Prenatal treatment of ornithine transcarbamylase deficiency.

PURPOSE OF STUDY: Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor. METHODS USED: Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery. SUMMARY OF RESULTS: Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years. CONCLUSION: Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

Changing Management of the Patent Ductus Arteriosus: Effect on Neonatal Outcomes and Resource Utilization.

Objective This historical cohort study investigated how a shift toward a more conservative approach of awaiting spontaneous closure of the patent ductus arteriosus (PDA) in preterm infants has affected neonatal outcomes and resource utilization. Methods We retrospectively studied very low birth weight infants diagnosed with a PDA by echocardiogram (ECHO) in 2006-2008 (era 1), when medical or surgical PDA management was emphasized, to those born in 2010-2012 (era 2) when conservative PDA management was encouraged. Multiple regression analyses adjusted for gestational age were performed to assess differences in clinical outcomes and resource utilization between eras. Results More infants in era 2 (35/89, 39%) compared with era 1 (22/120, 18%) had conservative PDA management (p < 0.01). Despite no difference in surgical ligation rate, infants in era 2 had ligation later (median 24 vs. 8 days, p < 0.0001). There was no difference in clinical outcomes between eras, while number of ECHOs per patient was the only resource measure that increased in era 2 (median 3 vs. 2 ECHOs, p = 0.003). Conclusion In an era of more conservative PDA management, no increase in adverse clinical outcomes or significant change in resource utilization was found. Conservative PDA management may be a safe alternative for preterm infants.

Red blood cell transfusion is not associated with necrotizing enterocolitis: a review of consecutive transfusions in a tertiary neonatal intensive care unit.

OBJECTIVE: To explore the association between red blood cell transfusion and necrotizing enterocolitis (NEC) in a neonatal intensive care unit with liberal transfusion practices. STUDY DESIGN: A retrospective cohort study was conducted for all infants weighing <1500 g who received at least 1 packed red blood cell transfusion between January 2008 and June 2013 in a tertiary neonatal intensive care unit. The primary outcome was NEC, defined as Bell stage II or greater. The temporal association of NEC and transfusion was assessed using multivariate Poisson regression. RESULTS: The study sample included 414 very low birth weight infants who received 2889 consecutive red blood cell transfusions. Twenty-four infants (5.8%) developed NEC. Four cases of NEC occurred within 48 hours of a previous transfusion event. Using multivariate Poisson regression, we did not find evidence of a temporal association between NEC and transfusion (P = .32). CONCLUSION: There was no association between NEC and red blood cell transfusion. Our results differ from previous studies and suggest that the association between NEC and transfusion may be contextual.

Anti-Ge3 causes late-onset hemolytic disease of the newborn: the fourth case in three Hispanic families.

BACKGROUND: The Gerbich (Ge) blood group system consists of 11 antigens carried on red blood cell (RBC) membrane glycophorins C and D; of these, Ge:3 antigen is of high prevalence, and the anti-Ge3 is found to be clinically significant. CASE REPORT: A 34-week neonate born to a Hispanic mother with anti-Ge3 developed late-onset hemolysis with hyperbilirubinemia and was successfully treated with transfusions from her mother. Relevant clinical findings and laboratory results for this case are summarized and compared to three other previously reported cases; all babies were born from a mother of Hispanic ethnicity. CONCLUSION: Hemolytic disease of the fetus and new born associated with anti-Ge3 is rare but should be considered when working up a broadly reactive RBC antibody screen in women of Hispanic ethnicity. Early identification of pregnant women with anti-Ge3 is recommended for prenatal transfusion planning and close monitoring of the newborn infant for evidence of late-onset anemia.

Using an Evidence-Based Approach to EMR Implementation to Optimize Outcomes and Avoid Unintended Consequences.

Implementation of an electronic medical record (EMR) with computerized physician order entry (CPOE) can provide an important foundation for preventing harm and improving outcomes. Incentivized by the recent economic stimulus initiative, healthcare systems are implementing vendor-based EMR systems at an unprecedented rate. Accumulating evidence suggests that local implementation decisions, rather than the specific EMR product or technology selected, are the primary drivers of the quality improvement performance of these systems. However, limited attention has been paid to effective approaches to EMR implementation. In this case report, we outline the evidence-based approach we used to make EMR implementation decisions in a pragmatic structure intended for replication at other sites.

Monitoring Approaches for a Pediatric Chronic Kidney Disease Machine Learning Model.

OBJECTIVE: The purpose of this study is to evaluate the ability of three metrics to monitor for a reduction in performance of a chronic kidney disease (CKD) model deployed at a pediatric hospital. METHODS: The CKD risk model estimates a patient's risk of developing CKD 3 to 12 months following an inpatient admission. The model was developed on a retrospective dataset of 4,879 admissions from 2014 to 2018, then run silently on 1,270 admissions from April to October, 2019. Three metrics were used to monitor its performance during the silent phase: (1) standardized mean differences (SMDs); (2) performance of a "membership model"; and (3) response distribution analysis. Observed patient outcomes for the 1,270 admissions were used to calculate prospective model performance and the ability of the three metrics to detect performance changes. RESULTS: The deployed model had an area under the receiver-operator curve (AUROC) of 0.63 in the prospective evaluation, which was a significant decrease from an AUROC of 0.76 on retrospective data (p = 0.033). Among the three metrics, SMDs were significantly different for 66/75 (88%) of the model's input variables (p <0.05) between retrospective and deployment data. The membership model was able to discriminate between the two settings (AUROC = 0.71, p <0.0001) and the response distributions were significantly different (p <0.0001) for the two settings. CONCLUSION: This study suggests that the three metrics examined could provide early indication of performance deterioration in deployed models' performance.

Early experiences with combined fellowship training in clinical informatics.

Given the ubiquitous nature of information systems in modern health care, interest in the pursuit of formal training in clinical informatics is increasing. This interest is not restricted to generalists-informatics training is increasingly being sought by future subspecialists. The traditional structure of Accreditation Council on Graduate Medical Education subspecialty training requires completion of both clinical and clinical informatics fellowship programs, and understandably lacks appeal due to the time commitment required. One approach to encourage clinical informatics training is to integrate it with clinical fellowships in order to confer dual-board eligibility. In this perspective, we describe 3 successful petitions for combined training in clinical informatics in order to support other programs and the American Board of Preventive Medicine in establishing pathways for training subspecialists in clinical informatics.

Clinical decision support tool for phototherapy initiation in preterm infants.

OBJECTIVE: Adherence to guidelines for phototherapy initiation in preterm infants was 39% in our academic NICU (61% of phototherapy was initiated at total bilirubin (TB) levels below recommended thresholds). We hypothesized that adoption of an electronic health record integrated clinical decision support (CDS) tool would improve adherence to phototherapy guidelines. STUDY DESIGN: We developed and implemented Premie BiliRecs (PBR), a novel CDS tool for phototherapy initiation in preterm infants from 27 through 34 weeks postmenstrual age. The primary outcome measure was the proportion of phototherapy initiation events consistent with recommended TB thresholds. RESULT: Following the implementation of PBR, adherence to guidelines for phototherapy initiation in preterm infants increased to 69.8% (p < 0.001), an improvement of 77%. There was no increase in the incidence of severe hyperbilirubinemia nor exchange transfusions. CONCLUSION: The adoption of PBR was associated with improved adherence to phototherapy guidelines in preterm infants without increased adverse events.

Your Patient Has a New Health App? Start With Its Data Source.

Recent regulatory and technological advances have enabled a new era of health apps that are controlled by patients and contain valuable health information. These health apps will be numerous and use novel interfaces that appeal to patients but will likely be unfamiliar to practitioners. We posit that understanding the origin of the health data is the most meaningful and versatile way for physicians to understand and effectively use these apps in patient care. This will allow providers to better support patients and encourage patient engagement in their own care.

Characteristics of the National Applicant Pool for Clinical Informatics Fellowships (2016-2017).

We conducted a national study to assess the numbers and diversity of applicants for 2016 and 2017 clinical informatics fellowship positions. In each year, we collected data on the number of applications that programs received from candidates who were ultimately successful vs. unsuccessful. In 2017, we also conducted an anonymous applicant survey. Successful candidates applied to an average of 4.2 and 5.5 programs for 2016 and 2017, respectively. In the survey, unsuccessful candidates reported applying to fewer programs. Assuming unsuccessful candidates submitted between 2-5 applications each, the total applicant pool numbered 42-69 for 2016 (competing for 24 positions) and 52-85 for 2017 (competing for 30 positions). Among survey respondents (n=33), 24% were female, 1 was black and none were Hispanic. We conclude that greater efforts are needed to enhance interest in clinical informatics among medical students and residents, particularly among women and members of underrepresented minority groups.

Health information exchange policies of 11 diverse health systems and the associated impact on volume of exchange.

BACKGROUND: Provider organizations increasingly have the ability to exchange patient health information electronically. Organizational health information exchange (HIE) policy decisions can impact the extent to which external information is readily available to providers, but this relationship has not been well studied. OBJECTIVE: Our objective was to examine the relationship between electronic exchange of patient health information across organizations and organizational HIE policy decisions. We focused on 2 key decisions: whether to automatically search for information from other organizations and whether to require HIE-specific patient consent. METHODS: We conducted a retrospective time series analysis of the effect of automatic querying and the patient consent requirement on the monthly volume of clinical summaries exchanged. We could not assess degree of use or usefulness of summaries, organizational decision-making processes, or generalizability to other vendors. RESULTS: Between 2013 and 2015, clinical summary exchange volume increased by 1349% across 11 organizations. Nine of the 11 systems were set up to enable auto-querying, and auto-querying was associated with a significant increase in the monthly rate of exchange (P = .006 for change in trend). Seven of the 11 organizations did not require patient consent specifically for HIE, and these organizations experienced a greater increase in volume of exchange over time compared to organizations that required consent. CONCLUSIONS: Automatic querying and limited consent requirements are organizational HIE policy decisions that impact the volume of exchange, and ultimately the information available to providers to support optimal care. Future efforts to ensure effective HIE may need to explicitly address these factors.

Development of a Web-Based Decision Support Tool to Operationalize and Optimize Management of Hyperbilirubinemia in Preterm Infants.

Premie BiliRecs is a novel electronic clinical decision support tool for the management of hyperbilirubinemia in moderately preterm infants less than 35 weeks gestational age. It serves to operationalize and automate current expert consensus-based guidelines, and to aid in the generation of new practice-based evidence to inform future guidelines.

Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children.

INTRODUCTION: Modification of alarm limits is one approach to mitigating alarm fatigue. We aimed to create and validate heart rate (HR) and respiratory rate (RR) percentiles for hospitalized children, and analyze the safety of replacing current vital sign reference ranges with proposed data-driven, age-stratified 5th and 95th percentile values. METHODS: In this retrospective cross-sectional study, nurse-charted HR and RR data from a training set of 7202 hospitalized children were used to develop percentile tables. We compared 5th and 95th percentile values with currently accepted reference ranges in a validation set of 2287 patients. We analyzed 148 rapid response team (RRT) and cardiorespiratory arrest (CRA) events over a 12-month period, using HR and RR values in the 12 hours prior to the event, to determine the proportion of patients with out-of-range vitals based upon reference versus data-driven limits. RESULTS: There were 24,045 (55.6%) fewer out-of-range measurements using data-driven vital sign limits. Overall, 144/148 RRT and CRA patients had out-of-range HR or RR values preceding the event using current limits, and 138/148 were abnormal using data-driven limits. Chart review of RRT and CRA patients with abnormal HR and RR per current limits considered normal by data-driven limits revealed that clinical status change was identified by other vital sign abnormalities or clinical context. CONCLUSIONS: A large proportion of vital signs in hospitalized children are outside presently used norms. Safety evaluation of data-driven limits suggests they are as safe as those currently used. Implementation of these parameters in physiologic monitors may mitigate alarm fatigue. Journal of Hospital Medicine 2015;11:817-823. © 2015 Society of Hospital Medicine.

Early experiences of accredited clinical informatics fellowships.

Since the launch of the clinical informatics subspecialty for physicians in 2013, over 1100 physicians have used the practice and education pathways to become board-certified in clinical informatics. Starting in 2018, only physicians who have completed a 2-year clinical informatics fellowship program accredited by the Accreditation Council on Graduate Medical Education will be eligible to take the board exam. The purpose of this viewpoint piece is to describe the collective experience of the first four programs accredited by the Accreditation Council on Graduate Medical Education and to share lessons learned in developing new fellowship programs in this novel medical subspecialty.

Immunization registries in the EMR Era.

BACKGROUND: The CDC established a national objective to create population-based tracking of immunizations through regional and statewide registries nearly 2 decades ago, and these registries have increased coverage rates and reduced duplicate immunizations. With increased adoption of commercial electronic medical records (EMR), some institutions have used unidirectional links to send immunization data to designated registries. However, access to these registries within a vendor EMR has not been previously reported. PURPOSE: To develop a visually integrated interface between an EMR and a statewide immunization registry at a previously non-reporting hospital, and to assess subsequent changes in provider use and satisfaction. METHODS: A group of healthcare providers were surveyed before and after implementation of the new interface. The surveys addressed access of the California Immunization Registry (CAIR), and satisfaction with the availability of immunization information. Information Technology (IT) teams developed a "smart-link" within the electronic patient chart that provides a single-click interface for visual integration of data within the CAIR database. RESULTS: Use of the tool has increased in the months since its initiation, and over 20,000 new immunizations have been exported successfully to CAIR since the hospital began sharing data with the registry. Survey data suggest that providers find this tool improves workflow and overall satisfaction with availability of immunization data. (p=0.009). CONCLUSIONS: Visual integration of external registries into a vendor EMR system is feasible and improves provider satisfaction and registry reporting.

Neonatal Informatics: Optimizing Clinical Data Entry and Display.

Displaying the vast amount of clinical data that exist in electronic medical records without causing information overload or interfering with provider thought processes is a challenge. To support the transformation of data into information and knowledge, effective electronic displays must be flexible and guide physicians' thought processes. Applying research from cognitive science and human factors engineering offers promise in improving the electronic display of clinical information. OBJECTIVES: After completing this article, readers should be able to: Appreciate the importance of supporting provider thought processes during both data entry and data review.Recognize that information does not need to be displayed and reviewed in the same way the data are entered.

Impact of an EMR-Based Daily Patient Update Letter on Communication and Parent Engagement in a Neonatal Intensive Care Unit.

OBJECTIVE: To evaluate the impact of using electronic medical record (EMR) data in the form of a daily patient update letter on communication and parent engagement in a level II neonatal intensive care unit (NICU). STUDY DESIGN: Parents of babies in a level II NICU were surveyed before and after the introduction of an EMR-generated daily patient update letter, Your Baby's Daily Update (YBDU). RESULTS: Following the introduction of the EMR-generated daily patient update letter, 89% of families reported using YBDU as an information source; 83% of these families found it "very useful", and 96% of them responded that they "always" liked receiving it. Rates of receiving information from the attending physician were not statistically significantly different pre- and post-implementation, 81% and 78%, respectively (p = 1). Though there was no statistically significant improvement in parents' knowledge of individual items regarding the care of their babies, a trend towards statistical significance existed for several items (p <.1), and parents reported feeling more competent to manage information related to the health status of their babies (p =.039). CONCLUSION: Implementation of an EMR-generated daily patient update letter is feasible, resulted in a trend towards improved communication, and improved at least one aspect of parent engagement-perceived competence to manage information in the NICU.

Neonatal Informatics: Transforming Neonatal Care Through Translational Bioinformatics.

The future of neonatal informatics will be driven by the availability of increasingly vast amounts of clinical and genetic data. The field of translational bioinformatics is concerned with linking and learning from these data and applying new findings to clinical care to transform the data into proactive, predictive, preventive, and participatory health. As a result of advances in translational informatics, the care of neonates will become more data driven, evidence based, and personalized.

Neonatal Informatics: Computerized Physician Order Entry.

Computerized physician order entry (CPOE) is the feature of electronic medical record (EMR) implementation that arguably offers the greatest quality and patient safety benefits. The gains are potentially greater for critically ill neonates, but the effect of CPOE on quality and safety is dependent upon local implementation decisions. OBJECTIVES: After completing this article, readers should be able to: Define the basic aspects of CPOE and clinical decision support (CDS) systems.Describe the potential benefits of implementing CPOE associated with CDS in a neonatal intensive care unit (NICU).