Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet

This paper provides three illustrations of how the “person-based approach” can be used to assess and enhance the acceptability and feasibility of an intervention during the early stages of development and evaluation. The person-based approach involves using mixed methods research to systematically investigate the beliefs, attitudes, needs and situation of the people who will be using the intervention. The in-depth understanding of users’ perspectives derived from this research then enables intervention developers to design or modify the intervention to make it more relevant, persuasive, accessible and engaging. The first illustration describes how relevant beliefs and attitudes of people with asthma were identified from the existing qualitative and quantitative literature and then used to create guiding principles to inform the design of a web-based intervention to improve quality of life. The second illustration describes how qualitative “think-aloud” interviews and patient and public involvement (PPI) input are used to improve the acceptability of a booklet for people with asthma. In the third illustration, iterative think-aloud methods are used to create a more accurate and accessible activity planner for people with diabetes. In the first illustration of the person-based approach, we present the guiding principles we developed to summarise key design issues/objectives and key intervention features to address them. The second illustration provides evidence from interviews that positive, non-medical messages and images were preferred in booklet materials for people with asthma. The third illustration demonstrates that people with diabetes found it difficult to complete an online activity planner accurately, resulting in incorrect personalised advice being given prior to appropriate modification of the planner. The person-based approach to intervention development can complement theory- and evidence-based development and participant input into intervention design, offering a systematic process for systematically investigating and incorporating the views of a wide range of users.

The intraerythrocytic development of Plasmodium falciparum correlates with increasing levels of the polyamines putrescine, spermidine, and spermine in the infected red blood cells; and compartmental analyses revealed that the majority is associated with the parasite. Since depletion of cellular polyamines is a promising strategy for inhibition of parasite proliferation, new inhibitors of polyamine biosynthesis were tested for their antimalarial activities. The ornithine decarboxylase (ODC) inhibitor 3-aminooxy-1-aminopropane (APA) and its derivatives CGP 52622A and CGP 54169A as well as the S -adenosylmethionine decarboxlyase (AdoMetDC) inhibitors CGP 40215A and CGP 48664A potently affected the bifunctional P. falciparum ODC-AdoMetDC, with K _i values in the low nanomolar and low micromolar ranges, respectively. Furthermore, the agents were examined for their in vitro plasmodicidal activities in 48-h incubation assays. APA, CGP 52622A, CGP 54169A, and CGP 40215A were the most effective, with 50% inhibitory concentrations below 3 μM. While the effects of the ODC inhibitors were completely abolished by the addition of putrescine, growth inhibition by the AdoMetDC inhibitor CGP 40215A could not be antagonized by putrescine or spermidine. Moreover, CGP 40215A did not affect the cellular polyamine levels, indicating a mechanism of action against P. falciparum independent of polyamine synthesis. In contrast, the ODC inhibitors led to decreased cellular putrescine and spermidine levels in P. falciparum , supporting the fact that they exert their antimalarial activities by inhibition of the bifunctional ODC-AdoMetDC.

Background: The value and importance of qualitative research and Patient and Public Involvement (PPI) for developing complex health interventions is widely recognised. However, there is often confusion between the two, with researchers relying on just one of these approaches, rather than using the two alongside one another. Methods: The Person-Based Approach (PBA) to developing health-related behaviour change interventions adapts and integrates methods from user-centred design and qualitative research. The PBA involves qualitative research at multiple stages of interventions to ensure they are acceptable, feasible, meaningful, and optimally engaging to the people who will use them. The qualitative research is carried out with research participants from a target population, who have no prior or continuing involvement in the wider research process and see the intervention from a fresh perspective. This enables in-depth understanding of the views and experiences of a wide range of target users and the contexts within which they engage with behavioural change. PPI in research is carried out with or by members of the public and is a key part of the research process. PPI contributors are involved at all stages of research design and interpretation. PPI provides input into interventions as members of the research team alongside other stakeholders, such as health professionals and behaviour change experts. Results: We advocate using qualitative research alongside PPI at all stages of intervention planning, development, and evaluation. We illustrate this with examples from recent projects developing complex health interventions, highlighting examples where PPI and PBA have pulled in different directions and how we have approached this, how PPI have helped optimise interventions based on PBA feedback, and how we have engaged PPI in community settings. Conclusions: PPI provides a valuable alternative to the traditional researcher-led approaches, which can be poorly matched to the needs of target users. Combining PPI with the PBA can help to create optimally engaging interventions by incorporating a greater diversity of feedback than would have been possible to achieve through PPI or qualitative approaches alone.

Objective: An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema. Methods: Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and Epistemonikos until 2 March 2021. Reviews were included if they assessed the safety of TCS in atopic eczema and searched > 1 database using a reproducible search strategy. Review quality was assessed using version 2 of 'A MeaSurement Tool to Assess systematic Reviews' (AMSTAR 2 tool). Results: 38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up were usually short (2–4 weeks). Key findings: TCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4% to 5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased. TCS versus topical calcineurin inhibitors: Meta-analysis showed higher relative risk of skin thinning with TCS (4.86, 95% CI 1.06 to 22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression. Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129). TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS). Conclusions: W e found no evidence of harm when TCS were used intermittently ‘as required’ to treat flares or ‘weekend therapy’ to prevent flares. However, long-term safety data were limited. PROSPERO registration number: CRD42018079409.

Objective: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. Design: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. Setting: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. Participants: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. Interventions: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. Main outcome measures: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator’s global assessment (IGA) for treatment success; and adverse reactions. Results: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. Conclusions: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. Trial registration: ISRCTN12892056