Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.

The spectinamides are novel, narrow-spectrum semisynthetic analogs of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead MBX-4888A (Lee-1810), exhibit promising therapeutic profiles in mice, as single drugs and as partner agents with other anti-tuberculosis antibiotics including rifampin and/or pyrazinamide. To demonstrate that this translates to more effective cure, we first confirmed the role of rifampin, with or without pyrazinamide, as essential to achieve effective bactericidal responses and sterilizing cure in the current standard of care regimen in chronically infected C3HeB/FeJ mice compared to BALB/c mice. Thus, demonstrating added value in testing clinically relevant regimens in murine models of increasing pathologic complexity. Next we show that MBX-4888A, given by injection with the front-line standard of care regimen, is treatment shortening in multiple murine tuberculosis infection models. The positive treatment responses to MBX-4888A combination therapy in multiple mouse models including mice exhibiting advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in caseum, along with favorable effects with rifampin and pyrazinamide under conditions achieved in necrotic lesions. This study also provides an additional data point regarding the safety and tolerability of spectinamide MBX-4888A in long-term murine efficacy studies.

Optimized Pyridazinone Nutrient Channel Inhibitors Are Potent and Specific Antimalarial Leads.

Human and animal malaria parasites increase their host erythrocyte permeability to a broad range of solutes as mediated by parasite-associated ion channels. Molecular and pharmacological studies have implicated an essential role in parasite nutrient acquisition, but inhibitors suitable for development of antimalarial drugs are missing. Here, we generated a potent and specific drug lead using Plasmodium falciparum, a virulent human pathogen, and derivatives of MBX-2366, a nanomolar affinity pyridazinone inhibitor from a high-throughput screen. As this screening hit lacks the bioavailability and stability needed for in vivo efficacy, we synthesized 315 derivatives to optimize drug-like properties, establish target specificity, and retain potent activity against the parasite-induced permeability. Using a robust, iterative pipeline, we generated MBX-4055, a derivative active against divergent human parasite strains. MBX-4055 has improved oral absorption with acceptable in vivo tolerability and pharmacokinetics. It also has no activity against a battery of 35 human channels and receptors and is refractory to acquired resistance during extended in vitro selection. Single-molecule and single-cell patch-clamp indicate direct action on the plasmodial surface anion channel, a channel linked to parasite-encoded RhopH proteins. These studies identify pyridazinones as novel and tractable antimalarial scaffolds with a defined mechanism of action. SIGNIFICANCE STATEMENT: Because antimalarial drugs are prone to evolving resistance in the virulent human P. falciparum pathogen, new therapies are needed. This study has now developed a novel drug-like series of pyridazinones that target an unexploited parasite anion channel on the host cell surface, display excellent in vitro and in vivo ADME properties, are refractory to acquired resistance, and demonstrate a well defined mechanism of action.

Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model.

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC50) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC50 for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.

The importance of nurturing trusting relationships to embed shared decision-making during pregnancy and childbirth.

OBJECTIVE: To generate greater awareness of the contextual and relational factors that influence women's capacity to participate in shared decision-making during childbirth. METHODS: A three-phase participatory action research approach involving in-depth interviews and co-operative inquiry meetings. SETTING: Dublin, Ireland in a large maternity hospital. PARTICIPANTS: Five postnatal women who gave birth to live healthy babies, and attended obstetric or midwifery-led care and 13 practising midwives. FINDINGS: This paper presents the findings from the third phase of a three-phase action research study exploring the action's women consider necessary to embed informed choice, into practice. The findings reveal that multiple organisational and relational factors influence how women can participate in shared decision-making including the model of care they attended, continuity of carer, power dynamics, hospital policies and trust in self and others. Women's relationships with maternity care professionals reveals that exercising choice is not only defined by but contingent on the degree of trust in their relationships with maternity care professionals.

trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo.

Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.

Competencies for respectful maternity care: Identifying those most important to midwives worldwide.

BACKGROUND: A respectful, person-centered philosophy of maternity care has been emerging over several decades. Research conducted on behalf of the International Confederation of Midwives (ICM) to identify essential competencies for midwifery practice also identified the knowledge, skills, and professional behaviors that should be hallmarks of respectful maternity care practices among the global community of midwives. METHODS: A three-round, online, modified Delphi survey was conducted between April 2016 and October 2016. A total of 895 individuals from 90 of the then-current 105 ICM member countries participated, with good representation across English, French, and Spanish speakers, high-income, medium-income, and low-income countries, and educators and clinicians. RESULTS: A total of 115 respectful maternity care (RMC)-related items were endorsed by participants in Round 1 or 2. These items received average scores of between 90.24% and 99.10%, well above the 85% threshold required to be identified as within the scope of global midwifery practice. These items were compared with the 12 domains of RMC identified by Shakibazadeh and colleagues that defined respectful care during childbirth in health facilities globally, and with similar RMC frameworks, and were found to be highly congruent, thus demonstrating the high value of RMC within the core of midwifery practice. DISCUSSION: ICM survey items were endorsed across all 12 RMC domains proposed by Shakibazadeh et al, and the findings affirmed that across ICM countries and regions, the philosophy of RMC was integrally related to the knowledge, skills, and professional behaviors that emerged as essential for basic midwifery practice.

Aminomethyl spectinomycins: a novel antibacterial chemotype for biothreat pathogens.

New antibiotics that are active against multi-drug-resistant strains and difficult-to-treat bacterial infections are needed. Synthetic modification of spectinomycin, a bacterial protein synthesis inhibitor, has been shown to increase antibacterial activity compared with spectinomycin. Aminomethyl spectinomycins are active against Gram-negative and Gram-positive bacterial pathogens. In this study, the ability of aminomethyl spectinomycins to treat biothreat pathogens is examined by MIC profiling, synergy testing, and in vivo efficacy experiments. Compound 1950 exhibited potent antibacterial activity against Gram-negative pathogens Brucella spp., Burkholderia mallei, and Francisella tularensis, but showed little to no growth inhibition against Burkholderia pseudomallei, Bacillus anthracis, and Yersinia pestis. Combination testing in checkerboard assays revealed that aminomethyl spectinomycin-antibiotic combinations had mainly an additive effect against the susceptible biodefense pathogens. The in vivo efficacy of compound 1950 was also demonstrated in mice infected with B. mallei (FMH) or F. tularensis (SchuS4). These results suggest that aminomethyl spectinomycins are promising new candidates for development of therapeutics against biodefense bacterial agents.

Efficacy of Aminomethyl Spectinomycins against Complex Upper Respiratory Tract Bacterial Infections.

The most frequent ailment for which antibiotics are prescribed is otitis media (ear infections), which is most commonly caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae Treatment of otitis media is complicated by the fact that the bacteria in the middle ear typically form biofilms, which can be recalcitrant to antibiotic treatment. Furthermore, bacterial respiratory infections can be greatly exacerbated by viral coinfection, which is particularly evidenced by the synergy between influenza and S. pneumoniae In this study, we sought to ascertain the in vivo efficacy of aminomethyl spectinomycin lead 1950, an effective antibacterial agent both in vitro and in vivo against Streptococcus pneumoniae in the context of complex respiratory infections and acute otitis media. A single dose of 1950 significantly reduced bacterial burden in the respiratory tract for all three pathogens, even when species were present in a coinfection model. Additionally, a single dose of 1950 effectively reduced pneumococcal acute otitis media from the middle ear. The agent 1950 also proved efficacious in the context of influenza-pneumococcal super infection. These data further support the development of this family of compounds as potential therapeutic agents against the common causes of complex upper respiratory tract infections and acute otitis media.

Abortion-related care and the role of the midwife: a global perspective.

INTRODUCTION: The International Confederation of Midwives (ICM) represents 132 midwifery associations in 113 countries. The ICM disseminates the Essential Competencies for Basic Midwifery Practice (EC) that describes the global scope of midwifery practice. The basic (core) and expanded (additional or optional) role of midwives in providing abortion-related care services was first described in 2010. A literature review about three items that are particularly critical to access to abortion services was conducted. Findings that emerged in the recent 2016-2017 update study about these three items are presented. METHODS: A modified Delphi study was administered via the Internet in a series of three rounds. Thirty-seven statements of abortion-related knowledge and skill were presented. RESULTS: A total of 895 individuals participated. The total of respondents across all three rounds represented 90 of the 105 member countries at the time of the study. The role of midwives in providing comprehensive abortion care, including referral for abortion and provision of postabortion family planning, achieved the necessary 85% agreement to be designated as essential (basic) knowledge or skill for the global scope of midwifery practice. The provision of medication abortion and performance of manual vacuum aspiration abortion were designated as optional for midwives who wished to provide these services. Endorsement of these latter practices was highest in both Francophone and Anglophone regions of Africa, Asian Pacific countries, and countries at a lower state of economic development. CONCLUSION: The role of midwives in provision of abortion-related care services was reaffirmed in the recent Delphi study to inform the update to the EC. The role of midwives as direct providers of medical and vacuum aspiration abortions was reaffirmed for those individual midwives who wish to obtain the requisite competency to provide those services, in jurisdictions where these services are legally authorized.

Competence for basic midwifery practice: Updating the ICM essential competencies.

OBJECTIVE: To obtain consensus amongst midwifery experts globally about the essential competencies for basic midwifery practice. DESIGN: A modified Delphi approach, involving a three-round online survey. PARTICIPANTS: Midwifery leaders, educators and regulators in all ICM regions, along with representatives of organisations affiliated to ICM. METHODS: The research team worked closely with a Core Working Group and a Task Force. An initial set of competencies and components was developed through a content analysis of existing competency documents and presented to participants in Round 1 of the survey. Items identified as essential by at least 85% of participants were endorsed. Remaining items and new items identified by participants were returned to participants in Rounds 2 and 3 for further rating. FINDINGS: The study achieved a wide sample representative of midwifery experts across all ICM regions and countries, language groups, and income categories. Only a small number of competencies relating to the wider role of the midwife were endorsed as essential competencies. Competencies and components relating to professional and personal attributes were extended. Although most competencies and components relating to core midwifery practice were endorsed as essential competencies, several were rejected relating to abortion-related care, cancer screening, infertility, and gynaecology. Findings are, nevertheless, highly consistent with the scope of practice delineated in the current 2010/2013 version of the ICM Essential Competencies for Basic Midwifery Practice. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The extension of professional and personal attributes reflects the recent emphasis on respectful midwifery care. The rejection of most of the additional competencies and components relating to the wider role of the midwife and endorsement of most of those considered to relate to core midwifery practice indicates that the scope of midwifery practice remains essentially unchanged through 2017.

Women's experiences of exercising informed choices as expressed through their sense of self and relationships with others in Ireland: A participatory action research study.

OBJECTIVE: To explore women's experiences of the concept of informed choice during pregnancy and childbirth. METHODS: A three-phase action research approach. In the second phase of the study (reported in this paper), 15 women were interviewed to establish their experiences of informed choice. SETTING: Dublin, Ireland in a large maternity hospital. FINDINGS: We found that multiple factors influence how women experience informed choice including; their sense of self and the quality of their relationships with maternity care professionals. Women's experiences as expressed through their sense of self reveal that informed choice, is not only defined by but contingent on the quality of women's relationships with their caregiver and their ability to engage in a process of shared decision-making with them. KEY CONCLUSIONS: Informed choice is experienced as a relational construct women's relationships with maternity care professionals can influence their perceptions of their sense of self following childbirth. Supportive relationships are key to supporting the concept of informed choice.

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections.

Bacterial sexually transmitted infections are widespread and common, with Neisseria gonorrhoeae (gonorrhea) and Chlamydia trachomatis (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy, and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial coinfections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections. The need for new antibiotics is great, but the pipeline for new drugs is alarmingly small. The aminomethyl spectinomycins, a new class of semisynthetic analogs of the antibiotic spectinomycin, were developed on the basis of a computational analysis of the spectinomycin binding site of the bacterial 30S ribosome and structure-guided synthesis. The compounds display particular potency against common respiratory tract pathogens as well as the sexually transmitted pathogens that cause gonorrhea and chlamydia. Here, we demonstrate the in vitro potencies of several compounds of this class against both bacterial species; the compounds displayed increased potencies against N. gonorrhoeae compared to that of spectinomycin and, significantly, demonstrated activity against C. trachomatis that is not observed with spectinomycin. Efficacies of the compounds were compared to those of spectinomycin and gentamicin in a murine model of infection caused by ceftriaxone/azithromycin-resistant N. gonorrhoeae; the aminomethyl spectinomycins significantly reduced the colonization load and were as potent as the comparator compounds. In summary, data produced by this study support aminomethyl spectinomycins as a promising replacement for spectinomycin and antibiotics such as ceftriaxone for treating drug-resistant gonorrhea, with the added benefit of treating chlamydial coinfections.

Design, Synthesis, and Evaluation of Novel Prodrugs of Transition State Inhibitors of Norovirus 3CL Protease.

Ester and carbamate prodrugs of aldehyde bisulfite adduct inhibitors were synthesized in order to improve their pharmacokinetic and pharmacodynamic properties. The inhibitory activity of the compounds against norovirus 3C-like protease in enzyme and cell-based assays was determined. The ester and carbamate prodrugs displayed equivalent potency to those of the precursor aldehyde bisulfite adducts and precursor aldehydes. Furthermore, the rate of ester cleavage was found to be dependent on alkyl chain length. The generated prodrugs exhibited low cytotoxicity and satisfactory liver microsomes stability and plasma protein binding. The methodology described herein has wide applicability and can be extended to the bisulfite adducts of common warheads employed in the design of transition state inhibitors of serine and cysteine proteases of medical relevance.

Exploring the strategies that midwives in British Columbia use to promote normal birth.

BACKGROUND: Rates of normal birth have been declining steadily over the past 20 years, despite the evidence of the benefits to mother and baby. This is most obvious in steadily increasing caesarean section rates across countries and studies of the factors involved suggest it may be more to do with the organization of maternity care and the preferences of healthcare providers than changes in maternal or demographic conditions. The proportion of women in British Columbia (BC) receiving care from a midwife continues to grow and there is a particular focus on promoting and supporting normal pregnancy and birth in the midwifery philosophy of care. In BC, women receiving care from a midwife are less likely to have a caesarean section and other birth interventions. METHODS: An interpretive approach, based on interpretive phenomenology was used to explore the experiences of midwives in BC of normal birth and the strategies that they use to keep birth normal. Fourteen experienced midwives were purposively selected from across the range of practice, geographical, and rural/urban contexts to participate in depth interviews. Data were analyzed using Thematic Network Analysis. RESULTS: Seven key themes were identified in the data: working with women from the early pregnancy, informing choice, the birth environment, careful watching and waiting, managing early labour, helping the woman to cope with labour, and tools in the tool kit. CONCLUSIONS: Midwives in BC work closely with women from early pregnancy to prepare them for a normal birth, and as "instruments of care" they adopt a range of approaches to support women to achieve this. The emphasis on continuity of care in the BC model of midwifery care plays a vital role in this.

A participatory action research study exploring women's understandings of the concept of informed choice during pregnancy and childbirth in Ireland.

OBJECTIVE: to explore women's understandings and definitions of the concept of informed choice during pregnancy and childbirth. METHODS: a three-phase action research approach. In the first phase of the study (reported in this paper), fifteen women were interviewed to establish their understandings and experiences of informed choice. SETTING: Dublin, Ireland in a large maternity hospital. PARTICIPANTS: fifteen postnatal women who gave birth to a live healthy infant, women attended obstetric or midwifery-led care. FINDINGS: we found that multiple factors influence how women define informed choice including; their expectations of exercising choice, their sense of responsibility towards their infant, their sense of self and the quality of their relationships with maternity care professionals. The interdependence of the mother-baby relationship deems that in the context of pregnancy and childbirth, women's definitions, perceptions and experiences of informed choice should be considered to be relational. Women consider that informed choice means more than just the provision of information; rather it requires an in-depth discussion with a professional who is known to them. Women's understandings reveal that informed choice, is not only defined by but contingent on the quality of women's relationships with their caregiver and their ability to engage in a process of shared decision-making with them. KEY CONCLUSION: Informed choice is defined and experienced as a relational construct, the support provided by maternity care professionals to women in contemporary maternity care must reflect this.

Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models.

Objectives: New drug regimens employing combinations of existing and experimental antimicrobial agents are needed to shorten treatment of tuberculosis (TB) in humans. The spectinamides are narrow-spectrum semisynthetic analogues of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead 1599, have been previously shown to exhibit a promising therapeutic profile in mice as single agents. Here we explore the in vivo activity of lead spectinamides when combined with other agents. Methods: The efficacy of 1599 or 1810 was tested in combination in three increasingly advanced TB mouse models. Mice were infected by aerosol and allowed to establish acute or chronic infection, followed by treatment (≤4 weeks) with the spectinamides alone or in two- and three-drug combination regimens with existing and novel therapeutic agents. Bacteria were enumerated from lungs by plating for cfu. Results: Herein we show the following: (i) 1599 exhibits additive or synergistic activity with most of the first-line agents; (ii) 1599 in combination with rifampicin and pyrazinamide or with bedaquiline and pyrazinamide promotes significantly improved efficacy in the high-dose aerosol model; (iii) 1599 enhances efficacy of rifampicin or pyrazinamide in chronically infected BALB/c mice; and (iv) 1599 is synergistic when administered in combination with rifampicin and pyrazinamide in the C3HeB/FeJ mouse model showing caseous necrotic pulmonary lesions. Conclusions: Spectinamides were effective partner agents for multiple anti-TB agents including bedaquiline, rifampicin and pyrazinamide. None of these in vivo synergistic interactions was predicted from in vitro MIC chequerboard assays. These data support further development of the spectinamides as combination partners with existing and experimental anti-TB agents.

Midwifery education in Canada.

OBJECTIVE: This article is part of a special series on midwifery education and describes the approach to midwifery education in Canada DESIGN: We begin with an overview of the model of midwifery practice introduced in Canada in the 1990s. We describe the model of midwifery education developed and report how it is implemented, with particular attention to the two longest established programs. SETTING: Midwifery education programs in Ontario and British Columbia. FINDINGS: Midwifery education programs in Canada are offered at the undergraduate baccalaureate level at universities and are typically four years in length. Programs are competence-based and follow a spiral curriculum. The first semesters focus on on core sciences, social sciences and introduction to midwifery concepts. Students spend fifty percent of the program in clinical practices with community-based midwives. Innovative education models enable students to be placed in distant placements and help to align theoretical and practice components. Clinically active faculty adds to the credibility of teaching but bring its own challenges for midwifery educators. CONCLUSIONS: The Canadian model of midwifery education has been very effective with low attrition rates and high demand for the number of places available. Further program expansion is warranted but is contingent on the growth of clinical placements.

Evaluating midwife-led antenatal care: choice, experience, effectiveness, and preparation for pregnancy.

OBJECTIVE: to evaluate midwife-led care (MLC) antenatal care compared with antenatal care provided in traditional obstetric-led hospital antenatal clinics (usual care). DESIGN: a mixed methods approach involving a chart audit, postal survey, focus group and in-depth interviews. SETTING: data were collected at a large maternity hospital and satellite clinics in Dublin from women attending for antenatal care between June 2011 and May 2012. PARTICIPANTS: 300 women with low-risk pregnancy who attended midwife-led antenatal care or usual clinics during the study period were randomly selected to participate. MEASUREMENTS: data were collected from 292 women׳s charts and from 186 survey participants (63% response rate). Nine women participated in in-depth interviews and a focus group. FINDINGS: MLC was as effective as usual care in relation to number of antenatal visits and ultrasound scans, referral to other clinicians, women׳s health in pregnancy, gestation at childbirth, and birth weight. Women attending MLC booked significantly earlier, fewer women attending MLC were admitted to hospital antenatally and more women breast fed their infant. Women attending MLC reported better choice and that shorter waiting times and having more time for discussion were important reasons for choosing MLC. Women attending MLC reported a better experience overall, and recorded better outcomes in relation to how they were treated, along with easier access to antenatal care and shorter waiting times to see a midwife. Although women attending MLC clinics reported higher satisfaction with the information that they received, they also identified that antenatal education could be improved in relation to labour, breast-feeding, depression and emotional well-being, and caring for the infant. KEY CONCLUSIONS: midwife-led antenatal care was as effective as usual care for women with low-risk pregnancy and better in relation to choice, breast feeding and women׳s experience of care.

Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds.

Herein we describe the synthesis and antibacterial evaluation of a new, unsymmetrical triaryl bisamidine compound series, [Am]-[indole]-[linker]-[HetAr/Ar]-[Am], in which [Am] is an amidine or amino group, [linker] is a benzene, thiophene or pyridine ring, and [HetAr/Ar] is a benzimidazole, imidazopyridine, benzofuran, benzothiophene, pyrimidine or benzene ring. When the [HetAr/Ar] unit is a 5,6-bicyclic heterocycle, it is oriented such that the 5-membered ring portion is connected to the [linker] unit and the 6-membered ring portion is connected to the [Am] unit. Among the 34 compounds in this series, compounds with benzofuran as the [HetAr/Ar] unit showed the highest potencies. Introduction of a fluorine atom or a methyl group to the triaryl core led to the more potent analogs. Bisamidines are more active toward bacteria while the monoamidines are more active toward mammalian cells (as indicated by low CC50 values). Importantly, we identified compound P12a (MBX 1887) with a relatively narrow spectrum against bacteria and a very high CC50 value. Compound P12a has been scaled up and is currently undergoing further evaluations for therapeutic applications.

Evaluating midwifery-led antenatal care: using a programme logic model to identify relevant outcomes.

BACKGROUND: a range of initiatives has been introduced in Ireland and internationally in recent years to establish midwifery-led models of care, generally aimed at increasing the choices available for women for maternity care. A midwifery-led antenatal clinic was first established at the study site (a large urban maternity hospital in Dublin) and extended over recent years. This paper reports on the design of an evaluation of these midwives clinics, in particular the use of a programme logic model to select outcomes to be included in the evaluation. AIMS AND OBJECTIVES: the programme logic model is used to identify the theory of a programme and is an integrative framework for the design and analysis of evaluations using qualitative and quantitative methods. Through an inclusive approach, the aim was to identify the most relevant outcomes to be included in the evaluation, by identifying and linking programme (midwifery-led antenatal clinic) outcomes to the goals, inputs and processes involved in the production of these outcomes. METHODS: the process involved a literature review, a review of policy documents and previous reviews of the clinics, interviews with midwives, obstetricians and managers to identify possible outcomes, a focus group with midwives, obstetricians, managers and women who had attended the clinics to refine and prioritise outcomes, and a follow-up survey to refine and prioritise the outcomes identified and to identify sources of data on each outcome. FINDINGS: seven categories of outcomes were identified: (1) choice, (2) relationship/interaction with caregiver, (3) experience of care, (4) preparation and education for childbirth and parenthood, (5) effectiveness of care, (6) organisational outcomes, and (7) programme viability. A range of sources of information was identified for each outcome, including existing documentation and data, chart audit, survey of women, and interviews and focus groups with midwives, obstetricians, managers and women. CONCLUSIONS: the programme logic model provided an inclusive, systematic and transparent approach to identifying relevant outcomes to be included in the evaluation. The information obtained has been used since to design the evaluation project, which is currently being concluded.