An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

Learning outcomes from a systematic review workshop series for junior doctors.

BACKGROUND: Systematic reviews provide the highest level of evidence about a topic. Ten-week workshops in conducting systematic reviews were held with hospital doctors in 2019 and 2020. AIM: This study analysed participants' feedback about the systematic review workshops to improve how we teach clinicians about conducting systematic reviews. METHODS: Attendees completed a post-workshop survey (with multiple-choice and free-text items) to assess knowledge and skills gained. We compared the responses of senior and junior doctors. We used descriptive statistics for the quantitative data and compared groups using Χ2 testing. Qualitative data were analysed using conceptual content analysis. RESULTS: Of 81 attendees, 52% completed the survey. Of those, 69% had no prior experience with systematic reviews, 93% reported increased knowledge and ability to conduct research and 69% reported increased ability to conduct systematic reviews. More senior than junior clinicians reported gaining knowledge about writing and publishing (37% vs 11%, P = 0.047) and making greater use of skills gained to conduct research (56% vs 23%, P = 0.029). Five themes were identified: learning through course structure; learning through course organisation; teaching style; flexible learning; and suggestions for progression and improvement. Respondents suggested running the workshops during protected teaching time, more time for some sessions, conducting the workshop series more often and making clinicians aware of the workshop series at hospital orientation. CONCLUSION: The skills learnt from the systematic review workshop series impacted not only participants' research knowledge and skills, and plans to conduct future research, but also facilitated looking up medical literature in daily clinical work, supporting evidence-based clinical practice.

A Randomized Controlled Trial of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children referred to specialist outpatient clinics by primary care providers often have long waiting times before being seen. We assessed whether an individualized, web-based, evidence-informed management support for children with urinary incontinence while waiting reduced requests for specialist appointments. MATERIALS AND METHODS: A multicenter, waitlisted randomized controlled trial was conducted for children (5-18 years) with urinary incontinence referred to tertiary pediatric continence clinics. Participants were randomized to the web-based eHealth program electronic Advice and Diagnosis Via the Internet following Computerized Evaluation (eADVICE), which used an embodied conversational agent to engage with the child at the time of referral (intervention) or 6 months later (control). The primary outcome was the proportion of participants requesting a clinic appointment at 6 months. Secondary outcomes included persistent incontinence, and the Paediatric incontinence Questionnaire (PinQ) score. RESULTS: From 2018 to 2020, 239 children enrolled, with 120 randomized to eADVICE and 119 to the control arm. At baseline, participants' mean age was 8.8 years (SD 2.2), 62% were males, mean PinQ score was 5.3 (SD 2.2), 36% had daytime incontinence, and 97% had nocturnal enuresis. At 6 months, 78% of eADVICE participants vs 84% of controls requested a clinic visit (relative risk 0.92, 95% CI 0.79, 1.06, P = .3), and 23% eADVICE participants vs 10% controls were completely dry (relative risk 2.23, 95% CI 1.10, 4.50, P = .03). The adjusted mean PinQ score was 3.5 for eADVICE and 3.9 for controls (MD -0.37, 95% CI -0.71, -0.03, P = .03). CONCLUSIONS: The eADVICE eHealth program for children awaiting specialist appointments doubled the proportion who were dry at 6 months and improved quality of life but did not reduce clinic appointment requests.

How Adolescents Trust Health Information on Social Media: A Systematic Review.

BACKGROUND: Given the potential for social media to spread health misinformation, it is important to understand how trusts impact adolescents' engagement with health content on social media. OBJECTIVE: To explore the concept of trust when adolescents (13-18 years) engage with health information on social media. Five relevant databases (MEDLINE, EMBASE, PsycINFO, ERIC, and CINAHL) were systematically searched alongside Google Scholar and reference lists of included papers. Studies were included if they examined adolescents' trust when engaging with health information on social media. STUDY APPRAISAL AND SYNTHESIS METHODS: Thematic analysis was used to synthesize the findings from this review. RESULTS: Thirty-four papers were included. Three key domains were explored: trust in the social media platform/service (general distrust of social media for health information; safety and privacy); trust in other users (mistrust of unknown users; fear of bullying or judgment; trust in friends or peers; celebrities and popularity; trust in others' experience and the importance of social support); trust in content (tone and appearance of health information; expertise and verification; advertising, pushed, and suggested content). LIMITATIONS: Narrow geographic representation of papers and limited quantitative studies. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Adolescents' trust in health information on social media involves a complex interplay between trust in: social media platforms, other users, and health content. Central to many of the findings is the social and identity work done by adolescents on and through social media.

Baseline characteristics of participants in the NAVKIDS2 trial: a patient navigator program in children with chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) require multidisciplinary care to meet their complex healthcare needs. Patient navigators are trained non-medical personnel who assist patients and caregivers to overcome barriers to accessing health services through care coordination. This trial aims to determine the effectiveness of a patient navigator program in children with CKD. METHODS: The NAVKIDS2 trial is a multi-center, waitlisted, randomized controlled trial of patient navigators in children with CKD conducted at five sites across Australia. Children (0-16 years) with CKD from low socioeconomic status rural or remote areas were randomized to an intervention group or a waitlisted control group (to receive intervention after 6 months). The study primary and secondary endpoints include the self-rated health (SRH) (primary), and utility-based quality of life, progression of kidney dysfunction of the child, SRH, and satisfaction with healthcare of the caregiver at 6 months post-randomization. RESULTS: The trial completed recruitment in October 2021 with expected completion of follow-up by October 2022. There were 162 patients enrolled with 80 and 82 patients randomized to the immediate intervention and waitlisted groups, respectively. Fifty-eight (36%) participants were from regional/remote areas, with a median (IQR) age of 9.5 (5.0, 13.0) years, 46% were of European Australian ethnicity, and 65% were male. A total of 109 children (67%) had CKD stages 1-5, 42 (26%) were transplant recipients, and 11 (7%) were receiving dialysis. CONCLUSION: The NAVKIDS2 trial is designed to evaluate the effectiveness of patient navigation in children with CKD from families experiencing socioeconomic disadvantage. A higher resolution version of the Graphical abstract is available as Supplementary information.

'Every Human Interaction Requires a Bit of Give and Take': Medical Students' Approaches to Pursuing Feedback in the Clinical Setting.

PhenomenonStudents, alongside teachers, play a key role in feedback. Student behavior in feedback processes may impact feedback outcomes. Student feedback behavior includes recognizing, seeking, evaluating, and utilizing feedback. Student feedback behavior is influenced by numerous student attributes and environmental factors. ApproachWe aimed to explore influences on medical student feedback behavior during clinical attachments. We adopted a subjective inductive qualitative approach. We conducted 7 focus groups with 46 medical students undertaking pediatric hospital-based attachments. We based our discussion framework on existing characterizations of student feedback behavior and the educational alliance model with its focus on the relationship between learners and teachers, and the active role played by both. During initial data analysis, we identified that our results exhibited aspects of Bandura's model of Triadic Reciprocal Causation within Social Cognitive Theory. In line with our subjective inductive approach, we adopted Triadic Reciprocal Causation at this point for further analysis and interpretation. This allowed us to conceptualize the emerging interactions between influences on feedback behavior. Findings We identified three key determinants of student feedback behavior: Environmental influences, Student attributes and Relationships between teachers and students. Environmental influences encompassed factors external to the student, including Teacher attributes and behaviors and The clinical learning context. Through the lens of Triadic Reciprocal Causation, the interrelationships between the determinants of feedback behavior gave rise to five key themes: Interactions between student feedback behavior and environmental influences of the clinical learning context, Interactions between student feedback behavior and environmental influences of teacher attributes and behaviors, Interactions between student attributes and student feedback behavior, Interactions between student attributes and environmental influences of teacher attributes and behaviors, and Relationships and the determinants of student feedback behavior. Insights: We apply the Triadic Reciprocal Causation model of Social Cognitive Theory to understand the influences on student feedback behavior and the interactions between them. We extend the model by situating relationships between students and teachers as a central factor. Future interventions to facilitate students' role in feedback will need to address student attributes, environmental factors, and student-teacher relationships, appreciating the codependent nature of these influences.

Adolescents' self-efficacy and digital health literacy: a cross-sectional mixed methods study.

BACKGROUND: The internet and social media are increasingly popular sources of health information for adolescents. Using online health information requires digital health literacy, consisting of literacy, analytical skills and personal capabilities such as self-efficacy. Appraising trustworthiness and relevance of online health information requires critical health literacy to discriminate between sources, critically analyse meaning and relevance, and use information for personal health. Adolescents with poor digital health literacy risk using misinformation, with potential negative health outcomes. We aimed to understand adolescents' contemporary digital health literacy and compared self-efficacy with capability. METHODS: Adolescents (12-17 years) completed an eHEALS self-report digital health literacy measure, a practical search task using a think-aloud protocol and an interview to capture perceived and actual digital health literacy. eHEALS scores were generated using descriptive statistics, search tasks were analysed using an observation checklist and interviews were thematically analysed based on Social Cognitive Theory, focussing on self-efficacy. RESULTS: Twenty-one participants generally had high self-efficacy using online health information but perceived their digital health literacy to be higher than demonstrated. They accessed online health information unintentionally on social media and intentionally via search engines. They appraised information medium, source and content using general internet searching heuristics taught at school. Information on social media was considered less trustworthy than websites, but participants used similar appraisal strategies for both; some search/appraisal heuristics were insufficiently nuanced for digital health information, sometimes resulting in misplaced trust or diminished self-efficacy. Participants felt anxious or relieved after finding online health information, depending on content, understanding and satisfaction. They did not act on information without parental and/or health professional advice. They rarely discussed findings with health professionals but would welcome discussions and learning how to find and appraise online health information. CONCLUSIONS: Whilst adolescents possess many important digital health literacy skills and generally feel self-efficacious in using them, their critical health literacy needs improving. Adolescents desire increased digital health literacy so they can confidently appraise health information they find online and on social media. Co-designed educational interventions with adolescents and health providers are required.

An Alarm Watch for Daytime Urinary Incontinence: A Randomized Controlled Trial.

OBJECTIVES: Daytime urinary incontinence is disabling and occurs in 17% of school-aged children. Timed-voiding is part of standard therapy. Can an alarm watch to aid timed-voiding improve treatment response to standard therapy? METHODS: The WATCH (Watch with Alarm for Timed-Voiding in Children) study is a randomized controlled trial. Participants were randomly assigned (1:1) to a vibrating alarm or nonalarming watch for 3-months. The primary outcome was the proportion who achieved a complete response (14 consecutive dry days) after 3-months of treatment. Children aged 5 to 13 years who were prescribed timed-voiding for daytime urinary incontinence. RESULTS: Overall, 243 children, with a mean age of 8 years, were enrolled, with 62% girls. At 3-months, the complete response rates were similar between the 2 groups (22% alarm versus 17% control; difference: 5%; 95% confidence interval (CI): -5% to 16%; P = .42). In the alarm group, treatment adherence was higher (40% vs 10%; difference: 30%; 95% CI: 20% to 40%; P < .001), frequency of incontinence was lower (25% dry; 40% had 1-3 wet days per week, 24% had 4-6 wet days per week, and 12% had daily wetting, compared with 19%, 30%, 35%, and 16%, respectively; P =.05), and fewer had abnormal postvoid residual urine volumes (12% vs 24%; difference: -12%; 95% CI: -21% to -1%; P = .04) compared with the control group. Improvement was transient and did not persist 6 months beyond the treatment period. CONCLUSIONS: Alarm watches do not appear to lead to complete resolution of urinary incontinence in children but did promote treatment adherence, normalization of postvoid residual volumes, and reduction in incontinent episodes while being used.

Urinary incontinence during laughter in children: Is it giggle incontinence?

AIM: Giggle incontinence is a distinct entity of childhood daytime urinary incontinence (DUI), where children wet themselves only when they laugh. The prevalence of true giggle incontinence is unknown, with confusion about the diagnosis of urinary incontinence occurring during laughter and true giggle incontinence. The aim of the study is to improve our understanding of urinary incontinence during laughter by comparing those children with children who have DUI at other times, but not with laughter. METHODS: We conducted a retrospective medical record review of children with DUI who presented to a tertiary continence service from 2017 to 2018, collecting data on age, gender, associated comorbidities, lower urinary tract symptoms, investigations, provisional diagnosis at first visit and initial treatment responses. Differences between those with DUI occurring during laughter and those with DUI at other times, but not with laughter were compared using standard statistical methods. RESULTS: Of the 277 new patients seen during the study period, 140 (51%) had DUI, and of these, 72 (51%) had DUI occurring during laughter. Children with incontinence occurring during laughter were more likely to have incontinence associated with other activities. One child had giggle incontinence according to the International Children's Continence Society's definition. Four other children were referred specifically for urinary incontinence associated with laughter, with the term giggle incontinence sometimes used by the referring doctor. CONCLUSION: Children with DUI commonly experience incontinence during laughter, but true giggle incontinence is rare. Correct diagnosis is essential as it directs treatment.

Toilet training children with special needs using a Potty Monkey toy device.

AIM: Toilet training children with special needs can be challenging and can result in long-term consequences if inadequately addressed. This study evaluates the use of a 'Potty Monkey' toy for toilet training children with special needs. METHODS: A pilot study using a 'Potty Monkey' to model timed voiding in children with special needs. We collected parental feedback and examined the experience of families using a 'Potty Monkey' to toilet train their child. Using logistic regression we explored patient factors for association with outcomes. RESULTS: Of 21 children in our study, 15 were male. Age ranged 4-10 years (median 6.3 years). Days that 'Potty Monkey' was used ranged 0-156 (median 22 days). At 6 months, nine children had improved, five were unchanged and four were worse (three were unknown). We found no evidence of association between patient factors (age, gender, days using 'Potty Monkey', baseline toileting ability, Paediatric Incontinence Questionnaire score) and toileting outcome. The experience of families was ambivalent. 10 families reported 'Potty Monkey' had been helpful however many complained it interfered with family schedules. Reasons for the child not responding positively were due to sensory issues, embarrassment and being developmentally not ready. Our study demonstrated the practical challenges of conducting research among children with special needs. CONCLUSION: Although some children's toileting improved after using 'Potty Monkey', we are uncertain 'Potty Monkey' is effective for toilet training children with special needs.

An educational intervention to increase student engagement in feedback.

BACKGROUND: The learner has a central role in feedback. We developed a feedback workshop for medical students grounded in two concepts: (1) Student agency in feedback and its interplay in the context of brief clinical attachments; (2) The educational alliance. AIMS: To determine whether a brief feedback training workshop prior to a series of two-week clinical attachments improves agentic student feedback behaviour (e.g. seeking, recognising, evaluating and utilising feedback) and student satisfaction with feedback. METHODS: We conducted surveys among three consecutive student cohorts undertaking three fortnightly paediatric clinical attachments. We pilot tested a workshop with Cohort 1 and implemented it for the entire Cohorts 2 (n = 58) and 3 (n = 68). Participants completed the same survey at the start and end of term, with different free-text items. Quantitative and qualitative responses were compared between groups. RESULTS: Student-reported agentic feedback behaviour increased across all outcomes except for feedback utilisation. Overall student satisfaction with feedback increased during the term in Cohorts 2 (23-65%, p = 0.002) and 3 (40-70%, p = 0.003) but not in Cohort 1 non-participating students (27-42%, p = 0.42). CONCLUSIONS: A brief one-off student-directed feedback workshop may improve agentic student feedback behaviours (e.g. feedback-seeking) and student satisfaction with feedback.

The Role of Trust When Adolescents Search for and Appraise Online Health Information.

OBJECTIVE: To assess the role of trust when adolescents search for and appraise online health information. STUDY DESIGN: A systematic search of online databases (MEDLINE, EMBASE, PsycINFO, and ERIC) was performed. Google Scholar and reference lists for included studies were manually searched for additional articles. Studies were included if they examined the role of trust when adolescents (in the 13- to 18-year-old age range) searched for and/or appraised online health information. Findings were synthesized using thematic analysis. RESULTS: There were 22 studies that met the inclusion criteria. Four key themes were identified: adolescents generally distrust the Internet but use it anyway (subthemes were why adolescents distrust online health information; why adolescents still use online health information), adolescents use heuristics to appraise the trustworthiness of online health information (subthemes were different heuristics used by different adolescents, range of heuristics used by adolescents), adolescents trust websites more than social media or social networking sites, and adolescents' level of trust in online health information guides their actions and responses. CONCLUSIONS: Adolescents often distrust health information from the Internet, but continue to use it. Adolescents are aware of the need to evaluate the trustworthiness of online health information; however, their approaches vary in sophistication. As the reach and content of the Internet expands, it is important to equip adolescents with effective eHealth literacy to assess the trustworthiness of online health information.

How Adolescents Search for and Appraise Online Health Information: A Systematic Review.

OBJECTIVE: To conduct a systematic review of the evidence concerning whether and how adolescents search for online health information and the extent to which they appraise the credibility of information they retrieve. STUDY DESIGN: A systematic search of online databases (MEDLINE, EMBASE, PsycINFO, ERIC) was performed. Reference lists of included papers were searched manually for additional articles. Included were studies on whether and how adolescents searched for and appraised online health information, where adolescent participants were aged 13-18 years. Thematic analysis was used to synthesize the findings. RESULTS: Thirty-four studies met the inclusion criteria. In line with the research questions, 2 key concepts were identified within the papers: whether and how adolescents search for online health information, and the extent to which adolescents appraise online health information. Four themes were identified regarding whether and how adolescents search for online health information: use of search engines, difficulties in selecting appropriate search strings, barriers to searching, and absence of searching. Four themes emerged concerning the extent to which adolescents appraise the credibility of online health information: evaluation based on Web site name and reputation, evaluation based on first impression of Web site, evaluation of Web site content, and absence of a sophisticated appraisal strategy. CONCLUSIONS: Adolescents are aware of the varying quality of online health information. Strategies used by individuals for searching and appraising online health information differ in their sophistication. It is important to develop resources to enhance search and appraisal skills and to collaborate with adolescents to ensure that such resources are appropriate for them.

An interprofessional approach to managing children with treatment-resistant enuresis: an educational review.

Enuresis (intermittent urinary incontinence during sleep in a child aged ≥ 5 years) is commonly seen in paediatric practice. Despite the availability of effective interventions, treatment resistance is encountered in up to 50% of children. In this educational review we attempt to provide insight into the causes of treatment resistance, and offer practical suggestions for addressing this condition using an interprofessional approach. We explore the pathophysiology of and standard treatments for enuresis and discuss why standard treatments may fail. An interprofessional approach to treatment resistance is proposed which utilises the expertise of professionals from different disciplines to address the problems and barriers to treatment. The two interprofessional approaches include a multidisciplinary approach that involves the patient being sent to experts in different disciplines at different times to address their treatment resistance utilising the skills of the respective experts, and an interdisciplinary approach that involves a patient being managed by members of interdisciplinary team who integrate their separate discipline perspectives into a single treatment plan. Although an interdisciplinary approach is ideal, interdisciplinary teams may not be available in all circumstances. Understanding the roles of other disciplines and engaging clinicians from other disciplines when appropriate can still be helpful when treatment resistance is encountered.

Moving beyond 'not enough time': factors influencing paediatric clinicians' participation in research.

BACKGROUND: Increasing the amount of clinical research that occurs in healthcare settings has been identified as an important mechanism to improve healthcare outcomes. While clinicians are key persons in achieving this aim, research participation amongst clinicians is generally limited. AIMS: To identify the factors (barriers and facilitators) influencing clinician research participation and determine how professional culture impacts on these factors. METHODS: Forty clinicians working at a tertiary children's hospital participated in six discipline-specific focus groups. Thematic analysis was performed using an inductive process based in grounded theory. RESULTS: Four major themes (cultural factors, personal factors, resources and solutions) and 16 subthemes were identified. Participants described how the current health system discourages clinician research. They reported that their research participation requires personal sacrifice of their own time; income or career progression. Research participation was seen to compete with other priorities in clinicians' workload and is disadvantaged because of the primacy of clinical work and the lack of immediate tangible benefit from research projects. Solutions suggested by our participants included better alignment of clinical and research goals, improved availability of research mentors and collaborative opportunities. Nurses and allied health professionals reported a changing professional culture that values research. Only doctors identified research participation to be important for career progression. CONCLUSIONS: For clinician research participation to flourish, significant changes in healthcare structure and priorities will be required that result in research becoming more embedded in healthcare delivery. Initiatives to improve collaboration between clinicians and universities may also support these aims.

Researchers', Regulators', and Sponsors' Views on Pediatric Clinical Trials: A Multinational Study.

BACKGROUND AND OBJECTIVE: The last decade has seen dramatic changes in the regulatory landscape to support more trials involving children, but child-specific challenges and inequitable conduct across income regions persist. The goal of this study was to describe the attitudes and opinions of stakeholders toward trials in children, to inform additional strategies to promote more high-quality, relevant pediatric trials across the globe. METHODS: Key informant semi-structured interviews were conducted with stakeholders (researchers, regulators, and sponsors) who were purposively sampled from low- to middle-income countries and high-income countries. The transcripts were thematically analyzed. RESULTS: Thirty-five stakeholders from 10 countries were interviewed. Five major themes were identified: addressing pervasive inequities (paucity of safety and efficacy data, knowledge disparities, volatile environment, double standards, contextual relevance, market-driven forces, industry sponsorship bias and prohibitive costs); contending with infrastructural barriers (resource constraints, dearth of pediatric trial expertise, and logistical complexities); navigating complex ethical and regulatory frameworks ("draconian" oversight, ambiguous requirements, exploitation, excessive paternalism and precariousness of coercion versus volunteerism); respecting uniqueness of children (pediatric research paradigms, child-appropriate approaches, and family-centered empowerment); and driving evidence-based child health (advocacy, opportunities, treatment access, best practices, and research prioritization). CONCLUSIONS: Stakeholders acknowledge that changes in the regulatory environment have encouraged more trials in children, but they contend that inequities and political, regulatory, and resource barriers continue to exist. Embedding trials as part of routine clinical care, addressing the unique needs of children, and streamlining regulatory approvals were suggested. Stakeholders recommended increasing international collaboration, establishing centralized trials infrastructure, and aligning research to child health priorities to encourage trials that address global child health care needs.

Stakeholder Views of Clinical Trials in Low- and Middle-Income Countries: A Systematic Review.

CONTEXT: Clinical trials are necessary to improve the health care of children, but only one-quarter are conducted in the low- to middle-income countries (LMICs) in which 98% of the global burden of disease resides. OBJECTIVE: To describe stakeholder beliefs and experiences of conducting trials in children in LMICs. DATA SOURCES: Electronic databases were searched to August 2014. STUDY SELECTION: Qualitative studies of stakeholder perspectives on conducting clinical trials among children in LMICs. DATA EXTRACTION: Findingswere analyzed by using thematic synthesis. RESULTS: Thirty-nine studies involving 3110 participants (children [n = 290], parents or caregivers [n = 1609], community representatives [n = 621], clinical or research team members [n = 376], regulators [n = 18], or sponsors [n = 15]) across 22 countries were included. Five themes were identified: centrality of community engagement (mobilizing community, representatives' pivotal role, managing expectations, and retaining involvement); cognizance of vulnerability and poverty (therapeutic opportunity and medical mistrust); contending with power differentials (exploitation, stigmatization, and disempowerment); translating research to local context (cultural beliefs, impoverishment constraints, and ethical pluralism); and advocating fair distribution of benefits (health care, sponsor obligation, and collateral community benefits). LIMITATIONS: Studies not published in English were excluded. CONCLUSIONS: Conducting trials in children in LMICs is complex due to social disadvantage, economic scarcity, idiosyncratic cultural beliefs, and historical disempowerment, all of which contribute to inequity, mistrust, and fears of exploitation. Effective community engagement in recruiting, building research capacities, and designing trials that are pragmatic, ethical, and relevant to the health care needs of children in LMICs may help to improve the equity and health outcomes of this vulnerable population.

Tricyclic and related drugs for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s. OBJECTIVES: To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (containing trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings), on 30 November 2015, and reference lists of relevant articles. SELECTION CRITERIA: We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author. MAIN RESULTS: Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response. AUTHORS' CONCLUSIONS: There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.

A randomised controlled trial of a code-word enuresis alarm.

OBJECTIVE: To compare a novel code-word alarm with a commercially available wireless alarm for treating enuresis. SETTING: A tertiary paediatric centre. PATIENTS: Children aged 6-18 with at least 3 wet nights per week in the previous 6 months referred by doctors. OUTCOMES: Primary outcome: the proportion who achieved a full response (14 consecutive dry nights) by 16 weeks. Secondary outcomes: change in frequency of wetting, duration of alarm training, percentage of wet nights that the child woke to the alarm, adherence to treatment, adverse events and satisfaction with treatment. RESULTS: Of the 353 participants, 176 were assigned to the code-word alarm and 177 to control. At 16 weeks, 54% (95% CI 47% to 61%) in the experimental group and 47% (95% CI 40% to 55%) in the control group had achieved a full response (p=0.22), with 74% and 66%, respectively, attaining a 50% or more reduction in wetting frequency (p=0.14). The experimental group woke more often than the control group (median percentage of waking 88% vs 77%, p=0.003) and had a greater reduction in wet nights (median reduction of 10 vs 9 nights per fortnight). Fewer in the experimental group discontinued therapy before achieving a full response (27% vs 37% discontinued, p=0.04). There were no significant differences in relapse rates at 6 months, adverse events or satisfaction between the two alarms. CONCLUSIONS: Although the code-word alarm increased waking, no difference in full response rates was demonstrated between the two alarms. TRIAL REGISTRATION NUMBER: ACTRN12609000070235.