A framework for measuring the cost to families of caring for children's health: the design, methodology, and study population of the r-Kids study.

BACKGROUND: All families experience financial and time costs related to caring for their children's health. Understanding the economic burden faced by families of children with chronic health conditions (CHC) is crucial for designing effective policies to support families. METHODS: In this prospective study we used electronic health records to identify children between 3 and 17 years old with autism spectrum disorder (ASD), asthma, or neither (control) from three Kaiser Permanente regions and several community health centers in the OCHIN network. We oversampled children from racial and ethnic minority groups. Parent/guardian respondents completed surveys three times, approximately four months apart. The surveys included the Family Economic Impact Inventory (measuring financial, time, and employment costs of caring for a child's health), and standardized measures of children's quality of life, behavioral problems, and symptom severity for children with ASD or asthma. We also assessed parenting stress and parent physical and mental health. All materials were provided in English and Spanish. RESULTS: Of the 1,461 families that enrolled (564 ASD, 468 asthma, 429 control), children were predominantly male (79%), with a mean age of 9.0 years, and racially and ethnically diverse (43% non-Hispanic white; 22% Hispanic; 35% Asian, Black, Native Hawaiian, or another race/ethnicity). The majority of survey respondents were female (86%), had a college degree (62%), and were married/partnered (79%). ASD group respondents were less likely to be employed (73%) than those in the asthma or control groups (both 80%; p = .023). Only 32% of the control group reported a household income ≤ $4,000/month compared with 41% of asthma and 38% of ASD families (p = .006). CONCLUSIONS: Utilizing a novel measure assessing family economic burden, we successfully collected survey responses from a large and diverse sample of families. Drawing upon the conceptual framework, survey measures, and self-report data described herein we will conduct future analyses to examine the economic burdens related to CHC and the incremental differences in these burdens between health groups. This information will help policy makers to design more equitable health and social policies that could reduce the burden on families.

Structural characterization of Class 2 OLD family nucleases supports a two-metal catalysis mechanism for cleavage.

Overcoming lysogenization defect (OLD) proteins constitute a family of uncharacterized nucleases present in bacteria, archaea, and some viruses. These enzymes contain an N-terminal ATPase domain and a C-terminal Toprim domain common amongst replication, recombination, and repair proteins. The in vivo activities of OLD proteins remain poorly understood and no definitive structural information exists. Here we identify and define two classes of OLD proteins based on differences in gene neighborhood and amino acid sequence conservation and present the crystal structures of the catalytic C-terminal regions from the Burkholderia pseudomallei and Xanthamonas campestris p.v. campestris Class 2 OLD proteins at 2.24 Å and 1.86 Å resolution respectively. The structures reveal a two-domain architecture containing a Toprim domain with altered architecture and a unique helical domain. Conserved side chains contributed by both domains coordinate two bound magnesium ions in the active site of B. pseudomallei OLD in a geometry that supports a two-metal catalysis mechanism for cleavage. The spatial organization of these domains additionally suggests a novel mode of DNA binding that is distinct from other Toprim containing proteins. Together, these findings define the fundamental structural properties of the OLD family catalytic core and the underlying mechanism controlling nuclease activity.

NCOA4 initiates ferritinophagy by binding GATE16 using two highly avid short linear interaction motifs.

Cells carefully regulate cytosolic iron, which is a vital enzymatic cofactor, yet is toxic in excess. In mammalian cells, surplus iron is sequestered in ferritin cages that, in iron limiting conditions, are degraded through the selective autophagy pathway ferritinophagy to liberate free iron. Prior work identified the ferritinophagy receptor protein NCOA4, which links ferritin and LC3/GABARAP-family member GATE16, effectively tethering ferritin to the autophagic machinery. Here, we elucidate the molecular mechanism underlying this interaction, discovering two short linear motifs in NCOA4 that each bind GATE16 with weak affinity. These binding motifs are highly avid and, in concert, support high-affinity NCOA4•GATE16 complex formation. We further find the minimal NCOA4383-522 fragment bearing these motifs is sufficient for ferritinophagy and that both motifs are necessary for this activity. This work suggests a general mechanism wherein selective autophagy receptors can distinguish between the inactive soluble pools of LC3/GABARAPs and the active membrane-conjugated forms that drive autophagy. Finally, we find that iron decreases NCOA4383-522's affinity for GATE16, providing a plausible mechanism for iron-dependent regulation of ferritinophagy.

Inappropriate use of proton pump inhibitors in hospitalized patients with lower gastrointestinal bleeding.

OBJECTIVES: Use of proton pump inhibitors (PPIs) is a mainstay in treating upper gastrointestinal bleeding (UGIB). However, the beneficial effects of PPIs are not anticipated to extend beyond the duodenum and may actually contribute to the risk of lower gastrointestinal bleeding (LGIB). However, in practice, PPIs are often used for inpatients with LGIB where no benefit exists. METHODS: A retrospective chart review was performed on inpatients during a 2-year period at an urban academic teaching hospital. Inpatients with consults to the gastroenterology (GI) service with confirmed or highly suspected LGIB were included. Outcomes regarding PPI use and the GI consulting service recommendations in these 225 patients were evaluated. RESULTS: About 37.8% of patients were started on a PPI during their inpatient course. Of those, 46% patients started on a PPI had no indication for PPI and 85% had no recommendation by the GI consultants to start a PPI. Of the 85 patients started on PPI, the GI consultants recommended stopping it in two (2.3%) patients. Lastly, 20 patients (9%) were discharged on PPI without an indication for PPI. CONCLUSION: To our knowledge, this is the first study that looked at the inappropriate utilization of PPIs in patients admitted for LGIBs utilizing GI consultant recommendations. Given the large proportion of patients started on PPI without a clinical indication and continued at discharge and the paucity of GI recommendations to discontinue inappropriate use, we found that clinical care may be improved with formal GI recommendations regarding use of PPI.

Diabetes treatment by conversion of gut epithelial cells to insulin-producing cells.

Insulin-deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi-closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high-risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin-producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin-deficient diabetes, these inhibitors have resulted in robust glucose-lowering responses and generation of insulin-producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

Emotional responses to favorite and relaxing music predict music-induced hypoalgesia.

Introduction: The hypoalgesic effect of music has long been established. However, the characteristics of music which are important for reducing pain have not been well-studied. Some research has compared subject-selected preferred music to unfamiliar music selected by researchers, and has typically found a superior effect from preferred music. In this study, we sought to discover what aspects of listeners' relationship with their preferred music was important in producing a hypoalgesic effect. Methods: We conducted a thermal pain and music listening experiment with 63 participants (14 male, 49 female, mean age = 21.3), in which music excerpts were paired with thermal stimulations. Pain ratings of intensity and unpleasantness, as well as emotional response variables, were rated on visual analog scales. We also conducted brief structured interviews about participants' favorite music, on which we conducted thematic content analysis. Themes and emotion variables were analyzed for their effects on pain ratings. Results: We first replicated the finding that favorite music outperforms experimenter-selected relaxing music in reducing pain unpleasantness (MD = -7.25, p < 0.001) and that the difference in hypoalgesia was partially mediated by an increase in musical chills (ab = -2.83, p < 0.01). We then conducted a theme analysis on the interview transcripts and produced four themes relating to emotional experience: moving/bittersweet, calming/relaxing, happy/cheerful, and energizing/activating. We found suggestive evidence that moving/bittersweet favorite music reduces pain unpleasantness through increased music pleasantness (ab = -5.48, p < 0.001) and more musical chills (ab = -0.57, p = 0.004). Discussion: We find that music pleasantness and musical chills are salient predictors of music-induced hypoalgesia, and that different categories of favorite music derived from qualitative analysis may engage these emotional pathways to different degrees.

Improvement in Blood Pressure Control in Safety Net Clinics Receiving 2 Versions of a Scalable Quality Improvement Intervention: BP MAP A Pragmatic Cluster Randomized Trial.

Background Uncontrolled blood pressure (BP) remains a leading cause of death in the United States. The American Medical Association developed a quality improvement program to improve BP control, but it is unclear how to efficiently implement this program at scale across multiple health systems. Methods and Results We conducted BP MAP (Blood Pressure Measure Accurately, Act Rapidly, and Partner With Patients), a comparative effectiveness trial with clinic-level randomization to compare 2 scalable versions of the quality improvement program: Full Support (with support from quality improvement expert) and Self-Guided (using only online materials). Outcomes were clinic-level BP control (<140/90 mm Hg) and other BP-related process metrics calculated using electronic health record data. Difference-in-differences were used to compare changes in outcomes from baseline to 6 months, between intervention arms, and to a nonrandomized Usual Care arm composed of 18 health systems. A total of 24 safety-net clinics in 9 different health systems underwent randomization and then simultaneous implementation. BP control increased from 56.7% to 59.1% in the Full Support arm, and 62.0% to 63.1% in the Self-Guided arm, whereas BP control dropped slightly from 61.3% to 60.9% in the Usual Care arm. The between-group differences-in-differences were not statistically significant (Full Support versus Self-Guided=+1.2% [95% CI, -3.2% to 5.6%], P=0.59; Full Support versus Usual Care=+3.2% [-0.5% to 6.9%], P=0.09; Self-Guided versus Usual Care=+2.0% [-0.4% to 4.5%], P=0.10). Conclusions In this randomized trial, 2 methods of implementing a quality improvement intervention in 24 safety net clinics led to modest improvements in BP control that were not statistically significant. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03818659.

Cross-sectional analysis of national electronic injury surveillance system for burn injuries presenting to United States emergency departments 2000-2018.

Patients with burns commonly present to Emergency Departments (EDs), in addition to burn centers. Patients at burn centers typically have more severe burns than those at EDs, and previous studies have analyzed burn center databases. To update the overall burn epidemiology in the United States (US), we analyzed burn injury trends and sources across all age groups using the National Electronic Injury Surveillance System (NEISS), which collects all injuries reported to US EDs. A total of 97,986 burn injuries were recorded in NEISS, 2000-2018. We found a downward trend in the pediatric burn rate and an upward trend in the adult burn rate. Almost half of burns were in children (48.41%), especially in those under 5 (29.79%), and slightly more common in men (53.93%). Most were treatable in the ED (87.83%) and hot water was the most common source overall (20.88%), followed by hair curlers for children less than 2 years old, ranges/ovens for 2 to <5 years, microwaves for 5 to <10 years, and cookware for 10 to <18 years and adults ≥18 years. The most common injured region was the hand for all age groups (34.44%). Although most burn injuries were potentially preventable, the overall burn rate did not decrease 2000-2018. Therefore, we offer guidance on prevention strategies for high-risk sources and age groups.

School-Based Health Centers and Pediatric Practice.

School-based health centers (SBHCs) are unique health care settings for our nation's school-aged children and adolescents. SBHCs represent the collaboration between the health and school communities to support the health and mental health needs and the academic achievements of children and adolescents, particularly students with health disparities or poor access to health care. SBHCs improve access to health care services for students by decreasing financial, geographic, age, and cultural barriers. This policy statement provides an overview of SBHCs, including the scope of services as well as some of the documented benefits and challenges. This policy statement also reviews the role of SBHCs in working with the pediatric medical home and provides recommendations that support the coordination of SBHCs with pediatric primary care providers and the pediatric medical home.

Knowledge and attitudes towards contraceptives among adolescents and young adults.

BACKGROUND: Despite endorsements supporting the use of intrauterine devices (IUDs) for adolescents and young adult women (AYA), they have limited knowledge about them Male partners can influence contraceptive decisions, however their perceived knowledge about IUDs is lower than their objective knowledge. We aim to establish current AYA baseline contraceptive knowledge and attitudes so providers can better target their sexual health educational interventions. METHODS: Females and males, aged 13 to 23 years old, from our suburban adolescent clinic, completed an anonymous survey that assessed their knowledge and attitudes towards methods of contraception, with an emphasis on the IUD. RESULTS: Completed surveys totaled 130 (99 females/31 males). Demographic results revealed 31.3% Black/African-American, 30.5% Latino/Hispanic, 17.6% White, 3.0% Asian, and 14.5% Other. The majority of participants (80%) were sexually active. The majority (69.5%) stated they/their partner were currently using a contraceptive method; only 2.6% used IUDs. Half of females (56.6%) and 10.1% of males had heard of IUDs. Despite this, male and female participants lacked knowledge regarding specific IUD facts. Of the participants who had used emergency contraception (EC), only 6.4% knew the copper IUD could be used for EC. CONCLUSION: Contraceptive knowledge deficits, especially regarding the IUD, continue to exist for AYA patients. Many participants stated they required EC despite "satisfaction" with their birth control method(s) and most were unaware that the copper IUD could be used as EC. These discrepancies highlight the importance of comprehensive contraceptive education for AYA patients. Enhanced and consistent contraceptive options counseling can help providers ensure that their AYA patients make well-informed decisions about family planning, thus improving their quality of life.

Talking is harder than listening: The time course of dual-task costs during naturalistic conversation.

Many studies have shown that the cognitive demands of language use are a substantial cause of central dual-task costs, including costs on concurrent driving performance. More recently, several studies have considered whether language production or comprehension is inherently more difficult with respect to costs on concurrent performance, with mixed results. This assessment is particularly difficult given the open question of how one should best equate and compare production and comprehension demands and performance. The present study used 2 very different approaches to address this question. Experiment 1 assessed manual tracking performance concurrently with a conventional labouratory task, comparing dual-task costs with comprehension and verification versus production of category items. Experiment 2 adopted an extreme ecological and functional approach to this question by assessing dual-task manual tracking costs concurrent with continuous, naturalistic, 2-way conversation, allowing event-related analysis of continuous tracking relative to onsets and offsets of natural production and comprehension events. Over both experiments, tracking performance was worse with concurrent production versus comprehension demands. We suggest that by at least 1 important functional metric-performance in natural, everyday conversation-talking is indeed harder than listening. (PsycINFO Database Record