Clinical outcomes in critically ill children on extracorporeal membrane oxygenation with severe thrombocytopenia.

INTRODUCTION: As international guidelines suggest keeping the platelet count between 50 and 100 × 109 cells/L in children on extracorporeal membrane oxygenation (ECMO), platelet transfusions are administered to two-thirds of ECMO days, and up to 70% of these patients still bleed. We aim to describe outcomes in critically ill children who develop severe thrombocytopenia on ECMO. METHODS: Single-center retrospective study, enrolling critically ill children on ECMO admitted at Children's Memorial Hermann, TX, between 1/2018 and 12/2022, with at least one platelet count below 50 × 109 cells/L (severe thrombocytopenia). Platelet counts were measured four times a day. We report platelet transfusion, bleeding, hemolysis, and clotting events within 6 h after transfusion, as well as ECMO duration and mortality. RESULTS: We enrolled 54 patients representing 337 ECMO days and 1190 platelet counts. Median weight was 3.7 kg and 54% were male. Severe thrombocytopenia was observed in 56% of platelet counts. Severe thrombocytopenia was not associated with bleeding in the subsequent 6 h (18% vs 20%, p = .95), but was associated with more frequent platelet transfusions (18% vs 11%, p = .001). There was no correlation between time spent with severe thrombocytopenia and the duration of ECMO (R2 = 0.03). While the time spent with severe thrombocytopenia was not associated with on-ECMO mortality rate (p = .36), there was an association with in-hospital mortality rate (p = .003). CONCLUSIONS: Our results indicate a restrictive platelet transfusion strategy is not associated with higher proportions of subsequent bleeding, duration of ECMO, or on-ECMO mortality rate. Multicenter studies are needed to evaluate further the appropriateness of this strategy.

A general framework for subgroup detection via one-step value difference estimation.

Recent statistical methodology for precision medicine has focused on either identification of subgroups with enhanced treatment effects or estimating optimal treatment decision rules so that treatment is allocated in a way that maximizes, on average, predefined patient outcomes. Less attention has been given to subgroup testing, which involves evaluation of whether at least a subgroup of the population benefits from an investigative treatment, compared to some control or standard of care. In this work, we propose a general framework for testing for the existence of a subgroup with enhanced treatment effects based on the difference of the estimated value functions under an estimated optimal treatment regime and a fixed regime that assigns everyone to the same treatment. Our proposed test does not require specification of the parametric form of the subgroup and allows heterogeneous treatment effects within the subgroup. The test applies to cases when the outcome of interest is either a time-to-event or a (uncensored) scalar, and is valid at the exceptional law. To demonstrate the empirical performance of the proposed test, we study the type I error and power of the test statistics in simulations and also apply our test to data from a Phase III trial in patients with hematological malignancies.

Health of Post-Institutionalized Haitian Children Adopted to the United States.

OBJECTIVES: Haiti remains a principal placement country for intercountry adoptees to the United States. This project reports the health status of children adopted from Haiti arriving to the U.S. and compares them to intercountry adoptees from other regions. METHODS: A retrospective chart review was conducted of adoptees placed in the U.S. from Haiti (n=87), age and sex matched with intercountry adoptees placed in the U.S. from Asia (n=87) and Latin America (n=87) between January 2010 and November 2019. Data on immunization status, contagious diseases, and nutrition and growth were analyzed via linear, logistic, and multinomial regression. RESULTS: After adjusting for age, sex, and standardized height, children adopted from Haiti, compared to adoptees from Latin America and Asia, demonstrated a lack of immunity to hepatitis B (OR=5.89;6.87), increased immunity to hepatitis A (OR=0.38;0.30), infection by two or more parasites (OR=8.43;38.48), high lead levels (OR=23.79;7.04), and anemia (OR=15.25;9.18). Unexpectedly, children adopted from Haiti had greater standardized height (-1.28 vs. -1.82 and -2.13) and standardized weight (-0.32 vs. -0.57 and -1.57) than their counterparts from Latin America and Asia. CONCLUSIONS: Children adopted from Haiti face complex medical challenges undoubtedly related to the country's low socioeconomic status (SES) and the impact of recurrent natural disasters and governmental neglect on public health infrastructure. Appropriate care is critical in preventing and avoiding transmission of infectious diseases in adoptees and family members. The high incidence of anemia and elevated lead levels may further exacerbate the developmental effects of early institutional deprivation.

Applying a Social Determinants of Health Approach to the Opioid Epidemic.

Ohio is one of the hardest-hit states in the United States when it comes to opioid overdose deaths. Confronted with over 4,000 opioid overdose deaths in 2017, the Ohio Department of Mental Health and Addiction Services launched the Community Collective Impact Model for Change (CCIM4C) initiative to encourage 12 Ohio counties to think more deeply about primary prevention. By moving upstream and taking a look at the causes of the opioid crisis, the counties involved in the CCIM4C initiative were able to expand the range of potential partners and potential solutions, moving from emergency response alone to broader efforts to support social connection, economic security, and other social determinants of health. Each county brought together a wide array of partners, including local employers, community colleges, health care organizations, faith leaders, youth-serving organizations, first responders, librarians, school board members, public health officials, parks and recreation staff, and people with lived experience. This article focuses on the efforts of three counties-Ashtabula, Lorain, and Lawrence-to take on the community conditions that increase the risk of unhealthy substance use and addiction. It describes what they learned as they went beyond a sole focus on preventing opioid overdoses and deaths-as critically important as that is-to transforming their communities to support health and well-being in the first place.

A treatment-specific marginal structural Cox model for the effect of treatment discontinuation.

Patients taking a prescribed medication often discontinue their treatment; however, this may negatively impact their health outcomes. If doctors had statistical evidence that discontinuing some prescribed medication shortened, on average, the time to a clinical event (e.g., death), they could use that knowledge to encourage their patients to stay on the prescribed treatment. We describe a treatment-specific marginal structural Cox model for estimation of the causal effect of treatment discontinuation on a survival endpoint. The effect of treatment discontinuation is quantified by the hazard ratio of the event hazard rate had the population followed the regime "take treatment a until it is discontinued at some time ν ," versus the event hazard rate had the population never discontinued treatment a . Valid causal analysis requires control for treatment confounding, regime confounding, and censoring due to regime violation. We propose new inverse probability of regime compliance weights to address the three issues simultaneously. We apply the framework to data from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) study. Patients from this study are treated with one of two types of oral anticoagulants (OACs). We test whether the causal effect of treatment discontinuation differs by type of OAC, and we also estimate the size and direction of the effect. We find evidence that OAC discontinuation increases the hazard for certain events, but we do not find evidence that this effect differs by treatment.

U.S. Abortion Care Providers' Perspectives on Self-Managed Abortion.

State-level restrictions on abortion access may prompt greater numbers of people to self-manage their abortion. The few studies exploring perspectives of providers towards self-managed abortion are focused on physicians and advanced practice clinicians. Little is known about the wider spectrum of abortion care providers who encounter self-managed abortion in their clinic-based work. To gain a deeper understanding of this issue and inform future care delivery, we conducted in-depth interviews with 46 individuals working in a range of positions in 46 abortion clinics across 29 states. Our interpretative analysis resulted in themes shaped by beliefs about safety and autonomy, and a tension between the two: that self-managed abortion is too great a risk, that people are capable of self-managing an abortion, and that people have a right to a self-managed abortion. Our findings highlight the importance of increasing knowledge and clarifying values among all abortion care providers, including clinic staff.

Learning pathways for engagement: Understanding drivers of pro-environmental behavior in the context of protected area management.

The participation of local communities in management decisions is critically important to the long-term salience and therefore, success, of protected areas. Engaging community members in meaningful ways requires knowledge of their behavior and its antecedents, particularly values. Understanding how learning influences cooperation in conservation initiatives is also fundamentally important for supporting decisions being made about public lands. However, there is little empirical evidence of how learning from different information sources works in conjunction with values that shape behavior. Using data from a household survey of residents living in the Denali region of Interior Alaska, U.S, we estimated a two-step structural equation model to understand the psychological reasons why stakeholders made decisions to collectively benefit the environment. Results showed that more diverse pathways by which learning occurred were instrumental in explaining why residents performed pro-environmental behaviors over the past year. Additionally, values that reflected the goals of eudaimonia influenced the transfer and negotiation of knowledge exchange among stakeholders as a correlate of behavior. Environmental concern and personal norms were positively associated with reported behaviors operationalized as social environmentalism and living in an environmentally conscientious manner, whereas environmental concern and willingness to pay for protected area management positively influenced civic engagement. We argue that broadening the range of learning spaces and considering a more diverse array of values in communities surrounding protected areas will encourage daily lifestyle changes, social interactions to support environmentalism, and more robust, pluralistic forms of public engagement in natural resource management.

Knowledge, interest, and motivations surrounding self-managed medication abortion among patients at three Texas clinics.

BACKGROUND: A rapid increase in restrictive abortion legislation in the United States has sparked renewed interest in self-managed abortion as a response to clinic access barriers. Yet little is known about knowledge of, interest in, and experiences of self-managed medication abortion among patients who obtain abortion care in a clinic. OBJECTIVES: We examined patients' knowledge of, interest in, and experience with self-managed medication abortion before presenting to the clinic. We characterized the clinic- and person-level factors associated with these measures. Finally, we examined the reasons why patients express an interest in or consider self-management before attending the clinic. MATERIALS AND METHODS: We surveyed 1502 abortion patients at 3 Texas clinics in McAllen, San Antonio, and Fort Worth. All individuals seeking abortion care who could complete the survey in English or Spanish were invited to participate in an anonymous survey conducted using iPads. The overall response rate was 90%. We examined the prevalence of 4 outcome variables, both overall and separately by site: (1) knowledge of self-managed medication abortion; (2) having considered self-managing using medications before attending the clinic; (3) interest in medication self-management as an alternative to accessing care at the clinic; and (4) having sought or tried any method of self-management before attending the clinic. We used binary logistic regression models to explore the clinic- and patient-level factors associated with these outcome variables. Finally, we analyzed the reasons reported by those who had considered medication self-management before attending the clinic, as well as the reasons reported by those who would be interested in medication self-management as an alternative to in-clinic care. RESULTS: Among all respondents, 30% knew about abortion medications available outside the clinic setting (37% in Fort Worth, 33% in McAllen, 19% in San Antonio, P < .001), and among those with prior knowledge, 28% had considered using this option before coming to the clinic (36% in McAllen, 25% in Fort Worth, 21% in San Antonio, P = .028). Among those without prior knowledge of self-management, 39% expressed interest in this option instead of coming to the clinic (54% in San Antonio, 30% in McAllen, 29% in Fort Worth, P < .001). Overall, 13% had sought out or tried any method of self-management before presenting to the clinic (16% in McAllen and 15% in Fort Worth vs 9% in San Antonio, P < .001). Experiencing barriers to clinic access was associated with having considered medication self-management (odds ratio, 2.2; 95% confidence interval, 1.7-3.0) and with seeking or trying any method of self-management before attending the clinic (odds ratio, 1.9; 95% confidence interval, 1.3-2.7). Difficulty affording the cost of in-clinic care was the most commonly cited reason for having considering medication self-management before attending the clinic. Reasons for interest in medication self-management as an alternative to clinic care included both access barriers and preferences for the privacy and comfort of home. CONCLUSION: Considering or attempting self-managed abortion may be part of the pathway to seeking in-clinic care, particularly among those experiencing access barriers. However, considerable interest in medication self-management as an alternative to the clinic also suggests a demand for more autonomous abortion care options.

Demand for Self-Managed Medication Abortion Through an Online Telemedicine Service in the United States.

Objectives. To examine demand for abortion medications through an online telemedicine service in the United States.Methods. We examined requests from US residents to the online telemedicine abortion service Women on Web (WoW) between October 15, 2017, and August 15, 2018. We calculated the population-adjusted rate of requests by state and examined the demographics, clinical characteristics, and motivations of those seeking services, comparing those in states with hostile versus supportive abortion policy climates.Results. Over 10 months, WoW received 6022 requests from US residents; 76% from hostile states. Mississippi had the highest rate of requests (24.9 per 100 000 women of reproductive age). In both hostile and supportive states, a majority (60%) reported a combination of barriers to clinic access and preferences for self-management. Cost was the most common barrier (71% in hostile states; 63% in supportive states; P < .001). Privacy was the most common preference (49% in both hostile and supportive states; P = .66).Conclusions. Demand for self-managed medication abortion through online telemedicine is prevalent in the United States. There is a public health justification to make these abortions as safe, effective, and supported as possible.

A Multicenter Study of Nutritional Adequacy in Neonatal and Pediatric Extracorporeal Life Support.

BACKGROUND: Malnutrition in critically ill patients is common in neonates and children, including those that receive extracorporeal life support (ECLS). We hypothesize that nutritional adequacy is highly variable, overall nutritional adequacy is poor, and enteral nutrition is underutilized in this population. MATERIALS AND METHODS: A retrospective study of neonates and children (age<18 y) receiving ECLS at 5 centers from 2012 to 2014 was performed. Demographic, clinical, and outcome data were analyzed. Continuous variables are presented as median [IQR]. Adequate nutrition was defined as meeting 66% of daily caloric goals during ECLS support. RESULTS: Two hundred and eighty three patients received ECLS; the median age was 12 d [3 d, 16.4 y] and 47% were male. ECLS categories were neonatal pulmonary 33.9%, neonatal cardiac 25.1%, pediatric pulmonary 17.7%, and pediatric cardiac 23.3%. The predominant mode was venoarterial (70%). Mortality was 41%. Pre-ECLS enteral and parenteral nutrition was present in 80% and 71.5% of patients, respectively. The median percentage days of adequate caloric and protein nutrition were 50% [0, 78] and 67% [22, 86], respectively. The median percentage days with adequate caloric and protein nutrition by the enteral route alone was 22% [0, 65] and 0 [0, 50], respectively. Gastrointestinal complications occurred in 19.7% of patients including hemorrhage (4.2%), enterocolitis (2.5%), intra-abdominal hypertension or compartment syndrome (0.7%), and perforation (0.4%). CONCLUSIONS: Although nutritional delivery during ECLS is adequate, the use of enteral nutrition is low despite relatively infrequent observed gastrointestinal complications.

Improved Sentinel Method for Surveillance and Collection of Filth Fly Parasitoids.

Parasitoids are important natural enemies of house flies and other muscoid flies. The two most commonly used methods for collecting fly parasitoids from the field have distinct advantages and disadvantages. Collections of wild puparia depend on the ability to find puparia in sufficient numbers and are prone to localized distortions in relative species abundance because of the overrepresentation of samples from hot spots of fly larval activity. Placement and retrieval of sentinel puparia is convenient and allows consistent sampling over time but is strongly biased in favor of Muscidifurax spp. over Spalangia spp. An improved sentinel method is described that combines some of the advantages of these two methods. Fly medium containing larvae is placed in containers, topped with a screen mesh bag of puparia, and placed in vertebrate-proof wire cages. Cages are placed at sites of actual or potential fly breeding and retrieved 3-7 d later. The modified method collected species profiles that more closely resembled those of collections of wild puparia than those from sentinel pupal bags. A method is also described for isolating puparia individually in 96-well tissue culture plates for parasitoid emergence. Use of the plate method provided a substantial saving of time and labor over the use of individual gelatin capsules for pupal isolation. Puparia from the collections that were housed individually in the wells of tissue culture plates had a higher proportion of emerged Spalangia species than puparia that were held in groups.

Beauveria bassiana Culturing and Harvesting for Bioassays With House Flies.

The entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Cordycipitaceae) has been widely studied against a wide range of arthropod pests, including many of medical and veterinary importance. New investigators must sort through a wide array of published methods for the production, harvest, storage, and bioassay methods for this pathogen. Simplified methods for production of conidia using Sabouraud dextrose agar with yeast (SDYA) plates and two conidial harvesting methods are described. Dry harvesting yields conidia that are ready to incorporate into dusts and food baits, but the fungal product includes mycelial debris that can hamper quantification and introduces variable amounts of unwanted bulk. Wet harvesting with filtration produces a cleaner product that is immediately ready for testing in liquid formulations. Examples of bioassays with house flies are presented that include conidia applied topically to the dorsal thorax for dose-mortality assays and conidial suspensions applied to filter paper disks for concentration mortality assays.

Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial.

OBJECTIVES: To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence. STUDY DESIGN: This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development. RESULTS: Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with ≥2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with ≥2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions. CONCLUSIONS: For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental. TRIAL REGISTRATION: clinicaltrials.gov: NCT00747396.

Evaluation of anti-diabetic effect and gall bladder function with 2-thio-5-thiomethyl substituted imidazoles as TGR5 receptor agonists.

A novel series of 2-thio-5-thiomethyl substituted imidazoles was discovered to be potent TGR5 agonists that possessed glucose-lowering effects while inhibiting gall bladder emptying in mice.

IMPACT OF JOINT ATTENTION ON SOCIAL-COMMUNICATION SKILLS IN INTERNATIONALLY ADOPTED CHILDREN.

Internationally adopted (IA) children have often experienced early adversity and are at risk for long-term deficiencies in multiple developmental domains. This study examined the association between IA children's joint attention (JA) soon after arrival and later cognitive, communicative, and socioemotional competency 6 months' postadoption. We expected a child's initial JA would positively predict later cognitive, communication, and social ability. IA children (n = 63) adopted from Eastern Europe were seen soon after their arrival into the United States to assess their JA. Their socioemotional competency, social communication, and cognitive abilities were measured at a follow-up session 6 months' postadoption. We found that higher order JA was positively associated with measures of social relatedness. Furthermore, individual hierarchical regressions of each measure of JA (higher order JA, initiating JA, responding to JA, and initiating behavior requests [BR]) considered with age-at-adoption showed that each measure was an independent and positive predictor of Mullen outcomes in the receptive and expressive language domains. These results suggest that JA may be a sensitive predictor of subsequent functioning in the social, communicative, and cognitive domains. Thus, assessing JA soon after arrival has the potential to identify at-risk IA children, and interventions targeting JA may support those children in overcoming the negative impacts of early adversity.

Micronutrient status and neurodevelopment in internationally adopted children.

AIM: To assess the status of nutrients relevant for brain development in internationally adoptees from disparate global regions and determine whether identified deficiencies are associated with neurodevelopment. METHODS: Participants included children adopted from Post-Soviet States (n = 15), Ethiopia (n = 26) or China (n = 17), ages 8-18 months. A comprehensive nutritional battery and a neurodevelopmental assessment were completed at baseline (within one month of arrival) and follow-up (six months later). RESULTS: At baseline, 35% were stunted, and 68% had at least one abnormal nutritional biochemical marker. The most common were low retinol-binding protein (33%), zinc deficiency (29%), vitamin D insufficiency/deficiency (21%), and iron deficiency (15%). There was significant catch-up growth in height and weight at follow-up, but little improvement in micronutrient deficiencies. Iron deficiency was associated with lower cognitive scores on the Bayley Scales of Infant Development-III, p = 0.027, and slower speed of processing, p = 0.012. Zinc deficiency was associated with compromised memory functioning, p = 0.001. CONCLUSION: Nutrient deficiencies were common during the early adoption period in internationally adoptees from three global regions, and iron and zinc deficiencies were associated with poorer neurodevelopmental outcomes. Results emphasise the importance of monitoring micronutrient status at arrival and during the early adoption period, irrespective of country of origin.

Predictors of developmental status in young children living in institutional care in Kazakhstan.

The main objective of this study was to assess the developmental status of children living in the severely adverse environment of institutional care and the examination of risk factors with regard to developmental status, including degree of stunting and emotional-behavioral and anemia status. The Bayley Scales of Infant Development were used to assess development status in 103 children aged 14.9 months (SD = 6.8) in six Kazakh institutions. The Behavioral Rating Scales were used to assess emotional-behavioral regulation. Physical growth measures were converted to z scores using World Health Organization growth charts. Venous blood was collected for assessment of anemia. Our findings indicated that young children in institutions were developmentally compromised, with duration of institutional care correlated with the severity of delay. Negative predictors of developmental status included: Poor emotional-behavioral regulation, degree of stunting and age at assessment. A particularly large percentage of children were found to be anemic. Additionally, low birth weight was found to be a significant negative predictor of development. Our findings indicate that institutional care has a detrimental impact on the development and emotional regulation of young children. Time in institutional care is a negative predictor for cognitive status for children placed at birth. Moreover stunting was found to be a useful indicator of the degree of impact of early adversity on cognitive development. Particular attention is needed for special-needs children such as those with low birth weight, since their development was found to be more sensitive to early adversity than that of normal birth weight children.

Discovery and SAR of 5-aminooctahydrocyclopentapyrrole-3a-carboxamides as potent CCR2 antagonists.

SAR study of 5-aminooctahydrocyclopentapyrrole-3a-carboxamide scaffold led to identification of several CCR2 antagonists with potent activity in both binding and functional assays. Their cardiovascular safety and pharmacokinetic properties were also evaluated.

The discovery and SAR of cyclopenta[b]furans as inhibitors of CCR2.

The discovery of a novel series of cyclopenta[b]furans as CCR2 inhibitors is discussed. This series has excellent CCR2 potency and PK characteristics, and good cardiovascular safety.