The impact of timing modified natural cycle frozen embryo transfer based on spontaneous luteinizing hormone surge.

PURPOSE: To evaluate whether adjusting timing of modified natural cycle frozen embryo transfer (mNC-FET) 1 day earlier in the setting of a spontaneous LH surge has an impact on pregnancy outcomes. METHODS: This retrospective cohort study evaluated all mNC-FET with euploid blastocysts from May 1, 2016 to March 30, 2019, at a single academic institution. Standard protocol for mNC-FET included ultrasound monitoring and hCG trigger when the dominant follicle and endometrial lining were appropriately developed. Patients had serum LH, estradiol, and progesterone checked on day of trigger. If LH was ≥ 20 mIU/mL, trigger was given that day and FET was performed 6 days after surge (LH/HCG+6), with the intent of transferring 5 days after ovulation. If LH was < 20 mIU/mL, FET was performed 7 days after trigger (hCG+7). Primary outcomes included clinical pregnancy and live birth rates. To account for correlation between cycles, a generalized estimating equation (GEE) method for multivariable logistic regression was used. RESULTS: Four hundred fifty-three mNC-FET cycles met inclusion criteria, of which 205 were in the LH/HCG+6 group and 248 were in the HCG+7 group. The overall clinical pregnancy rate was 64% and clinical miscarriage rate was 4.8%, with similar rates between the two groups. The overall live birth rate was 60.9% (61.0% in LH/HCG+6 group and 60.9% in HCG+7 group). After implementing GEE, the odds of CP (aOR 0.97, 95% CI [0.65-1.45], p = 0.88) and LB (aOR 0.98, 95% CI [0.67-1.45], p = 0.93) were similar in both groups. CONCLUSIONS: In our study cohort, mNC-FET based on LH/HCG+6 versus HCG+7 had similar pregnancy outcomes.

Clinical Information Systems - From Yesterday to Tomorrow.

OBJECTIVES: To review the history of clinical information systems over the past twenty-five years and project anticipated changes to those systems over the next twenty-five years. METHODS: Over 250 Medline references about clinical information systems, quality of patient care, and patient safety were reviewed. Books, Web resources, and the author's personal experience with developing the HELP system were also used. RESULTS: There have been dramatic improvements in the use and acceptance of clinical computing systems and Electronic Health Records (EHRs), especially in the United States. Although there are still challenges with the implementation of such systems, the rate of progress has been remarkable. Over the next twenty-five years, there will remain many important opportunities and challenges. These opportunities include understanding complex clinical computing issues that must be studied, understood and optimized. Dramatic improvements in quality of care and patient safety must be anticipated as a result of the use of clinical information systems. These improvements will result from a closer involvement of clinical informaticians in the optimization of patient care processes. CONCLUSIONS: Clinical information systems and computerized clinical decision support have made contributions to medicine in the past. Therefore, by using better medical knowledge, optimized clinical information systems, and computerized clinical decision, we will enable dramatic improvements in both the quality and safety of patient care in the next twenty-five years.

Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden.

Although many studies indicate the interplay of genetic and environmental factors in the etiology of autism spectrum disorder (ASD), our limited understanding of the underlying mechanisms hampers the development of effective ways of detecting and preventing the disorder. Recent studies support the hypothesis that prenatal androgen exposure contributes to the development of ASD. This would suggest that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring. We conducted a matched case-control study nested within the total population of Sweden (children aged 4-17 who were born in Sweden from 1984 to 2007). The sample consisted of 23 748 ASD cases and 208 796 controls, matched by birth month and year, sex and region of birth. PCOS and ASD were defined from ICD codes through linkage to health-care registers. Maternal PCOS increased the odds of ASD in the offspring by 59%, after adjustment for confounders (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.34-1.88). The odds of offspring ASD were further increased among mothers with both PCOS and obesity, a condition common to PCOS that is related to more severe hyperandrogenemia (OR 2.13, 95% CI 1.46-3.10). Risk estimates did not differ between sexes. In conclusion, children of women with PCOS appear to have a higher risk of developing ASD. This finding awaits confirmation, and exploration of potentially underlying mechanisms, including the role of sex steroids in the etiology of ASD.

Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis.

Although primary infections with Toxoplasma gondii or herpes viruses during pregnancy are established teratogens, chronic maternal infections with these pathogens are considered far less serious. However, such chronic infections have been associated with neuropsychiatric disorders in the offspring. The risks of non-affective psychoses, including schizophrenia, in offspring associated with these exposures during pregnancy have not been completely defined. We used data from neonatal dried blood samples from 199 cases of non-affective psychosis and 525 matched controls (born 1975-1985). We measure immunoglobulin G antibodies directed at T. gondii, cytomegalovirus and herpes simplex virus type-1 and -2, as well as levels of nine acute phase proteins (APPs). We assessed the interaction between maternal antibodies and neonatal APP in terms of risk of non-affective psychosis. Among controls, maternal exposure to T. gondii or cytomegalovirus, but not to the other herpes viruses, was associated with significantly higher levels of neonatal APPs. Among cases, none of the maternal exposures were associated with any significant change in APPs. We observed increased RR for non-affective psychosis associated with maternal infection with T. gondii (odds ratio 2.1, 95% confidence interval 1.1-4.0) or cytomegalovirus (1.7, 0.9-3.3) only among neonates with low APP levels. These findings suggest that chronic maternal infection with T. gondii or cytomegalovirus affect neonatal markers of innate immunity. Deficient fetal immune responses in combination with maternal chronic infections may contribute to subsequent risk for psychosis. A greater understanding of the maternal-fetal immunological interplay may ultimately lead to preventive strategies toward neuropsychiatric disorders.

Neonatal levels of acute phase proteins and later risk of non-affective psychosis.

Mounting evidence suggests that immune disturbances in early life may be implicated in the etiology of non-affective psychoses. Our aim was to assess the levels of neonatal acute phase proteins (APPs), central to innate immune function as well as central nervous system development, in neonatal dried blood spots and their association with later risk of non-affective psychoses. This case-control study included 196 individuals with a verified register-based diagnosis of non-affective psychosis and 502 controls matched on age, sex and hospital of birth. Concentrations of nine different APPs were measured in eluates from dried blood spots using a bead-based multiplex assay. Odds ratios (OR) for non-affective psychoses were calculated for log(2)-transformed (continuous) as well as tertiles of APP concentrations. In continuous analysis, higher concentrations of two APPs, tissue plasminogen activator (tPA; OR: 0.90, 95% confidence interval (CI): 0.85-0.96) and serum amyloid P (SAP; OR: 0.88, 95% CI: 0.78-0.99) were protective in terms of risk of non-affective psychosis. These relationships were not affected by the addition of covariates relevant to maternal health, pregnancy and delivery to the model. Tertile analysis confirmed a protective relationship for higher levels of tPA and SAP, as well as for procalcitonin (highest tertile OR: 0.54, 95% CI:0.32-0.91). Our results suggest that persons who develop non-affective psychoses have lower levels of certain APPs at the time of birth. These differences may render individuals more susceptible to infectious diseases or cause deficiencies in pathways critical for neurodevelopment.

Comparing the effectiveness of computerized adverse drug event monitoring systems to enhance clinical decision support for hospitalized patients.

OBJECTIVE: Performance of computerized adverse drug event (ADE) monitoring of electronic health records through a prospective ADE Monitor and ICD9-coded clinical text review operating independently and simultaneously on the same patient population for a 10-year period are compared. Requirements are compiled for clinical decision support in pharmacy systems to enhance ADE detection. METHODS: A large tertiary care facility in Utah, with a history of quality improvement using its advanced hospital information system, was leveraged in this study. ICD9-based review of clinical charts (ICD9 System) was compared quantitatively and qualitatively to computer-assisted pharmacist-verified ADEs (ADE Monitor). The capture-recapture statistical method was applied to the data to determine an estimated prevalence of ADEs. RESULTS: A total estimated ADE prevalence of 5.53% (13,420/242,599) was calculated, with the ICD9 system identifying 2,604 or 19.4%, and the ADE monitor 3,386 or 25.2% of all estimated ADEs. Both methods commonly identified 4.9% of all estimated ADEs and matched 62.0% of the time, each having its strength in detecting a slightly different domain of ADEs. 70% of the ADE documentation in the clinical notes was found in the discharge summaries. CONCLUSION: Coupled with spontaneous reporting, computerized methods account for approximately half of all ADEs that can currently be detected. To enhance ADE monitoring and patient safety in a hospitalized setting, pharmacy information systems should incorporate prospective structuring and coding of the text in clinical charts and using that data alongside computer-generated alerts of laboratory results and drug orders. Natural language processing can aid computerized detection by automating the coding, in real-time, of physician text from clinical charts so that decision support rules can be created and applied. New detection strategies and enhancements to existing systems should be researched to enhance the detection of ADEs since approximately half are not currently detected.

An international summer school on health informatics: a collaborative effort of the Amsterdam Medical Informatics Program and IPhiE--the International Partnership for Health Informatics Education.

PURPOSE: Today, the need for health informatics training for health care professionals is acknowledged and educational opportunities for these professionals are increasing. To contribute to these efforts, a new initiative was undertaken by the Medical Informatics Program of the University of Amsterdam-Academic Medical Center and IPHIE (IPhiE)-the International Partnership for Health Informatics Education. In the year 2004, a summer school on health informatics was organized for advanced medical students from all over the world. METHODS: We elaborate on the goals and the program for this summer school. In developing the course, we followed the international guidelines of the International Medical Informatics Association-IMIA. Students provided feedback for the course through both summative and formative evaluations. As a result of these evaluations, we outline the lessons we have learned and what consequences these results have had in revising the course. RESULTS: Overall the results of both the summative and formative evaluation of the summer school showed that we succeeded in the goals we set at the beginning of the course. Students highly appreciated the course content and indicated that the course fulfilled their educational needs. The decision support and image processing computer practicums however proved too high level. We therefore will redesign these practicums to competence requirements of medical doctors as defined by IMIA. All participants recommended the summer school event to other students. CONCLUSIONS: Our experiences demonstrated a true need for health informatics education among medical students and that even a 2 weeks course can fulfill health informatics educational needs of these future physicians. Further establishment of health informatics courses for other health professions is recommended.

Impact of CPOE on mortality rates--contradictory findings, important messages.

OBJECTIVE: To analyze the seemingly contradictory results of the Han study (Pediatrics 2005) and the Del Beccaro study (Pediatrics 2006), both analyzing the effect of CPOE systems on mortality rates in pediatric intensive care settings. METHODS: Seven CPOE system experts from the United States and Europe comment on these papers. RESULTS: The two studies are not contradictory, but almost non-comparable due to differences in design and implementation. They demonstrate the range of outcomes that can be obtained from introducing informatics applications in complex health care settings. Implementing informatics applications is a sociotechnical activity, which often depends more on the organizational context than on a specific technology. As health informaticians, we must not only learn from failures, but also avoid both uncritical scepticism that may arise from drawing overly general conclusions from one negative trial, as much as uncritical optimism from limited successful ones. CONCLUSION: The commentaries emphasize the need to promote systematic studies for assessing the socio-technical factors that influence the introduction of increasingly sophisticated informatics applications within complex organizations. The emergence of evidence-based health informatics will be based both on evaluation guidelines and implementation guidelines, both of which increase the chances of successful implementation. In addition, well-educated health informaticians are needed to manage and guide the implementation processes.

The International Partnership for Health Informatics Education: lessons learned from six years of experience.

OBJECTIVES: To inform the medical and health informatics community on the rational, goals, and the achievements of the International Partnership for Health Informatics Education--IPHIE, (I phi E), that was established at six universities in 1999. METHODS: We elaborate on the overall goals of I phi E and describe the current state of affairs: the activities undertaken and faculty and student experience related to these activities. In addition we outline the lessons we have learned over these past six years and our plans for the future. RESULTS: I phi E members first started to collaborate by supporting and encouraging the exchange of talented students and faculty and by establishing joint master classes for honors students. Following the success of these activities, new initiatives were undertaken such as the organization of student workshops at medical informatics conferences and a joint course on strategic information management in hospitals in Europe. CONCLUSIONS: International partnerships such as I phi E take time to establish, and, if they are to be successful, maintaining leadership continuity is critically important. We are convinced that I phi E promotes professionalism of future medical informatics specialists. There will be a continuing growth of globalization in higher education. It will therefore become increasingly important to offer educational programs with international components.

The International Partnership in Health Informatics Education.

The International Partnership for Health Informatics Education (IPHIE) seeks to promote education through international collaboration of graduate and undergraduate training programs in Medical and Health Informatics. In 1998 an International Partnership of Health Informatics Education was established at six universities: The University of Amsterdam, the Universities of Heidelberg and Heilbronn, the University of Health Informatics and Technology Tyrol at Innsbruck, the University of Minnesota and the University of Utah. The overall goal of this cooperation was to form a network for training and educating medical informatics faculty and students in order to prepare them for leading international positions in medical information and communication technology. In this paper we describe the current state of affairs of IPhiE: the activities undertaken, our experiences, the lessons we have learned over these past five years. In addition we outline our plans for the future.

Clinicians' response to computerized detection of infections.

OBJECTIVE: To analyze whether computer-generated reminders about infections could influence clinicians' practice patterns and consequently improve the detection and management of nosocomial infections. DESIGN: The conclusions produced by an expert system developed to detect and manage infections were presented to the attending clinicians in a pediatric hospital to determine whether this information could improve detection and management. Clinician interventions were compared before and after the implementation of the system. MEASUREMENTS: The responses of the clinicians (staff physicians, physician assistants, and nurse practitioners) to the reminders were determined by review of paper medical charts. Main outcome measures were the number of suggestions to treat and manage infections that were followed before and after the implementation of COMPISS (Computerized Pediatric Infection Surveillance System). The clinicians' opinions about the system were assessed by means of a paper questionnaire distributed following the experiment. RESULTS: The results failed to show a statistical difference between the clinicians' treatment strategies before and after implementation of the system (P: > 0.33 for clinicians working in the emergency room and P: > 0.45 for clinicians working in the pediatric intensive care unit). The questionnaire results showed that the respondents appreciated the information presented by the system. CONCLUSION: The computer-generated reminders about infections were unable to influence the practice patterns of clinicians. The methodologic problems that may have contributed to this negative result are discussed.

In vivo regulation of syndecan-3 expression in the rat uterus by 17 beta-estradiol.

The immature rat uterus has been extensively used as an in vivo model system to study the molecular mechanisms of steroid hormone actions. In this study, we demonstrated the regulated expression of syndecan-3 in the rat uterus by the steroid hormone 17 beta-estradiol. Administration of a single physiological dose of 17 beta-estradiol (40 microg/kg) to ovariectomized immature animals induced a rapid and transient increase in uterine syndecan-3 mRNA. Transcript levels reached a peak elevation of 3-fold above saline control tissues 4 h after hormone administration. Inhibition of message up-regulation by actinomycin D but not cycloheximide indicated a hormone response dependent on RNA transcription but not new protein synthesis. The estrogenic ligands estriol and tamoxifen were also effective at raising syndecan-3 mRNA levels; however, nonestrogenic ligands, including progesterone, 5 alpha-dihydrotestosterone, and dexamethasone, failed to stimulate a change in mRNA levels. Hormone-induced changes in mRNA led to transient changes in syndecan-3 protein content and significant alteration in the temporal and spatial expression in endometrial epithelial cells. Collectively, these data show that the steroid hormone 17 beta-estradiol, regulates transcription of the syndecan-3 gene in the uterus via an estrogen receptor-dependent mechanism. This estrogen-regulated expression of syndecan-3 may play an important role in changes in tissue ultrastructure crucial for proper uterine growth.

Predictors of eating disorder scores in children ages 6 through 14: a longitudinal study.

The objective of this study was to identify variables that predict higher eating disorder scores in non-clinical boys and girls ages 6 through 14. Two hundred sixteen children participated and were tested annually for 3 years. A TV-video procedure was used to measure the accuracy of body size judgments. Variables examined included demographic, familial, sociocultural, social, esteem, and clinical variables. Predictors of higher eating disorder scores for both sexes included height and weight, children's perceptions of parental concerns about their body size, low body esteem, and depression. For girls only, a larger perceived body size and smaller idealized body size were also predictors. Teasing was a predictor for boys only. An analysis of longitudinal changes suggests that low body esteem becomes a significant factor around age 9, depression emerges as a predictor at age 10, and body size judgments in perceived and ideal sizes at ages 11 and 12. Changes over 2 years in individuals' weight and height, teasing, body dissatisfaction, and eating disorder scores were also found to predict higher eating disorder scores.

Old and new scales for the assessment of body image: a reply to Stunkard (2000).

Avoidance of shortcomings of older scales of body image and use of additional measurements in newer scales are stated.

IPHIE: an International Partnership in Health Informatics Education.

Medical informatics contributes significantly to high quality and efficient health care and medical research. The need for well educated professionals in the field of medical informatics therefore is now worldwide recognized. Students of medicine, computer science/informatics are educated in the field of medical informatics and dedicated curricula on medical informatics have emerged. To advance and further develop the beneficial role of medical informatics in the medical field, an international orientation of health and medical informatics students seems an indispensable part of their training. An international orientation and education of medical informatics students may help to accelerate the dissemination of acquired knowledge and skills in the field and the promotion of medical informatics research results on a more global level. Some years ago, the departments of medical informatics of the university of Heidelberg/university of applied sciences Heilbronn and the university of Amsterdam decided to co-operate in the field of medical informatics. Now, this co-operation has grown out to an International Partnership of Health Informatics Education (IPHIE) of 5 universities, i.e. the university of Heidelberg, the university of Heilbronn, the university of Minnesota, the university of Utah and the university of Amsterdam. This paper presents the rationale behind this international partnership, the state of the art of the co-operation and our future plans for expanding this international co-operation.