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Background MyDiabetesPlan is a web-based, interactive patient decision aid that facilitates patient-centred, diabetes-specific, goal-setting and shared decision-making (SDM) with interprofessional health care teams. Objective Assess the feasibility of (1) conducting a cluster randomized controlled trial (RCT) and (2) integrating MyDiabetesPlan into interprofessional primary care clinics. Methods We conducted a cluster RCT in 10 interprofessional primary care clinics with patients living with diabetes and at least two other comorbidities; half of the clinics were assigned to MyDiabetesPlan and half were assigned to usual care. To assess recruitment, retention, and resource use, we used RCT conduct logs and financial account summaries. To assess intervention fidelity, we used RCT conduct logs and website usage logs. To identify barriers and facilitators to integration of MyDiabetesPlan into clinical care across the IP team, we used audiotapes of clinical encounters in the intervention groups. Results One thousand five hundred and ninety-seven potentially eligible patients were identified through searches of electronic medical records, of which 1113 patients met the eligibility criteria upon detailed chart review. A total of 425 patients were randomly selected; of these, 213 were able to participate and were allocated (intervention: n = 102; control: n = 111), for a recruitment rate of 50.1%. One hundred and fifty-one patients completed the study, for a retention rate of 70.9%. A total of 5745 personnel-hours and $6104 CAD were attributed to recruitment and retention activities. A total of 179 appointments occurred (out of 204 expected appointments—two per participant over the 12-month study period; 87.7%). Forty (36%), 25 (23%), and 32 (29%) patients completed MyDiabetesPlan at least twice, once, and zero times, respectively. Mean time for completion of MyDiabetesPlan by the clinician and the patient during initial appointments was 37 min. From the clinical encounter transcripts, we identified diverse strategies used by clinicians and patients to integrate MyDiabetesPlan into the appointment, characterized by rapport building and individualization. Barriers to use included clinician-related, patient-related, and technical factors. Conclusion An interprofessional approach to SDM using a decision aid was feasible. Lower than expected numbers of diabetes-specific appointments and use of MyDiabetesPlan were observed. Addressing facilitators and barriers identified in this study will promote more seamless integration into clinical care. Trial registration Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: February 11, 2015. Protocol version: Version 1; February 26, 2015.

Objective This study sought to evaluate the sustained value of an early pregnancy assessment clinic (EPAC) in the management of early pregnancy complications and its effect on the incidence emergency room (ER) visits. Methods A 10-year retrospective study (January 2006 to December 2015) was conducted. The number of patients assessed, sources and reasons for referral, and treatments provided were reviewed. The numbers of ER assessments and reassessments for abortion, hemorrhage, and ectopic pregnancy from January 2004 to December 2005 (pre-EPAC) and January 2006 to December 2015 (post-EPAC) were also reviewed. Results There were 11 349 new referrals and 10 764 follow-up visits. The reasons for referral were threatened miscarriage (n = 3568, 31.4%), missed miscarriage (n = 3056, 26.9%), incomplete miscarriage (n = 1064, 9.4%), complete miscarriage (n = 991, 8.7%), ectopic pregnancy (n = 857, 7.6%), hyperemesis gravidarum (n = 139, 1.2%), and others (n = 1674, 14.8%). There has been a significant decreasing trend (tau = −0.60, P = 0.0127) and a significant decrease in the post-EPAC rate of ER reassessments (P = 0.0396) for hemorrhage, with a concomitant decrease in EPAC visits for hemorrhage. In addition, there has been a significant increasing trend (tau = 0.64, P = 0.0081) and a significant increase in the post-EPAC rate of ER assessments (P = 0.00001) for ectopic pregnancies. Conclusion Over the 10-year period, the EPAC has remained a vital service for managing early pregnancy complications for women. However, the clinic has not yet had a sustained impact on ER visits for miscarriage, ectopic pregnancy, and hemorrhage. It is possible that a reduction in ER assessments and reassessments for early pregnancy complications can be achieved through a clinic with daily access.

BACKGROUND We previously developed MyDiabetesPlan, an evidence-based, online, interactive patient decision-aid to facilitate patient-centred, diabetes-specific goal-setting and action-planning, using shared decision making (SDM) with interprofessional (IP) healthcare teams. OBJECTIVE The aim of this study is to assess the feasibility of (1) integrating MyDiabetesPlan into routine workflows in IP primary care clinics, and (2) conducting a cluster randomized controlled trial (RCT). METHODS We conducted a pilot cluster-RCT in 10 IP primary care clinics with patients living with diabetes and 2+ other comorbidities; half of the clinics were assigned to the MyDiabetesPlan intervention and the remainder were assigned to usual care. For Objective 1, we used RCT conduct logs and financial account summaries to assess recruitment, retention metrics, and resource use. For Objective 2, we used RCT conduct logs and website usage logs to assess intervention fidelity and resource usage. We used audiotapes of clinical encounters in the intervention groups to identify barriers and facilitators to integration of MyDiabetesPlan into clinical care across the IP team. RESULTS Objective 1: 1597 potentially eligible patients were identified through electronic medical record-based searches, of which 1113 patients met eligibility criteria upon detailed chart review. A total of 425 patients were randomly selected; of these, 213 were able to participate and were allocated (intervention: n=102; control: n=111), for a recruitment rate of 50.1%. 151 patients completed the study, for a retention rate of 70.9%. A total of 5745 personnel-hours and $6104 CAD were attributed to recruitment and retention activities. Objective 2: A total of 179 appointments occurred (out of a total of 204 expected appointments - 2 per participant over the 12-month study period; 87.7%). Forty (36%), 25 (23%) and 32 (29%) patients completed MyDiabetesPlan at least twice, once, and zero times respectively. Mean time for completion of MyDiabetesPlan by the clinician and the patient during initial appointments was 37 minutes. From the clinical encounter transcripts, we identified diverse strategies used by health care providers and patients to integrate MyDiabetesPlan into the appointment, characterized by rapport-building and individualization. Barriers to use included MyDiabetesPlan-related factors (e.g. limited selection of potential diabetes management strategies), clinician-related factors (e.g. discomfort with asking certain questions), and patient-related factors (e.g. computer literacy). CONCLUSIONS We evaluated the feasibility of an IPSDM approach using decision aids to help establish treatment priorities in patients with diabetes and found that it would be feasible. A total of 151 (70.9%) patients were retained for 12 months, which required 38 personnel hours and $40.42 CAD per participant who completed the study. Lower than expected numbers of diabetes-specific appointments were observed, and only 39% of patients completed MyDiabetesPlan twice. Addressing facilitators and barriers identified in this study will improve feasibility and promote more complete and seamless integration into clinical care. CLINICALTRIAL Clinicaltrials.gov Identifier: NCT02379078 Date of Registration: February 11, 2015

Adverse birth outcomes are common in HIV-positive pregnant women receiving combination antiretroviral therapy (cART), especially when cART is initiated in early pregnancy. The mechanisms remain poorly understood. Using a mouse model we demonstrate that protease inhibitor based-cART exposure beginning on day 1 of pregnancy was associated with a pro-angiogenic/pro-branching shift in the placenta driven by lower Flt-1 levels and higher Gcm-1 expression. Micro-CT imaging revealed an increase in the number of arterioles in cART-treated placentas, which correlated with fetal growth restriction. Delaying initiation of cART, or supplementing cART-treated mice with progesterone, prevented the pro-angiogenic/pro-branching shift and the associated placenta vascular changes. In agreement with our mouse findings, we observed an increase in the number of terminal-villi capillaries in placentas from HIV-positive cART-exposed women compared to HIV-negative controls. Capillary number was inversely correlated to maternal progesterone levels. Our study provides evidence that cART exposure during pregnancy influences placenta vascular formation that may in turn contribute to fetal growth restriction. Our findings highlight the need for closer investigation of the placenta in HIV-positive pregnancies, particularly for pregnancies exposed to cART from conception, and suggest that progesterone supplementation could be investigated as a possible intervention to improve placenta function in HIV-positive pregnant women.

Context Serum concentrations of liver enzymes and the hepatokine fetuin-A have been linked to the risk of type 2 diabetes, but their longitudinal impact on insulin resistance and β-cell dysfunction is unclear. Objective To evaluate the impact of changes over 2 years in fetuin-A and the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) on changes in insulin sensitivity, β-cell function, and glycemia in women with varying degrees of previous gestational dysglycemia, reflecting a range of future diabetic risk. Design/Setting/Participants In total, 336 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT and measurement of ALT/AST/GGT/fetuin-A at both 1 year and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: gestational diabetes (n = 104), gestational impaired glucose tolerance (n = 59), abnormal GCT with normal OGTT (n = 98), and normal GCT/OGTT (n = 75). Results At 1 and 3 years postpartum, ALT, AST, GGT, and fetuin-A did not differ across the four groups, but the intervening change in ALT/AST ratio was greater in the gestational dysglycemia groups (P = 0.05). Higher baseline ALT/AST (t = -1.99, P = 0.05) and fetuin-A (t = -3.17, P = 0.002) predicted lower insulin sensitivity (Matsuda) at 3 years, as did their respective changes from 1 to 3 years (ALT/AST: t = -5.47, P < 0.0001; fetuin-A: t = -3.56, P = 0.0004). Change in ALT/AST predicted lower β-cell function (t = -2.33, P = 0.02) and higher fasting glucose at 3 years (t = 2.55, P = 0.01). Moreover, baseline fetuin-A predicted prediabetes/diabetes at 3 years (OR, 1.38; 95% CI, 1.01 to 1.88). Conclusion Circulating hepatic markers, particularly ALT/AST ratio and fetuin-A, track with changes in insulin sensitivity and β-cell function, supporting a pathophysiologic basis in their prediction of diabetic risk.

To compare the total number of patient visits required for the conservative, medical, or surgical management of early pregnancy loss in an early pregnancy assessment clinic (EPAC).A retrospective study of the number of patient visits at an EPAC for conservative, medical, or surgical management of early spontaneous abortion from October 2013 to September 2015 was undertaken. Visits counted included initial assessment, follow-up visits, and surgery date, if separate from a clinic visit.A total of 945 patients were seen, with 2144 visits during the study period. Conservative management required an average of 3.01 visits (n = 159, median = 3, SD = 1.16, range [1,7]) and misoprostol treatment required an average of 2.51 visits (n = 329, median = 2, SD = 0.83, range [1,6]) to achieve a complete abortion. Dilatation and curettage (DC) required an average of 1.60 visits (n = 417, median = 1, SD = 0.80, range [1-6]), when including scheduling limitations or an average of 1.13 visits when excluding these limitations. The difference in the number of visits required for the three management options was statistically significant (P 0.0001). Management with DC was more likely to require less than two visits to achieve complete abortion compared with the other options (93.8% for DC vs. 64.5% for misoprostol vs. 37.8% for conservative).An EPAC provides a significant value in the management of early pregnancy losses. There is a significant difference in the total number of visits required for different treatment options. Patients may find this information helpful when considering and deciding upon their preferred treatment option.

Problem The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. Method of study Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks). EVT explants and Swan71 cells were used to assess HLA-C and HLA-F during active EVT migration. Results HLA-G, HLA-C, and HLA-F were expressed by 1st-trimester EVT and became intracellular and weaker as gestation progressed. HLA-E was only expressed in 1st-trimester placenta. HLA-F and HLA-C mRNA and protein expression levels showed a significant increase in the fetal villous mesenchyme across gestation. HLA-C levels increased with labor. We detected a 100-kDa HLA-F band in early pregnancy suggesting dimer formation on the EVT surface. These results were confirmed in EVT outgrowths and Swan71 trophoblast which showed that HLA-F and HLA-G are increased on the cell surface of migrating EVT, while HLA-C was internalized. Conclusion Expression of HLA-F and HLA-G on the cell surface of actively migrating EVT supports their specific role in early EVT invasion and interactions with uterine natural killer cells. HLA-C's limited expression to the proliferative EVT suggests a protective role in the earliest events of implantation but not in active EVT invasion. We also show for the first time that HLA-C may be involved in parturition.

s / Placenta 34 (2013) A1–A99 A75 rate, but clones were significantly smaller. The onset of yolk-sac development was not normal in clones. In addition, later steps differed from the condition in vivo in all three groups in that the yolk-sac was yellowish and juxtaposed with the amnion. Vascularisation of the chorioallantoic membrane was relatively late and low in NT gestations, but normal in the others. Conclusion: In conclusion, the yolk-sac seems to be most vulnerable to morphogenetic alterations. Future studies will focus on gene expression and early vascularisation processes to investigate whether these changes may be responsible for the high incidence of intrauterine mortality, especially in clones. http://dx.doi.org/10.1016/j.placenta.2013.06.220 P2.55. THE PLACENTAL EXPRESSION OF HUMAN LEUKOCYTE ANTIGEN HLA-F AND HLA-E IN EARLY NORMAL PLACENTATION Rinat Hackmon , Lakmini Pinnaduwage , John Kingdom , Gideon Koren , Dan Geraghty , Stephen Lye , Caroline Dunk 4 University of Toronto Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto/ON, Canada; University of Toronto Department of Clinical Pharmacolgy, Sick Kids Hospital, Toronto/ON, Canada; University of Toronto Department of Physiology, Toronto/ON, Canada; 4 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto/ON, Canada; 5 Fred Hutchinson Cancer Research Institute, Clinical Division, Seattle/WA, USA Objective: Human pregnancy is arguably one of the most interesting examples of immune tolerance seen in mammalian biology. A key-organ, the placenta, does not express the classical MHC class I or II antigens, and instead is the single organ tissue expressing simultaneously each of the nonclassical MHC class I antigens on its EVT HLA-E, F, and G, and possibly HLA-C. The function of HLA-F and E in the placental environment is still unknown. Prior results also demonstrated that HLA-F is surface expressed on activated lymphocytes. We hypothesised that HLA-F and E may contribute to the immuno inhibitory response in early placentation. Methods: Immunohistochemistry and RT-PCR were used to examine HLAE and HLA-F expression at different time points of pregnancy. Results: Analysis showed that HLA-F protein expression localised to the syncytiotrophoblast (SYN) cells andwas maximal at 5-7 weeks of gestation and decreased throughout gestation. During the 2nd trimester HLA-F expression was surface expressed, while at term, intracellular. HLA-F protein was expressed in the anchoring cell columns of early 1st trimester placenta and also in invasive interstitial and endovascular EVT within the decidua basalis throughout gestation. HLA-E protein expression was observed in SYN cells and EVT cell columns at 5 weeks gestation and was not detectable from the 7th week until the end of gestation. HLA-F mRNA expression levels showed significant increase across gestation compared to 1st trimester, while HLA-E mRNA levels did not vary. Conclusions: These results support our hypothesis that both surface HLA-F andHLA-Eproteins areexpressed in thehumanplacenta at thehighest levels in early placentation and decrease toward term. This expression of HLA-F suggests a specific role and potential interaction with decidual receptors such as KIR3 2D, that may contribute to immune tolerance of pregnancy. http://dx.doi.org/10.1016/j.placenta.2013.06.221 P2.56. CYTOKINE PROFILE OF CD4+ T-CELLS IN DECIDUA AND CIRCULATION IN 3RD TRIMESTER PREGNANCY Guro Mork Johnsen , Kjetil Tasken , Anne Cathrine Staff 1,4 Department of Obstetrics and Department of Gynaecology, Oslo University Hospital Ulleval, Oslo, Norway; NCMM Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway; 3 The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway; 4 Faculty of Medicine, University of Oslo, Oslo, Norway Objectives: In pregnancy there is a maternal immunologic tolerance toward the semi-allogeneic fetus. Different T-cell subsets and cytokines are important in regulation of this process. Maternal tolerance at the fetalmaternal interface (decidua) has been explained by predominant Th2 immunity. Now, there is an emerging role for regulatory T-cells since they suppress proliferation and cytokine production of different immune cells. Preeclampsia is associated with a pro-inflammatory Th1/Th17 type immunity. Our objective was to analyze Th1/Th2/Th17 cytokines secreted from CD4+ T-cells from decidua and blood from 3rd trimester pregnant women as a basis for investigating possible pathogenic changes in preeclampsia. Methods: Blood and decidua samples were obtained from women with healthy pregnancies or preeclampsia undergoing cesarean section (N1⁄48). PBMCs were isolated from freshly collected blood. Decidua was harvested by vacuum suction from the placental bed after delivery of the placenta, and cells were isolated by enzymatic tissue digestion. CD4+ T-cells were isolated using magnetic bead separation and incubated for 4 days with Tcell activation beads (Miltenyi). Cell supernatants where harvested and cytokine concentrations analyzed using Cytokine Bead Array (BD-Biosciences) for IL-2, IL-4, IL-6, IL-10, TNF, INFg and IL-17A by LSRFortessa flow-cytometer. Results: Preliminary results show that cytokine secretion after stimulation of CD4+ T-cells was lower in cells from decidua compared to blood. The Th1 cytokines IFNg, IL-2 and TNF were highly expressed in CD4+ T-cells from both tissues, while the expression of Th2 cytokine IL-4 and Th17 IL17A was low. Interestingly, the expression of IL-10, an anti-inflammatory cytokine that can be produced by all Th subsets, was significantly higher in circulating than in decidual T-cells. Conclusion: There seems to be a blunted T-cell response in decidua, with reduced cytokine production. These findings add to the notion that there are significant differences between immunological processes in the periphery and the decidua during pregnancy. http://dx.doi.org/10.1016/j.placenta.2013.06.222 P2.57. DECIDUAL NATURAL KILLER CELL RECEPTOR EXPRESSION IS ALTERED IN PREGNANCIES WITH IMPAIRED SPIRAL ARTERY REMODELLING Alison Wallace, Amanda Host, Guy Whitley, Judith Cartwright St George's, University of London, London, UK Objectives: Decidual natural killer (dNK) cells are distinct to peripheral blood (pb) NK cells with regard to both surface receptor expression and function. Decidual NK cells are predominantly CD56brightCD16-, are noncytotoxic and are thought to function primarily through the secretion of cytokines. The role played by dNK cell inhibitory and activating receptors in spiral artery (SA) remodelling is unknown. Uterine artery Doppler resistance index (RI) in the first trimester of pregnancy can be used as a proxy measure of the extent of remodelling of the SA. We have used this technique to identify pregnancies with a high RI, indicative of impaired SA remodelling. Comparisons of the expression of activating and inhibitory receptors on dNK cells from normal RI and high-RI pregnancies were made. Methods: Decidual NK cells were isolated with local ethical approval from first trimester terminations of pregnancy screened by uterine artery Doppler ultrasound. A panel of cell surface receptors was investigated by flow cytometry immediately after dNK cell isolation, and percentage of cells expressing the receptor was measured. The functional outcomes of altered receptor expression were considered. Results: There was no significant difference in expression of the receptors NKp46, NKp30, NKp44, NKG2A, NKG2C, NKG2D, CD160 and KIR2DL2/S2 between dNK cells isolated from high and normal RI pregnancies. However, a greater percentage of dNK cells from normal RI pregnancies