Tocolysis compared with no tocolysis in women with threatened preterm birth and ruptured membranes: A propensity score analysis.

INTRODUCTION: In women with preterm ruptured membranes and contractions, the administration of tocolysis is controversial. This study compares tocolysis with no tocolysis in women with threatened preterm birth and ruptured membranes. OBJECTIVE: To compare tocolysis with no tocolysis in women with threatened preterm birth and ruptured membranes. STUDY DESIGN: Data from the APOSTEL III RCT was combined with data from the National Maternity Hospital, Dublin. In the APOSTEL III trial, women with threatened preterm birth were randomized to atosiban or nifedipine. Patient data from Ireland were obtained from a cohort of women with threatened preterm birth with ruptured membranes. The Irish women received no tocolytic treatment. Only women with ruptured membranes and contractions were selected. We studied women with singleton or twin pregnancies and a gestational age between 25+0 and 33+6 weeks. Propensity score matching was performed to create comparable groups. Primary outcome was a composite adverse neonatal outcome. Secondary outcomes were individual components of the primary outcome, as well as neonatal intensive care unit (NICU) admission, gestational age at delivery, prolongation of pregnancy and mode of delivery. RESULTS: 153 women from the Apostel III trial were compared with 51 eligible women of the Irish cohort. We could match 46 women who received tocolysis and 46 women who received no tocolysis. All women had ruptured membranes. Maternal age, BMI, parity and gestational age at study entry were comparable between the groups after matching. There were no statistically significant differences in neonatal composite outcome (9.6 % in the tocolysis group versus 18 % in the control group, OR 0.46, 95 % CI 0.13-1.63). We found a lower incidence of NICU admission in the tocolysis group (63 %) than in the control group (94 %; OR 0.11, 95 % CI 0.03-0.41), which could be explained by differences in national admission policies. There were no statistically significant differences between tocolysis and no tocolysis in any of the other outcomes including sepsis, gestational age at delivery and time to delivery. CONCLUSION: In this propensity score analysis of women with threatened preterm birth and ruptured membranes, tocolytic therapy did not alter composite adverse neonatal outcome or time to delivery.

Strategies and technical challenges in allele level Class II typing in 2578 bone marrow transplantation donor-recipient pairs.

Human leukocyte antigen typing of 2578 donor-recipient pairs whose transplantation was facilitated by the National Marrow Donor Program allowed for an in-depth analysis of the accuracy of high-volume allele level testing data. The methods employed provided allele level typing at DRB1/3/5, DQA1, DQB1, DPA1, and DPB1 using sequence-specific oligonucleotide probe hybridization (SSOPH), polymerase chain reaction (PCR) restriction fragment length polymorphism analysis, sequence specific PCR, and direct sequence-based typing (SBT). Each typing was independently tested by two laboratories in Phase 1, and in subsequent phases targeted samples were typed in duplicate by SBT to monitor typing quality. Comparison with prior transplant center typing was also evaluated. SSOPH detected discrepancies ranged from 0.6% at DPB1 to 5.1% at DQB1 in Phase 1. The majority of discrepancies, 62%, resulted from human error such as sample handling, result interpretation, or clerical errors. Alleles that are frequently discrepant have been identified in this predominantly white population.

[Fibronectin test in threatened preterm labour: cost-saving but not yet widely implemented in the Netherlands]. / Fibronectinetest bij dreigende vroeggeboorte.

OBJECTIVE: Analysis of national implementation of the foetal fibronectin test in the diagnostics of threatened preterm labour in the Netherlands, and indication of the possible obstacles and consequences of implementation or no implementation. DESIGN: National questionnaire, retrospective cohort study and cost-effectiveness calculation. METHODS: We approached all hospitals in the Netherlands (n = 86) with a questionnaire on use of the fibronectin test. We also collected data on women who were referred to the Academic Medical Center (AMC), a tertiary care centre in Amsterdam, with symptoms of threatened preterm labour. We investigated whether the referred patients gave birth within 7 days, and whether unnecessary transfer to a centre with a neonatal intensive care unit (NICU) could have been avoided by implementation of the fibronectin test in the referring hospital. RESULTS: The fibronectin test was used in 34% of the hospitals and an additional 17% were in the process of implementation. The most important reasons not to use the fibronectin test were of a financial nature (50%). The cohort study included 96 women who were referred from secondary care. In our cohort, 36% of all transfers could have been avoided by implementation of the fibronectin test in secondary care. CONCLUSION: The fibronectin test can greatly reduce overtreatment and unnecessary transfer in threatened preterm labour, but implementation remains limited. Costs of the test are an obstacle for the referring hospitals, while implementation prevents unnecessary transport, admission and treatment of pregnant women, giving a potential saving of at least EUR 1,027,930 per year. Inclusion in the Netherlands Society for Obstetrics and Gynaecology (Nederlandse Vereniging voor Obstetrie en Gynaecologie, NVOG) guidelines would be a first step towards wider implementation. Slow implementation exemplifies a more widespread problem: the current reimbursement system does not stimulate such cost-saving innovations.

Patient-Centered Network of Learning Health Systems: Developing a resource for clinical translational research.

INTRODUCTION: The Learning Health System Network clinical data research network includes academic medical centers, health-care systems, public health departments, and health plans, and is designed to facilitate outcomes research, pragmatic trials, comparative effectiveness research, and evaluation of population health interventions. METHODS: The Learning Health System Network is 1 of 13 clinical data research networks assembled to create, in partnership with 20 patient-powered research networks, a National Patient-Centered Clinical Research Network. RESULTS AND CONCLUSIONS: Herein, we describe the Learning Health System Network as an emerging resource for translational research, providing details on the governance and organizational structure of the network, the key milestones of the current funding period, and challenges and opportunities for collaborative science leveraging the network.

The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs.

A comprehensive analysis of the HLA-D region loci, DRB1, DRB3, DRB5, DQA1, DQB1, DPA1 and DPB1, was performed to determine allelic diversity and underlying HLA disparity in 1259 bone marrow recipients and their unrelated donors transplanted through the National Marrow Donor Program. Although 43.0% of DRB1 alleles known to exist at the beginning of the study were found in this predominantly Caucasian transplant population, a few alleles predominated at each locus. In recipients, 67.1% of DRB1 alleles identified were one or two of six common DRB1 alleles. Only 118 (9.4%) donor-recipient pairs were matched for all alleles of DRB1, DQA1, DQB1, DPA1 and DPB1. While 79.4% of the pairs were matched for DRB1, only 13.2% were matched for DPB1 alleles. Almost 66% of pairs differed by more than one allele mismatch and 59.0% differed at more than one HLA-D locus. DQB1 was matched in 85.9% of DRB1-matched pairs. In contrast, only 13.9% of the pairs matched for DRB1, DQA1 and DQB1 were also matched for DPA1 and DPB1. This database, highlighting the underlying HLA disparity within the pairs, forms the foundation of an ongoing study to establish the relationship between HLA matching and successful outcome in unrelated allogeneic stem cell transplant.

Care everywhere, a point-to-point HIE tool: utilization and impact on patient care in the ED.

BACKGROUND: Emergency departments (EDs) routinely struggle with gaps in information when providing patient care. A point to point health information exchange (HIE) model has the potential to effectively fill those gaps. OBJECTIVE: To examine the utility, perceived and actual, of a point-to-point HIE tool called Care Everywhere (CE) and its impact on patient care in the ED. METHODS: This mixed methods study was performed at four large hospital EDs between January 2012 and November 2012. Retrospective data was extracted from the electronic health record (EHR) to evaluate CE utilization since implementation. ED notes data were extracted from ED visits occurring between January 2012 and June 2012 and were reviewed to evaluate the impact of exchanged information on patient care. RESULTS: Per focus group discussions, physicians thought the information received via CE was of value to patient care, particularly laboratory results, imaging, medication lists, discharge summaries and ECG interpretations. They feel the greatest impact of HIE is the avoidance of duplicative diagnostic testing and the identification of drug-seeking behavior. Nursing and ancillary staff expressed somewhat less enthusiasm but still felt HIE positively impacted patient care. Over a period of six months, CE was used in approximately 1.46% of ED encounters. A review of ED provider notes over that time period revealed CE use resulted in 560 duplicate diagnostic procedures being avoided and 28 cases of drug seeking behavior identified. CONCLUSION: Our study provides insight into the perceived value of HIE from the point of view of our ED physicians and staff. It also demonstrates that a point-to-point HIE tool such as Epic System's Care Everywhere has the potential to generate greater efficiencies within the ED and impact to patient care through elimination of duplicative diagnostic imaging or testing and resource utilization associated with those procedures.

Four new DP alleles identified in a study of 500 unrelated bone marrow donor-recipient pairs.

HLA-DP genotyping of 500 donor recipient pairs in a retrospective analysis sponsored by the National Marrow Donor Program (NMDP) identified four new DP alleles, two DPB1 and two DPA1. DNA sequencing confirmed that DPB1*8001 and *8101, each found in a single individual, are novel combinations of previously described sequence motifs in the six variable regions of DPB1. DPA1*02014, found in two individuals, is identical to DPA1*02011 except for a novel silent substitution, a G to A transition at the third position of codon 14. DPA1*01032, found in one individual, is identical to DPB1*01031 except for a silent G to A transition at the third position of codon 20. The identification of these novel alleles brings the total number of reported DPB1 alleles to 85 and DPA1 alleles to 15.

Maintaining updated DNA-based HLA assignments in the National Marrow Donor Program Bone Marrow Registry.

The National Marrow Donor Program (NMDP) has instituted an approach to address the impact of new alleles on the DNA-based HLA assignments obtained during volunteer donor typing. This approach was applied to the DRB typing results from 371,187 donors received from 14 laboratories in 1999. Samples were tested with a standardized set of sequence specific oligonucleotide reagents and the positive and negative hybridization results transmitted electronically to the NMDP. A software program interpreted the primary data into HLA assignments and rejected assignments which did not produce a result at the specified level of resolution. Comparison of the HLA assignments derived by the NMDP software to the assignments made by the laboratories using several local software prograins showed 90.5% of the assignments to be identical. Differences in assignments were explained by varying levels of typing resolution, variation in the inclusion of the second expressed DRB loci, disparity arising when alternative assignments were summarized, and failure to submit correct information. When the primary data collected in 1999 were interpreted into HLA assignments using the set of alleles defined in July 2000, 74% of the HLA-DRB assignments were altered by the description of new alleles, justifying the development of this software.