Non-invasive imaging and clinical skin scores in juvenile localised scleroderma.

OBJECTIVES: To evaluate whether in juvenile localised scleroderma (JLS), non-invasive imaging can differentiate affected from non-affected skin and whether imaging correlates with a validated skin score (Localised Scleroderma Cutaneous Assessment Tool, LoSCAT). METHODS: 25 children with JLS were recruited into a prospective study and a single 'target' lesion selected. High frequency ultrasound (HFUS, measuring skin thickness), infrared thermography (IRT, skin temperature), laser Doppler imaging (LDI, skin blood flow) and multispectral imaging (MSI, oxygenation), were performed at four sites: two of affected skin (centre and inner edge of lesion) and two of non-affected skin (one cm from edge of lesion 'outer' and contralateral non-affected side), at 4 visits at 3 monthly intervals. RESULTS: Differences between affected and non-affected skin were detected with all 4 techniques. Compared with non-affected skin, affected skin was thinner (p< 0.001) with higher temperature (p< 0.001-0.006), perfusion (p< 0.001-0.039) and oxygenation (p< 0.001-0.028). Lesion skin activity (LoSCAT) was positively correlated with centre HFUS (r = 0.32; 95% CI [0.02, 0.61]; p= 0.036) and negatively correlated with centre LDI (r=-0.26; 95% CI [-0.49, -0.04]; p= 0.022). Lesion skin damage was positively correlated with centre and inner IRT (r = 0.43; 95% CI [0.19, 0.67]; p< 0.001, r = 0.36, 95% CI [0.12, 0.59]; p= 0.003, respectively) and with centre and inner LDI (r = 0.37; 95% CI [0.05, 0.69]; p= 0.024, r = 0.41; 95% CI [0.08, 0.74]; p= 0.015, respectively). CONCLUSION: Non-invasive imaging can detect differences between affected and non-affected skin in JLS and may help to differentiate between activity (thicker, less well perfused skin) and damage (thinner, highly perfused skin).

The effectiveness of digital delivery versus group-based face-to-face delivery of the English National Health Service Type 2 Diabetes Prevention Programme: a non-inferiority retrospective cohort comparison study.

BACKGROUND: Face-to-face group-based diabetes prevention programmes have been shown to be effective in many settings. Digital delivery may suit some patients, but research comparing the effectiveness of digital with face-to-face delivery is scarce. The aim was to assess if digital delivery of the English National Health Service Diabetes Prevention Programme (NHS DPP) is non-inferior to group-based face-to-face delivery in terms of weight change, and evaluate factors associated with differential change. METHODS: The study included those recruited to the NHS DPP in 2017-2018. Individual-level data from a face-to-face cohort was compared to two cohorts on a digital pilot who (i) were offered no choice of delivery mode, or (ii) chose digital over face-to-face. Changes in weight at 6 and 12 months were analysed using mixed effects linear regression, having matched participants from the digital pilot to similar participants from face-to-face. RESULTS: Weight change on the digital pilot was non-inferior to face-to-face at both time points: it was similar in the comparison of those with no choice (difference in weight change: -0.284 kg [95% CI: -0.712, 0.144] at 6 months) and greater in digital when participants were offered a choice (-1.165 kg [95% CI: -1.841, -0.489]). Interactions between delivery mode and sex, ethnicity, age and deprivation were observed. CONCLUSIONS: Digital delivery of the NHS DPP achieved weight loss at least as good as face-to-face. Patients who were offered a choice and opted for digital experienced better weight loss, compared to patients offered face-to-face only.

'Finishing the race' - a cohort study of weight and blood glucose change among the first 36,000 patients in a large-scale diabetes prevention programme.

BACKGROUND: The NHS Diabetes Prevention Programme for England, "Healthier You", encourages behaviour change regarding healthy eating and physical exercise among people identified to be at high risk of developing type 2 diabetes. The aim of this research was to examine change, and factors associated with change, in measures of HbA1c and weight in participants and completers of the programme between 2016 and 2019. METHODS: Participant-level data collected by programme service providers on referrals prior to March 2018 was analysed. Changes from baseline to both 6 months and completion in HbA1c and weight were examined using mixed effects linear regression, adjusting for patient characteristics, service provider and site. RESULTS: Completers had average improvements in HbA1c of 2.1 mmol/mol [95% CI: - 2.2, - 2.0] (0.19% [95% CI: - 0.20, - 0.18]) and reductions of 3.6 kg [95% CI: - 3.6, - 3.5] in weight, in absolute terms. Variation across the four providers was observed at both time points: two providers had significantly smaller average reductions in HbA1c and one provider had a significantly smaller average reduction in weight compared to the other providers. At both time points, ex- or current smokers had smaller reductions in HbA1c than non-smokers and those from minority ethnic groups lost less weight than White participants. For both outcomes, associations with other factors were small or null and variation across sites remained after adjustment for provider and case mix. CONCLUSIONS: Participants who completed the programme, on average, experienced improvements in weight and HbA1c. There was substantial variation in HbA1c change and smaller variation in weight loss between providers and across different sites. Aside from an association between HbA1c change and smoking, and between weight loss and ethnicity, results were broadly similar regardless of patient characteristics.

The impact of moderator by confounder interactions in the assessment of treatment effect modification: a simulation study.

BACKGROUND: When performed in an observational setting, treatment effect modification analyses should account for all confounding, where possible. Often, such studies only consider confounding between the exposure and outcome. However, there is scope for misspecification of the confounding adjustment when estimating moderation as the effects of the confounders may themselves be influenced by the moderator. The aim of this study was to investigate bias in estimates of treatment effect modification resulting from failure to account for an interaction between a binary moderator and a confounder on either treatment receipt or the outcome, and to assess the performance of different approaches to account for such interactions. METHODS: The theory behind the reason for bias and factors that impact the magnitude of bias is explained. Monte Carlo simulations were used to assess the performance of different propensity scores adjustment methods and regression adjustment where the adjustment 1) did not account for any moderator-confounder interactions, 2) included moderator-confounder interactions, and 3) was estimated separately in each moderator subgroup. A real-world observational dataset was used to demonstrate this issue. RESULTS: Regression adjustment and propensity score covariate adjustment were sensitive to the presence of moderator-confounder interactions on outcome, whilst propensity score weighting and matching were more sensitive to the presence of moderator-confounder interactions on treatment receipt. Including the relevant moderator-confounder interactions in the propensity score (for methods using this) or the outcome model (for regression adjustment) rectified this for all methods except propensity score covariate adjustment. For the latter, subgroup-specific propensity scores were required. Analysis of the real-world dataset showed that accounting for a moderator-confounder interaction can change the estimate of effect modification. CONCLUSIONS: When estimating treatment effect modification whilst adjusting for confounders, moderator-confounder interactions on outcome or treatment receipt should be accounted for.

Evaluation of the I-PLAN Intervention to Promote Hearing Aid Use in New Adult Users: a Randomized Controlled Trial.

OBJECTIVE: Provision of information is already part of standard care and may not be sufficient to promote hearing aid use. The I-PLAN is a behavior change intervention that is designed to promote hearing aid use in adults. It consists of a prompt, an action plan and provision of information. The objective was to test the effectiveness of the I-PLAN prompt and plan components in promoting hearing aid use and benefit. Hypotheses were: there would be greater hearing aid use, benefit, self-regulation, and hearing aid use habit among participants who received the prompt or plan component, compared with no prompt or no plan component, and the effect would be the greatest in participants who received both prompt and plan; and self-regulation and habit would mediate the effect of prompt and/or plan components on hearing aid use and benefit. DESIGN: A 2 x 2 factorial randomized controlled trial design. Two hundred forty new adult patients (60 in each group) were randomized to: information (info) only; info + prompt; info + plan; or info + prompt + plan. All participants received treatment as usual in addition to I-PLAN components, which were provided in a sealed envelope at the end of the hearing aid fitting consultation. Participants in the prompt group were instructed to use their hearing aid box as a physical prompt to remind them to use the device. Participants in the plan group were instructed to write an action plan to encourage them to turn their intentions into action. Participants, audiologists, and researchers were blinded to group allocation. The primary outcome was self-reported proportion of time hearing aids were used in situations where they had listening difficulties. Secondary outcomes were hearing aid use derived from data logging, self-reported hearing aid benefit, self-reported self-regulation, and habit. Outcomes were measured at 6-week post-fitting. RESULTS: Contrary to predictions, participants who received the prompt component reported using their hearing aid less than participants without the prompt (p = 0.03; d = 0.24). The mean proportion of time hearing aid were used was 73.4% of the time in the prompt group compared with 79.9% of the time in the no prompt group. Participants who received the plan component reported using their hearing aids more frequently than those who did not receive the plan (Meanplan = 81.0% vs Meannoplan = 71.8% of the time; p = 0.01; d = 0.34). Receiving both prompt and plan components did not change self-reported proportion of time hearing aids were used but data-logging use was significantly reduced. The prompt reduced self-regulation of hearing aid use compared with the no prompt (p = 0.04; d = 0.28), while the plan promoted stronger hearing aid use habits than the no plan group (p = 0.02; d = 0.30). CONCLUSIONS: Audiologists should consider using action plans to promote hearing aid use. Despite the decrease in hearing aid use when using the hearing aid box as a physical prompt, hearing aid use was still high (≈70% of the time). The hearing aid box may have slightly reduced hearing aid use by undermining self-regulation. Participants may have delegated responsibility for hearing aid use to the prompt. Subsequent studies should evaluate different prompts and test the long-term benefit of the plan on hearing aid use via habit formation.

Self-reported hearing difficulties are associated with loneliness, depression and cognitive dysfunction during the COVID-19 pandemic.

OBJECTIVE: To investigate whether hearing difficulties exacerbate the damaging effects of enforced social distancing due to the COVID-19 pandemic on isolation and loneliness, and lead to accelerated mental health issues and cognitive dysfunction. DESIGN: Rapid online survey. Participants completed a series of online questionnaires regarding hearing ability, socialisation (pre- and during-pandemic), loneliness, anxiety, depression and cognitive function. STUDY SAMPLE: A total of 80 participants over the age of 70 with access to the internet. RESULTS: There was a significant reduction in socialisation levels from pre-pandemic in this population. Hearing difficulties were significantly associated with greater levels of loneliness, depression and self-perceived cognitive dysfunction after controlling for age, gender, and level of education. Additionally, compared to pre-pandemic, people with hearing difficulties had increased odds of reporting worsened anxiety, depression, and memory during the COVID-19 pandemic, although only the effect of hearing difficulties on the change in memory reached statistical significance after controlling for age, gender, and level of education. CONCLUSIONS: The worse the self-reported hearing abilities are, the greater the negative impact of enforced social distancing on depression, loneliness and cognitive function.

Uptake of internet-delivered UK adult hearing assessment.

OBJECTIVE: To evaluate uptake of the internet-based hearing test, with respect to the 11% of UK adults that have hearing loss but do not use hearing aids. DESIGN: Feasibility study in a primary care practice in the North of England. STUDY SAMPLE: Adults aged 50-74 years were sent postal invitations to complete an internet hearing test (N = 600). Those who completed the test, those who failed (>35 dB HL in the better ear) and demographic correlates (age, gender, ethnicity and socioeconomic level) were recorded. RESULTS: 11.2% of invited adults completed the hearing test and 7.7% failed it. Those who took the test tended to have a higher socioeconomic background than those who did not. There were no differences in age, ethnicity or gender between those who took the test and those who did not. CONCLUSIONS: An estimated 70% (7.7%/11.0%) of adults with hearing loss but who do not use hearing aids took the test. Uptake was equitable across most demographic categories. Uptake was high among a study sample that was substantially more deprived than the general UK population. Internet-based hearing testing offers an efficient paradigm for identifying hearing loss.

Long-term benefits of digital cognitive behavioural therapy for insomnia: Follow-up report from a randomized clinical trial.

Digital cognitive behavioural therapy (dCBT) is an effective treatment for chronic insomnia and also improves well-being and quality of life (QoL). We assessed whether these benefits are sustained and if the effects of dCBT extend to the use of sleep medication and healthcare. In total 1,711 adults (48.0 ± 13.8 years, 77.6% female) with complaints of chronic insomnia participated in a previously published randomized controlled trial (ISRCTN 60530898) comparing dCBT (n = 853) with sleep hygiene education (SHE, n = 858). At weeks 0, 4, 8, 24, 36 and 48, we assessed functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale); psychological well-being (Warwick-Edinburgh Mental Well-being Scale) and sleep-related QoL (Glasgow Sleep Impact Index), prescribed and non-prescribed sleep medication use, and healthcare utilization. At week 25, those who received SHE at baseline were offered dCBT. dCBT improved functional health (difference: 2.45, 95% confidence interval [CI]: 2.03; 2.88, Cohen's d: 0.50, p < .001), psychological well-being (difference: 4.34, 95% CI: 3.70; 4.98, Cohen's d: 0.55, p < .001) and sleep-related QoL (difference: -44.61, 95%CI: -47.17; -42.05, Cohen's d: -1.44, p < .001) at week 48 compared to baseline. At week 24 dCBT, compared to SHE, also reduced use of prescription and non-prescription sleep medication up to week 24 (adjusted rate ratio [RR]: 0.64, 95% CI: 0.42; 0.97, p = .037 and adjusted RR: 0.52, 95% CI: 0.37; 0.74, p < .0001, respectively), but not healthcare utilization. Uncontrolled follow-up suggests that these effects were sustained for non-prescribed sleep medication (RR: 0.52, 95% CI: 0.40; 0.67, p < .001). In conclusion, this study suggests that dCBT results in sustained benefits to insomnia and its daytime outcomes.

Relationship Between Diet, Tinnitus, and Hearing Difficulties.

OBJECTIVES: Diet may affect susceptibility of the inner ear to noise and age-related effects that lead to tinnitus and hearing loss. This study used complementary single nutrient and dietary pattern analysis based on statistical grouping of usual dietary intake in a cross-sectional analysis of tinnitus and hearing difficulties in a large population study sample. DESIGN: The research was conducted using the UK Biobank resource. Tinnitus was based on report of ringing or buzzing in one or both ears that lasts more than five minutes at a time and is currently experienced at least some of the time. Identification of a hearing problem was based on self-reported difficulties with hearing. Usual dietary intake and dietary patterns (involving statistical grouping of intake to account for how foods are combined in real-life diets) were estimated based on between two and five administrations of the Oxford Web-Q 24-hour dietary recall questionnaire over the course of a year for 34,576 UK adult participants aged 40 to 69. RESULTS: In a multivariate model, higher intake of vitamin B12 was associated with reduced odds of tinnitus, while higher intakes of calcium, iron, and fat were associated with increased odds (B12, odds ratio [OR] 0.85, 95% confidence interval [CI] 0.75 to 0.97; Calcium, OR 1.20, 95% CI 1.08 to 1.34; Iron, OR 1.20, 95% CI 1.05 to 1.37; Fat, OR 1.33, 95% CI 1.09 to 1.62, respectively, for quintile 5 versus quintile 1). A dietary pattern characterised by high protein intake was associated with reduced odds of tinnitus (OR 0.90, 95% CI 0.82 to 0.99 for quintile 5 versus quintile 1). Higher vitamin D intake was associated with reduced odds of hearing difficulties (OR 0.90, 95% CI 0.81 to 1.00 for quintile 5 versus quintile 1), as were dietary patterns high in fruit and vegetables and meat and low in fat (Prudent diet: OR 0.89, 95% CI 0.83 to 0.96; High protein: OR 0.88, 95% CI 0.82 to 0.95; High fat: OR 1.16, 95% CI 1.08 to 1.24, respectively, for quintile 5 versus quintile 1). CONCLUSIONS: There were associations between both single nutrients and dietary patterns with tinnitus and hearing difficulties. Although the size of the associations was small, universal exposure for dietary factors indicates that there may be a substantial impact of diet on levels of tinnitus and hearing difficulties in the population. This study showed that dietary factors might be important for hearing health.

Recording Obligatory Cortical Auditory Evoked Potentials in Infants: Quantitative Information on Feasibility and Parent Acceptability.

OBJECTIVES: With the advent of newborn hearing screening and early intervention, there is a growing interest in using supra-threshold obligatory cortical auditory evoked potentials (CAEPs) to complement established pediatric clinical test procedures. The aim of this study was to assess the feasibility, and parent acceptability, of recording infant CAEPs. DESIGN: Typically developing infants (n = 104) who had passed newborn hearing screening and whose parents expressed no hearing concerns were recruited. Testing was not possible in 6 infants, leaving 98, age range 5 to 39 weeks (mean age = 21.9, SD = 9.4). Three short duration speech-like stimuli (/m/, /g/, /t/) were presented at 65 dB SPL via a loudspeaker at 0° azimuth. Three criteria were used to assess clinical feasibility: (i) median test duration <30 min, (ii) >90% completion rate in a single test session, and (iii) >90% response detection for each stimulus. We also recorded response amplitude, latency, and CAEP signal to noise ratio. Response amplitudes and residual noise levels were compared for Fpz (n = 56) and Cz (n = 42) noninverting electrode locations. Parental acceptability was based on an 8-item questionnaire (7-point scale, 1 being best). In addition, we explored the patient experience in semistructured telephone interviews with seven families. RESULTS: The median time taken to complete 2 runs for 3 stimuli, including preparation, was 27 min (range 17 to 59 min). Of the 104 infants, 98 (94%) were in an appropriate behavioral state for testing. A further 7 became restless during testing and their results were classified as "inconclusive." In the remaining 91 infants, CAEPs were detected in every case with normal bilateral tympanograms. Detection of CAEPs in response to /m/, /g/, and /t/ in these individuals was 86%, 100%, and 92%, respectively. Residual noise levels and CAEP amplitudes were higher for Cz electrode recordings. Mean scores on the acceptability questionnaire ranged from 1.1 to 2.6. Analysis of interviews indicated that parents found CAEP testing to be a positive experience and recognized the benefit of having an assessment procedure that uses conversational level speech stimuli. CONCLUSIONS: Test duration, completion rates, and response detection rates met (or were close to) our feasibility targets, and parent acceptability was high. CAEPs have the potential to supplement existing practice in 3- to 9-month olds.

The effect on work presenteeism of job retention vocational rehabilitation compared to a written self-help work advice pack for employed people with inflammatory arthritis: protocol for a multi-centre randomised controlled trial (the WORKWELL trial).

BACKGROUND: Work problems are common in people with inflammatory arthritis. Up to 50% stop work within 10 years due to their condition and up to 67% report presenteeism (i.e. reduced work productivity), even amongst those with low disease activity. Job retention vocational rehabilitation (JRVR) may help prevent or postpone job loss and reduce presenteeism through work assessment, work-related rehabilitation and enabling job accommodations. This aims to create a better match between the person's abilities and their job demands. The objectives of the Workwell trial are to test the overall effectiveness and cost-effectiveness of JRVR (WORKWELL) provided by additionally trained National Health Service (NHS) occupational therapists compared to a control group who receive self-help information both in addition to usual care. METHODS: Based on the learning from a feasibility trial (the WORK-IA trial: ISRCTN76777720 ), the WORKWELL trial is a multi-centre, pragmatic, individually-randomised parallel group superiority trial, including economic evaluation, contextual factors analysis and process evaluation. Two hundred forty employed adults with rheumatoid arthritis, undifferentiated inflammatory arthritis or psoriatic arthritis (in secondary care), aged 18 years or older with work instability will be randomised to one of two groups: a self-help written work advice pack plus usual care (control intervention); or WORKWELL JRVR plus a self-help written work advice pack and usual care. WORKWELL will be delivered by occupational therapists provided with additional JRVR training from the research team. The primary outcome is presenteeism as measured using the Work Limitations Questionnaire-25. A comprehensive range of secondary outcomes of work, health, contextual factors and health resource use are included. Outcomes are measured at 6- and 12- months (with 12-months as the primary end-point). A multi-perspective within-trial cost-effectiveness analyses will also be conducted. DISCUSSION: This trial will contribute to the evidence base for provision of JRVR to people with inflammatory arthritis. If JRVR is found to be effective in enabling people to keep working, the findings will support decision-making about provision of JRVR by rheumatology teams, therapy services and healthcare commissioners, and providing evidence of the effectiveness of JRVR and the economic impact of its implementation. TRIAL REGISTRATION: Clinical Trials.Gov: NCT03942783 . Registered 08/05/2019 ( https://clinicaltrials.gov/ct2/show/NCT03942783 ); ISRCTN Registry: ISRCTN61762297 . Registered:13/05/2019 ( http://www.isrctn.com/ISRCTN61762297 ). Retrospectively registered.

A pragmatic qualitative study to explore women's and clinicians' experience of access to systemic anti-cancer therapies for the treatment of secondary breast cancer.

PURPOSE: An estimated 57,000 women are currently living with secondary (metastatic) breast cancer across the UK. Equitable access to treatment has been associated with improved clinical outcomes, however geographical disparities have been reported which remain poorly understood. The purpose of our study was to explore women and clinicians' experience of geographic access to systemic anti-cancer therapies for the treatment of secondary breast cancer. METHOD: The study setting was the integrated cancer system across the northwest region of Greater Manchester UK. A pragmatic qualitative study design was used. Women aged >18 years with a confirmed SBC diagnosis and clinicians responsible for the care and treatment of women with a secondary breast cancer diagnosis were interviewed using semi structured interviews to elicit their experience and perspectives on geographic access to treatment. Data were analysed using thematic analysis to identify emergent themes. RESULTS: Eighteen interviews with women and 12 interviews with clinicians were completed. Four meta-themes were identified for geographic access, the influence of the health care system, person centred factors and the impact of Covid-19 on treatment access and receipt. CONCLUSION: Our study was the first of its kind to explore women and clinicians experience of geographic access to systemic anti-cancer therapies for the treatment of secondary breast cancer. Findings provided a greater understanding of distance decay and the influence of the health care system on treatment access. This included the importance and availability of clinical trials as a potential treatment option. This provided important insights and contributed to ongoing debate.

Geographic and sociodemographic access to systemic anticancer therapies for secondary breast cancer: a systematic review.

BACKGROUND: The review aimed to investigate geographic and sociodemographic factors associated with receipt of systemic anticancer therapies (SACT) for women with secondary (metastatic) breast cancer (SBC). METHODS: Included studies reported geographic and sociodemographic factors associated with receipt of treatment with SACT for women > 18 years with an SBC diagnosis. Information sources searched were Ovid CINAHL, Ovid MEDLINE, Ovid Embase and Ovid PsychINFO. Assessment of methodological quality was undertaken using the Joanna Briggs Institute method. Findings were synthesised using a narrative synthesis approach. RESULTS: Nineteen studies published between 2009 and 2023 were included in the review. Overall methodological quality was assessed as low to moderate. Outcomes were reported for treatment receipt and time to treatment. Overall treatment receipt ranged from 4% for immunotherapy treatment in one study to 83% for systemic anticancer therapies (unspecified). Time to treatment ranged from median 54 days to 95 days with 81% of patients who received treatment < 60 days. Younger women, women of White origin, and those women with a higher socioeconomic status had an increased likelihood of timely treatment receipt. Treatment receipt varied by geographical region, and place of care was associated with variation in timely receipt of treatment with women treated at teaching, research and private institutions being more likely to receive treatment in a timely manner. CONCLUSIONS: Treatment receipt varied depending upon type of SACT. A number of factors were associated with treatment receipt. Barriers included older age, non-White race, lower socioeconomic status, significant comorbidities, hospital setting and geographical location. Findings should however be interpreted with caution given the limitations in overall methodological quality of included studies and significant heterogeneity in measures of exposure and outcome. Generalisability was limited due to included study populations. Findings have practical implications for the development and piloting of targeted interventions to address specific barriers in a socioculturally sensitive manner. Addressing geographical variation and place of care may require intervention at a commissioning policy level. Further qualitative research is required to understand the experience and of women and clinicians. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196490.

Comparison of weight change between face-to-face and digital delivery of the English National Health service diabetes prevention programme: An exploratory non-inferiority study with imputation of plausible weight outcomes.

Worldwide evidence suggests face-to-face diabetes prevention programmes are effective in preventing and delaying the onset of type 2 diabetes by encouraging behaviour change towards weight loss, healthy eating, and increased exercise. There is an absence of evidence on whether digital delivery is as effective as face-to-face. During 2017-18 patients in England were offered the National Health Service Diabetes Prevention Programme as group-based face-to-face delivery, digital delivery ('digital-only') or a choice between digital and face-to-face ('digital-choice'). The contemporaneous delivery allowed for a robust non-inferiority study, comparing face-to-face with digital only and digital choice cohorts. Changes in weight at 6 months were missing for around half of participants. Here we take a novel approach, estimating the average effect in all 65,741 individuals who enrolled in the programme, by making a range of plausible assumptions about weight change in individuals who did not provide outcome data. The benefit of this approach is that it includes everyone who enrolled in the programme, not restricted to those who completed. We analysed the data using multiple linear regression models. Under all scenarios explored, enrolment in the digital diabetes prevention programme was associated with clinically significant reductions in weight which were at least equivalent to weight loss in the face-to-face programme. Digital services can be just as effective as face-to-face in delivering a population-based approach to the prevention of type 2 diabetes. Imputation of plausible outcomes is a feasible methodological approach, suitable for analysis of routine data in settings where outcomes are missing for non-attenders.

Access to systemic anti-cancer therapies for women with secondary breast cancer-protocol for a mixed methods systematic review.

BACKGROUND: It is well recognised that access and receipt of appropriate guideline recommended treatment with systemic anti-cancer therapies for secondary breast cancer is a key determinant in overall survival. Where there is disparity in access this may result in unwarranted variation and disparity in outcomes. Individual, clinical and wider contextual factors have been associated with these disparities, however this remains poorly understood for women with secondary breast cancer. The purpose of the review is to examine individual, clinical and contextual factors which influence access to evidence-based systemic anti-cancer therapies for women with secondary breast cancer. This will include barriers and facilitators for access and receipt of treatment and an exploration of women and clinicians experience and perspectives on access. METHODS: A mixed methods approach with a segregated design will be used to examine and explore factors which influence access to systemic anti-cancer therapies for women with secondary breast cancer. Electronic databases to be searched from January 2000 onwards will be EBSCO CINAHL Plus, Ovid MEDLINE, Ovid EMBASE, PsychINFO and the Cochrane Library and JBI database. This will include NHS Evidence which will be searched for unpublished studies and gray literature. Title and abstract citations and full-text articles will be screened by the author and second reviewer. Data will be extracted by the author and validated by the second reviewer. An overarching synthesis will be produced which brings together quantitative and qualitative findings. Methodological quality and risk of bias will be assessed using the Mixed Methods Appraisal Tool. DISCUSSION: Understanding individual, clinical and wider contextual factors associated with access and receipt of systemic anti-cancer therapies for secondary breast cancer is a complex phenomenon. These will be examined to determine any association with access. Review findings will be used to guide future research in this area and the development of an evidence-based service level intervention designed to address unwarranted variation in access based upon the Medical Research Council (MRC) approach to the development, implementation and evaluation of complex interventions. SYSTEMATIC REVIEW REGISTRATION: The review protocol has been registered in PROSPERO CRD42020196490 .

A Quasi-Randomized Controlled Trial of the I-PLAN Intervention to Promote Hearing Aid Use Among First-Time Adult Hearing Aid Users.

Suboptimal hearing aid use negatively impacts health and well-being. The aim of this study was to conduct a controlled trial of a behavior change intervention to promote hearing aid use. This study was a quasi-randomized controlled trial with two arms. A total of 160 first-time hearing aid users were recruited at their hearing aid fitting appointments. The control arm received standard care. In addition to standard care, the intervention arm received I-PLAN, which comprised (a) information about the consequences of hearing aid use/nonuse, (b) reminder prompt to use the hearing aids, and (c) an action plan. The primary outcome, measured at 6 weeks, was self-reported proportion of time the hearing aid was used in situations that caused hearing difficulty. Secondary outcomes were data-logged hearing aid use, self-reported hearing aid benefit, self-regulation, and habit formation. The results showed that the proportion of time the hearing aids were used in situations that caused hearing difficulty was similar in both groups. There were no statistically significant differences between groups in any outcome measure including data-logged hearing aid use. The relatively high levels of hearing aid use across research participants may have limited the potential for the intervention to impact on hearing aid use. Although the intervention materials proved acceptable and deliverable, future intervention trials should target suboptimal hearing aid users.

The implications of outcome truncation in reproductive medicine RCTs: a simulation platform for trialists and simulation study.

BACKGROUND: Randomised controlled trials in reproductive medicine are often subject to outcome truncation, where the study outcomes are only defined in a subset of the randomised cohort. Examples include birthweight (measurable only in the subgroup of participants who give birth) and miscarriage (which can only occur in participants who become pregnant). These outcomes are typically analysed by making a comparison between treatment arms within the subgroup (for example, comparing birthweights in the subgroup who gave birth or miscarriages in the subgroup who became pregnant). However, this approach does not represent a randomised comparison when treatment influences the probability of being observed (i.e. survival). The practical implications of this for the design and interpretation of reproductive trials are unclear however. METHODS: We developed a simulation platform to investigate the implications of outcome truncation for reproductive medicine trials. We used this to perform a simulation study, in which we considered the bias, type 1 error, coverage, and precision of standard statistical analyses for truncated continuous and binary outcomes. Simulation settings were informed by published assisted reproduction trials. RESULTS: Increasing treatment effect on the intermediate variable, strength of confounding between the intermediate and outcome variables, and the presence of an interaction between treatment and confounder were found to adversely affect performance. However, within parameter ranges we would consider to be more realistic, the adverse effects were generally not drastic. For binary outcomes, the study highlighted that outcome truncation could cause separation in smaller studies, where none or all of the participants in a study arm experience the outcome event. This was found to have severe consequences for inferences. CONCLUSION: We have provided a simulation platform that can be used by researchers in the design and interpretation of reproductive medicine trials subject to outcome truncation and have used this to conduct a simulation study. The study highlights several key factors which trialists in the field should consider carefully to protect against erroneous inferences. Standard analyses of truncated binary outcomes in small studies may be highly biassed, and it remains to identify suitable approaches for analysing data in this context.

Observational and Reported Measures of Language and Pragmatics in Young People with Autism: A Comparison of Respondent Data and Gender Profiles.

Female children with autism spectrum disorder (FwASD) and performance intelligence quotient (PIQ) over 70 were compared with male children with ASD (MwASD) and typically developing (TD) controls (age 8-11 years) using a range of language and pragmatic measures. Functional ability was assessed using clinical observations and parent, teacher and self-reports. Results were compared between measures, and with direct assessments of language and pragmatics, in order to identify potential biases. This study found that FwASD performed better than MwASD but worse than TD controls on clinical observations of pragmatic ability. FwASD also performed worst overall on a parental measure of emotions. Additionally, there were patterns of differences between clinician, parent, teacher and self- reports and direct assessments, which indicate the need for assessment data to be collected from multiple informants. Findings also have implications for the accurate identification of ASD in females and appropriate provision of support.

The effect of glucocorticoid therapy on mortality in patients with rheumatoid arthritis and concomitant type II diabetes: a retrospective cohort study.

BACKGROUND: Patients with rheumatoid arthritis (RA) have increased cardiovascular (CV) and mortality risk. Patients with RA are also frequently prescribed glucocorticoids (GCs) which have been associated with increased risk of mortality. In addition, for patients who have concomitant diabetes mellitus (DM), GCs are known to worsen glycaemic control and hence may further increase CV and mortality risk. This study aimed to understand the relationship between GCs, DM and mortality in patients with RA. METHODS: This was a retrospective cohort study of patients with incident RA identified from UK primary care electronic medical records. Patients with linkage to Office for National Statistics (ONS) for mortality data (N = 9085) were included. DM was identified through Read codes, prescriptions and blood tests, and GC use was identified through prescriptions. Mortality rate ratios (RR) and rate differences (RD) were calculated across the different exposure groups. Cox proportional hazards regression models were used to estimate interaction on the multiplicative and additive scales. RESULTS: In those without DM GC use had a 4.4-fold increased all-cause mortality RR (95% confidence interval (CI): 3.83 to 5.14) compared to non-use, whilst those with DM had a lower RR for GC use (3.02 (95% CI: 2.34, 3.90)). However, those with DM had a higher RD associated with GC use because of their higher baseline risk. In those with DM, GC use was associated with an additional 46.7 deaths/1000 person-years (pyrs) (95% CI: 34.1 to 59.3) compared to non-use, while in those without DM GC use was associated with an additional 36.2 deaths/1000 pyrs (95% CI: 31.6 to 40.8). A similar pattern was seen for CV mortality. The adjusted Cox proportional hazards model showed no evidence of multiplicative interaction, but additive interaction indicated a non-significant increased risk. For CV mortality there was no interaction on either scale. CONCLUSIONS: GC use was associated with higher mortality rates in people with comorbid DM compared to people without DM, despite apparently reassuring similar relative risks. Clinicians need to be aware of the higher baseline risk in patients with DM, and consider this when prescribing GCs in patients with RA and comorbid DM.

The effects of digital cognitive behavioral therapy for insomnia on cognitive function: a randomized controlled trial.

STUDY OBJECTIVES: We sought to examine the impact of digital cognitive behavioral therapy (dCBT) for insomnia on both self-reported cognitive impairment and objective cognitive performance. METHODS: The Defining the Impact of Sleep improvement on Cognitive Outcomes (DISCO) trial was an online, two-arm, single-blind, randomized clinical trial of dCBT versus wait-list control. Participants were aged 25 years and older, met DSM-5 diagnostic criteria for insomnia disorder, and reported difficulties with concentration or memory. Assessments were carried out online at baseline, and 10 and 24 weeks post-randomization. The primary outcome measure was self-reported cognitive impairment, assessed with the British Columbia Cognitive Complaints Inventory (BC-CCI). Secondary outcomes included tests of cognitive performance, insomnia symptoms, cognitive failures, fatigue, sleepiness, depression, and anxiety. RESULTS: Four hundred and ten participants with insomnia were recruited and assigned to dCBT (N = 205) or wait-list control (N = 205). At 10 weeks post-randomization the estimated adjusted mean difference for the BC-CCI was -3.03 (95% CI: -3.60, -2.47; p < 0.0001, d = -0.86), indicating that participants in the dCBT group reported less cognitive impairment than the control group. These effects were maintained at 24 weeks (d = -0.96) and were mediated, in part, via reductions in insomnia severity and increased sleep efficiency. Treatment effects in favor of dCBT, at both 10 and 24 weeks, were found for insomnia severity, sleep efficiency, cognitive failures, fatigue, sleepiness, depression, and anxiety. We found no between-group differences in objective tests of cognitive performance. CONCLUSIONS: Our study shows that dCBT robustly decreases self-reported cognitive impairment at post-treatment and these effects are maintained at 6 months.