Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Genetic and structural basis of the human anti-α-galactosyl antibody response.

Humans lack the capacity to produce the Galα1-3Galß1-4GlcNAc (α-gal) glycan, and produce anti-α-gal antibodies upon exposure to the carbohydrate on a diverse set of immunogens, including commensal gut bacteria, malaria parasites, cetuximab, and tick proteins. Here we use X-ray crystallographic analysis of antibodies from α-gal knockout mice and humans in complex with the glycan to reveal a common binding motif, centered on a germline-encoded tryptophan residue at Kabat position 33 (W33) of the complementarity-determining region of the variable heavy chain (CDRH1). Immunoglobulin sequencing of anti-α-gal B cells in healthy humans and tick-induced mammalian meat anaphylaxis patients revealed preferential use of heavy chain germline IGHV3-7, encoding W33, among an otherwise highly polyclonal antibody response. Antigen binding was critically dependent on the presence of the germline-encoded W33 residue for all of the analyzed antibodies; moreover, introduction of the W33 motif into naive IGHV3-23 antibody phage libraries enabled the rapid selection of α-gal binders. Our results outline structural and genetic factors that shape the human anti-α-galactosyl antibody response, and provide a framework for future therapeutics development.

Quality improvement interventions to increase the uptake of magnesium sulphate in preterm deliveries for the prevention of cerebral palsy (PReCePT study): a cluster randomised controlled trial.

OBJECTIVE: To compare two quality improvement (QI) interventions to improve antenatal magnesium sulphate (MgSO4 ) uptake in preterm births for the prevention of cerebral palsy. DESIGN: Unblinded cluster randomised controlled trial. SETTING: Academic Health Sciences Network, England, 2018. SAMPLE: Maternity units with ≥10 preterm deliveries annually and MgSO4 uptake of ≤70%; 40 (27 NPP, 13 enhanced support) were included (randomisation stratified by MgSO4 uptake). METHODS: The National PReCePT Programme (NPP) gave maternity units QI materials (clinical guidance, training), regional support, and midwife backfill funding. Enhanced support units received this plus extra backfill funding and unit-level QI coaching. MAIN OUTCOME MEASURES: MgSO4 uptake was compared using routine data and multivariable linear regression. Net monetary benefit was estimated, based on implementation costs, lifetime quality-adjusted life-years and societal costs. The implementation process was assessed through qualitative interviews. RESULTS: MgSO4 uptake increased in all units, with no evidence of any difference between groups (0.84 percentage points lower uptake in the enhanced group, 95% CI -5.03 to 3.35). The probability of enhanced support being cost-effective was <30%. NPP midwives gave more than their funded hours for implementation. Units varied in their support needs. Enhanced support units reported better understanding, engagement and perinatal teamwork. CONCLUSIONS: PReCePT improved MgSO4 uptake in all maternity units. Enhanced support did not further improve uptake but may improve teamwork, and more accurately represented the time needed for implementation. Targeted enhanced support, sustainability of improvements and the possible indirect benefits of stronger teamwork associated with enhanced support should be explored further.

Is well-becoming important for children and young people? Evidence from in-depth interviews with children and young people and their parents.

PURPOSE: This study explores how important well-becoming factors appear to be to children during childhood. We define well-becoming as the indicators which predict children and young people's future wellbeing and opportunities. The priority for this work was to explore whether well-becoming might be an important factor to include in outcome measures for children and young people. The inclusion of well-becoming indicators could ensure that opportunities to invest in promoting wellbeing in children's futures are not missed. METHODS: In-depth, qualitative interviews (N = 70) were undertaken with children and young people aged 6-15 years and their parents. Analysis used constant comparison and framework methods to investigate whether well-becoming factors were considered important by informants to children and young people's current wellbeing. RESULTS: The findings of the interviews suggested that children and young people and their parents are concerned with future well-becoming now, as factors such as future achievement, financial security, health, independence, identity, and relationships were identified as key to future quality of life. Informants suggested that they considered it important during childhood to aspire towards positive outcomes in children and young people's futures. CONCLUSION: The study findings, taken alongside relevant literature, have generated evidence to support the notion that future well-becoming is important to current wellbeing. We have drawn on our own work in capability wellbeing measure development to demonstrate how we have incorporated a well-becoming attribute into our measures. The inclusion of well-becoming indicators in measures could aid investment in interventions which more directly improve well-becoming outcomes for children and young people.

Randomised pilot and feasibility trial of a group intervention for men who perpetrate intimate partner violence against women.

BACKGROUND: There is a need for robust evidence on the effectiveness and cost-effectiveness of domestic abuse perpetrator programmes in reducing abusive behaviour and improving wellbeing for victim/survivors. While any randomised controlled trial can present difficulties in terms of recruitment and retention, conducting such a trial with domestic abuse perpetrators is particularly challenging. This paper reports the pilot and feasibility trial of a voluntary domestic abuse perpetrator group programme in the United Kingdom. METHODS: This was a pragmatic individually randomised pilot and feasibility trial with an integrated qualitative study in one site (covering three local-authority areas) in England. Male perpetrators were randomised to either the intervention or usual care. The intervention was a 23-week group programme for male perpetrators in heterosexual relationships, with an average of three one-to-one sessions, and one-to-one support for female current- or ex-partners delivered by third sector organisations. There was no active control treatment for men, and partners of control men were signposted towards domestic abuse support services. Data were collected at three-monthly intervals for nine months from male and female participants. The main objectives assessed were recruitment, randomisation, retention, data completeness, fidelity to the intervention model, and acceptability of the trial design. RESULTS: This study recruited 36 men (22 randomly allocated to attend the intervention group programme, 14 to usual care), and 15 current- or ex-partners (39% of eligible partners). Retention and completeness of data were high: 67% of male (24/36), and 80% (12/15) of female participants completed the self-reported questionnaire at nine months. A framework for assessing fidelity to the intervention was developed. In interviews, men who completed all or most of the intervention gave positive feedback and reported changes in their own behaviour. Partners were also largely supportive of the trial and were positive about the intervention. Participants who were not allocated to the intervention group reported feeling disappointed but understood the rationale for the trial. CONCLUSIONS: It was feasible to recruit, randomise and retain male perpetrators and female victim/survivors of abuse and collect self-reported outcome data. Participants were engaged in the intervention and reported positive benefits. The trial design was seen as acceptable. TRIAL REGISTRATION: ISRCTN71797549, submitted 03/08/2017, retrospectively registered 27/05/2022.

'Does it matter how old I feel?' The role of subjective age in a psychosocial intervention for improving depressive symptomatology among older adults in Brazil (PROACTIVE).

OBJECTIVES: Depression is a prevalent mental health condition that also often affects older adults. The PROACTIVE psychosocial intervention was developed to reduce depressive symptomatology among older adults within primary care settings in Brazil. An important psychological marker that affects individuals' aging experience relates to how old people feel. Known as subjective age, this marker has been shown to be a risk factor for experiencing greater depressive symptoms if individuals report feeling older than their (chronological) age. In this study, we perform secondary analyses of the PROACTIVE cluster-randomized controlled trial to examine the role of subjective age. METHOD: The sample included 715 Brazilian older adults (74% female, Mage 68.6, SD = 6.9, age range: 60-94 years) randomized to intervention (n = 360, 74% female, Mage 68.4, SD = 6.6, age range: 60-89 years) or control (n = 355, 74% female, Mage 68.9, SD = 7.2, age range: 60-94 years) arms. Here our primary outcome was depressive symptoms at the 8-month follow-up assessed with the 9-item Patient Health Questionnaire (PHQ-9) as a continuous variable. Our previous analyses demonstrated improved recovery from depression at follow-up in the intervention compared with the control arm. RESULTS: Relevant main effects and interactions in regression models for PHQ-9 presented here found that those reporting older subjective age had worse depressive symptoms at follow-up but that they benefitted more from the intervention when initial levels of depression were high. For participants who reported younger subjective ages the intervention showed positive effects that were independent of initial levels of depression. CONCLUSION: Our findings emphasize the importance of investigating possible underlying mechanisms that can help clarify the impact of mental health interventions.

The STAR care pathway for patients with chronic pain after total knee replacement: four-year follow-up of a randomised controlled trial.

BACKGROUND: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. METHODS: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0-10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. RESULTS: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and - 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. CONCLUSIONS: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. TRIAL REGISTRATION: ISRCTN: 92,545,361.

How much change is enough? Evidence from a longitudinal study on depression in UK primary care.

BACKGROUND: The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists. METHODS: A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a 'global rating of change' scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R). RESULTS: For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) -26.7 to -14.9) on the PHQ-9; 23% (95% CI -27.8 to -18.0) on the BDI-II and 26.8% (95% CI -33.5 to -20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were -1.7, -3.5 and -1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement. CONCLUSIONS: An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit. FUNDING: Funding. National Institute for Health Research.

Functional and quality of life outcomes of localised prostate cancer treatments (Prostate Testing for Cancer and Treatment [ProtecT] study).

OBJECTIVE: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. PATIENTS AND METHODS: Men aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. RESULTS: Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. CONCLUSION: Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes.

Depressive and subthreshold depressive symptomatology among older adults in a socioeconomically deprived area in Brazil.

Depressive and subthreshold depressive symptomatology are common but often neglected in older adults. OBJECTIVE: This study aimed to assess rates of depressive and subthreshold depressive symptomatology, and the characteristics associated, among older adults living in a socioeconomically deprived area of Brazil. METHODS: This study is part of the PROACTIVE cluster randomised controlled trial. 3356 adults aged 60+ years and registered in 20 primary health clinics were screened for depressive symptomatology with the Patient Health Questionnaire-9 (PHQ-9). Depressive status was classified according to the total PHQ-9 score and the presence of core depressive symptoms (depressed mood and anhedonia) as follows: no depressive symptomatology (PHQ-9 score 0-4, or 5-9 but with no core depressive symptom); subthreshold depressive symptomatology (PHQ-9 score 5-9 and at least one core depressive symptom); and depressive symptomatology (PHQ-9 score ≥ 10). Sociodemographic information and self-reported chronic conditions were collected. Relative risk ratios and 95% CIs were obtained using a multinomial regression model. RESULTS: Depressive and subthreshold depressive symptomatology were present in 30% and 14% of the screened sample. Depressive symptomatology was associated with female gender, low socioeconomic conditions and presence of chronic conditions, whereas subthreshold depressive symptomatology was only associated with female gender and having hypertension. CONCLUSIONS: Depressive and subthreshold depressive symptomatology is highly prevalent in this population registered with primary care clinics. Strategies managed by primary care non-mental health specialists can be a first step for improving this alarming and neglected situation among older adults.

A clinical tool to identify older women with back pain at high risk of osteoporotic vertebral fractures (Vfrac): a population-based cohort study with exploratory economic evaluation.

BACKGROUND: osteoporotic vertebral fractures (OVFs) identify people at high risk of future fractures, but despite this, less than a third come to clinical attention. The objective of this study was to develop a clinical tool to aid health care professionals decide which older women with back pain should have a spinal radiograph. METHODS: a population-based cohort of 1,635 women aged 65+ years with self-reported back pain in the previous 4 months were recruited from primary care. Exposure data were collected through self-completion questionnaires and physical examination, including descriptions of back pain and traditional risk factors for osteoporosis. Outcome was the presence/absence of OVFs on spinal radiographs. Logistic regression models identified independent predictors of OVFs, with the area under the (receiver operating) curve calculated for the final model, and a cut-point was identified. RESULTS: mean age was 73.9 years and 209 (12.8%) had OVFs. The final Vfrac model comprised 15 predictors of OVF, with an AUC of 0.802 (95% CI: 0.764-0.840). Sensitivity was 72.4% and specificity was 72.9%. Vfrac identified 93% of those with more than one OVF and two-thirds of those with one OVF. Performance was enhanced by inclusion of self-reported back pain descriptors, removal of which reduced AUC to 0.742 (95% CI: 0.696-0.788) and sensitivity to 66.5%. Health economic modelling to support a future trial was favourable. CONCLUSIONS: the Vfrac clinical tool appears to be valid and is improved by the addition of self-reported back pain symptoms. The tool now requires testing to establish real-world clinical and cost-effectiveness.

Development of guidelines to reduce, handle and report missing data in palliative care trials: A multi-stakeholder modified nominal group technique.

BACKGROUND: Missing data can introduce bias and reduce the power, precision and generalisability of study findings. Guidelines on how to address missing data are limited in scope and detail, and poorly implemented. AIM: To develop guidelines on how best to (i) reduce, (ii) handle and (iii) report missing data in palliative care clinical trials. DESIGN: Modified nominal group technique. SETTING/PARTICIPANTS: Patient and public research partners, palliative care clinicians, trialists, methodologists and statisticians attended a 1-day workshop, following which a multi-stakeholder development group drafted the guidelines. RESULTS: Seven main recommendations for reducing missing data, nine for handling missing data and twelve for reporting missing data were developed. The top five recommendations were: (i) train all research staff on missing data, (ii) prepare for missing data at the trial design stage, (iii) address missing data in the statistical analysis plan, (iv) collect the reasons for missing data and (v) report descriptive statistics comparing the baseline characteristics of those with missing and observed data. Reducing missing data, preparing for missing data and understanding the reasons for missing data were greater priorities for stakeholders than how to deal with missing data once they had occurred. CONCLUSION: Comprehensive guidelines on how to address missing data were developed by stakeholders involved in palliative care trials. Implementation of the guidelines will require endorsement of research funders and research journals.

Psychometric properties of the PHQ-9 measure of depression among Brazilian older adults.

Objectives: To obtain evidence on the psychometric properties of the Patient Health Questionnaire - 9 (PHQ-9, one of the most extensively used tools for assessing depression) in the Brazilian older population.Method: Data on 3,356 Brazilian adults aged 60+ years living in Guarulhos, São Paulo state were used. The factor structure of the questionnaire was analysed using a factor analysis approach. The questionnaire's measurement equivalence was tested across gender, age, personal income, and education level groups. The scores were compared across groups based on the highest level of equivalence achieved. The questionnaire's internal consistency was analysed considering its factor structure.Results: A one-factor solution was identified as the most adequate factor structure, with the factor explaining 57.6% of the items' variance. The correlation of the resulting latent score with the overall raw sum score in the PHQ-9 was r = 0.96. Measurement equivalence regarding thresholds and loadings was achieved for all tested groups. On average, women, older, less educated, and poorer people had higher latent scores on the depression factor. The measure showed a good internal consistency with Revelle's omega total ωt=0.92.Conclusion: The results suggest that, among Brazilian older adults living in Guarulhos, São Paulo state, the PHQ-9 measures depressive symptomatology equivalently across different sociodemographic subgroups. Moreover, it can be scored using the raw sum of the item scores to adequately reflect different levels of depressive symptomatology.

Comparison between self-administered depression questionnaires and patients' own views of changes in their mood: a prospective cohort study in primary care.

BACKGROUND: Self-administered questionnaires are widely used in primary care and other clinical settings to assess the severity of depressive symptoms and monitor treatment outcomes. Qualitative studies have found that changes in questionnaire scores might not fully capture patients' experience of changes in their mood but there are no quantitative studies of this issue. We examined the extent to which changes in scores from depression questionnaires disagreed with primary care patients' perceptions of changes in their mood and investigated factors influencing this relationship. METHODS: Prospective cohort study assessing patients on four occasions, 2 weeks apart. Patients (N = 554) were recruited from primary care surgeries in three UK sites (Bristol, Liverpool and York) and had reported depressive symptoms or low mood in the past year [68% female, mean age 48.3 (s.d. 12.6)]. Main outcome measures were changes in scores on patient health questionnaire (PHQ-9) and beck depression inventory (BDI-II) and the patients' own ratings of change. RESULTS: There was marked disagreement between clinically important changes in questionnaire scores and patient-rated change, with disagreement of 51% (95% CI 46-55%) on PHQ-9 and 55% (95% CI 51-60%) on BDI-II. Patients with more severe anxiety were less likely, and those with better mental and physical health-related quality of life were more likely, to report feeling better, having controlled for depression scores. CONCLUSIONS: Our results illustrate the limitations of self-reported depression scales to assess clinical change. Clinicians should be cautious in interpreting changes in questionnaire scores without further clinical assessment.

Challenges in developing capability measures for children and young people for use in the economic evaluation of health and care interventions.

Methods for measuring outcomes suitable for economic evaluations of health and care interventions have primarily focused on adults. The validity of such methods for children and young people is questionable in areas including the outcome domains measured and how they are measured and valued, with most existing measures narrowly focusing on health. Novel methods for assessing benefits beyond health by focusing on a person's capability have also concentrated on adults to date. This paper aims to set out the rationale for capability measures in children and young people. It argues for the need to expand the evaluative space beyond health functioning towards broader capabilities, with children and young people playing an integral role in capability measure development. Drawing from existing literature, specific challenges related to the identification, measurement, and valuation of capabilities in children and young people are also discussed. Finally, the practical implications for conducting economic evaluation when measuring and valuing capabilities at different stages across the life-course are illustrated. We develop an alternative framework based on conceiving capabilities as evolving across the life-course. This framework may also be helpful in thinking about how to model health outcomes across the life-course.

Acceptability and fidelity of a psychosocial intervention (PROACTIVE) for older adults with depression in a basic health unit in São Paulo, Brazil: a qualitative study.

BACKGROUND: Depression is a common condition in older adults, being often detected and treated initially in primary care. Collaborative care models including, for example, task-shifting and stepped-care approaches have been investigated to overcome the current scarcity of strategies and trained mental health professionals to treat depression. The PROACTIVE study developed a psychosocial intervention, which makes extensive use of technology in an intervention delivered mainly by non-specialists to treat older adults with depression. The aim of this qualitative study is to assess: 1. Health workers' fidelity to the intervention protocol; 2. Acceptability of the psychosocial intervention from the viewpoint of older adult participants; and 3. Perceptions of the psychosocial intervention by the health workers. METHODS: Qualitative methods were used to achieve our aims. The sample included participants (N = 31) receiving the intervention in the pilot trial and health workers (N = 11) working in a Basic Health Unit in the northern area of São Paulo, Brazil. Focus group, non-participant observation and structured interviews were used. Data were analysed using a thematic analysis approach. RESULTS: 1. Health workers' fidelity to the intervention protocol: training, supervision and the structured intervention were crucial and guaranteed health workers' fidelity to the protocol. 2. Acceptability of the psychosocial intervention from the viewpoint of older adult participants: Collaborative care, task-shifting, and stepped-care approaches were well accepted. The structured protocol of the intervention including different activities and videos was important to adherence of older adult participants 3. Perceptions of the psychosocial intervention by the health workers: It was feasible to have the home psychosocial sessions conducted by health workers, who are non-mental health specialists and received 3-day training. Training and supervision were perceived as crucial to support health workers before and during the intervention. Technology served as a tool to structure the sessions, obtain and store patient data, present multi-media content, guarantee fidelity to the protocol and facilitate communication among members of the team. However, extra burden was mentioned by the health workers indicating the need of adjustments in their daily duties. CONCLUSIONS: The PROACTIVE intervention was demonstrated to be feasible and accepted by both health workers and older adult participants. The qualitative assessments suggested improvements in training and supervision to ensure fidelity to protocol. To assess effectiveness a randomised controlled trial of the intervention will be conducted with the addition of improvements suggested by this qualitative study. TRIAL REGISTRATION: The pilot study of which the present study gives support to was registered at the Brazilian Clinical Trials, UTN code: U1111-1218-6717 on 26/09/2018.

Educational outcomes associated with persistent speech disorder.

BACKGROUND: Children with persistent speech disorder (PSD) are at higher risk of difficulties with literacy, with some evidence suggesting an association with poorer educational attainment. However, studies to date have either used small clinical samples, which exclude children who have not been referred to clinical services, or relied on parent-teacher report of children's speech development. There is a need for an inclusive study to investigate the impact of PSD on educational outcomes using a population-based sample and robust measures of speech development. AIM: Using a large prospective UK population-based study-the Avon Longitudinal Study of Parents and Children (ALSPAC)-this study investigated: (1) how children identified with PSD at age 8 years perform on educational attainment tests at ages 10-11 and 13-14 years in comparison with children without PSD; and (2) whether children identified with PSD at age 8 years are more likely to receive a label of special educational needs (SEN) in secondary school. METHODS & PROCEDURES: We examined the data for 263 children with PSD and 6399 controls who had speech assessed at age 8 years in a research clinic. Educational attainment was measured using data from English school standard attainment tests. Data on SEN categorization were obtained between 11 and 13 years of age. Children with PSD and controls were compared using regression analyses adjusted for biological sex, maternal age, verbal, performance and full-scale IQ. OUTCOMES & RESULTS: Children with PSD at age 8 years were more likely to achieve lower attainment scores at ages 10-11 years in English and mathematics and across all three subjects of English, mathematics and science at ages 13-14 years after controlling for biological sex and maternal education; score below target levels for English at both time points after controlling for verbal IQ, and at ages 13-14 years after controlling for performance IQ; and receive a label of SEN (typically for the category of cognition and learning needs or communication and interaction needs) in secondary school. CONCLUSIONS & IMPLICATIONS: PSD identified at age 8 years is associated with poor educational attainment at ages 10-11 and 13-14 years in the core subjects of English, mathematics and science. Children with PSD at age 8 years are more likely to be identified with SEN at ages 11-13 years, particularly cognition and learning needs, and communication and interaction needs. We need to be aware of the potential for the long-term impact of PSD on educational attainment in providing appropriate and effective support throughout school. What this paper adds What is already known on the subject Speech-sound disorder is associated with reading and spelling difficulties, with some evidence to suggest that PSD is associated with a higher risk of literacy difficulties. Limited evidence also suggests that speech-sound disorder may be associated with poorer educational attainment. However, studies to date have used small clinical samples or parent-teacher report of speech development and there is a need to determine whether the association is observed in larger and more inclusive population-based samples. What this paper adds to existing knowledge This prospective, longitudinal study of a large community-based sample of English children has shown that PSD is associated with poorer educational attainment at the end of primary school and at ages 13-14 years. Children with PSD are also more likely to be identified as having SEN in secondary school, especially communication and interaction needs but also including cognition and learning needs. What are the potential or actual clinical implications of this work? Understanding the long-term implications of PSD on educational attainment highlights the importance of ongoing monitoring and support to enable children to reach their potential throughout primary and secondary school. The identification of children with a history of PSD during transition to secondary school will enable effective support to be put in place. The intervention for children with PSD should involve close collaboration between speech and language therapists and education professionals.

Effect of a Digital Intervention on Depressive Symptoms in Patients With Comorbid Hypertension or Diabetes in Brazil and Peru: Two Randomized Clinical Trials.

Importance: Depression is a leading contributor to disease burden globally. Digital mental health interventions can address the treatment gap in low- and middle-income countries, but the effectiveness in these countries is unknown. Objective: To investigate the effectiveness of a digital intervention in reducing depressive symptoms among people with diabetes and/or hypertension. Design, Setting, and Participants: Participants with clinically significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) who were being treated for hypertension and/or diabetes were enrolled in a cluster randomized clinical trial (RCT) at 20 sites in São Paulo, Brazil (N=880; from September 2016 to September 2017; final follow-up, April 2018), and in an individual-level RCT at 7 sites in Lima, Peru (N=432; from January 2017 to September 2017; final follow-up, March 2018). Interventions: An 18-session, low-intensity, digital intervention was delivered over 6 weeks via a provided smartphone, based on behavioral activation principles, and supported by nurse assistants (n = 440 participants in 10 clusters in São Paulo; n = 217 participants in Lima) vs enhanced usual care (n = 440 participants in 10 clusters in São Paulo; n = 215 participants in Lima). Main Outcomes and Measures: The primary outcome was a reduction of at least 50% from baseline in PHQ-9 scores (range, 0-27; higher score indicates more severe depression) at 3 months. Secondary outcomes included a reduction of at least 50% from baseline PHQ-9 scores at 6 months. Results: Among 880 patients cluster randomized in Brazil (mean age, 56.0 years; 761 [86.5%] women) and 432 patients individually randomized in Peru (mean age, 59.7 years; 352 [81.5%] women), 807 (91.7%) in Brazil and 426 (98.6%) in Peru completed at least 1 follow-up assessment. The proportion of participants in São Paulo with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 40.7% (159/391 participants) in the digital intervention group vs 28.6% (114/399 participants) in the enhanced usual care group (difference, 12.1 percentage points [95% CI, 5.5 to 18.7]; adjusted odds ratio [OR], 1.6 [95% CI, 1.2 to 2.2]; P = .001). In Lima, the proportion of participants with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 52.7% (108/205 participants) in the digital intervention group vs 34.1% (70/205 participants) in the enhanced usual care group (difference, 18.6 percentage points [95% CI, 9.1 to 28.0]; adjusted OR, 2.1 [95% CI, 1.4 to 3.2]; P < .001). At 6-month follow-up, differences across groups were no longer statistically significant. Conclusions and Relevance: In 2 RCTs of patients with hypertension or diabetes and depressive symptoms in Brazil and Peru, a digital intervention delivered over a 6-week period significantly improved depressive symptoms at 3 months when compared with enhanced usual care. However, the magnitude of the effect was small in the trial from Brazil and the effects were not sustained at 6 months. Trial Registration: ClinicalTrials.gov: NCT02846662 (São Paulo) and NCT03026426 (Lima).

The ProtecT randomised trial cost-effectiveness analysis comparing active monitoring, surgery, or radiotherapy for prostate cancer.

BACKGROUND: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. METHODS: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. RESULTS: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. CONCLUSIONS: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Correction to: Identifying Scoliosis in Population­Based Cohorts: Automation of a Validated Method Based on Total Body Dual Energy X­ray Absorptiometry Scans.

In the original version of the article, the co-author would like to add to the acknowledgements section to highlight their funding stream (EPSRC). The revised acknowledgements is given below.