barriers and prompts to help-seeking. RESULTS: Of 3025 (40.1%) participants who experienced a potential cancer symptom, 44.8% (1355/3025) had not contacted their general practitioner (GP). Odds of help-seeking were higher among participants with disability (adjusted OR (aOR)=1.38, 95% CI 1.11 to 1.71) and who experienced more symptoms (aOR=1.68, 95% CI 1.56 to 1.82), and lower among those who perceived COVID-19 as the cause of symptom(s) (aOR=0.36, 95% CI 0.25 to 0.52). Barriers included worries about wasting the doctor's time (1158/7543, 15.4%), putting strain on healthcare services (945, 12.6%) and not wanting to make a fuss (907, 12.0%). Interviewees reported reluctance to contact the GP due to concerns about COVID-19 and fear of attending hospitals, and described putting their health concerns on hold. CONCLUSIONS: Many people avoided healthcare services despite experiencing potential cancer symptoms during the COVID-19 pandemic. Alongside current help-seeking campaigns, well-timed and appropriate nationally coordinated campaigns should signal that services are open safely for those with unusual or persistent symptoms. TRIAL REGISTRATION NUMBER: ISRCTN17782018.

Identifying factors associated with spontaneous restoration of hearing in children with otitis media with effusion.

OBJECTIVES: To identify predictors of acceptable hearing at 5 weeks, 6 and 12 months in children with bilateral otitis media with effusion (OME). DESIGN AND SETTING: Secondary analysis of OSTRICH data, conducted in hospital ear, nose and throat (ENT) and paediatric audiology and audiovestibular medicine departments across Wales and England. PARTICIPANTS: The OSTRICH study included 389 children aged 2-8 years with bilateral hearing loss attributable toOME for at least 3 months. MAIN OUTCOME MEASURES: Baseline, 5-week, 6- and 12-month audiology measurements were collected and logistic regression models used to identify pre-randomisation baseline variables that predicted return of acceptable hearing, which was defined as less than or equal to 20 dB hearing loss averaged within the frequencies of 0.5, 1, 2 and 4 kHz in at least one ear in children assessed by pure tone audiometry, ear-specific insert visual reinforcement audiometry or ear-specific play audiometry less than or equal to 25 dB hearing loss averaged within the frequencies of 0.5, 1, 2 and 4 kHz in children assessed by sound-field visual reinforcement audiometry or sound-field performance/play audiometry, based on national guidelines. RESULTS: Less severe baseline hearing loss across both ears most consistently predicted acceptable hearing at 5 weeks (adjusted odds ratio [aOR] 0.91, 95% CI 0.87-0.95), 6 months (0.94 [0.90-0.98]) and 12 months (0.93 [0.89-0.97]). Negative history of atopy (2.05 [1.16-3.61]), never using hearing aids (aOR 2.16 [1.04-4.48]), and being male (1.75 [1.02-2.99]) were significant at 6 months, but not at 12 months. Symptom duration was a predictor at 5 weeks, but not at 6 or 12 months. CONCLUSIONS: Milder baseline hearing loss most consistently predicts acceptable hearing at 5 weeks, 6 and 12 months in children with chronic OME. Negative history of atopy, never using hearing aids, and male gender are associated with better prognosis. These predictors can be used to identify children that may not require treatment.

Alternative approaches to managing respiratory tract infections: a survey of public perceptions.

BACKGROUND: Respiratory tract infections (RTIs) are a common reason for people to consult in primary care, and contribute to antibiotic overuse and antimicrobial resistance (AMR). Alternative approaches to supporting patients with RTIs may help, but it is important to understand public perceptions about these approaches before they are widely implemented. AIM: To describe public perceptions regarding finger-prick testing, back-up antibiotic prescriptions (BUPs), and alternatives to traditional consultations for RTIs, and identify factors associated with favouring these approaches. DESIGN & SETTING: Online national survey (HealthWise Wales) with linked primary care health record data. METHOD: Survey item response distributions were described. Associations between responses about consultation alternatives, BUP, and finger-prick point-of-care testing (POCT), and potential explanatory variables, were explored using logistic regression. RESULTS: A total of 8752 participants completed the survey between 2016 and 2018. The survey found 76.7% (n = 3807/4,966) and 71.2% (n = 3529/4,953) of responders with valid responses were in favour of being able to consult with a pharmacist or nurse in their GP surgery, or with a community pharmacist, respectively. It also showed 92.8% (n = 8034/8659) of responders indicated they would be happy to have a finger-prick test to guide antibiotic prescribing, and 31.8% (n = 2746/8646) indicated they would like to be given a BUP if their clinician thought immediate antibiotics were not required. In addition, 47.4% (n = 2342/4944) and 42.3% (n = 2095/4949) were in favour of having video and email consultations, respectively. Characteristics associated with different response options were identified. CONCLUSION: Consulting with pharmacists, using electronic communication tools, and finger-prick testing are widely acceptable approaches. BUP was described as acceptable less often, and is likely to require greater information and support when used.

The effect of ventilation tube insertion on quality of life in children with persistent otitis media with effusion.

OBJECTIVES: To determine the effect of ventilation tube (VT) surgery on quality of life (QoL) in children with persistent otitis media with effusion (OME). DESIGN: Secondary analysis of trial data (oral steroids versus placebo for persistent OME), comparing QoL by history of VT surgery performed between 5 weeks and 12 months post-randomisation. Multilevel regression models were used to identify the association between VT surgery and QoL scores at 12 months, controlling for pre-exposure risk factors associated with surgery, including pre-surgery hearing level. SETTING: Ear, nose and throat (ENT), paediatric audiology and audiovestibular medicine (AVM) departments in Wales and England. PARTICIPANTS: A total of 327 children aged 2-8 years with OME symptoms for at least three months and audiometry-proven bilateral hearing loss with VT surgery status. MAIN OUTCOME MEASURES: Otitis Media questionnaire (OM8-30) and Paediatric Quality of Life Inventory (PedsQL) total and subscale scores, and the Health Utilities Index Mark 3 (HUI3) at 12 months post-randomisation. RESULTS: Participants who had VT surgery had no significant difference in OM8-30, PedsQL or HUI total scores. OM8-30 hearing difficulty (HD) subscale scores at 12 months were better in those who had VT surgery (adjusted mean difference (aMD) = -0.46 (95% confidence interval: -0.69 to -0.23), P < .001), and this varied by when the surgery occurred (aMD for surgery between 5 weeks and 6 months = -0.4 [-0.67 to -0.13], P = .004 and between 6 and 12 months = -0.54, [-0.87 to -0.22], P = .001). CONCLUSION: Ventilation tube surgery was associated with an improvement in HD-related functional health status but no change in overall QoL.

A Validation and Calibration Process for Self-reported Tobacco Use With Participants' Cotinine Levels: An Example From the Building Blocks Trial.

INTRODUCTION: Reducing smoking in pregnancy was a primary outcome in our Building Blocks trial of the Family Nurse Partnership. We calibrated maternal reports of smoking using cotinine values derived from urine samples to assess tobacco use. This involves identifying the extent to which an individual accurately reports smoking and requires complete and synchronized data collection over time. However, some urine samples may be missed or collected at a different time from self-report (non-synchronized. METHODS: We used statistical validation processes to address both non-synchronized and incomplete data. First, we examined consistency in reporting behaviors at baseline and follow-up for participants grouped by extent of non-synchronized time of collection. Second, we used data from complete cases to infer values for mothers with missing urine samples at follow-up. We then used Markov chain transition rate matrix constructed to assess the robustness of such inferences. RESULTS: Maternal underreporting and overreporting of smoking were consistent across the 870 participants grouped by different levels of noncontemporary data collection (Breslow-Day test: p = .24; chi-square test: p = .69). Using participants' baseline reporting behaviors to infer their follow-ups provided comparable smoking outcomes (4.5 cigarettes/day with SD of 5.5) to the simulated counterparts (4.5 cigarettes/day with SD of 6.0). CONCLUSION: We have demonstrated consistent reporting behavior over time and minimal impact due to nonaligned follow-up urine sample collection. For studies collecting smoking data, this proposed method provided a pragmatic solution to facilitate the calibration process of self-reported tobacco use and retain adequate power without introducing undue bias. IMPLICATIONS: Synchronized and completed data collection is essential but very often hard to achieve in smoking related studies. When violated, proper statistical validation process should be followed to minimize the potential bias and loss of power in trial analyses. For this purpose, we provided the Building Block trial as an example to demonstrate how to deal with the non-synchronization and incompleteness issues in data collection.

Oral steroids for hearing loss associated with otitis media with effusion in children aged 2-8 years: the OSTRICH RCT.

BACKGROUND: Children with hearing loss associated with otitis media with effusion (OME) are commonly managed through surgical intervention, hearing aids or watchful waiting. A safe, inexpensive, effective medical treatment would enhance treatment options. Small, poorly conducted trials have found a short-term benefit from oral steroids. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of a 7-day course of oral steroids in improving hearing at 5 weeks in children with persistent OME symptoms and current bilateral OME and hearing loss demonstrated by audiometry. DESIGN: Double-blind, individually randomised, placebo-controlled trial. SETTING: Ear, nose and throat outpatient or paediatric audiology and audiovestibular medicine clinics in Wales and England. PARTICIPANTS: Children aged 2-8 years, with symptoms of hearing loss attributable to OME for at least 3 months, a diagnosis of bilateral OME made on the day of recruitment and audiometry-confirmed hearing loss. INTERVENTIONS: A 7-day course of oral soluble prednisolone, as a single daily dose of 20 mg for children aged 2-5 years or 30 mg for 6- to 8-year-olds, or matched placebo. MAIN OUTCOME MEASURES: Acceptable hearing at 5 weeks from randomisation. Secondary outcomes comprised acceptable hearing at 6 and 12 months, tympanometry, otoscopic findings, health-care consultations related to OME and other resource use, proportion of children who had ventilation tube (grommet) surgery at 6 and 12 months, adverse effects, symptoms, functional health status, health-related quality of life, short- and longer-term cost-effectiveness. RESULTS: A total of 389 children were randomised. Satisfactory hearing at 5 weeks was achieved by 39.9% and 32.8% in the oral steroid and placebo groups, respectively (absolute difference of 7.1%, 95% confidence interval -2.8% to 16.8%; number needed to treat = 14). This difference was not statistically significant. The secondary outcomes were consistent with the picture of a small or no benefit, and we found no subgroups that achieved a meaningful benefit from oral steroids. The economic analysis showed that treatment with oral steroids was more expensive and accrued fewer quality-adjusted life-years than treatment as usual. However, the differences were small and not statistically significant, and the sensitivity analyses demonstrated large variation in the results. CONCLUSIONS: OME in children with documented hearing loss and attributable symptoms for at least 3 months has a high rate of spontaneous resolution. Discussions about watchful waiting and other interventions will be enhanced by this evidence. The findings of this study suggest that any benefit from a short course of oral steroids for OME is likely to be small and of questionable clinical significance, and that the treatment is unlikely to be cost-effective and, therefore, their use cannot be recommended. FUTURE WORK: Studies exploring optimal approaches to sharing natural history data and enhancing shared decision-making are needed for this condition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49798431 and EudraCT 2012-005123-32. 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. 22, No. 61. See the NIHR Journals Library website for further project information.

The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. METHODS/DESIGN: We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16-60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least -2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. DISCUSSION: This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions-recall memory (verbal and non-verbal) and executive function-in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether larger-scale trials are indicated and to explore suitable outcome measures and analytical methods for neurocognitive trial design. TRIAL REGISTRATION: ISRCTN09739757 . Registered on 28 Dec 2011.

Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial.

BACKGROUND: Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. METHODS: We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. FINDINGS: Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64-1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI -47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99-1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77-1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother-child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention. INTERPRETATION: Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge. FUNDING: Department of Health Policy Research Programme.

The effectiveness and cost-effectiveness of the Family Nurse Partnership home visiting programme for first time teenage mothers in England: a protocol for the Building Blocks randomised controlled trial.

BACKGROUND: The Nurse Family Partnership programme was developed in the USA where it is made available to pregnant young mothers in some socially deprived geographic areas. The related Family Nurse Partnership programme was introduced in England by the Department of Health in 2006 with the aim of improving outcomes for the health, wellbeing and social circumstances of young first-time mothers and their children. METHODS / DESIGN: This multi-centre individually randomised controlled trial will recruit 1600 participants from 18 Primary Care Trusts in England, United Kingdom. The trial will evaluate the effectiveness of Family Nurse Partnership programme and usual care versus usual care for nulliparous pregnant women aged 19 or under, recruited by 24 weeks gestation and followed until the child's second birthday. Data will be collected from participants at baseline, 34-36 weeks gestation, 6, 12, 18 and 24 months following birth. Routine clinical data will be collected from maternity, primary care and hospital episodes statistics. Four primary outcomes are to be reported from the trial: birth weight; prenatal tobacco use; child emergency attendances and/or admissions within two years of birth; second pregnancy within two years of first birth. DISCUSSION: This trial will evaluate the effectiveness and cost effectiveness of the Family Nurse Partnership in England. The findings will provide evidence on pregnancy and early childhood programme outcomes for policy makers, health professionals and potential recipients in three domains (pregnancy and birth, child health and development, and parental life course and self-sufficiency) up to the child's second birthday. TRIAL REGISTRATION: Trial registration number: ISRCTN23019866.

Excision of malignant melanomas in North Wales: effect of location and surgeon on time to diagnosis and quality of excision.

BACKGROUND: The epidemiology of melanoma is changing and its current management is variable, with some lesions being removed in general practice. We aimed to determine the quality of excision and time to diagnosis relating to the excising surgeon and the place of excision. METHOD: Analysis of data from the North Wales Melanoma Database. RESULTS: In total, 578 cases were diagnosed 1993-2001. There was a gender difference with anatomical location, with 107 (65%) males with lesions on their trunk compared to 57 (35%) females. Median Breslow thickness was 1.10 mm (range 0.05-16.0 mm). Ninety-five (16%) lesions were removed in general practice, of which 49 (52%) were referred on to hospital. In total, 266 (61%) lesions were excised with 'adequate' margins and 170 (39%) excised with margins narrower than the guidelines. General practice excisions were from a younger group than hospital excisions. There were no differences in quality of excision between general practice and hospital excisions. Time to diagnosis was shorter overall for general practice excisions than hospital excisions (median 12 versus 41 days, P < 0.001). CONCLUSION: These findings are of policy importance in that there is no evidence from this study that general practice excisions are managed poorly or have a worse prognosis.