How can patient experience of abortion care be improved? Evidence from the SACHA study.

BACKGROUND: Models of abortion care have changed significantly in the last decade, most markedly during the COVID-19 pandemic, when home management of early medical abortion with telemedical support was approved in Britain. OBJECTIVE: Our study aimed to examine women's satisfaction with abortion care and their suggestions for improvements. DESIGN: Qualitative, in-depth, semi-structured interviews. METHODS: A purposive sample of 48 women with recent experience of abortion was recruited between July 2021 and August 2022 from independent sector and National Health Service abortion services in Scotland, Wales and England. Interviews were conducted by phone or via video call. Women were asked about their abortion experience and for suggestions for any improvements that could be made along their patient journey - from help-seeking, the initial consultation, referral, treatment, to aftercare. Data were analyzed using the Framework Method. RESULTS: Participants were aged 16-43 years; 39 had had a medical abortion, 8 a surgical abortion, and 1 both. The majority were satisfied with their clinical care. The supportive, kind and non-judgmental attitudes of abortion providers were highly valued, as was the convenience afforded by remotely supported home management of medical abortion. Suggestions for improvement across the patient journey centred around the need for timely care; greater correspondence between expectations and reality; the importance of choice; and the need for greater personal and emotional support. CONCLUSION: Recent changes in models of care present both opportunities and challenges for quality of care. The perspectives of patients highlight further opportunities for improving care and support. The principles of timely care, choice, management of expectations, and emotional support should inform further service configuration.

How can patients' experience of abortion care in Britain be improved?Provision of abortion care and support in Britain has changed in recent decades. The COVID-19 pandemic also brought called for new ways of managing early medical abortions, at home, with remote support. We wanted to know how women in Britain felt about this kind of abortion care, and what ideas they had to make it better. Between July 2021 and August 2022, we spoke with 48 women who had recently had an abortion in Scotland, Wales and England. Some received got care from independent clinics, and some from the National Health Service (NHS). We talked to them over the phone or through video calls. We asked about their experiences, and what could be done to improve different parts of their care journey ­ from looking fo asking for help, the first appointment, the treatment, to the follow-up care. Most women generally felt satisfied with how they were taken care of by the medical staff. They appreciated the supportive, kind and non-judgmental attitude of the health professionals providing abortion care. They also liked the convenience of telemedicine and remote care, which made it easier to have a medical abortion at home. The changes in provision of abortion care and support have mostly had positive effects on women's experience. Yet the feedback from women interviewed shows that there are still more opportunities to make improvements, focusing on prompt care, offering choices of abortion method and location, managing expectations better, and providing more emotional support. These principles should guide how services are set up in the future.

Patient and public involvement in abortion research: reflections from the Shaping Abortion for Change (SACHA) Study.

Patient and public involvement (PPI) is limited within abortion-related research. Possible reasons for this include concerns about engaging with a stigmatised patient group who value confidentiality and may be reluctant to re-engage with services. Structural barriers, including limited funding for abortion-related research, also prevent researchers from creating meaningful PPI opportunities. Here, we describe lessons learnt on undertaking PPI as part of the Shaping Abortion for Change (SACHA) Study, which sought to create an evidence base to guide new directions in abortion care in Britain.Two approaches to PPI were used: involving patients and the public in the oversight of the research and its dissemination as lay advisors, and group meetings to obtain patients' views on interpretation of findings and recommendations. All participants observed the SACHA findings aligned with their own experiences of having an abortion in Britain. These priorities aligned closely with those identified in a separate expert stakeholder consultation undertaken as part of the SACHA Study. One additional priority which had not been identified during the research was identified by the PPI participants.We found abortion patients to be highly motivated to engage in the group meetings, and participation in them actively contributed to the destigmatisation of abortion by giving them a space to share their experiences. This may alleviate any ethical concerns about conducting research and PPI on abortion, including the assumption that revisiting an abortion experience will cause distress. We hope that our reflections are useful to others considering PPI in abortion-related research and service improvement.

Liver biopsy for assessment of suspected drug-induced liver injury in metabolic dysfunction-associated steatohepatitis clinical trials: Expert consensus from the Liver Forum.

BACKGROUND: Causality assessment of suspected drug-induced liver injury (DILI) during metabolic dysfunction-associated steatohepatitis (MASH) clinical trials can be challenging, and liver biopsies are not routinely performed as part of this evaluation. While the field is moving away from liver biopsy as a diagnostic and prognostic tool, information not identified by non-invasive testing may be provided on histology. AIM: To address the appropriate utilisation of liver biopsy as part of DILI causality assessment in this setting. METHODS: From 2020 to 2022, the Liver Forum convened a series of webinars on issues pertaining to liver biopsy during MASH trials. The Histology Working Group was formed to generate a series of consensus documents addressing these challenges. This manuscript focuses on liver biopsy as part of DILI causality assessment. RESULTS: Expert opinion, guidance and recommendations on the role of liver biopsy as part of causality assessment of suspected DILI occurring during clinical trials for a drug(s) being developed for MASH are provided. Lessons learned from prior MASH programs are reviewed and gaps identified. CONCLUSIONS: Although there are no pathognomonic features, histologic evaluation of suspected DILI during MASH clinical trials may alter patient management, define the pattern and severity of injury, detect findings that favour a diagnosis of DILI versus MASH progression, identify prognostic features, characterise the clinicopathological phenotype of DILI, and/or define lesions that influence decisions about trial discontinuation and further development of the drug.

Rates of sexual partner acquisition from nationally representative surveys: variation between countries and by age, sex, wealth, partner and HIV status.

BACKGROUND: Knowing levels and determinants of partnership acquisition will help inform interventions that try to reduce transmission of sexually transmitted infections (STIs) including HIV. METHODS: We used population-based, cross-sectional data from 47 Demographic and Health Surveys to calculate rates of partner acquisition among men and women (15-49years), and identified socio-demographic correlates for partner acquisition. Partner acquisition rates were estimated as the total number of acquisitions divided by the person-time in the period covered by the survey. For each survey and by sex, we estimated age-specific partner acquisition rates and used age-adjusted piecewise exponential survival models to explore whether there was any association between wealth, HIV status and partner status with partner acquisition rates. RESULTS: Across countries, the median partner acquisition rates were 30/100 person-years for men (interquartile range 21-45) and 13/100 person-years for women (interquartile range 6-18). There were substantial variations in partner acquisition rates by age. Associations between wealth and partner acquisition rates varied across countries. People with a cohabiting partner were less likely to acquire a new one, and this effect was stronger for women than men and varied substantially between countries. Women living with HIV had higher partner acquisition rates than HIV-negative women but this association was less apparent for men. At a population level, partner acquisition rates were correlated with HIV incidence. CONCLUSIONS: Partner acquisition rates are variable and are associated with important correlates of STIs and thus could be used to identify groups at high risk of STIs.

Development and Validation of a Brief Measure of Sexual Wellbeing for Population Surveys: The Natsal Sexual Wellbeing Measure (Natsal-SW).

Sexual wellbeing is an important aspect of population health. Addressing and monitoring it as a distinct issue requires valid measures. Our previous conceptual work identified seven domains of sexual wellbeing: security; respect; self-esteem; resilience; forgiveness; self-determination; and comfort. Here, we describe the development and validation of a measure of sexual wellbeing reflecting these domains. Based on the analysis of 40 semi-structured interviews, we operationalized domains into items, and refined them via cognitive interviews, workshops, and expert review. We tested the items via two web-based surveys (n = 590; n = 814). Using data from the first survey, we carried out exploratory factor analysis to assess and eliminate poor performing items. Using data from the second survey, we carried out confirmatory factor analysis to examine model fit and associations between the item reduced measure and external variables hypothesized to correlate with sexual wellbeing (external validity). A sub-sample (n = 113) repeated the second survey after 2 weeks to evaluate test-retest reliability. Confirmatory factor analysis indicated that a "general specific model" had best fit (RMSEA: 0.064; CFI: 0.975, TLI: 0.962), and functioned equivalently across age group, gender, sexual orientation, and relationship status. The final Natsal-SW measure comprised 13 items (from an initial set of 25). It was associated with external variables in the directions hypothesized (all p < .001), including mental wellbeing (0.454), self-esteem (0.564), body image (0.232), depression (-0.384), anxiety (-0.340), sexual satisfaction (0.680) and sexual distress (-0.615), and demonstrated good test-retest reliability (ICC = 0.78). The measure enables sexual wellbeing to be quantified and understood within and across populations.

Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism.

The pathogenesis of hepatic fibrosis is driven by dysregulated metabolism precipitated by chronic inflammation. Rho-associated coiled-coil-containing protein kinases (ROCKs) have been implicated in these processes, however the ability of selective ROCK2 inhibition to target simultaneously profibrotic, pro-inflammatory and metabolic pathways remains undocumented. Here we show that therapeutic administration of GV101, a selective ROCK2 inhibitor with more than 1000-fold selectivity over ROCK1, attenuates established liver fibrosis induced by thioacetamide (TAA) in combination with high-fat diet in mice. GV101 treatment significantly reduces collagen levels in liver, associated with downregulation of pCofilin, pSTAT3, pAkt, while pSTAT5 and pAMPK levels are increased in tissues of treated mice. In vitro, GV101 inhibits profibrogenic markers expression in fibroblasts, adipogenesis in primary adipocytes and TLR-induced cytokine secretion in innate immune cells via targeting of Akt-mTOR-S6K signaling axis, further uncovering the ROCK2-specific complex mechanism of action and therapeutic potential of highly selective ROCK2 inhibitors in liver fibrosis.

Improving experience of medical abortion at home in a changing therapeutic, technological and regulatory landscape: a realist review.

OBJECTIVE: To inform UK service development to support medical abortion at home, appropriate for person and context. DESIGN: Realist review SETTING/PARTICIPANTS: Peer-reviewed literature from 1 January 2000 to 9 December 2021, describing interventions or models of home abortion care. Participants included people seeking or having had an abortion. INTERVENTIONS: Interventions and new models of abortion care relevant to the UK. OUTCOME MEASURES: Causal explanations, in the form of context-mechanism-outcome configurations, to test and develop our realist programme theory. RESULTS: We identified 12 401 abstracts, selecting 944 for full text assessment. Our final review included 50 papers. Medical abortion at home is safe, effective and acceptable to most, but clinical pathways and user experience are variable and a minority would not choose this method again. Having a choice of abortion location remains essential, as some people are unable to have a medical abortion at home. Choice of place of abortion (home or clinical setting) was influenced by service factors (appointment number, timing and wait-times), personal responsibilities (caring/work commitments), geography (travel time/distance), relationships (need for secrecy) and desire for awareness/involvement in the process. We found experiences could be improved by offering: an option for self-referral through a telemedicine consultation, realistic information on a range of experiences, opportunities to personalise the process, improved pain relief, and choice of when and how to discuss contraception. CONCLUSIONS: Acknowledging the work done by patients when moving medical abortion care from clinic to home is important. Patients may benefit from support to: prepare a space, manage privacy and work/caring obligations, decide when/how to take medications, understand what is normal, assess experience and decide when and how to ask for help. The transition of this complex intervention when delivered outside healthcare environments could be supported by strategies that reduce surprise or anxiety, enabling preparation and a sense of control.

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.

Achieving proportional representation in a reproductive health survey through social media: process and recommendations.

BACKGROUND: The narrative surrounding women's reproductive health has shifted from a medical model to an emphasis on reproductive well-being over different life-stages. We developed and piloted a tracker survey for monitoring women's reproductive health and well-being in England, recruiting respondents online. This paper reports on the success of the online recruitment strategies in achieving a sample proportionally representative of the England general population. METHODS: Recruitment was through Facebook and Instagram advertisements and dissemination through Twitter and a blog. At the end week one, the sample was reviewed and compared to the 2011 Census England population. From week two, recruitment targeted under-represented groups. Key data were compared with prevalence estimates from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). RESULTS: Between 1 July-17 August 2021, 13,962 people initiated the online survey, with 11,578 completing it. Numbers were low initially, but peaked at 1700 survey initiations per day after increasing the daily advertisement budget on day seven. At the end of week one, minority ethnic groups and people without a degree or equivalent were under-represented. From week two, we altered the advertisement settings to show to people whose profile indicated they were a 'high school leaver' had 'up to some high school', worked in industries that do not typically require a degree or lived in local authorities with a high proportion of ethnic minority residents. This had a modest effect, with the final sample short of proportional representation in terms of ethnicity and education but close in terms of region and age. Compared to Natsal-3, we found consistency in the proportion of respondents reporting an abortion and a live birth in the last year, however, the proportion of our sample reporting ever having experienced infertility was significantly higher than in Natsal-3, as was the proportion of 'planned' pregnancies in the last year. CONCLUSIONS: It is possible to recruit large numbers of respondents online, relatively quickly, to complete a reproductive health survey. This will be valuable to track reproductive health and well-being at a national level over time. More work is needed to understand reasons for non-response among under-represented groups.

The impact of COVID-19 lockdown on abortion care: a time series analysis of data from Marie Stopes Nepal.

The COVID-19 pandemic significantly impacted sexual and reproductive health and rights. Nepal implemented a nationwide lockdown in March 2020, limiting population movement and service access. The 36 clinics run by Marie Stopes Nepal (MSN) closed for varying periods at the beginning of lockdown. This study assesses the impact of lockdown and associated clinic closures on abortion services within MSN's network. An interrupted time-series analysis of clinic-level MSN data compared abortion service use in the pre-closure and post-reopening periods, focusing on the following outcomes: number of abortion care visits, proportion of abortion-related visits, gestational age at time of abortion care and demographics of patients accessing abortion care. Subsequent meta-analyses combined clinic-level results to generate outcome-specific pooled effect estimates. As MSN clinics reopened, during ongoing wider lockdown, weekly visits for abortion care decreased by 37% on average, but abortion increased as a proportion of services post-reopening (OR: 1.53) compared with pre-closure, with no evidence of a change in the proportion of higher gestation abortions. The demographic profile of abortion care clients was altered, with post-reopening clients more likely to have completed primary education (OR: 1.54) and be aged 25 years or older (OR: 1.31) compared with pre-closure clients. COVID-19 lockdown and associated clinic closures reduced the absolute number of abortion services provided within MSN's network, impacting the composition of service provision. Reductions in safe abortion and wider SRH access will have wide-ranging consequences, curtailing crucial reproductive rights. Policy-makers must ensure ongoing abortion access to protect rights and ensure access.

Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments. An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease (NAFLD) to MAFLD, including a proposal for how the disease should be diagnosed. As allies with the many stakeholders in MAFLD care-including patients, patients' advocates, clinicians, researchers, nurse and allied health groups, regional societies, and others-we are aware of the negative consequences of the NAFLD term and definition. We share the sense of urgency for change and will act in new ways to achieve our goals. Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends, the MAFLD initiative provides a firm foundation to build on. It provides a roadmap for moving forward toward more efficient care and affordable, sustainable drug and device innovation in MAFLD care. We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe's largest and costliest public health burdens. From this viewpoint, we have revisited this initiative through the perspectives of drug development and regulatory science.

Should COVID-specific arrangements for abortion continue? The views of women experiencing abortion in Britain during the pandemic.

BACKGROUND: During the COVID-19 pandemic, the British governments issued temporary approvals enabling the use of both medical abortion pills, mifepristone and misoprostol, at home. This permitted the introduction of a fully telemedical model of abortion care with consultations taking place via telephone or video call and medications delivered to women's homes. The decision was taken by the governments in England and Wales to continue this model of care beyond the original end date of April 2022, while at time of writing the approval in Scotland remains under consultation. METHODS: We interviewed 30 women who had undergone an abortion in England, Scotland or Wales between August and December 2021. We explored their views on the changes in abortion service configuration during the pandemic and whether abortion via telemedicine and use of abortion medications at home should continue. RESULTS: Support for continuation of the permission to use mifepristone and misoprostol at home was overwhelmingly positive. Reasons cited included convenience, comfort, reduced stigma, privacy and respect for autonomy. A telemedical model was also highly regarded for similar reasons, but for some its necessity was linked to safety measures during the pandemic, and an option to have an in-person interaction with a health professional at some point in the care pathway was endorsed. CONCLUSIONS: The approval to use abortion pills at home via telemedicine is supported by women having abortions in Britain. The voices of patients are essential to shaping acceptable and appropriate abortion service provision.

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.

Contraception in Person-Contraception Online (CiP-CO) cohort study.

BACKGROUND: Online contraception services increasingly provide information, clinical assessment and home-delivered oral contraceptives (OCs). Evidence is lacking on the effects of online contraceptive service use on short-term contraceptive continuation. METHODS: Cohort study comparing contraceptive continuation between new users of a free-to-access online OC service in South East London with those from other, face-to-face services in the same area. Online questionnaires collected data on participants' sociodemographic characteristics, motivations for OC access, service ratings, OC knowledge and contraceptive use. Contraceptive use in the 4-month study period was measured using health service records. Unadjusted and multivariable logistic regression models compared outcomes between the online service group and those using other services. RESULTS: Online service-users (n=138) were more likely to experience short-term continuation of OCs compared with participants using other services (n=98) after adjusting for sociodemographic and other characteristics (adjusted OR 2.94, 95% CI 1.52 to 5.70). Online service-users rated their service more highly (mean 25.22, SD 3.77) than the other services group (mean 22.70, SD 4.35; p<0.001), valuing convenience and speed of access. Among progestogen-only pill users, knowledge scores were higher for the online group (mean 4.83, SD 1.90) than the other services group (mean 3.87, SD 1.73; p=0.007). Among combined oral contraceptive users, knowledge scores were similar between groups. CONCLUSIONS: Free-to-access, online contraception has the potential to improve short-term continuation of OCs. Further research using a larger study population and analysis of longer-term outcomes are required to understand the impact of online services on unintended pregnancy.

Mobile phone-based interventions for improving adherence to medication prescribed for the primary prevention of cardiovascular disease in adults.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of disability and mortality globally. Premature fatal and non-fatal CVD is considered to be largely preventable through the control of risk factors by lifestyle modifications and preventive medication. Lipid-lowering and antihypertensive drug therapies for primary prevention are cost-effective in reducing CVD morbidity and mortality among high-risk people and are recommended by international guidelines. However, adherence to medication prescribed for the prevention of CVD can be poor. Approximately 9% of CVD cases in the EU are attributed to poor adherence to vascular medications. Low-cost, scalable interventions to improve adherence to medications for the primary prevention of CVD have potential to reduce morbidity, mortality and healthcare costs associated with CVD. OBJECTIVES: To establish the effectiveness of interventions delivered by mobile phone to improve adherence to medication prescribed for the primary prevention of CVD in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two other databases on 7 January 2020. We also searched two clinical trials registers on 5 February 2020. We searched reference lists of relevant papers. We applied no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials investigating interventions delivered wholly or partly by mobile phones to improve adherence to cardiovascular medications prescribed for the primary prevention of CVD. We only included trials with a minimum of one-year follow-up in order that the outcome measures related to longer-term, sustained medication adherence behaviours and outcomes. Eligible comparators were usual care or control groups receiving no mobile phone-delivered component of the intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The main outcomes of interest were objective measures of medication adherence (blood pressure (BP) and cholesterol), CVD events, and adverse events. We contacted study authors for further information when this was not reported. MAIN RESULTS: We included 14 trials with 25,633 randomised participants. Participants were recruited from community-based primary and tertiary care or outpatient clinics. The interventions varied widely from those delivered solely through short messaging service (SMS) to those involving a combination of modes of delivery, such as SMS in addition to healthcare worker training, face-to-face counselling, electronic pillboxes, written materials, and home blood pressure monitors. Some interventions only targeted medication adherence, while others additionally targeted lifestyle changes such as diet and exercise. Due to heterogeneity in the nature and delivery of the interventions and study populations, we reported most results narratively, with the exception of two trials which were similar enough to meaningfully pool in meta-analyses. The body of evidence for the effect of mobile phone-based interventions on objective outcomes of adherence (BP and cholesterol) was of low certainty, due to most trials being at high risk of bias, and inconsistency in outcome effects. Two trials were at low risk of bias. Among five trials (total study enrolment: 5441 participants) recording low-density lipoprotein cholesterol (LDL-C), two studies found evidence for a small beneficial intervention effect on reducing LDL-C (-5.30 mg/dL, 95% confidence interval (CI) -8.30 to -2.30; and -9.20 mg/dL, 95% CI -17.70 to -0.70). The other three studies found results varying from a small reduction (-7.7 mg/dL) to a small increase in LDL-C (0.77 mg/dL). All of which had wide confidence intervals that included no effect. Across 13 studies (25,166 participants) measuring systolic blood pressure, effect estimates ranged from a large reduction (MD -12.45 mmHg, 95% CI -15.02 to -9.88) to a small increase (MD 2.80 mmHg, 95% CI 0.30 to 5.30). We found a similar range of effect estimates for diastolic BP, ranging from -12.23 mmHg (95% CI 14.03 to -10.43) to 1.64 mmHg (95% CI -0.55 to 3.83) (11 trials, 19,716 participants). Four trials showed intervention benefits for systolic and diastolic BP with confidence intervals excluding no effect, and among these were all three of the trials evaluating self-monitoring of blood pressure with mobile phone-based telemedicine. The fourth trial included SMS and provider support (with additional varied features). Seven studies (19,185 participants) reported 'controlled' BP as an outcome, and intervention effect estimates varied from negligible effects (odds ratio (OR) 1.01, 95% CI 0.76 to 1.34) to large improvements in BP control (OR 2.41, 95% CI: 1.57 to 3.68). The three trials of clinician training or decision support combined with SMS (with additional varied features) had confidence intervals encompassing benefits and harms, with point estimates close to zero. Pooled analyses of the two trials of interventions solely delivered through SMS were indicative of little or no beneficial intervention effect on systolic BP (MD -1.55 mmHg, 95% CI -3.36 to 0.25; I2 = 0%) and small increases in controlled BP (OR 1.32, 95% CI 1.06 to 1.65; I2 = 0%). Based on four studies (12,439 participants), there was very low-certainty evidence (downgraded twice for imprecision and once for risk of bias) relating to the intervention effect on combined (fatal and non-fatal) CVD events. Two studies (2535 participants) provided low-certainty evidence for the effect of the intervention on cognitive outcomes, with little or no difference between trial arms for perceived quality of care and satisfaction with treatment. There was moderate-certainty evidence (downgraded due to risk of bias) that the interventions did not cause harm, based on six studies (8285 participants). Three studies reported no adverse events attributable to the intervention. One study reported no difference between groups in experience of adverse effects of statins, and that no participants reported intervention-related adverse events. One study stated that potential side effects were similar between groups. One study reported a similar number of deaths in each arm, but did not provide further information relating to potential adverse events. AUTHORS' CONCLUSIONS: There is low-certainty evidence on the effects of mobile phone-delivered interventions to increase adherence to medication prescribed for the primary prevention of CVD. Trials of BP self-monitoring with mobile-phone telemedicine support reported modest benefits. One trial at low risk of bias reported modest reductions in LDL cholesterol but no benefits for BP. There is moderate-certainty evidence that these interventions do not result in harm. Further trials of these interventions are warranted.

Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials.

Causality assessment for suspected drug-induced liver injury (DILI) during drug development and following approval is challenging. The IQ DILI Causality Working Group (CWG), in collaboration with academic and regulatory subject matter experts (SMEs), developed this manuscript with the following objectives: (1) understand and describe current practices; (2) evaluate the utility of new tools/methods/practice guidelines; (3) propose a minimal data set needed to assess causality; (4) define best practices; and (5) promote a more structured and universal approach to DILI causality assessment for clinical development. To better understand current practices, the CWG performed a literature review, took a survey of member companies, and collaborated with SMEs. Areas of focus included best practices for causality assessment during clinical development, utility of adjudication committees, and proposals for potential new avenues to improve causality assessment. The survey and literature review provided renewed understanding of the complexity and challenges of DILI causality assessment as well as the use of non-standardized approaches. Potential areas identified for consistency and standardization included role and membership of adjudication committees, standardized minimum dataset, updated assessment tools, and best practices for liver biopsy and rechallenge in the setting of DILI. Adjudication committees comprised of SMEs (i.e., utilizing expert opinion) remain the standard for DILI causality assessment. A variety of working groups continue to make progress in pursuing new tools to assist with DILI causality assessment. The minimum dataset deemed adequate for causality assessment provides a path forward for standardization of data collection in the setting of DILI. Continued progress is necessary to optimize and advance innovative tools necessary for the scientific, pharmaceutical, and regulatory community.

Sexual health interventions delivered to participants by mobile technology: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The use of mobile technologies to prevent STIs is recognised as a promising approach worldwide; however, evidence has been inconclusive, and the field has developed rapidly. With about 1 million new STIs a day globally, up-to-date evidence is urgently needed. OBJECTIVE: To assess the effectiveness of mobile health interventions delivered to participants for preventing STIs and promoting preventive behaviour. METHODS: We searched seven databases and reference lists of 49 related reviews (January 1990-February 2020) and contacted experts in the field. We included randomised controlled trials of mobile interventions delivered to adolescents and adults to prevent sexual transmission of STIs. We conducted meta-analyses and assessed risk of bias and certainty of evidence following Cochrane guidance. RESULTS: After double screening 6683 records, we included 22 trials into the systematic review and 20 into meta-analyses; 18 trials used text messages, 3 used smartphone applications and 1 used Facebook messages as delivery modes. The certainty of evidence regarding intervention effects on STI/HIV occurrence and adverse events was low or very low. There was moderate certainty of evidence that in the short/medium-term text messaging interventions had little or no effect on condom use (standardised mean differences (SMD) 0.02, 95% CI -0.09 to 0.14, nine trials), but increased STI/HIV testing (OR 1.83, 95% CI 1.41 to 2.36, seven trials), although not if the standard-of-care control already contained an active text messaging component (OR 1.00, 95% CI 0.68 to 1.47, two trials). Smartphone application messages also increased STI/HIV testing (risk ratio 1.40, 95% CI 1.22 to 1.60, subgroup analysis, two trials). The effects on other outcomes or of social media or blended interventions is uncertain due to low or very low certainty evidence. CONCLUSIONS: Text messaging interventions probably increase STI/HIV testing but not condom use in the short/medium term. Ongoing trials will report the effects on biological and other outcomes.

A SNP in the Cache 1 Signaling Domain of Diguanylate Cyclase STM1987 Leads to Increased In Vivo Fitness of Invasive Salmonella Strains.

Nontyphoidal Salmonella (NTS) strains are associated with gastroenteritis worldwide but are also the leading cause of bacterial bloodstream infections in sub-Saharan Africa. The invasive NTS (iNTS) strains that cause bloodstream infections differ from standard gastroenteritis-causing strains by >700 single-nucleotide polymorphisms (SNPs). These SNPs are known to alter metabolic pathways and biofilm formation and to contribute to serum resistance and are thought to signify iNTS strains becoming human adapted, similar to typhoid fever-causing Salmonella strains. Identifying SNPs that contribute to invasion or increased virulence has been more elusive. In this study, we identified a SNP in the cache 1 signaling domain of diguanylate cyclase STM1987 in the invasive Salmonella enterica serovar Typhimurium type strain D23580. This SNP was conserved in 118 other iNTS strains analyzed and was comparatively absent in global S Typhimurium isolates associated with gastroenteritis. STM1987 catalyzes the formation of bis-(3',5')-cyclic dimeric GMP (c-di-GMP) and is proposed to stimulate production of cellulose independent of the master biofilm regulator CsgD. We show that the amino acid change in STM1987 leads to a 10-fold drop in cellulose production and increased fitness in a mouse model of acute infection. Reduced cellulose production due to the SNP led to enhanced survival in both murine and human macrophage cell lines. In contrast, loss of CsgD-dependent cellulose production did not lead to any measurable change in in vivo fitness. We hypothesize that the SNP in stm1987 represents a pathoadaptive mutation for iNTS strains.