Impact of the COVID-19 Pandemic on People Living With Rare Diseases and Their Families: Results of a National Survey.

BACKGROUND: With more than 103 million cases and 1.1 million deaths, the COVID-19 pandemic has had devastating consequences for the health system and the well-being of the entire US population. The Rare Diseases Clinical Research Network funded by the National Institutes of Health was strategically positioned to study the impact of the pandemic on the large, vulnerable population of people living with rare diseases (RDs). OBJECTIVE: This study was designed to describe the characteristics of COVID-19 in the RD population, determine whether patient subgroups experienced increased occurrence or severity of infection and whether the pandemic changed RD symptoms and treatment, and understand the broader impact on respondents and their families. METHODS: US residents who had an RD and were <90 years old completed a web-based survey investigating self-reported COVID-19 infection, pandemic-related changes in RD symptoms and medications, access to care, and psychological impact on self and family. We estimated the incidence of self-reported COVID-19 and compared it with that in the US population; evaluated the frequency of COVID-19 symptoms according to self-reported infection; assessed infection duration, complications and need for hospitalization; assessed the influence of the COVID-19 pandemic on RD symptoms and treatment, and whether the pandemic influenced access to care, special food and nutrition, or demand for professional psychological assistance. RESULTS: Between May 2, 2020, and December 15, 2020, in total, 3413 individuals completed the survey. Most were female (2212/3413, 64.81%), White (3038/3413, 89.01%), and aged ≥25 years (2646/3413, 77.53%). Overall, 80.6% (2751/3413) did not acquire COVID-19, 2.08% (71/3413) acquired it, and 16.58% (566/3413) did not know. Self-reported cases represented an annual incidence rate of 2.2% (95% CI 1.7%-2.8%). COVID-19 cases were more than twice the expected (71 vs 30.3; P<.001). COVID-19 was associated with specific symptoms (loss of taste: odds ratio [OR] 38.9, 95% CI 22.4-67.6, loss of smell: OR 30.6, 95% CI 17.7-53.1) and multiple symptoms (>9 symptoms vs none: OR 82.5, 95% CI 29-234 and 5-9: OR 44.8, 95% CI 18.7-107). Median symptom duration was 16 (IQR 9-30) days. Hospitalization (7/71, 10%) and ventilator support (4/71, 6%) were uncommon. Respondents who acquired COVID-19 reported increased occurrence and severity of RD symptoms and use or dosage of select medications; those who did not acquire COVID-19 reported decreased occurrence and severity of RD symptoms and use of medications; those who did not know had an intermediate pattern. The pandemic made it difficult to access care, receive treatment, get hospitalized, and caused mood changes for respondents and their families. CONCLUSIONS: Self-reported COVID-19 was more frequent than expected and was associated with increased prevalence and severity of RD symptoms and greater use of medications. The pandemic negatively affected access to care and caused mood changes in the respondents and family members. Continued surveillance is necessary.

Dynamic use of historical controls in clinical trials for rare disease research: A re-evaluation of the MILES trial.

BACKGROUND: Randomized controlled trials offer the best design for eliminating bias in estimating treatment effects but can be slow and costly in rare disease research. Additionally, an equal randomization approach may not be optimal in studies in which prior evidence of superiority of one or more treatments exist. Supplementing prospectively enrolled, concurrent controls with historical controls can reduce recruitment requirements and provide patients a higher likelihood of enrolling in a new and possibly superior treatment arm. Appropriate methods need to be employed to ensure comparability of concurrent and historical controls to minimize bias and variability in the treatment effect estimates and reduce the chances of drawing incorrect conclusions regarding treatment benefit. METHODS: MILES was a phase III placebo-controlled trial employing 1:1 randomization that led to US Food and Drug Administration approval of sirolimus for treating patients with lymphangioleiomyomatosis. We re-analyzed the MILES trial data to learn whether substituting concurrent controls with controls from a historical registry could have accelerated subject enrollment while leading to similar study conclusions. We used propensity score matching to identify exchangeable historical controls from a registry balancing the baseline characteristics of the two control groups. This allowed more new patients to be assigned to the sirolimus arm. We used trial data and simulations to estimate key outcomes under an array of alternative designs. RESULTS: Borrowing information from historical controls would have allowed the trial to enroll fewer concurrent controls while leading to the same conclusion reached in the trial. Simulations showed similar statistical performance for borrowing as for the actual trial design without producing type I error inflation and preserving power for the same study size when concurrent and historical controls are comparable. CONCLUSION: Substituting concurrent controls with propensity score-matched historical controls can allow more prospectively enrolled patients to be assigned to the active treatment and enable the trial to be conducted with smaller overall sample size, while maintaining covariate balance and study power and minimizing bias in response estimation. This approach does not fully eliminate the concern that introducing non-randomized historical controls in a trial may lead to bias in estimating treatment effects, and should be carefully considered on a case-by-case basis. Borrowing historical controls is best suited when conducting randomized controlled trials with conventional designs is challenging, as in rare disease research. High-quality data on covariates and outcomes must be available for candidate historical controls to ensure the validity of these designs. Additional precautions are needed to maintain blinding of the treatment assignment and to ensure comparability in the assessment of treatment safety.MILES ClinicalTrials.gov Number: NCT00414648.

Lung Transplantation Advanced Prediction Tool: Determining Recipient's Outcome for a Certain Donor.

BACKGROUND: Many risk-prediction models for lung transplantation are centered on recipient characteristics and do not account for impact of donor and transplant-related factors or only examine short-term outcomes (eg, predicted 1-y survival). We sought to develop a comprehensive model guiding recipient-donor matching. METHODS: We identified double lung transplant recipients (≥12 y old) in the United Network for Organ Sharing Registry (2005-2020) to develop a risk scoring tool. Cohort was divided into derivation and validation sets. A total of 42 recipient, donor, and transplant factors were included in the analysis. Lasso method was used for variable selection. Survival was estimated using Cox-proportional hazard models. An interactive web-based tool was developed for clinical use. RESULTS: A derivation cohort (n = 10 660) informed the model with 13-recipient, 4-donor, and 2-transplant variables. Adjusted risk scores were computed for every transplant and grouped into 3 clusters. Model-estimated survival probabilities were similar to the observed in the validation cohort (n = 4464) for all clusters. The mortality increases for medium- and high-risk groups was similar in both derivation and validation cohorts (C statistics for 1-, 5-, and 10-y survival were 0.67, 0.64, and 0.72, respectively). The web-based application estimated 1-, 5-, 10-y survival and half-life for low- (92%, 73%, 52%; 10.5 y), medium- (89%, 62%, 38%; 7.3 y), and high-risk clusters (85%, 52%, 26%; 5.2 y). CONCLUSIONS: Advanced methods incorporating machine/deep learning led to a risk scoring model (including recipient, donor, and transplant factors) and a web-based clinical tool providing short- and long-term survival probabilities for recipient-donor matches. This will enable risk-based matching that could improve utilization of and benefit from a limited donor pool.

The Geospatial Distribution of Myositis and Its Phenotypes in the United States and Associations With Roadways: Findings From a National Myositis Patient Registry.

Background: Little is known about the spatial distribution of idiopathic inflammatory myopathies (IIM) in the United States (U.S.), or their geospatial associations. Methods: We studied a national myositis patient registry, with cases diagnosed in the contiguous U.S. from 1985-2011 and comprised of dermatomyositis (DM, n = 484), polymyositis (PM, n = 358), and inclusion body myositis (IBM, n = 318) patients. To assess the association of myositis prevalence with distance from roads, we employed log-Gaussian Cox process models, offset with population density. Results: The U.S. IIM case distribution demonstrated a higher concentration in the Northest. DM, IBM, and cases with lung disease were more common in the East, whereas PM cases were more common in the Southeast. One area in the West and one area in the South had a significant excess in cases of DM relative to PM and of cases with lung disease relative to those without lung disease, respectively. IIM cases tended to cluster, with between-points interactions more intense in the Northeast and less in the South. There was a trend of a higher prevalence of IIM and its major phenotypes among people living within 50 m of a roadway relative to living beyond 200 m. Demographic characteristics, rural-urban commuting area, and female percentage were significantly associated with the prevalence of IIM and with major phenotypes. Conclusions: Using a large U.S. database to evaluate the spatial distribution of IIM and its phenotypes, this study suggests clustering in some regions of the U.S. and a possible association of proximity to roadways.

Impact of the Covid-19 epidemic on a US sample of patients with myasthenia gravis.

Introduction: The Covid-19 pandemic has devastated the world and demonstrated the inadequacy of health care in the United States. To assess its impact, the Rare Disease Clinical Research Network conducted a survey to assess the pandemic on the rare disease community of patients, including those with myasthenia gravis (MG). Methods: A cross-sectional survey was designed to target people or their care givers who live in the United States, have a rare disease, and are under 90 years of age. Respondents logged onto a dedicated web page and completed the survey online, which requested demographic, disease-specific, drug treatment, and symptom information as well as assessment of Covid-19 impact on them. The survey was open from May 2020 to December 2020. Results: Five hundred ninety-four with self-reported myasthenia gravis completed the survey, which was the largest number of respondents. Sixty percent of respondents were women with a mean age of 60 years. Eighty-nine percent identified as White. Respondents did not appreciate a worsening of symptoms after the pandemic. Only 7 respondents reported the diagnosis of Covid-19 but 11% indicated they had difficulty accessing care at the time of the survey. Discussion and Conclusion: Patients with MG complained of worse access to medical care during the early months of the pandemic, including challenges in diagnosis of suspected Covid-19 infection. A major limitation of the survey is its inability to access minority populations. Nevertheless, the results of the Rare Disease Clinical Research Network (RCDRN) survey of patients with MG provide clear evidence that the pandemic has demonstrated the deficiencies in US healthcare.

Impact of Covid-19 Pandemic on Patients with Myasthenia Gravis Deeper understanding of the consequences of the Covid-19 pandemic on people with rare diseases is critically important in order to enhance health care in the future. The Rare Disease Clinical Research Network (RDCRN) performed a web-based survey of individuals with rare diseases in the first year of the pandemic utilizing questions to assess the impact of the pandemic on their symptoms, access to healthcare, and medication use. Five hundred and ninety-four respondents reported having myasthenia gravis (MG). The average age was 60 years and 60% were women. Nearly ninety percent were White. A large minority indicated difficulty accessing health care and nearly a third used telemedicine. Only seven respondents indicated a diagnosis of Covid-19 but many more had symptoms consistent with infection. Overall, there was no increase in symptoms of MG after the beginning of the pandemic. The pandemic has demonstrated the deficiencies in US healthcare, and these are appreciated in the results of the RCDRN survey of patients with MG. The RDCRN will continue to survey the rare disease community to understand the ongoing impact of the Covid-19 pandemic.

Quality Improvement Initiative to Improve Healthcare Providers' Attitudes towards Mothers with Opioid Use Disorder.

INTRODUCTION: Individuals with opioid use disorder often report feelings of shame and describe feeling judged negatively. These feelings are especially true for pregnant women with opioid use disorder. The Ohio Perinatal Quality Collaborative conducted a multimodal quality improvement initiative for infants born with Neonatal Abstinence Syndrome (NAS). An important component of the project was focused on improving staff attitudes toward mothers of infants with NAS. METHODS: The Ohio Perinatal Quality Collaborative implemented an education program for healthcare providers at 39 participating hospital units regarding opioid use as a chronic disease and principles of nonjudgmental, trauma-informed care. Healthcare providers partnered with the mother of infants with NAS in the care of the infant and connected with local community resources. This work was a subcomponent of an overall multimodal quality improvement project. Healthcare provider attitudes were measured with the "Attitude Measurement: Brief Scales" questionnaire anonymously, at 3 different time points throughout the project. Attitude change was measured by pretraining and posttraining scores. ANOVA methods were used to compare individual items and a summary score across the 3 surveys. RESULTS: Summary scores improved significantly from 18.99 at baseline (January-March 2014) to 19.94 (P < 0.0001) in February 2015 and were maintained at 20.05 in July 2016. CONCLUSIONS: A nonjudgmental attitude toward mothers of infants with NAS is an important component of compassionate care. Improving healthcare provider attitudes can benefit a mother of an infant with NAS and help preserve the mother-infant dyad.

Respiratory Colonization and Short-Term Temporal Changes in the Urinary Metabolome of Children.

The human metabolome may vary based on age, over time, and in the presence of viral carriage and bacterial colonization-a common scenario in children. We used nuclear magnetic resonance spectroscopy to identify and quantify urinary metabolites of children without signs or symptoms of respiratory illness. A urine sample and two nasopharyngeal swabs were collected to test for respiratory viral pathogens and colonization by Streptococcus pneumoniae (Sp). Urine samples were collected at the initial visit, 24 h post-enrollment, and 10-14 days post-enrollment. Of the 122 children enrolled, 24% had a virus detected and 19.7% had Sp detected. Intraclass correlation coefficients demonstrated greater within-subject versus between-subject variability for all metabolites detected. In linear mixed models adjusted for age, time, history of asthma, Sp, and viruses, 1-methylnicotinamide was increased by 50% in children with Sp and decreased by 35% in children with rhinovirus/enterovirus. Children with Sp had 83% higher levels of trimethylamine-N-oxide compared with those without Sp. However, when adjusting for multiple comparisons, the association was no longer statistically significant. In conclusion, there appear to be short-term changes within the urinary metabolome of healthy children, but levels of metabolites did not statistically differ in children with viral carriage or Sp detected.

The psychosocial work environment, musculoskeletal disorders and their functional consequences among pediatric healthcare providers.

OBJECTIVE: The goal of this study was to examine the association between aspects of the psychosocial work environment and prevalence of musculoskeletal disorders (MSDs) and associated functional consequences among pediatric healthcare providers. BACKGROUND: The psychosocial work demands make pediatric care providers susceptible to MSDs and subsequent functional consequences, but research on this at-risk group is lacking. METHODS: Randomly selected pediatric registered nurses, behavioral health specialists, and patient care assistants (N = 569) completed a survey assessing psychosocial factors, MSDs, and functional consequences (e.g., missing work). Logistic regression was used to assess associations between psychosocial factors and outcomes. RESULTS: The analysis yielded moderate-to-strong, significant associations between psychosocial environment factors and MSDs and their functional consequences. The odds of MSDs increased nearly three-fold in the highest quartile of the psychosocial summary score vs. the lowest (OR: 2.7, 95% CI: 1.6-4.5). The highest quartiles of the psychosocial environment measures were significantly associated with functional consequences of MSDs. CONCLUSION: Results confirm knowledge about the association between the psychosocial environment and MSDs and demonstrates the association also exists among pediatric providers. Our study highlights the importance of studying the functional consequences of MSDs, which characterize the impact of MSD burden at work and elsewhere.

Effectiveness of a Universally Offered Chlamydia and Gonorrhea Screening Intervention in the Pediatric Emergency Department.

PURPOSE: Adolescents represent more than half of the newly diagnosed sexually transmitted infections in the U.S. annually. Emergency departments (EDs) may serve as an effective, nontraditional setting to screen for chlamydia/gonorrhea (CT/GC). The objective was to evaluate the effectiveness of a universally offered CT/GC screening program in two pediatric ED settings. METHODS: This was a prospective, delayed start pragmatic study conducted over 18 months in two EDs within the same academic institution among ED adolescents aged 14-21 years with any chief complaint. Using a tablet device, adolescents were confidentially informed of CT/GC screening recommendations and were offered screening. If patients agreed to CT/GC testing, a clinical decision support tool was triggered to inform the provider and order testing. The main and key secondary outcomes were the proportion of CT/GC testing and positive CT/GC test results in each respective ED. RESULTS: Both EDs experienced modest but statistically significant increases in CT/GC testing post- versus pre-intervention (main: 11.5% vs. 7.9%; confidence interval [CI]: 2.9-4.2; p < .0001 and satellite: 3.8% vs. 2.6%; 95% CI: .7-1.7; p < .0001). Among those tested, the positivity rate at the main ED did not significantly change post- versus pre-intervention (24.1% vs. 23.2%; 95% CI: -1.9 to 3.8; p = .71) but significantly decreased at the satellite ED (7.6% vs. 14.8%; 95% CI: -12.2 to -2.2; p = .01). CONCLUSIONS: A universally offered screening intervention increased the proportion of adolescents who were tested at both EDs and the detection rates for CT/GC at the main ED, but patient acceptance of screening was low.

The Management of Health Hazards Related to Municipal Solid Waste on Fire in Europe: An Environmental Justice Issue?

Landfilling should be the last option in an integrated Municipal Solid Waste (MSW) management approach. In the European Union (EU), the policy framework to protect the environment and the public health against the impact of health hazards related to urban solid waste management has been consistently implemented in recent decades. A growing interest in the negative impact of fires in waste landfills on the environment and people's health was reported in some European countries. In Italy, an increasing occurrence of arsons in MSW and landfills has been reported in recent years. During the summer of 2012, a multi-site arson occurred in the Palermo Municipal solid waste landfill of Bellolampo (western Sicily), giving rise to an environmental emergency of public health concern. Local health authorities reacted by creating an inter-institutional multidisciplinary task force with the aim to implement measures to prevent and control the risk of exposure by delimiting a protection area to be taken under strict monitoring. Environmental and epidemiological investigations were put in place by air, soil, and farm product sampling. A syndromic surveillance of the exposed population was conducted as well. The air monitoring stations system in place detected an increase in the concentrations of dioxins and dioxin-like substances with the PM10 highest emission pick documented within the first 24 h and estimated at about 60 µg/m3. Levels of heavy metals above the limits permitted by law were detected in the top- and sub-soil samples collected within the two landfill sampling sites and also in other nearby sites. Non-conforming concentration values of dioxins and dioxin-like substances were detected in samples taken from farms, milk, and water. The health syndromic surveillance did not document any daily increase in the notification of emergency admissions related to acute respiratory diseases or any other health effect potentially related to the waste arson, but these findings were limited by the non-systematic collection of data. The experience reported in the present case report, as declined within the European Union policy framework and in the view of environmental justice, documented the need to structure a permanent collaboration between the different institutional actors involved in environmental and public health protection activities in order to develop specific protocols to manage events related to the occurrence of waste-related environmental emergencies or disasters.

Orchestrated Testing of Formula Type to Reduce Length of Stay in Neonatal Abstinence Syndrome.

BACKGROUND: Despite the standardization of care, formula feeding varied across sites of the Ohio Perinatal Quality Collaborative (OPQC). We used orchestrated testing (OT) to learn from this variation and improve nonpharmacologic care of infants with neonatal abstinence syndrome (NAS) requiring pharmacologic treatment in Ohio. METHODS: To test the impact of formula on length of stay (LOS), treatment failure, and weight loss among infants hospitalized with NAS, we compared caloric content (high versus standard) and lactose content (low versus standard) using a 22 factorial design. During October 2015 to June 2016, OPQC sites joined 1 of 4 OT groups. We used response plots to examine the effect of each factor and control charts to track formula use and LOS. We used the OT results to revise the nonpharmacologic bundle and implemented it during 2017. RESULTS: Forty-seven sites caring for 546 NAS infants self-selected into the 4 OT groups. Response plots revealed the benefit of high-calorie formula (HCF) on weight loss, treatment failure, and LOS. The nonpharmacologic treatment bundle was updated to recommend HCF when breastfeeding was not possible. During implementation, HCF use increased, and LOS decreased from 17.1 to 16.4 days across the OPQC. CONCLUSIONS: OT revealed that HCF was associated with shorter LOS in OPQC sites. Implementation of a revised nonpharmacologic care bundle was followed by additional LOS improvement in Ohio. Despite some challenges in the implementation of OT, our findings support its usefulness for learning in improvement networks.

Information Technology-Assisted Screening for Gonorrhea and Chlamydia in a Pediatric Emergency Department.

PURPOSE: The aim of the study was to design and implement a novel, universally offered, computerized clinical decision support (CDS) gonorrhea and chlamydia (GC/CT) screening tool embedded in the emergency department (ED) clinical workflow and triggered by patient-entered data. METHODS: The study consisted of the design and implementation of a tablet-based screening tool based on qualitative data of adolescent and parent/guardian acceptability of GC/CT screening in the ED and an advisory committee of ED leaders and end users. The tablet was offered to adolescents aged 14-21 years and informed patients of Centers for Disease Control and Prevention GC/CT screening recommendations, described the testing process, and assessed whether patients agreed to testing. The tool linked to CDS that streamlined the order entry process. The primary outcome was the patient capture rate (proportion of patients with tablet data recorded). The secondary outcomes included rates of patient agreement to GC/CT testing and provider acceptance of the CDS. RESULTS: Outcomes at the main and satellite EDs, respectively, were as follows: 1-year patient capture rates were 64.6% and 64.5%; 9.9% and 4.4% of patients agreed to GC/CT testing, and of those, the provider ordered testing for 73% and 72%. CONCLUSIONS: Implementation of this computerized screening tool embedded in the clinical workflow resulted in patient capture rates of almost two-thirds and clinician CDS acceptance rates >70% with limited patient agreement to testing. This screening tool is a promising method for confidential GC/CT screening among youth in an ED setting. Additional interventions are needed to increase adolescent agreement for GC/CT testing.

Propensity score analysis for correlated subgroup effects.

As individuals may respond differently to treatment, estimating subgroup effects is important to understand the characteristics of individuals who may benefit. Factors that define subgroups may be correlated, complicating evaluation of subgroup effects, especially in observational studies requiring control of confounding variables. We address this problem when propensity score methods are used for confounding control. A common practice is to evaluate candidate subgroup identifiers one at a time without adjusting for other candidate identifiers. We show that this practice can be misleading if the treatment effect modification attributed to a candidate identifier is in truth due to the effect of other correlated true effect modifiers. Whereas jointly analyzing multiple identifiers provides estimates of the desired subgroup effects adjusted for the effects of the other identifiers, it requires the propensity scores to adequately reflect the underlying treatment selection processes and balance the covariates within each subgroup of interest. Satisfying the requirement in practice is hard since the number of strata may increase quickly, while the per stratum sample size may decrease dramatically. A practically helpful approach is utilizing the whole cohort for the propensity score estimation with modeling of interaction terms to reflect the potentially different treatment selection processes across strata. We empirically examine the performance of the whole cohort approach by itself and with subjecting the interaction terms to variable selection. Our results using both simulations and real data analysis suggest that the whole cohort approach should explore inclusion of high-order interactions in the propensity score model to ensure adequate covariate balance across strata, and that variable selection is of limited utility.

Do emissions from landfill fires affect pregnancy outcomes? A retrospective study after arson at a solid waste facility in Sicily.

OBJECTIVES: In response to public health concern about effects of arson at solid waste management plants in July 2012, we analysed vital statistics data to evaluate any potential effect on pregnancies at different gestational ages of pollutants emitted from the landfill on fire. SETTING: A community living near the largest landfill plant in Sicily. PARTICIPANTS: The study group comprised 551 births, live births and stillbirths from pregnancies of mothers residing in the extra-urban exposed area, conceived during a 40 week period during which the highest fire's peak might have influenced pregnancy. PRIMARY AND SECONDARY OUTCOME MEASURES: Birth outcomes (gestational age <37 and <32 weeks, low birth weight, very low birth weight and small for gestational age) in the study group were compared with the ones of a reference group of women residing in areas of Sicily with similarly low population density and industrial development. RESULTS: Among singleton live births we observed a three-fold increase in risk of very preterm birth between the extra-urban area and the remaining low inhabitants density and unindustrialised areas for births whose pregnancies were in the third trimester (OR adjusted for maternal age and infant gender=3.41; 95% CI 1.04 to 11.16). There was an excess of very low birth weight singleton infants in the study group as compared with the reference group, which was limited to births to mothers exposed during periconception period (OR adjusted for maternal age and infant gender=4.64; 95% CI 1.04 to 20.6) and first trimester (OR adjusted for maternal age and infant gender=3.66; 95% CI 1.11 to 12.1). The association estimates were imprecise due to the small number of outcomes recorded. CONCLUSIONS: The study documented an excess of very preterm and very low birth weight among infants born to mothers exposed to the landfill fire emissions during conception or early pregnancy.

Parental Adverse Childhood Experiences and Pediatric Healthcare Use by 2 Years of Age.

OBJECTIVE: To determine whether maternal and paternal exposure to adverse childhood experiences (ACEs) has an association with offspring healthcare use by 2 years of age. STUDY DESIGN: A retrospective cohort study was performed on 454 patients at a large suburban pediatric primary care practice whose mother (n = 374) or father (n = 156) or both (n = 123) completed an ACE survey between October 2012 and June 2014. The association between self-reported parental ACEs and healthcare use by 2 years of age, including number of missed well-child visits, sick visits, and delayed or missed immunizations, was modeled using multivariable negative binomial regression. All analyses adjusted for child sex, payer source, and preterm birth. RESULTS: Maternal, but not paternal, ACE exposure was significantly associated with missed well-child visits by 2 years of age. For each additional maternal ACE, there was a significant 12% increase in the incidence rate of missed well-child visits (relative risk, 1.12; 95% CI, 1.03-1.22; P = .010). Maternal and paternal ACE scores were not significantly associated with increased sick visits or delayed or missed immunizations. CONCLUSIONS: The ACE exposure of mothers is negatively associated with adherence to preventive healthcare visits among their children early in life. Future research is needed to elucidate the mechanisms of this association and to develop and implement family-based intervention strategies.

Enhancing the detection of injuries and near-misses among patient care staff in a large pediatric hospital.

Objectives Compared to other industries, healthcare has one of the highest rates of non-fatal occupational injury/illness. Evidence indicates these rates are underestimated, highlighting the need for improved injury surveillance. This study aims to demonstrate the feasibility of integrating active data collection in a passive injury surveillance system to improve detection of injuries in a healthcare establishment. Methods Using digital voice recorders (DVR), pediatric healthcare providers prospectively recorded events throughout their shift for two weeks. This sample-based active injury surveillance was then integrated into an institutional surveillance system (ISS) centered on passive data collection initiated by employee reports. Results Injuries reported using DVR during two-week intervals from February 2014 to July 2015 were 40.7 times more frequent than what would be expected on the basis of the usual ISS reports. Psychological injuries (eg, stress, conflict) and near-misses were captured at a rate of 16.1 per 1000 days [95% confidence interval (CI) 14.1-18.3] and 35.6 per 1000 days (95% CI 32.7-38.8), respectively. Finally, 68% (95% CI 65-72%) of participants preferred using DVR either as an alternative or complement to the existing ISS. Conclusions This study showed that it is feasible to improve injury surveillance in a healthcare establishment by integrating active data collection based on voice recording within a passive injury surveillance system. Enhanced surveillance provides richer information that can guide the development of effective injury prevention strategies.

Ohio Perinatal Quality Collaborative Improves Care of Neonatal Narcotic Abstinence Syndrome.

OBJECTIVES: Neonatal abstinence syndrome (NAS) after an infant's in-utero exposure to opioids has increased dramatically in incidence. No treatment standards exist, leading to substantial variations in practice, degree of opioid exposure, and hospital length of stay. METHODS: The Ohio Perinatal Quality Collaborative conducted an extensive multi-modal quality improvement initiative with the goal to (1) standardize identification, nonpharmacologic and pharmacologic treatment in level-2 and 3 NICUs in Ohio, (2) reduce the use of and length of treatment with opioids, and (3) reduce hospital length of stay in pharmacologically treated newborns with NAS. RESULTS: Fifty-two of 54 (96%) Ohio NICUs participated in the collaborative. Compliance with the nonpharmacologic bundle improved from 37% to 59%, and the pharmacologic bundle improved from 59% to 68%. Forty-eight percent of the 3266 opioid-exposed infants received pharmacologic treatment of symptoms of NAS, and this rate did not change significantly across the time period. Regardless of the opioid used to pharmacologically treat infants with NAS, the length of treatment decreased from 13.4 to 12.0 days, and length of stay decreased from 18.3 to 17 days. CONCLUSIONS: Standardized approaches to the identification and nonpharmacologic and pharmacologic care were associated with a reduced length of opioid exposure and hospital stay in a large statewide collaborative. Other states and institutions treating opioid-exposed infants may benefit from the adoption of these practices.

Parental Adverse Childhood Experiences and Offspring Development at 2 Years of Age.

OBJECTIVES: The study objective was to determine if maternal and paternal exposure to adverse childhood experiences (ACEs) have a significant association with negative offspring development at 24 months of age in a suburban pediatric primary care population. METHODS: A retrospective cohort study was conducted of 311 mother-child and 122 father-child dyads who attended a large pediatric primary care practice. Children were born from October 2012 to June 2014, and data were collected at the 2-, 4-, and 24-month well-child visits. Multivariable Poisson regression with robust error variance was used to model the relationship between self-reported parental ACEs and the outcomes of suspected developmental delay at 24 months and eligibility for early intervention services. RESULTS: For each additional maternal ACE, there was an 18% increase in the risk for a suspected developmental delay (relative risk: 1.18, 95% confidence interval: 1.08-1.29). A similar trend was observed for paternal ACEs (relative risk: 1.34, 95% confidence interval: 1.07-1.67). Three or more maternal ACEs (versus <3 ACEs) was associated with a significantly increased risk for a suspected developmental delay that affected multiple domains. Similar effects were observed for early intervention services. CONCLUSIONS: Parental ACE exposures can negatively impact child development in multiple domains, including problem solving, communication, personal-social, and motor skills. Research is needed to elucidate the psychosocial and biological mechanisms of intergenerational risk. This research has implications for the value of parental ACE screening in the context of pediatric primary care.

Accounting for misclassification bias of binary outcomes due to underscreening: a sensitivity analysis.

BACKGROUND: Diagnostic tests are performed in a subset of the population who are at higher risk, resulting in undiagnosed cases among those who do not receive the test. This poses a challenge for estimating the prevalence of the disease in the study population, and also for studying the risk factors for the disease. METHODS: We formulate this problem as a missing data problem because the disease status is unknown for those who do not receive the test. We propose a Bayesian selection model which models the joint distribution of the disease outcome and whether testing was received. The sensitivity analysis allows us to assess how the association of the risk factors with the disease outcome as well as the disease prevalence change with the sensitivity parameter. RESULTS: We illustrated our model using a retrospective cohort study of children with asthma exacerbation that were evaluated for pneumonia in the emergency department. Our model found that female gender, having fever during ED or at triage, and having severe hypoxia are significantly associated with having radiographic pneumonia. In addition, simulation studies demonstrate that the Bayesian selection model works well even under circumstances when both the disease prevalence and the screening proportion is low. CONCLUSION: The Bayesian selection model is a viable tool to consider for estimating the disease prevalence and in studying risk factors of the disease, when only a subset of the target population receive the test.