A dynamic and collaborative approach to trial recruitment in safetxt, a UK sexual health randomised controlled trial.

BACKGROUND/AIMS: Recruiting to target in randomised controlled trials is crucial for providing reliable results, yet many trials struggle to achieve their target sample size. Many trials do not report sufficient, if any, details of their recruitment strategy for others to adapt for their own trials. Furthermore, much of the available evidence describes strategies to improve recruitment aimed at participants, as opposed to strategies aimed at engaging and motivating recruiting staff who are deemed essential for recruitment success. The safetxt trial aimed to recruit 6250 participants, aged 16-24 years, who had either tested positive, or received treatment, for chlamydia/gonorrhoea/non-specific urethritis in the last 2 weeks, from across the United Kingdom into a randomised controlled trial investigating a text message intervention to improve sexual health outcomes. In this article, we describe in detail the recruitment strategies we employed that were primarily aimed at recruiters. METHODS: Recruitment began in April 2016. We built on our recruitment methods established in the pilot trial and developed several strategies to increase recruitment as the trial progressed including optimising site set-up, monitoring recruitment progress and identifying issues, facilitating shared learning, tailored recruitment materials, sustaining motivation, and communication. We describe these strategies in detail and provide practical examples for each. RESULTS: We combine our strategies for increasing recruitment into one cyclical approach whereby progress is continuously monitored, and interventions to improve recruitment are implemented. The site initiation visits were used to develop a clear recruitment plan and establish good relationships with local site staff. Screening logs were particularly helpful for monitoring recruitment challenges. We facilitated shared learning by organising meetings with recruiting sites and conducting site visits. Tailored recruitment materials helped to promote the trial in clinic environments, and rewards and goals helped sustain motivation among recruiting staff. Finally, at the centre of the approach is good communication which ensured we maintained good relationships with local site staff. CONCLUSION: We conducted a large, multi-centre trial and successfully recruited to target. Our dynamic collaborative approach to recruitment described in this paper builds upon previous research by combining suggested good practice into one cyclical approach to recruitment, and providing detailed examples of each strategy. It is not possible to attribute a causal link between our approach and recruitment success overall, or with specific sites or recruiting staff. Nonetheless we describe the processes we used to build a good relationship with recruiting staff and sites, and maintain recruitment of large numbers of participants over the 32 months of the trial. Other researchers can use our approach and adapt our examples for their own trials.

Catastrophic health expenditure during the COVID-19 pandemic in five countries: a time-series analysis.

BACKGROUND: The COVID-19 pandemic disrupted health systems in 2020, but it is unclear how financial hardship due to out-of-pocket (OOP) health-care costs was affected. We analysed catastrophic health expenditure (CHE) in 2020 in five countries with available household expenditure data: Belarus, Mexico, Peru, Russia, and Viet Nam. In Mexico and Peru, we also conducted an analysis of drivers of change in CHE in 2020 using publicly available data. METHODS: In this time-series analysis, we defined CHE as when OOP health-care spending exceeds 10% of consumption expenditure. Data for 2004-20 were obtained from individual and household level survey microdata (available for Mexico and Peru only), and tabulated data from the National Statistical Committee of Belarus and the World Bank Health Equity and Financial Protection Indicator database (for Viet Nam and Russia). We compared 2020 CHE with the CHE predicted from historical trends using an ensemble model. This method was also used to assess drivers of CHE: insurance coverage, OOP expenditure, and consumption expenditure. Interrupted time-series analysis was used to investigate the role of stay-at-home orders in March, 2020 in changes in health-care use and sector (ie, private vs public). FINDINGS: In Mexico, CHE increased to 5·6% (95% uncertainty interval [UI] 5·1-6·2) in 2020, higher than predicted (3·2%, 2·5-4·0). In Belarus, CHE was 13·5% (11·8-15·2) in 2020, also higher than predicted (9·7%, 7·7-11·3). CHE was not different than predicted by past trends in Russia, Peru, and Viet Nam. Between March and April, 2020, health-care visits dropped by 4·6 (2·6-6·5) percentage points in Mexico and by 48·3 (40·6-56·0) percentage points in Peru, and the private share of health-care visits increased by 7·3 (4·3-10·3) percentage points in Mexico and by 20·7 (17·3-24·0) percentage points in Peru. INTERPRETATION: In three of the five countries studied, health systems either did not protect people from the financial risks of health care or did not maintain health-care access in 2020, an indication of health systems failing to maintain basic functions. If the 2020 response to the COVID-19 pandemic accelerated shifts to private health-care use, policies to cover costs in that sector or motivate patients to return to the public sector are needed to maintain financial risk protection. FUNDING: The Bill & Melinda Gates Foundation.

Effectiveness of a behavioural intervention delivered by text messages (safetxt) on sexually transmitted reinfections in people aged 16-24 years: randomised controlled trial.

OBJECTIVE: To quantify the effects of a series of text messages (safetxt) delivered in the community on incidence of chlamydia and gonorrhoea reinfection at one year in people aged 16-24 years. DESIGN: Parallel group randomised controlled trial. SETTING: 92 sexual health clinics in the United Kingdom. PARTICIPANTS: People aged 16-24 years with a diagnosis of, or treatment for, chlamydia, gonorrhoea, or non-specific urethritis in the past two weeks who owned a mobile phone. INTERVENTIONS: 3123 participants assigned to the safetxt intervention received a series of text messages to improve sex behaviours: four texts daily for days 1-3, one or two daily for days 4-28, two or three weekly for month 2, and 2-5 monthly for months 3-12. 3125 control participants received a monthly text message for one year asking for any change to postal or email address. It was hypothesised that safetxt would reduce the risk of chlamydia and gonorrhoea reinfection at one year by improving three key safer sex behaviours: partner notification at one month, condom use, and sexually transmitted infection testing before unprotected sex with a new partner. Care providers and outcome assessors were blind to allocation. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of chlamydia or gonorrhoea reinfection at one year, assessed by nucleic acid amplification tests. Safety outcomes were self-reported road traffic incidents and partner violence. All analyses were by intention to treat. RESULTS: 6248 of 20 476 people assessed for eligibility between 1 April 2016 and 23 November 2018 were randomised. Primary outcome data were available for 4675/6248 (74.8%). At one year, the cumulative incidence of chlamydia or gonorrhoea reinfection was 22.2% (693/3123) in the safetxt arm versus 20.3% (633/3125) in the control arm (odds ratio 1.13, 95% confidence interval 0.98 to 1.31). The number needed to harm was 64 (95% confidence interval number needed to benefit 334 to ∞ to number needed to harm 24) The risk of road traffic incidents and partner violence was similar between the groups. CONCLUSIONS: The safetxt intervention did not reduce chlamydia and gonorrhoea reinfections at one year in people aged 16-24 years. More reinfections occurred in the safetxt group. The results highlight the need for rigorous evaluation of health communication interventions. TRIAL REGISTRATION: ISRCTN registry ISRCTN64390461.

Recorded infection control messages delay inter-professional communication but are not associated with COVID-19 prevalence or mortality: insights from a national switchboard analysis.

Appropriate dissemination of information to the general public is a key component of the pandemic response. In 2018, recorded infection control advice messages were affixed to 30% of England's automated hospital switchboards during the seasonal influenza and norovirus outbreaks. As the majority of messages were mandatory for all callers, healthcare professionals using the hospital switchboard - including during time-critical emergencies - had their enquiries significantly delayed by these measures. Importantly, published analyses did not demonstrate an association between these messages and patient outcomes. As of May 2020, 85% of NHS trusts made use of infection control messages; on average, these delayed healthcare professionals by 59.4 seconds per call, but had no clear association with patient outcomes from COVID-19. An ongoing national switchboard quality improvement project seeks to establish a gold standard whereby healthcare professionals with urgent enquiries can press 'X' to skip past infection control messages and have their calls triaged immediately.

Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes.

The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of the transcriptomic response of this pathway to variations in nutrient availability.