Assessing the validity and reliability of self-report data on contraception use in the MObile Technology for Improved Family Planning (MOTIF) randomised controlled trial.

BACKGROUND: A variety of different approaches to measuring contraceptive use have been used or proposed, either to assess current use or adherence over time, using subjective or objective measures. This paper reports an overview of approaches to measuring adherence to the oral contraceptive, intra-uterine device, sub-dermal implant, and injectable and describes how we assessed contraception use in the MObile Technology for Improved Family Planning (MOTIF) trial in Cambodia. MAIN BODY: We summarise and discuss advantages and disadvantages of different subjective and objective approaches to measuring adherence to the oral contraceptive, intra-uterine device, sub-dermal implant, and injectable such as self-reports, clinic records, electronic monitoring devices, clinical examination and biomarkers. For the MOTIF trial, we did not consider it feasible to measure objective contraception use as many participants lived a long distance from the clinic and we were concerned whether it was appropriate to ask women to return to clinic for a physical examination simply to verify self-report information already provided. We aimed to assess the validity of the four-month data with 50 participants, calculating the sensitivity and specificity of self-reported data compared with objective measurement. For the 46 valid measurements obtained, the sensitivity and specificity was 100% for self-reported contraception use compared to objective measurement but this study had some limitations. To assess reliability of self-report data we compared calendar data collected on effective contraception use at months 1-4 post-abortion, collected separately at four and 12 months. Agreement ranged from 80 to 84% with a kappa statistic ranging from 0·59 to 0·67 indicating fair to good agreement. CONCLUSION: There is no perfect method of assessing contraception use and researchers designing future studies should give consideration of what to measure, for example current use or detailed patterns of use over time, and remain mindful of what will be feasible and acceptable to the study population. Although self-reported data on contraception use are considered less reliable, and prone to social desirability bias, it is often the standard approach for contraception research and provides data comparable to previous studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01823861 . Registered: March 30, 2013

Initial Coupling of Binding to Gating Mediated by Conserved Residues in the Muscle Nicotinic Receptor

We examined functional consequences of intrasubunit contacts in the nicotinic receptor α subunit using single channel kinetic analysis, site-directed mutagenesis, and structural modeling. At the periphery of the ACh binding site, our structural model shows that side chains of the conserved residues αK145, αD200, and αY190 converge to form putative electrostatic interactions. Structurally conservative mutations of each residue profoundly impair gating of the receptor channel, primarily by slowing the rate of channel opening. The combined mutations αD200N and αK145Q impair channel gating to the same extent as either single mutation, while αK145E counteracts the impaired gating due to αD200K, further suggesting electrostatic interaction between these residues. Interpreted in light of the crystal structure of acetylcholine binding protein (AChBP) with bound carbamylcholine (CCh), the results suggest in the absence of ACh, αK145 and αD200 form a salt bridge associated with the closed state of the channel. When ACh binds, αY190 moves toward the center of the binding cleft to stabilize the agonist, and its aromatic hydroxyl group approaches αK145, which in turn loosens its contact with αD200. The positional changes of αK145 and αD200 are proposed to initiate the cascade of perturbations that opens the receptor channel: the first perturbation is of β-strand 7, which harbors αK145 and is part of the signature Cys-loop, and the second is of β-strand 10, which harbors αD200 and connects to the M1 domain. Thus, interplay between these three conserved residues relays the initial conformational change from the ACh binding site toward the ion channel

Women's views and experiences of a mobile phone-based intervention to support post-abortion contraception in Cambodia.

BACKGROUND: The MObile Technology for Improved Family Planning (MOTIF) trial assessed a mobile phone-based intervention comprising voice messages and counsellor support to increase post-abortion contraception at four Marie Stopes International clinics in Cambodia. The aim of this process evaluation was to assess women's views and experiences of receiving the MOTIF intervention, gain insights into the mechanism of action of the intervention and seek recommendations for improvements. METHODS: We conducted a qualitative study comprising15 semi-structured interviews with women who had received the intervention and undertook a simple thematic analysis. RESULTS: We identified themes relating to communication via mobile phone, supporting contraception use, broader post-abortion care, interaction with family and friends and suggestions for improvement. The majority of women were positive about the mobile phone-based intervention to support contraception use and reported it to be a convenient way to ask questions or get advice without going to a health centre, although a few women found the voice messages intrusive. The intervention supported contraception use by provision of information, encouragement, reminders to return to clinic, reassurance and advice for problems and had a positive effect on contraceptive uptake and continuation. Women reported a sense of being cared for and received support for additional physical and emotional issues. Most women thought that the duration of the intervention and frequency of messages were acceptable. CONCLUSIONS: The majority of women were positive about the mobile phone-based intervention which provided support for contraception use as well as additional physical and emotional issues. The study provides some insights into how the intervention might have worked and considers how the intervention could be improved

Nicotinic Receptor Interloop Proline Anchors β1-β2 and Cys loops in Coupling Agonist Binding to Channel Gating

Nicotinic acetylcholine receptors (AChRs) mediate rapid excitatory synaptic transmission throughout the peripheral and central nervous systems. They transduce binding of nerve-released ACh into opening of an intrinsic channel, yet the structural basis underlying transduction is not fully understood. Previous studies revealed a principal transduction pathway in which αArg 209 of the pre-M1 domain and αGlu 45 of the β1–β2 loop functionally link the two regions, positioning αVal 46 of the β1–β2 loop in a cavity formed by αPro 272 through αSer 269 of the M2–M3 loop. Here we investigate contributions of residues within and proximal to this pathway using single-channel kinetic analysis, site-directed mutagenesis, and thermodynamic mutant cycle analysis. We find that in contributing to channel gating, αVal 46 and αVal 132 of the signature Cys loop couple energetically to αPro 272. Furthermore, these residues are optimized in both their size and hydrophobicity to mediate rapid and efficient channel gating, suggesting naturally occurring substitutions at these positions enable a diverse range of gating rate constants among the Cys-loop receptor superfamily. The overall results indicate that αPro 272 functionally couples to flanking Val residues extending from the β1–β2 and Cys loops within the ACh binding to channel opening transduction pathway

Development of an Intervention to Support the Reproductive Health of Cambodian Women Who Seek Medical Abortion: Research Protocol.

BACKGROUND: In Cambodia, abortion has been legally permitted on request during the first trimester of pregnancy since 1997. However, although there has been an increase in the percentage of women having induced abortion and medical abortion, there has also been a decrease in the percentage of women who say they received help from a health worker with their abortion. These data point toward the demedicalization of abortion, and although medical abortion has been shown to be safe, there are concerns about safety, given the variety of available products and counseling provided. These concerns are particularly relevant for female factory workers, who typically come from rural areas where access to good health care and information about reproductive health care is limited. OBJECTIVE: This study aims to understand the reproductive health needs of female Cambodian garment factory workers after medical abortion from a multidisciplinary and mixed-methods perspective, focusing on how they seek and share medical abortion- and health-related information; how they use their mobile phones for this and other purposes; what cultural challenges exist around reproductive health; and how they might be magnified or mitigated by mobile phones, linguistic challenges around health care, and mobile phone use. The main purpose of this study is to combine multidisciplinary methods, theories, and expertise to gain new, culturally grounded insights into family planning and medical abortion in Cambodia, but the findings could help inform the development of a relevant intervention to support comprehensive postabortion care. METHODS: The methods proposed are interviews and participant observation among factory workers, health providers, and mobile phone providers; a linguistic analysis of relevant data (interview transcripts, web-based sources, and other fieldwork materials); and digital methods to understand what kind of information about medical abortion exists on the web in Cambodia and how it is accessed by the targeted population. RESULTS: The data collection part of the project will end on December 31, 2020. The team conducted 67 semistructured interviews with female factory workers, women who sought a medical abortion, health providers, and mobile phone providers; participant observation with factory workers and health providers; and an analysis of YouTube and Facebook to understand what kind of information is available, who creates it, and how it is used. The team is currently performing data analysis, and the findings are clustered around (1) the use of mobile phones and digital resources for health-related and medical abortion-related information, (2) the experience of medical abortion care, and (3) the development of an intervention through edutainment videos. CONCLUSIONS: The project highlights both the widely untapped potential of using digital platforms (especially YouTube and Facebook) to distribute accurate information on medical abortion and the challenges in providing individual information via mobile phones while respecting individuals' privacy. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17779

Predictors of postabortion contraception use in Cambodia.

OBJECTIVE: To evaluate which characteristics collected at the point of abortion are associated with contraceptive use over the extended postabortion period for women in Cambodia. METHODS: The study includes a cohort of 500 women who attended a Marie Stopes International Cambodia clinic for an induced abortion. The primary outcomes are use of effective contraception ≥80% of the time over the 4- and 12-month period postabortion. We conducted a bivariate analysis to assess the association between each characteristic and the outcome, followed by multivariable modeling to identify the strongest predictors of the outcomes. RESULTS: Nearly 44% of the women used contraception for more than 80% of the time during both follow-up periods. Several sociodemographic and reproductive factors were crudely associated with the outcomes. In the multivariable model, prior use of contraception, intention to use postabortion contraception, increased number of children and medical abortion were associated with increased contraceptive use over the year postabortion. Occupation was a predictor at 4 months only, and abortion method was a predictor at 12 months only. CONCLUSIONS: The models were satisfactory in predicting the outcome of contraceptive continuation both at 4 and 12 months. The paper sets out a methodology for modeling these predictors that can help inform more client-centered counseling and services for women. IMPLICATIONS: Factors known when attending a clinic for induced abortion can help inform more targeted and client-centered postabortion family planning counseling and services for women in Cambodia

Process evaluation of a mobile phone-based intervention to support post-abortion contraception in Cambodia.

BACKGROUND: The MObile Technology for Improved Family Planning (MOTIF) trial assessed a mobile phone-based intervention comprising voice messages and counsellor support to increase post-abortion contraception at four Marie Stopes International clinics in Cambodia. The aim of this process evaluation was to assess participants' interaction with the intervention from a service provider perspective. METHODS: (1) We conducted a descriptive analysis to assess participants' interaction with the intervention. (2) In order to explore how the intervention might work, we assessed associations between interaction with the intervention and contraception use using logistic regression analysis. (3) We undertook a logistic regression analysis to assess associations between baseline socio-demographic factors and ever requesting to speak to a counsellor (pressing '1'), a variable found to be associated with contraception use. RESULTS: Amongst 249 women that received six interactive voice messages +/- counsellor support for contraception, around half actively requested to speak to a counsellor (pressed '1') and over 90% spoke to a counsellor at some stage. Women who spoke to the counsellor having requested to (by pressing '1') were more than four times as likely to be using effective contraception at four months compared to women who didn't request or speak to the counsellor (Odds Ratio 4.39; 95% CI: 1.15-16.71). There was a small, non-statistically significant increase in contraception use amongst women that spoke to the counsellor without requesting a call. Increased parity, a history of >2 previous induced abortions, lower socio-economic status, and medical abortion (after adjusting for age, socio-economic status and residence) were associated with requesting to speak to a counsellor. CONCLUSIONS: The interactive message can identify a subgroup of women in whom counselling will be more effective and appears to be equitable in terms of engaging those most in-need. The intervention could be adapted based on the findings of this study

Mobile Technology for Improved Family Planning (MOTIF): the development of a mobile phone-based (mHealth) intervention to support post-abortion family planning (PAFP) in Cambodia.

BACKGROUND: The objective of this paper is to outline the formative research process used to develop the MOTIF mobile phone-based (mHealth) intervention to support post-abortion family planning in Cambodia. METHODS: The formative research process involved literature reviews, interviews and focus group discussions with clients, and consultation with clinicians and organisations implementing mHealth activities in Cambodia. This process led to the development of a conceptual framework and the intervention. RESULTS: Key findings from the formative research included identification of the main reasons for non-use of contraception and patterns of mobile phone use in Cambodia. We drew on components of existing interventions and behaviour change theory to develop a conceptual framework. A multi-faceted voice-based intervention was designed to address health concerns and other key determinants of contraception use. CONCLUSIONS: Formative research was essential in order to develop an appropriate mHealth intervention to support post-abortion contraception in Cambodia. Each component of the formative research contributed to the final intervention design

How online sexual health services could work; generating theory to support development.

BACKGROUND: Online sexual health services are an emerging area of service delivery. Theory of change critically analyses programmes by specifying planned inputs and articulating the causal pathways that link these to anticipated outcomes. It acknowledges the changing and contested nature of these relationships. METHODS: We developed two versions of a theory of change for an online sexual health service. The first articulated the theory presented in the original programme proposal and the second documented its development in the early stages of implementation through interviews with key programme stakeholders. RESULTS: The programme proposal described an autonomous and empowered user completing a sexual health check using a more convenient, accessible and discreet online service and a shift from clinic based to online care. The stakeholder interviews confirmed this and described new and more complex patterns of service use as the online service creates opportunities for providers to contact users outside of the traditional clinic visit and users move between online and clinic based care. They described new types of user/provider relationships which we categorised as: those influenced by an online retail culture; those influenced by health promotion outreach and surveillance and those acknowledging the need for supported access. CONCLUSIONS: This analysis of stakeholder views on the likely the impacts of online sexual health services suggests three areas for further thinking and research. 1. Co-development of clinic and online services to support complex patterns of service use. 2. Developing access to online services for those who could use them with support. 3. Understanding user experience of sexual health services as increasing user autonomy and choice in some situations; creating exclusion and a need for support in others and intrusiveness and a lack of control in still others. This work has influenced the evaluation of this programme which will focus on; mapping patterns of use to understand how users move between the online and clinic based services; barriers to use of online services among some populations and how to overcome these; understanding user perceptions of autonomy in relation to online services

Using a business model approach and marketing techniques for recruitment to clinical trials

Randomised controlled trials (RCTs) are generally regarded as the gold standard for evaluating health care interventions. The level of uncertainty around a trial's estimate of effect is, however, frequently linked to how successful the trial has been in recruiting and retaining participants. As recruitment is often slower or more difficult than expected, with many trials failing to reach their target sample size within the timescale and funding originally envisaged, the results are often less reliable than they could have been. The high number of trials that require an extension to the recruitment period in order to reach the required sample size potentially delays the introduction of more effective therapies into routine clinical practice. Moreover, it may result in less research being undertaken as resources are redirected to extending existing trials rather than funding additional studies.Poor recruitment to publicly-funded RCTs has been much debated but there remains remarkably little clear evidence as to why many trials fail to recruit well, which recruitment methods work, in which populations and settings and for what type of intervention. One proposed solution to improving recruitment and retention is to adopt methodology from the business world to inform and structure trial management techniques. We review what is known about interventions to improve recruitment to trials. We describe a proposed business approach to trials and discuss the implementation of using a business model, using insights gained from three case studies.</p