Clinical and cost-effectiveness of pessary self-management versus clinic-based care for pelvic organ prolapse in women: the TOPSY RCT with process evaluation.

Background: Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend clinics for pessary care. Objectives: To determine the clinical effectiveness and cost-effectiveness of vaginal pessary self-management on prolapse-specific quality of life for women with prolapse compared with clinic-based care; and to assess intervention acceptability and contextual influences on effectiveness, adherence and fidelity. Design: A multicentre, parallel-group, superiority randomised controlled trial with a mixed-methods process evaluation. Participants: Women attending UK NHS outpatient pessary services, aged ≥ 18 years, using a pessary of any type/material (except shelf, Gellhorn or Cube) for at least 2 weeks. Exclusions: women with limited manual dexterity, with cognitive deficit (prohibiting consent or self-management), pregnant or non-English-speaking. Intervention: The self-management intervention involved a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a local clinic telephone helpline number. Clinic-based care involved routine appointments determined by centres' usual practice. Allocation: Remote web-based application; minimisation was by age, pessary user type and centre. Blinding: Participants, those delivering the intervention and researchers were not blinded to group allocation. Outcomes: The patient-reported primary outcome (measured using the Pelvic Floor Impact Questionnaire-7) was prolapse-specific quality of life, and the cost-effectiveness outcome was incremental cost per quality-adjusted life-year (a specifically developed health Resource Use Questionnaire was used) at 18 months post randomisation. Secondary outcome measures included self-efficacy and complications. Process evaluation data were collected by interview, audio-recording and checklist. Analysis was by intention to treat. Results: Three hundred and forty women were randomised (self-management, n = 169; clinic-based care, n = 171). At 18 months post randomisation, 291 questionnaires with valid primary outcome data were available (self-management, n = 139; clinic-based care, n = 152). Baseline economic analysis was based on 264 participants (self-management, n = 125; clinic-based care, n = 139) with valid quality of life and resource use data. Self-management was an acceptable intervention. There was no group difference in prolapse-specific quality of life at 18 months (adjusted mean difference -0.03, 95% confidence interval -9.32 to 9.25). There was fidelity to intervention delivery. Self-management was cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, with an estimated incremental net benefit of £564.32 and an 80.81% probability of cost-effectiveness. At 18 months, more pessary complications were reported in the clinic-based care group (adjusted mean difference 3.83, 95% confidence interval 0.81 to 6.86). There was no group difference in general self-efficacy, but self-managing women were more confident in pessary self-management activities. In both groups, contextual factors impacted on adherence and effectiveness. There were no reported serious unexpected serious adverse reactions. There were 32 serious adverse events (self-management, n = 17; clinic-based care, n = 14), all unrelated to the intervention. Skew in the baseline data for the Pelvic Floor Impact Questionnaire-7, the influence of the global COVID-19 pandemic, the potential effects of crossover and the lack of ethnic diversity in the recruited sample were possible limitations. Conclusions: Self-management was acceptable and cost-effective, led to fewer complications and did not improve or worsen quality of life for women with prolapse compared with clinic-based care. Future research is needed to develop a quality-of-life measure that is sensitive to the changes women desire from treatment. Study registration: This study is registered as ISRCTN62510577. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/82/01) and is published in full in Health Technology Assessment; Vol. 28, No. 23. See the NIHR Funding and Awards website for further award information.

Pelvic organ prolapse is a common and distressing condition experienced by large numbers of women. Prolapse is when the organs that are usually in the pelvis drop down into the vagina. Women experience a feeling of something coming down into the vagina, along with bowel, bladder and sexual problems. One possible treatment is a vaginal pessary. The pessary is a device that is inserted into the vagina and holds the pelvic organs back in their usual place. Women who use a vaginal pessary usually come back to clinic every 6 months to have their pessary removed and replaced; this is called clinic-based care. However, it is possible for a woman to look after the pessary herself; this is called self-management. This study compared self-management with clinic-based care. Three hundred and forty women with prolapse took part; 171 received clinic-based care and 169 undertook self-management. Each woman had an equal chance of being in either group. Women in the self-management group received a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a telephone number for their local centre. Women in the clinic-based care group returned to clinic as advised by the treating healthcare professional. Self-management was found to be acceptable. Women self-managed their pessary in ways that suited their lifestyle. After 18 months, there was no difference between the groups in women's quality of life. Women in the self-management group experienced fewer pessary complications than women who received clinic-based care. Self-management costs less to deliver than clinic-based care. In summary, self-management did not improve women's quality of life more than clinic-based care, but it did lead to women experiencing fewer complications and cost less to deliver in the NHS. The findings support self-management as a treatment pathway for women using a pessary for prolapse.

Effect of 3 months and 12 months of financial incentives on 12-month postpartum smoking cessation maintenance: A randomized controlled trial.

BACKGROUND AND AIMS: Offering financial incentives is effective for smoking cessation during pregnancy. We tested the effectiveness of financial incentives for maintaining postpartum cessation, comparing 12-month and 3-month incentives with each other and with usual care (UC). DESIGN, SETTING AND PARTICIPANTS: This study was a pragmatic, multi-centre, three-arm randomized controlled trial involving four English, National Health Service, stop smoking services. A total of 462 postpartum women (aged ≥ 16 years) took part, who stopped smoking during pregnancy with financial incentives, validated as abstinent from smoking at end of pregnancy or early postpartum. INTERVENTIONS: Interventions comprised (i) UC; (ii) UC plus up to £60 of financial voucher incentives offered to participants and £60 offered to an optional significant-other supporter, over 3 months postpartum, contingent upon validated abstinence ('3-month incentives'); or (iii) UC plus '3-month incentives' plus £180 of vouchers offered to participants over 9 months postpartum, contingent upon abstinence ('12-month incentives'). MEASUREMENTS: Primary outcome: biochemically validated abstinence at 1 year postpartum. To adjust for testing all comparisons between groups with equal precision, P < 0.017 was necessary for significance. SECONDARY OUTCOMES: self-reported and validated abstinence at 3 months postpartum; self-reported abstinence at 1 year postpartum. FINDINGS: Primary outcome ascertainment: abstinence was 39.6% (63/159) 12 months incentives, 21.4% (33/154) 3 months incentives and 28.2% (42/149) UC. Adjusted odds ratios [95% confidence interval (CI)] = 12-month versus 3-month incentives OR = 2.41 (95% CI = 1.46-3.96), P = 0.001; 12 months versus UC 1.67 (1.04-2.70), P = 0.035; 3 months versus UC 0.69 (0.41-1.17), P = 0.174. Bayes factors indicated that for 12-month versus 3-month incentives and 12 months versus UC there was good evidence for the alternative hypothesis, and for 3 months versus UC there was good evidence for the null hypothesis. CONCLUSIONS: This randomized controlled trial provides weak evidence that up to £300 of voucher incentives over 12 months is effective for maintaining smoking abstinence postpartum compared with usual care. There was good evidence that 12-month incentives are superior to those over only 3 months, for which there was no evidence of effectiveness relative to usual care.

Cost-effectiveness of 2 Models of Pessary Care for Pelvic Organ Prolapse: Findings From the TOPSY Randomized Controlled Trial.

OBJECTIVES: Pelvic organ prolapse is the descent of one or more reproductive organs from their normal position, causing associated negative symptoms. One conservative treatment option is pessary management. This study aimed to to investigate the cost-effectiveness of pessary self-management (SM) when compared with clinic-based care (CBC). A decision analytic model was developed to extend the economic evaluation. METHODS: A randomized controlled trial with health economic evaluation. The SM group received a 30-minute SM teaching session, information leaflet, 2-week follow-up call, and a local helpline number. The CBC group received routine outpatient pessary appointments, determined by usual practice. The primary outcome for the cost-effectiveness analysis was incremental cost per quality-adjusted life year (QALY), 18 months post-randomization. Uncertainty was handled using nonparametric bootstrap analysis. In addition, a simple decision analytic model was developed using the trial data to extend the analysis over a 5-year period. RESULTS: There was no significant difference in the mean number of QALYs gained between SM and CBC (1.241 vs 1.221), but mean cost was lower for SM (£578 vs £728). The incremental net benefit estimated at a willingness to pay of £20 000 per QALY gained was £564, with an 80.8% probability of cost-effectiveness. The modeling results were consistent with the trial analysis: the incremental net benefit was estimated as £4221, and the probability of SM being cost-effective at 5 years was 69.7%. CONCLUSIONS: Results suggest that pessary SM is likely to be cost-effective. The decision analytic model suggests that this result is likely to persist over longer durations.

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study.

OBJECTIVE: To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone. DESIGN: Population-based cohort study. SETTING: Scotland, UK. PARTICIPANTS: Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above. MAIN OUTCOME MEASURES: All-cause mortality, drug-related deaths and non-drug related deaths. SECONDARY OUTCOME: ORT continuous treatment duration. ANALYSIS: Cox regression with time-varying covariates. RESULTS: During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30). CONCLUSION: Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction. TRIAL REGISTRATION NUMBER: NCT04622995.

Assessment of patients with head and neck cancer using the MD Anderson Dysphagia Inventory: Results of a study into its comprehensiveness, comprehensibility and relevance to clinical practice.

BACKGROUND: The MD Anderson Dysphagia Inventory (MDADI) is a widely used patient-reported outcome measure (PROM) which assesses dysphagia-related quality of life (QoL) in head and neck cancer (HNC). Despite its common use in HNC research and clinical practice, few of its psychometric properties have been reappraised since its inception. The aim of this study was to perform a survey-based qualitative analysis of UK HNC clinicians' perceptions of the content validity of the MDADI, evaluating it across the parameters of relevance, comprehensiveness and comprehensibility as per the COSMIN guideline for PROM assessment. RESULTS: Four themes relating to the content validity of the MDADI were identified: (1) MDADI items lack clarity of definition of the terms 'swallowing', 'eating' and 'dysphagia'; (2) the MDADI is perceived to be overly negative in tone including items that service users may find distressing or disempowering; (3) items in the tool are exclusory to specific subgroups of patients, such as those who are nil by mouth or socially isolated; and (4) modifications to the MDADI were suggested and encouraged to make it more clinically useful and patient-centred. CONCLUSIONS: This study indicates that MDADI's content validity is 'insufficient' when rated by COSMIN parameters. This has significant implications for its continued use in HNC research and clinical practice. Further re-evaluation of the content validity of the MDADI is warranted, with potential future amendment of items being indicated if the results of this study are corroborated in subsequent research. WHAT THIS PAPER ADDS: What is already known on the subject The MD Anderson Dysphagia Inventory (MDADI) patient-reported outcome measure of dysphagia-related quality of life is widely used in clinical practice and international clinical trials. Content validity is considered to be the most important property of a tool when assessing its psychometric strengths and weaknesses; however, the MDADI's content validity has not been reappraised since its initial development. What this paper adds to existing knowledge This study presents UK speech and language therapists' opinions and experience of the content validity of the MDADI and this first reappraisal of its content validity since its initial development highlights several issues with this psychometric parameter of the tool. This study highlights that further re-evaluation of the content validity of the MDADI is warranted, with potential future amendment of items being indicated if the results of this study are corroborated in subsequent research. What are the potential or actual clinical implications of this work? Clinicians cannot assume that commonly used outcomes tools have strong psychometric profiles. Consideration of the content validity of outcomes tools during selection for use in clinical and research practice should be key, as this will encourage use of tools that produce relevant, valid data that can contribute meaningfully to patient-centred care.

When is the best time to screen for perinatal anxiety? A longitudinal cohort study.

BACKGROUND: For screening for anxiety during pregnancy and after birth to be efficient and effective it is important to know the optimal time to screen in order to identify women who might benefit from treatment. AIMS: To determine the optimal time to screen for perinatal anxiety to identify women with anxiety disorders and those who want treatment. A secondary aim was to examine the stability and course of perinatal anxiety over time. METHODS: Prospective longitudinal cohort study of 2243 women who completed five screening questionnaires of anxiety and mental health symptoms in early pregnancy (11 weeks), mid-pregnancy (23 weeks), late pregnancy (32 weeks) and postnatally (8 weeks). Anxiety and mental health questionnaires were the GAD7, GAD2, SAAS, CORE-10 and Whooley questions. To establish presence of anxiety disorders diagnostic interviews were conducted with a subsample of 403 participants. RESULTS: Early pregnancy was the optimal time to screen for anxiety to identify women with anxiety disorders and women wanting treatment at any time during pregnancy or postnatally. These findings were consistent across all five questionnaires of anxiety and mental health. Receiving treatment for perinatal mental health problems was most strongly associated with late pregnancy and/or postnatal assessments. Anxiety symptoms were highest in early pregnancy and decreased over time. CONCLUSION: Findings show that screening in early pregnancy is optimal for identifying women who have, or develop, anxiety disorders and who want treatment. This has clear implications for practice and policy for anxiety screening during the perinatal period.

Assessment of perinatal anxiety: diagnostic accuracy of five measures.

BACKGROUND: Anxiety in pregnancy and after giving birth (the perinatal period) is highly prevalent but under-recognised. Robust methods of assessing perinatal anxiety are essential for services to identify and treat women appropriately. AIMS: To determine which assessment measures are most psychometrically robust and effective at identifying women with perinatal anxiety (primary objective) and depression (secondary objective). METHOD: We conducted a prospective longitudinal cohort study of 2243 women who completed five measures of anxiety and depression (Generalized Anxiety Disorder scale (GAD) two- and seven-item versions; Whooley questions; Clinical Outcomes in Routine Evaluation (CORE-10); and Stirling Antenatal Anxiety Scale (SAAS)) during pregnancy (15 weeks, 22 weeks and 31 weeks) and after birth (6 weeks). To assess diagnostic accuracy a sample of 403 participants completed modules of the Mini-International Neuropsychiatric Interview (MINI). RESULTS: The best diagnostic accuracy for anxiety was shown by the CORE-10 and SAAS. The best diagnostic accuracy for depression was shown by the CORE-10, SAAS and Whooley questions, although the SAAS had lower specificity. The same cut-off scores for each measure were optimal for identifying anxiety or depression (SAAS ≥9; CORE-10 ≥9; Whooley ≥1). All measures were psychometrically robust, with good internal consistency, convergent validity and unidimensional factor structure. CONCLUSIONS: This study identified robust and effective methods of assessing perinatal anxiety and depression. We recommend using the CORE-10 or SAAS to assess perinatal anxiety and the CORE-10 or Whooley questions to assess depression. The GAD-2 and GAD-7 did not perform as well as other measures and optimal cut-offs were lower than currently recommended.

Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial.

Background: Prolapse affects 30-40% of women. Those using a pessary for prolapse usually receive care as an outpatient. This trial determined effectiveness and cost-effectiveness of pessary self-management (SM) vs clinic-based care (CBC) in relation to condition-specific quality of life (QoL). Methods: Parallel-group, superiority randomised controlled trial, recruiting from 16 May 2018 to 7 February 2020, with follow-up to 17 September 2021. Women attending pessary clinics, ≥18 years, using a pessary (except Shelf, Gellhorn or Cube), with pessary retained ≥2 weeks were eligible. Limited manual dexterity; cognitive deficit; pregnancy; or requirement for non-English teaching were exclusions. SM group received a 30-min teaching session; information leaflet; 2-week follow-up call; and telephone support. CBC group received usual routine appointments. The primary clinical outcome was pelvic floor-specific QoL (PFIQ-7), and incremental net monetary benefit for cost-effectiveness, 18 months post-randomisation. Group allocation was by remote web-based application, minimised on age, user type (new/existing) and centre. Participants, intervention deliverers, researchers and the statistician were not blinded. The primary analysis was intention-to-treat based. Trial registration: https://doi.org/10.1186/ISRCTN62510577. Findings: The requisite 340 women were randomised (169 SM, 171 CBC) across 21 centres. There was not a statistically significant difference between groups in PFIQ-7 at 18 months (mean SM 32.3 vs CBC 32.5, adjusted mean difference SM-CBC -0.03, 95% CI -9.32 to 9.25). SM was less costly than CBC. The incremental net benefit of SM was £564 (SE £581, 95% CI -£576 to £1704). A lower percentage of pessary complications was reported in the SM group (mean SM 16.7% vs CBC 22.0%, adjusted mean difference -3.83%, 95% CI -6.86% to -0.81%). There was no meaningful difference in general self-efficacy. Self-managing women were more confident in self-management activities. There were no reported suspected unexpected serious adverse reactions, and 31 unrelated serious adverse events (17 SM, 14 CBC). Interpretation: Pessary self-management is cost-effective, does not improve or worsen QoL compared to CBC, and has a lower complication rate. Funding: National Institute for Health and Care Research, Health Technology Assessment Programme (16/82/01).

The Quality of Life of Patients Living with a Urinary Catheter and Its Associated Factors: A Cross-Sectional Study in Egypt.

BACKGROUND: In Arabic countries, no research has focused on the experience of patients with indwelling urinary catheters. This cross-sectional study is the first to evaluate the catheter-specific quality of life (QoL) of patients living with a urinary catheter in Egypt. METHODS: This study was conducted from April to September 2017, using a convenience sample of patients from a University Hospital. Data were collected using the International Consultation on Incontinence Questionnaire-Long-Term Catheter QoL (ICIQ-LTCQoL) instrument, along with a demographic datasheet. RESULTS: 141 were enrolled, with 47.5% inpatients, 52.5% outpatients. A total of 70.9% reported problems with catheter function, and 92.2% reported that the catheter affected their daily lives. Place (inpatient or outpatient) was significantly associated with the total score of the ICIQ-LTCQoL (mean difference (MD) 6.34 (95% CI: 3.0 to 9.73)) and both subscales (catheter function subscale: MD = 4.92 (95% CI: 2.12 to 7.73) and lifestyle impact subscale: MD = 1.44 (95% CI: 0.3 to 2.63)), suggesting that outpatients have poorer QoL than inpatients. Moreover, catheter material was significantly related to the catheter function domain with Silicone Foley Catheter (100% Silicon) users experiencing poorer QoL related to catheter function than those with Latex Foley Catheter (Silicon-coated) (MD 4.43 (95% CI: 0.62 to 8.24). Workers/employees were found to have poorer QoL than those who were retired (MD = 4.94 (95% CI: 0.3 to 9.63)). CONCLUSION: The results highlight the necessity of assessing function and concern regarding urinary catheter use and its impact on QoL, as well as its determinants. Evidence-based educational programs should be designed to enhance patients' self-care abilities to relieve their sense of distress and enhance their confidence in caring for their catheters.

Potential for Treatment Interval Extension in Eyes with nAMD Disease Activity Post Loading Phase in HAWK and HARRIER.

INTRODUCTION: The HAWK and HARRIER studies evaluated the efficacy and safety of brolucizumab versus aflibercept in treatment-naïve eyes with neovascular age-related macular degeneration. Based on the study design, brolucizumab-treated eyes adjusted to a q8w regimen because the presence of disease activity (DA) at the end of the matched loading phase (Week 16) could not subsequently extend to a q12w interval. The aim of this post hoc analysis was to assess subsequent DA in this subgroup to determine the potential for interval extensions during the first year of treatment. METHODS: Pooled data from the brolucizumab 6 mg arms and aflibercept arms of HAWK and HARRIER were included. Presence of DA was determined by the masked investigator based on their assessment of functional and anatomical parameters measured by optical coherence tomography. DA was compared at DA assessments, conducted at Weeks 16, 20, 32, and 44; fluid was also assessed at the primary analysis at Week 48. RESULTS: Fewer brolucizumab- (22.8%) than aflibercept-treated (32.2%) eyes had DA at the first DA assessment at Week 16. In eyes with investigator-identified DA at Week 16, BCVA change from baseline to Week 96 was comparable between treatment arms. Fewer brolucizumab- than aflibercept-treated eyes had DA at each subsequent DA assessment in Year 1: 31.8% vs 39.1% (Week 20), 27.3% vs 43.5% (Week 32), and 17.3% vs 31.2% (Week 44). Fewer eyes treated with brolucizumab than aflibercept had intraretinal and/or subretinal fluid: 35.3% vs 43.5% (Week 20), 55.8% vs 69.6% (Week 32), 30.0% vs 43.1% (Week 44), and 48.6% vs 68.6% (Week 48). CONCLUSION: These findings indicate that, in eyes that still had DA 8 weeks after the final dose of loading phase, brolucizumab-treated eyes had improved fluid resolution and higher potential for treatment interval extension than aflibercept-treated eyes during the first year of treatment.

Impact of standardised packaging in the UK on warning salience, appeal, harm perceptions and cessation-related behaviours: a longitudinal online survey.

INTRODUCTION: In the UK, since 20 May 2017, tobacco companies must sell cigarettes and rolling tobacco in standardised packs. METHODS: Three waves of a longitudinal online survey with smokers (≥16) before standardised packaging (wave 1 (W1): April to May 2016) and after standardised packaging (wave 2 (W2): September to November 2017; wave 3 (W3): May to July 2019). Of the 6233 smokers at W1, 4293 responded at W2 and 3175 at W3. We explored smokers' response to warning salience, appeal (appeal, quality, value, satisfaction and taste compared with a year ago), harm (harmfulness compared with a year ago, harm compared with other brands and whether some brands have more harmful substances), and quit plans, attempts and quitting. RESULTS: Compared with W1, the proportions noticing warnings first on packs, and rating cigarettes/rolling tobacco less appealing and worse value than a year ago, were higher at W2 and W3. Disagreeing that some brands contain more harmful substances was higher at W2. Interactions between social grade and survey wave for warning salience, and each appeal and harm outcome, were non-significant. Smokers switching from not noticing warnings first at W1 to noticing warnings first at W2, or who had a lower composite appeal score at W2, were more likely to plan to quit and to have made a quit attempt at W2. Smokers who switched to disagreeing that some brands contain more harmful substances at W2, after giving a different response at W1, were more likely to quit at W3. CONCLUSIONS: Standardised packaging appears to be having the intended impacts.

Implementation of a national smoke-free prison policy: an economic evaluation within the Tobacco in Prisons (TIPs) study.

OBJECTIVE: To determine the cost-effectiveness of a smoke-free prison policy in Scotland, through assessments of the trade-offs between costs (healthcare and non-healthcare-related expenditure) and outcomes (health and non-health-related non-monetary consequences) of implementing the policy. DESIGN: A health economic evaluation consisting of three analyses (cost-consequence, cost-effectiveness and cost-utility), from the perspectives of the healthcare payer, prison service, people in custody and operational staff, assessed the trade-offs between costs and outcomes. Costs associated with the implementation of the policy, healthcare resource use and personal spend on nicotine products were considered, alongside health and non-health outcomes. The cost-effectiveness of the policy was evaluated over 12-month and lifetime horizons (short term and long term). SETTING: Scotland's national prison estate. PARTICIPANTS: People in custody and operational prison staff. INTERVENTION: Implementation of a comprehensive (indoor and outdoor) smoke-free policy. MAIN OUTCOME MEASURES: Concentration of secondhand smoke, health-related quality of life (health utilities and quality-adjusted life-years (QALY)) and various non-health outcomes (eg, incidents of assaults and fires). RESULTS: The short-term analyses suggest cost savings for people in custody and staff, improvements in concentration of secondhand smoke, with no consistent direction of change across other outcomes. The long-term analysis demonstrated that implementing smoke-free policy was cost-effective over a lifetime for people in custody and staff, with approximate cost savings of £28 000 and £450, respectively, and improvement in health-related quality of life of 0.971 QALYs and 0.262, respectively. CONCLUSION: Implementing a smoke-free prison policy is cost-effective over the short term and long term for people in custody and staff.

Efficacy and safety of brolucizumab versus aflibercept in eyes with early persistent retinal fluid: 96-week outcomes from the HAWK and HARRIER studies.

OBJECTIVE: Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER. METHODS: After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12. RESULTS: A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: -202 µm vs. -145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm. CONCLUSION: In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

Long-term effects and costs of pelvic floor muscle training for prolapse: trial follow-up record-linkage study.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse affects around 40% of women aged over 50 years. A multicentre parallel group randomised trial (the Pelvic Organ Prolapse PhysiotherapY (POPPY) trial) demonstrated that pelvic floor muscle training (PFMT) was effective in reducing prolapse symptoms compared with no treatment. However, insight into the long-term impact of PFMT on health outcomes and health-service utilisation is scarce. METHODS: This study utilised linkage of Scottish administrative health records to follow-up POPPY trial participants resident in Scotland over 11 years. Mixed effects logistic regression determined the likelihood of receiving further prolapse treatment for those in the PFMT and control groups. Analyses were adjusted for age group, prolapse stage, baseline symptom severity and attitude towards surgery. A cost assessment estimated longitudinal costs to the UK National Health Service (in Scotland) of accessing further prolapse treatment for each trial group. RESULTS: Two hundred and ninety-three women, aged 25 to 79 years, were followed up. One hundred and forty-one women (48.1%) had received further prolapse treatment: 65 (of 149; 43.6%) in the PFMT group compared with 76 (of 144; 52.8%) in the control group. PFMT was associated with a reduction in the odds of any prolapse treatment during follow-up (AOR 0.61; 95% CI 0.37 to 0.99). Total cost of secondary care was £154,544 (GBP) in the PFMT group and £172,549 (GBP) in the control group. CONCLUSIONS: Although PFMT did not lead to significant differences in total costs for further prolapse treatment over a post-intervention period of more than 10 years, it reduced the overall long-term risk of requiring hospital-based treatment for pelvic floor disorders.

Pterygoid muscle activity in speech: A preliminary investigation.

BACKGROUND: Speaking depends on refined control of jaw opening and closing movements. The medial pterygoid muscle (MPT), involved in jaw closing, and the lateral pterygoid muscle (LPT), involved in jaw opening, are two key mandibular muscles in mastication and are likely to be recruited for controlled movements in speech. OBJECTIVES: Three hypotheses were investigated, that during speech the MPT and LPT: (1) were both active, (2) but exhibited different patterns of activity, (3) which fluctuated with the vowels and consonants in speech. METHODS: Intramuscular EMG recordings were made from the right inferior head of the LPT and/or the right MPT in five participants during production of 40 target nonsense words (NWs) consisting of three syllables in the form /V1 C1 V2 C2 ə/ (V = vowel; C = consonant; ə = unstressed, reduced vowel), spoken by each participant 10 times per NW; analysis focussed on the target syllable, C1 V2 . RESULTS: Both MPT and LPT exhibited robust increases in EMG activity during utterance of most NWs, relative to rest. Peak LPT activation was time-locked to the final part of the target consonant (C1 ) interval when the jaw begins opening for the target vowel (V2 ), whereas peak MPT activation occurred around the temporal midpoint of V2 , when the jaw begins closing for C2 . EMG amplitude peaks differed in magnitude between "high" vowels, i.e., for which the tongue/jaw are high (e.g., in SEEK), and "low" vowels, i.e., for which the tongue/jaw are low (e.g., in SOCK). CONCLUSIONS: These novel findings suggest a key role for the LPT and MPT in the fine control of speech production. They imply that speech may impose major synergistic demands on the activities of the MPT and the LPT, and thereby provide insights into the possible interactions between speech activities and orofacial activities (e.g. mastication) and conditions (e.g. Temporomandibular Disorders) that involve the masticatory muscles.

Characteristics and outcomes of referrals to CAMHS for children who are thinking about or attempted suicide: A retrospective cohort study in two Scottish CAMHS.

Suicide among children and young people (CYP) is a leading cause of death. In the UK children identified as suicidal are referred to Child and Adolescent Mental Health Services (CAMHS) for assessment and treatment. However, the number of children referred for suicidality, and their care journey is unknown. This retrospective cohort study conducted in two distinct CAMHS teams, in Scotland, UK, aimed to quantify the numbers of children referred for suicidality, describing this population and the outcomes of these referrals. All CAMHS referrals (n = 1159) over a 6-month period (Jan-June 2019) were screened to identify those referred primarily for suicidality. Data extracted included: age, gender, source of referral, reason for referral including underlying issues, whether offered an assessment, and referral outcome. Area based deprivation scores were attached to each referral. Associations between the referred CYP's characteristics (including source of referral and underlying issues) and referral outcomes were explored using Chi Square, Fishers Exact test, and one-way ANOVA. Referrals for 284 children were identified as being for suicidality across the two sites (Site A n = 104; Site B n = 180). These represented 25% of all referrals to these CAMHS over a six-month period. One third of these concerned children under 12. The underlying issues, referrals sources, and demographic indicators were similar in both sites. In site A 31% were offered an assessment, whilst in Site B which had a dedicated team for suicidal CYP, 82% were offered an assessment. Similarly, more children in Site B were offered treatment (47.8%), than Site A (7.7%). Referrals from A&E were prioritized in both areas, and those who had attempted suicide offered an assessment more often. Older children were more likely to be offered treatment, although they were more likely to present with a history of self-harming behavior and/or previous suicide attempt. There are high numbers of children being referred to CAMHS for suicidality, and many are young children (<12). There is variation within and between services in terms of assessment, referral outcomes and care pathways for these children. Having a dedicated team to respond to referrals for suicidality appears to support access to assessment and treatment.

Fluid Control in Neovascular Age-Related Macular Degeneration with Brolucizumab: An Analysis of the HAWK and HARRIER Phase 3 Trials.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is characterized by exudation of fluid from abnormally growing blood vessels in the macula. Anti-vascular endothelial growth factor (VEGF) therapy is standard treatment for nAMD. Fluid resolution is used both as an indicator of disease control and to guide the frequency of treatment because of anti-VEGF therapy effectiveness in reducing neovascularization-related exudation. Herein reports a post hoc assessment of the HAWK and HARRIER trials comparing the efficacy and safety of brolucizumab with aflibercept in patients with nAMD. MATERIALS AND METHODS: HAWK randomized 1,078 patients with untreated, active choroidal neovascularization due to AMD in the study eye to receive brolucizumab 3, 6 mg or aflibercept 2 mg. In HARRIER, 739 patients received brolucizumab 6 mg or aflibercept 2 mg. Brolucizumab was injected at weeks 0, 4, and 8, and thereafter q12w unless disease activity was identified (injection interval: q8w). Aflibercept was injected q8w after the loading phase, aligned with approved dosing at study initiation. The objective of this analysis was to assess effects of brolucizumab versus aflibercept on retinal fluid resolution during two phase 3 trials (HAWK and HARRIER) in patients with nAMD. Anatomical assessments for intraretinal fluid (IRF) and subretinal fluid (SRF) were performed every 4 weeks by spectral domain optical coherence tomography. Sustained dryness was defined as a patient being fluid-free (SRF and IRF) on ≥3 consecutive visits. Time to sustained dryness was determined by Kaplan-Meier estimates. RESULTS: At week 96, fluid resolution (absence of IRF and SRF) was achieved by more brolucizumab- (6 mg; 76.1%) versus aflibercept-treated patients (63.1%; p = 0.0002, HAWK); 75.4% versus 61.8% (p < 0.0001, HARRIER). More patients achieved sustained dryness with brolucizumab versus aflibercept: at 96 weeks, 87.9% (brolucizumab 3 mg) and 86.1% (brolucizumab 6 mg) versus 82.0% (aflibercept) in HAWK, and 91.2% (brolucizumab) versus 78.0% (aflibercept) in HARRIER. Sustained dryness was achieved faster and hence with fewer brolucizumab injections. DISCUSSION/CONCLUSION: Brolucizumab dried the macula in patients with nAMD faster and to a greater degree than aflibercept. Achieving sustained dryness faster, and therefore with fewer injections, provides an opportunity for earlier decisions relating to treatment interval extension potentially reducing treatment burden.

Exploring the role of authentic leadership in nursing.

Authentic leadership is a relatively new concept in nursing, with limited studies undertaken into its application in healthcare. Authentic leadership emphasises the importance of the leader being true to their personal core values and developing honest relationships with team members, valuing their contributions, and behaving ethically and transparently. Trust is a central tenet of authentic leadership that aims to lead to increased staff engagement, and enhanced individual and team performance. This article explores the principles, benefits and challenges of authentic leadership, as well as examining its potential role in nursing.

Purchasing of tobacco-related and e-cigarette-related products within prisons before and after implementation of smoke-free prison policy: analysis of prisoner spend data across Scotland, UK.

OBJECTIVES: To examine the effect of smoke-free prison policy implementation in November 2018 on purchasing patterns in the prison canteen (shop). DESIGN: Interrupted time series. SETTING: All 12 closed, publicly run prisons in Scotland, UK. PARTICIPANTS: People in custody (PiC) between August 2018 and end of March 2019 (n=11 944). INTERVENTIONS: Implementation of smoke-free prisons policy. OUTCOME MEASURES: Total spent on all products, nicotine-related products, and food and beverage products per week. METHODS: Canteen data were provided for the period July 2018-September 2019 by the Scottish Prison Service. In a series of generalised linear mixed effects models, the amount spent before and after implementation of smoke-free prison policy was compared for all purchases in the time period, and for PiC identified as 'smokers' and 'non-smokers' from their pre-implementation tobacco purchasing patterns. RESULTS: The amount spent on nicotine-related products significantly decreased from pre-implementation to post implementation (incident rate ratio (IRR) 0.40; 99% CI 0.33 to 0.51, p<0.001). However, total canteen spend did not change over the study period (IRR 0.92; 99% CI 0.84 to 1.00). Post implementation about 25% of previous 'smokers' total canteen spend was on nicotine-related products. The amount spent by previous 'smokers' on food and beverages increased from £8.67 (99% CI 8.23 to 9.13) pre-implementation to £10.24 in the post implementation period (99% CI 9.58 to 10.90). CONCLUSION: Although the amount of money previous 'smokers' in prison spent on nicotine-related products decreased after smoke-free policy, nicotine products still account for a large proportion of canteen spend among PiC in smoke-free prisons in Scotland. Results indicate that many PiC may continue to use nicotine in smoke-free prisons where e-cigarettes are permitted.