Managing Interruptions to Improve Diagnostic Decision-Making: Strategies and Recommended Research Agenda.

Interruptions are an inevitable occurrence in health care. Interruptions in diagnostic decision-making are no exception and can have negative consequences on both the decision-making process and well-being of the decision-maker. This may result in inaccurate or delayed diagnoses. To date, research specific to interruptions on diagnostic decision-making has been limited, but strategies to help manage the negative impacts of interruptions need to be developed and implemented. In this perspective, we first present a modified model of interruptions to visualize the interruption process and illustrate where potential interventions can be implemented. We then consider several empirically tested strategies from the fields of health care and cognitive psychology that can lay the groundwork for additional research to mitigate effects of interruptions during diagnostic decision-making. We highlight strategies to minimize the negative impacts of interruptions as well as strategies to prevent interruptions altogether. Additionally, we build upon these strategies to propose specific research priorities within the field of diagnostic safety. Identifying effective interventions to help clinicians better manage interruptions has the potential to minimize diagnostic errors and improve patient outcomes.

A multi-pronged investigation of option generation using depression, PET and modafinil.

Option generation is a critical process in decision making, but previous studies have largely focused on choices between options given by a researcher. Consequently, how we self-generate options for behaviour remain poorly understood. Here, we investigated option generation in major depressive disorder and how dopamine might modulate this process, as well as the effects of modafinil (a putative cognitive enhancer) on option generation in healthy individuals. We first compared differences in self-generated options between healthy non-depressed adults [n = 44, age = 26.3 years (SD 5.9)] and patients with major depressive disorder [n = 54, age = 24.8 years (SD 7.4)]. In the second study, a subset of depressed individuals [n = 22, age = 25.6 years (SD 7.8)] underwent PET scans with 11C-raclopride to examine the relationships between dopamine D2/D3 receptor availability and individual differences in option generation. Finally, a randomized, double-blind, placebo-controlled, three-way crossover study of modafinil (100 mg and 200 mg), was conducted in an independent sample of healthy people [n = 19, age = 23.2 years (SD 4.8)] to compare option generation under different doses of this drug. The first study revealed that patients with major depressive disorder produced significantly fewer options [t(96) = 2.68, P = 0.009, Cohen's d = 0.54], albeit with greater uniqueness [t(96) = -2.54, P = 0.01, Cohen's d = 0.52], on the option generation task compared to healthy controls. In the second study, we found that 11C-raclopride binding potential in the putamen was negatively correlated with fluency (r = -0.69, P = 0.001) but positively associated with uniqueness (r = 0.59, P = 0.007). Hence, depressed individuals with higher densities of unoccupied putamen D2/D3 receptors in the putamen generated fewer but more unique options, whereas patients with lower D2/D3 receptor availability were likely to produce a larger number of similar options. Finally, healthy participants were less unique [F(2,36) = 3.32, P = 0.048, partial η2 = 0.16] and diverse [F(2,36) = 4.31, P = 0.021, partial η2 = 0.19] after taking 200 mg versus 100 mg and 0 mg of modafinil, while fluency increased linearly with dosage at a trend level [F(1,18) = 4.11, P = 0.058, partial η2 = 0.19]. Our results show, for the first time, that option generation is affected in clinical depression and that dopaminergic activity in the putamen of patients with major depressive disorder may play a key role in the self-generation of options. Modafinil was also found to influence option generation in healthy people by reducing the creativity of options produced.

Electronic Health Records' Support for Primary Care Physicians' Situation Awareness: A Metanarrative Review.

OBJECTIVE: Situation awareness (SA) refers to people's perception and understanding of their dynamic environment. In primary care, reduced SA among physicians increases errors in clinical decision-making and, correspondingly, patients' risk of experiencing adverse outcomes. Our objective was to understand the extent to which electronic health records (EHRs) support primary care physicians (PCPs)' SA during clinical decision-making. METHOD: We conducted a metanarrative review of papers in selected academic databases, including CINAHL and MEDLINE. Eligible studies included original peer-reviewed research published between January 2012 and August 2020 on PCP-EHR interactions. We iteratively queried, screened, and summarized literature focused on EHRs supporting PCPs' clinical decision-making and care management for adults. Then, we mapped findings to an established SA framework to classify external factors (individual, task, and system) affecting PCPs' levels of SA (1-Perception, 2-Comprehension, and 3-Projection) and identified SA barriers. RESULTS: From 1504 articles identified, we included and synthesized 19 studies. Study designs were largely noninterventional. Studies described EHR workflow misalignments, usability issues, and communication challenges. EHR information, including lab results and care plans, was characterized as incomplete, untimely, or irrelevant. Unmet information needs made it difficult for PCPs to obtain even basic SA, Level 1 SA. Prevalent barriers to PCPs developing SA with EHRs were errant mental models, attentional tunneling, and data overload. CONCLUSION: Based on our review, EHRs do not support the development of higher levels of SA among PCPs. Review findings suggest SA-oriented design processes for health information technology could improve PCPs' SA, satisfaction, and decision-making.

Dose-dependent seizure control with MEK inhibitor therapy for progressive glioma in a child with neurofibromatosis type 1.

BACKGROUND: Low-grade gliomas (LGGs) occurring in children can result in many different neurologic complications, including seizures. MEK inhibitors are increasingly being used to treat LGG, but their effect on associated neurologic symptoms has not been established. RESULTS: Here, we report a patient with neurofibromatosis type 1 (NF1), medically refractory epilepsy (MRE), and an extensive optic pathway glioma (OPG) who developed dose-dependent seizure control while being treated with selumetinib. Seizure frequency rebounded after dose reduction for cardiac toxicity, then improved, and finally ceased after restarting full dosing, allowing confidence in the cause of improvement. CONCLUSION: Selumetinib may have promise in epilepsy management in other children with NF1 or LGG.

Conceptus interferon gamma is essential for establishment of pregnancy in the pig†.

Establishment and maintenance of pregnancy in the pig is a complex process that relies on conceptus regulation of the maternal proinflammatory response to endometrial attachment. Following elongation, pig conceptuses secrete interferon gamma (IFNG) during attachment to the endometrial luminal epithelium. The objective here was to determine if conceptus production of IFNG is important for early development and establishment of pregnancy. CRISPR/Cas9 gene editing and somatic cell nuclear transfer technologies were used to create an IFNG loss-of-function study in pigs. Wild-type (IFNG+/+) and null (IFNG-/-) fibroblast cells were used to create embryos through somatic cell nuclear transfer. IFNG expression was not detected in IFNG-/- conceptuses on either day 15 or day 17 of pregnancy. Ablation of conceptus IFNG production resulted in the reduction of stromal CD3+ and mast cells, which localized to the site of conceptus attachment on day 15. The uteri of recipients with IFNG-/- conceptuses were inflamed, hyperemic and there was an abundance of erythrocytes in the uterine lumen associated with the degenerating conceptuses. The endometrial stromal extracellular matrix was altered in the IFNG-/- embryo pregnancies and there was an increased endometrial mRNA levels for collagen XVII (COL17A1), matrilin 1 (MATN1), secreted phosphoprotein 1 (SPP1), and cysteine-rich secretory protein 3 (CRISP3), which are involved with repair and remodeling of the extracellular matrix. These results indicate conceptus IFNG production is essential in modulating the endometrial proinflammatory response for conceptus attachment and survival in pigs.

Gene editing to investigate the role of conceptus factors in the establishment of pregnancy in the pig.

Development of viviparity in mammals requires that the placenta evolves as an intermediate interface between the fetus and maternal uterus. In addition to the retention of the fetus and secretion of nutrients to support growth and development to term, it is essential that viviparous species modify or inhibit the maternal immune system from recognizing the semi-allogeneic fetus. Following blastocyst hatching from its zona pellucida, trophoblast differentiation provides the initial communication to the maternal endometrium to regulate maintenance of progesterone production from the corpus luteum and biological pathways in uterine and conceptus development necessary in the establishment and maintenance of pregnancy. Many conceptus factors have been proposed to serve in the establishment and maintenance of pregnancy. CRISPR-Cas9 gene-editing technology provides a specific and efficient method to generate animal models to perform loss-of-function studies to investigate the role of specific conceptus factors. The utilization of CRISPR-Cas9 gene editing has provided a direct approach to investigate the specific role of conceptus factors in the development and establishment of pregnancy in the pig. This technology has helped address a number of questions concerning peri-implantation development and has altered our understanding of maternal recognition and maintenance of pregnancy in the pig.

Advancing Diagnostic Safety Research: Results of a Systematic Research Priority Setting Exercise.

BACKGROUND: Diagnostic errors are a major source of preventable harm but the science of reducing them remains underdeveloped. OBJECTIVE: To identify and prioritize research questions to advance the field of diagnostic safety in the next 5 years. PARTICIPANTS: Ninety-seven researchers and 42 stakeholders were involved in the identification of the research priorities. DESIGN: We used systematic prioritization methods based on the Child Health and Nutrition Research Initiative (CHNRI) methodology. We first invited a large international group of expert researchers in various disciplines to submit research questions while considering five prioritization criteria: (1) usefulness, (2) answerability, (3) effectiveness, (4) potential for translation, and (5) maximal potential for effect on diagnostic safety. After consolidation, these questions were prioritized at an in-person expert meeting in April 2019. Top-ranked questions were subsequently reprioritized through scoring on the five prioritization criteria using an online questionnaire. We also invited non-research stakeholders to assign weights to the five criteria and then used these weights to adjust the final prioritization score for each question. KEY RESULTS: Of the 207 invited researchers, 97 researchers responded and 78 submitted 333 research questions which were then consolidated. Expert meeting participants (n = 21) discussed questions in different breakout sessions and prioritized 50, which were subsequently reduced to the top 20 using the online questionnaire. The top 20 questions addressed mostly system factors (e.g., implementation and evaluation of information technologies), teamwork factors (e.g., role of nurses and other health professionals in the diagnostic process), and strategies to engage patients in the diagnostic process. CONCLUSIONS: Top research priorities for advancing diagnostic safety in the short-term include strengthening systems and teams and engaging patients to support diagnosis. High-priority areas identified using these systematic methods can inform an actionable research agenda for reducing preventable diagnostic harm.

Inactivation of porcine interleukin-1ß results in failure of rapid conceptus elongation.

Conceptus expansion throughout the uterus of mammalian species with a noninvasive epitheliochorial type of placentation is critical establishing an adequate uterine surface area for nutrient support during gestation. Pig conceptuses undergo a unique rapid morphological transformation to elongate into filamentous threads within 1 h, which provides the uterine surface to support development and maintain functional corpora lutea through the production of estrogen. Conceptus production of a unique interleukin 1ß, IL1B2, temporally increases during the period of trophoblast remodeling during elongation. CRISPR/Cas9 gene editing was used to knock out pig conceptus IL1B2 expression and the secretion of IL1B2 during the time of conceptus elongation. Trophoblast elongation occurred on day 14 in wild-type (IL1B2+/+) conceptuses but did not occur in ILB2-null (IL1B2-/-) conceptuses. Although the morphological transition of IL1B2-/- conceptuses was inhibited, expression of a number of conceptus developmental genes was not altered. However, conceptus aromatase expression and estrogen secretion were decreased, indicating that IL1B2 may be involved in the spatiotemporal increase in conceptus estrogen synthesis needed for the establishment of pregnancy in the pig and may serve to regulate the proinflammatory response of endometrium to IL1B2 during conceptus elongation and attachment to the uterine surface.

Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pig†.

Pig conceptuses secrete estrogens (E2), interleukin 1 beta 2 (IL1B2), and prostaglandins (PGs) during the period of rapid trophoblast elongation and establishment of pregnancy. Previous studies established that IL1B2 is essential for rapid conceptus elongation, whereas E2 is not essential for conceptus elongation or early maintenance of the corpora lutea. The objective of the present study was to determine if conceptus expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and release of PG are important for early development and establishment of pregnancy. To understand the role of PTGS2 in conceptus elongation and pregnancy establishment, a loss-of-function study was conducted by editing PTGS2 using CRISPR/Cas9 technology. Wild-type (PTGS2+/+) and null (PTGS2-/-) fibroblast cells were used to create embryos through somatic cell nuclear transfer. Immunolocalization of PTGS2 and PG production was absent in cultured PTGS2-/- blastocysts on day 7. PTGS2+/+ and PTGS2-/- blastocysts were transferred into surrogate gilts, and the reproductive tracts were collected on either days 14, 17, or 35 of pregnancy. After flushing the uterus on days 14 and 17, filamentous conceptuses were cultured for 3 h to determine PG production. Conceptus release of total PG, prostaglandin F2⍺ (PGF2α), and PGE in culture media was lower with PTGS2-/- conceptuses compared to PTGS2+/+ conceptuses. However, the total PG, PGF2α, and PGE content in the uterine flushings was not different. PTGS2-/- conceptus surrogates allowed to continue pregnancy were maintained beyond 30 days of gestation. These results indicate that pig conceptus PTGS2 is not essential for early development and establishment of pregnancy in the pig.

Patient Perspectives on the Usefulness of an Artificial Intelligence-Assisted Symptom Checker: Cross-Sectional Survey Study.

BACKGROUND: Patients are increasingly seeking Web-based symptom checkers to obtain diagnoses. However, little is known about the characteristics of the patients who use these resources, their rationale for use, and whether they find them accurate and useful. OBJECTIVE: The study aimed to examine patients' experiences using an artificial intelligence (AI)-assisted online symptom checker. METHODS: An online survey was administered between March 2, 2018, through March 15, 2018, to US users of the Isabel Symptom Checker within 6 months of their use. User characteristics, experiences of symptom checker use, experiences discussing results with physicians, and prior personal history of experiencing a diagnostic error were collected. RESULTS: A total of 329 usable responses was obtained. The mean respondent age was 48.0 (SD 16.7) years; most were women (230/304, 75.7%) and white (271/304, 89.1%). Patients most commonly used the symptom checker to better understand the causes of their symptoms (232/304, 76.3%), followed by for deciding whether to seek care (101/304, 33.2%) or where (eg, primary or urgent care: 63/304, 20.7%), obtaining medical advice without going to a doctor (48/304, 15.8%), and understanding their diagnoses better (39/304, 12.8%). Most patients reported receiving useful information for their health problems (274/304, 90.1%), with half reporting positive health effects (154/302, 51.0%). Most patients perceived it to be useful as a diagnostic tool (253/301, 84.1%), as a tool providing insights leading them closer to correct diagnoses (231/303, 76.2%), and reported they would use it again (278/304, 91.4%). Patients who discussed findings with their physicians (103/213, 48.4%) more often felt physicians were interested (42/103, 40.8%) than not interested in learning about the tool's results (24/103, 23.3%) and more often felt physicians were open (62/103, 60.2%) than not open (21/103, 20.4%) to discussing the results. Compared with patients who had not previously experienced diagnostic errors (missed or delayed diagnoses: 123/304, 40.5%), patients who had previously experienced diagnostic errors (181/304, 59.5%) were more likely to use the symptom checker to determine where they should seek care (15/123, 12.2% vs 48/181, 26.5%; P=.002), but they less often felt that physicians were interested in discussing the tool's results (20/34, 59% vs 22/69, 32%; P=.04). CONCLUSIONS: Despite ongoing concerns about symptom checker accuracy, a large patient-user group perceived an AI-assisted symptom checker as useful for diagnosis. Formal validation studies evaluating symptom checker accuracy and effectiveness in real-world practice could provide additional useful information about their benefit.

New perspective on conceptus estrogens in maternal recognition and pregnancy establishment in the pig†.

The proposed signal for maternal recognition of pregnancy in pigs is estrogen (E2), produced by the elongating conceptuses between days 11 to 12 of pregnancy with a more sustained increase during conceptus attachment and placental development on days 15 to 30. To understand the role of E2 in porcine conceptus elongation and pregnancy establishment, a loss-of-function study was conducted by editing aromatase (CYP19A1) using CRISPR/Cas9 technology. Wild-type (CYP19A1+/+) and (CYP19A1-/-) fibroblast cells were used to create embryos through somatic cell nuclear transfer, which were transferred into recipient gilts. Elongated and attaching conceptuses were recovered from gilts containing CYP19A1+/+ or CYP19A1-/- embryos on day 14 and 17 of pregnancy. Total E2 in the uterine flushings of gilts with CYP19A1-/- embryos was lower than recipients containing CYP19A1+/+ embryos with no difference in testosterone, PGF2α, or PGE2 on either day 14 or 17. Despite the loss of conceptus E2 production, CYP19A1-/- conceptuses were capable of maintaining the corpora lutea. However, gilts gestating CYP19A1-/- embryos aborted between days 27 and 31 of gestation. Attempts to rescue the pregnancy of CYP19A1-/- gestating gilts with exogenous E2 failed to maintain pregnancy. However, CYP19A1-/- embryos could be rescued when co-transferred with embryos derived by in vitro fertilization. Endometrial transcriptome analysis revealed that ablation of conceptus E2 resulted in disruption of a number biological pathways. Results demonstrate that intrinsic E2 conceptus production is not essential for pre-implantation development, conceptus elongation, and early CL maintenance, but is essential for maintenance of pregnancy beyond 30 days .

Pediatric clinician perspectives on communicating diagnostic uncertainty.

OBJECTIVE: Diagnosis often evolves over time, involves uncertainty, and is vulnerable to errors. We examined pediatric clinicians' perspectives on communicating diagnostic uncertainty to patients' parents and how this occurs. DESIGN: We conducted semi-structured interviews, which were audiotaped, transcribed, and analyzed using content analysis. Two researchers independently coded transcripts and then discussed discrepancies to reach consensus. SETTING: A purposive sample of pediatric clinicians at two large academic medical institutions in Texas. PARTICIPANTS: Twenty pediatric clinicians participated: 18 physicians, 2 nurse practitioners; 7 males, 13 females; 7 inpatient, 11 outpatient, and 2 practicing in mixed settings; with 0-16 years' experience post-residency. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pediatric clinician perspectives on communication of diagnostic uncertainty. RESULTS: Pediatric clinicians commonly experienced diagnostic uncertainty and most were comfortable seeking help and discussing with colleagues. However, when communicating uncertainty to parents, clinicians used multiple considerations to adjust the degree to which they communicated. Considerations included parent characteristics (education, socioeconomic status, emotional response, and culture) and strength of parent-clinician relationships. Communication content included setting expectations, explaining the diagnostic process, discussing most relevant differentials, and providing reassurance. Responses to certain parent characteristics, however, were variable. For example, some clinicians were more open to discussing diagnostic uncertainty with more educated parents- others were less. CONCLUSIONS: While pediatric clinicians are comfortable discussing diagnostic uncertainty with colleagues, how they communicate uncertainty to parents appears variable. Parent characteristics and parent-clinician relationships affect extent of communication and content discussed. Development and implementation of optimal strategies for managing and communicating diagnostic uncertainty can improve the diagnostic process.

Isolating red flags to enhance diagnosis (I-RED): An experimental vignette study.

OBJECTIVE: To investigate effects of a cognitive intervention based on isolation of red flags (I-RED) on diagnostic accuracy of 'do-not-miss diagnoses.' DESIGN: A 2 × 2 randomized case vignette-based experiment with manipulation of I-RED strategy between subjects and case complexity within subjects. SETTING: Two university-based residency programs. PARTICIPANTS: One-hundred and nine pediatric residents from all levels of training. INTERVENTIONS: Participants were randomly assigned to the I-RED vs. control group, and within each group, they were further randomized to the order in which they saw simple and complex cases. The I-RED strategy involved an instruction to look for a constellation of symptoms, signs, clinical data or circumstances that should heighten suspicion for a serious condition. MAIN OUTCOME MEASURES: Primary outcome was diagnostic accuracy, scored as 1 if any of the three differentials given by participants included the correct diagnosis, and 0 if not. We analyzed effects of I-RED strategy on diagnostic accuracy using logistic regression. RESULTS: I-RED strategy did not yield statistically higher diagnostic accuracy compared to controls (62 vs. 48%, respectively; odd ratio = 2.07 [95% confidence interval, 0.78-5.5], P = 0.14) although participants reported higher decision confidence compared to controls (7.00 vs. 5.77 on a scale of 1 to 10, P < 0.02) in simple but not complex cases. I-RED strategy significantly shortened time to decision (460 vs. 657 s, P < 0.001) and increased the number of red flags generated (3.04 vs. 2.09, P < 0.001). CONCLUSIONS: A cognitive strategy of prompting red flag isolation prior to differential diagnosis did not improve diagnostic accuracy of 'do-not-miss diagnoses.' Given the paucity of evidence-based solutions to reduce diagnostic error and the intervention's potential effect on confidence, findings warrant additional exploration.

Development and Validation of Trigger Algorithms to Identify Delays in Diagnostic Evaluation of Gastroenterological Cancer.

BACKGROUND & AIMS: Colorectal cancer (CRC) and hepatocellular cancer (HCC) are common causes of death and morbidity, and patients benefit from early detection. However, delays in follow-up of suspicious findings are common, and methods to efficiently detect such delays are needed. We developed, refined, and tested trigger algorithms that identify patients with delayed follow-up evaluation of findings suspicious of CRC or HCC. METHODS: We developed and validated two trigger algorithms that detect delays in diagnostic evaluation of CRC and HCC using laboratory, diagnosis, procedure, and referral codes from the Department of Veteran Affairs National Corporate Data Warehouse. The algorithm initially identified patients with positive test results for iron deficiency anemia or fecal immunochemical test (for CRC) and elevated α-fetoprotein results (for HCC). Our algorithm then excluded patients for whom follow-up evaluation was unnecessary, such as patients with a terminal illness or those who had already completed a follow-up evaluation within 60 days. Clinicians reviewed samples of both delayed and nondelayed records, and review data were used to calculate trigger performance. RESULTS: We applied the algorithm for CRC to 245,158 patients seen from January 1, 2013, through December 31, 2013 and identified 1073 patients with delayed follow up. In a review of 400 randomly selected records, we found that our algorithm identified patients with delayed follow-up with a positive predictive value of 56.0% (95% CI, 51.0%-61.0%). We applied the algorithm for HCC to 333,828 patients seen from January 1, 2011 through December 31, 2014, and identified 130 patients with delayed follow-up. During manual review of all 130 records, we found that our algorithm identified patients with delayed follow-up with a positive predictive value of 82.3% (95% CI, 74.4%-88.2%). When we extrapolated the findings to all patients with abnormal results, the algorithm identified patients with delayed follow-up evaluation for CRC with 68.6% sensitivity (95% CI, 65.4%-71.6%) and 81.1% specificity (95% CI, 79.5%-82.6%); it identified patients with delayed follow-up evaluation for HCC with 89.1% sensitivity (95% CI, 81.8%-93.8%) and 96.5% specificity (95% CI, 94.8%-97.7%). Compared to nonselective methods, use of the algorithm reduced the number of records required for review to identify a delay by more than 99%. CONCLUSIONS: Using data from the Veterans Affairs electronic health record database, we developed an algorithm that greatly reduces the number of record reviews necessary to identify delays in follow-up evaluations for patients with suspected CRC or HCC. This approach offers a more efficient method to identify delayed diagnostic evaluation of gastroenterological cancers.

Patient perspectives on how physicians communicate diagnostic uncertainty: An experimental vignette study.

OBJECTIVE: We evaluated the effects of three different strategies for communicating diagnostic uncertainty on patient perceptions of physician competence and visit satisfaction. DESIGN/SETTING: Experimental vignette-based study design involving pediatric cases presented to a convenience sample of parents living in a large US city. PARTICIPANTS/INTERVENTION(S): Three vignettes were developed, each describing one of three different ways physicians communicated diagnostic uncertainty to parents-(i) explicit expression of uncertainty ('not sure' about diagnosis), (ii) implicit expression of uncertainty using broad differential diagnoses and (iii) implicit expression of uncertainty using 'most likely' diagnoses. Participants were randomly assigned to one of the three vignettes and then answered a 37-item web-based questionnaire. MAIN OUTCOME MEASURE(S): Outcome variables included parent-perceived technical competence of physician, trust and confidence, visit satisfaction and adherence to physician instructions. Differences between the three groups were compared using analysis of variance, followed by individual post hoc analyses with Bonferroni correction. RESULTS: Seventy-one participants completed the vignette questions. Demographic characteristics and scores on activation (parent activation measure [PAM]) and intolerance to uncertainty were similar across the three groups. Explicit expression of uncertainty was associated with lower perceived technical competence, less trust and confidence, and lower patient adherence as compared to the two groups with implicit communication. These latter two groups had comparable outcomes. CONCLUSION: Parents may react less negatively in terms of perceived competence, physician confidence and trust, and intention to adhere when diagnostic uncertainty is communicated using implicit strategies, such as using broad differential diagnoses or most likely diagnoses. Evidence-based strategies to communicate diagnostic uncertainty to patients need further development.

Rapid conceptus elongation in the pig: An interleukin 1 beta 2 and estrogen-regulated phenomenon.

Establishment and maintenance of pregnancy in the pig involves activating many physiological, cellular, and molecular signaling pathways between the developing conceptus and hormonally regulated maternal endometrium. Rapid elongation of the pig trophoblast allows for the establishment of sufficient placental surface area for the transport of nutrients to the fetus throughout pregnancy. Estrogens secreted by the conceptus during elongation act on uterine epithelia to induce secretion of uterine factors required for conceptus development and for preventing endocrine secretion of prostaglandin F2α, which would cause luteolysis. Thus, trophoblast expansion within the uterine lumen during early gestation is an essential process for implantation and maintenance of pregnancy in species with an epitheliochorial form of placentation. In the pig, rapid conceptus elongation involves the unique expression of interleukin-1 beta 2 (IL1B2), which establishes pro-inflammatory effects that may be tempered by the spatiotemporal secretion of estrogen from the conceptuses. The present review provides current information on pig conceptus remodeling and signaling via estrogen and IL1B2 pathways, as well as endometrial responses to those conceptus factors leading to establishment of pregnancy.

Electronic Detection of Delayed Test Result Follow-Up in Patients with Hypothyroidism.

BACKGROUND: Delays in following up abnormal test results are a common problem in outpatient settings. Surveillance systems that use trigger tools to identify delayed follow-up can help reduce missed opportunities in care. OBJECTIVE: To develop and test an electronic health record (EHR)-based trigger algorithm to identify instances of delayed follow-up of abnormal thyroid-stimulating hormone (TSH) results in patients being treated for hypothyroidism. DESIGN: We developed an algorithm using structured EHR data to identify patients with hypothyroidism who had delayed follow-up (>60 days) after an abnormal TSH. We then retrospectively applied the algorithm to a large EHR data warehouse within the Department of Veterans Affairs (VA), on patient records from two large VA networks for the period from January 1, 2011, to December 31, 2011. Identified records were reviewed to confirm the presence of delays in follow-up. KEY RESULTS: During the study period, 645,555 patients were seen in the outpatient setting within the two networks. Of 293,554 patients with at least one TSH test result, the trigger identified 1250 patients on treatment for hypothyroidism with elevated TSH. Of these patients, 271 were flagged as potentially having delayed follow-up of their test result. Chart reviews confirmed delays in 163 of the 271 flagged patients (PPV = 60.1%). CONCLUSIONS: An automated trigger algorithm applied to records in a large EHR data warehouse identified patients with hypothyroidism with potential delays in thyroid function test results follow-up. Future prospective application of the TSH trigger algorithm can be used by clinical teams as a surveillance and quality improvement technique to monitor and improve follow-up.

Finding Diagnostic Errors in Children Admitted to the PICU.

OBJECTIVES: To determine whether the Safer Dx Instrument, a structured tool for finding diagnostic errors in primary care, can be used to reliably detect diagnostic errors in patients admitted to a PICU. DESIGN AND SETTING: The Safer Dx Instrument consists of 11 questions to evaluate the diagnostic process and a final question to determine if diagnostic error occurred. We used the instrument to analyze four "high-risk" patient cohorts admitted to the PICU between June 2013 and December 2013. PATIENTS: High-risk cohorts were defined as cohort 1: patients who were autopsied; cohort 2: patients seen as outpatients within 2 weeks prior to PICU admission; cohort 3: patients transferred to PICU unexpectedly from an acute care floor after a rapid response and requiring vasoactive medications and/or endotracheal intubation due to decompensation within 24 hours; and cohort 4: patients transferred to PICU unexpectedly from an acute care floor after a rapid response without subsequent decompensation in 24 hours. INTERVENTIONS: Two clinicians used the instrument to independently review records in each cohort for diagnostic errors, defined as missed opportunities to make a correct or timely diagnosis. Errors were confirmed by senior expert clinicians. MEASUREMENTS AND MAIN RESULTS: Diagnostic errors were present in 26 of 214 high-risk patient records (12.1%; 95% CI, 8.2-17.5%) with the following frequency distribution: cohort 1: two of 16 (12.5%); cohort 2: one of 41 (2.4%); cohort 3: 13 of 44 (29.5%); and cohort 4: 10 of 113 (8.8%). Overall initial reviewer agreement was 93.6% (κ, 0.72). Infections and neurologic conditions were the most commonly missed diagnoses across all high-risk cohorts (16/26). CONCLUSIONS: The Safer Dx Instrument has high reliability and validity for diagnostic error detection when used in high-risk pediatric care settings. With further validation in additional clinical settings, it could be useful to enhance learning and feedback about diagnostic safety in children.