Metformin Monotherapy Alters the Human Plasma Lipidome Independent of Clinical Markers of Glycemic Control and Cardiovascular Disease Risk in a Type 2 Diabetes Clinical Cohort.

Type 2 diabetes (T2D) is a rising pandemic worldwide. Diet and lifestyle changes are typically the first intervention for T2D. When this intervention fails, the biguanide metformin is the most common pharmaceutical therapy. Yet its full mechanisms of action remain unknown. In this work, we applied an ultrahigh resolution, mass spectrometry-based platform for untargeted plasma metabolomics to human plasma samples from a case-control observational study of nondiabetic and well-controlled T2D subjects, the latter treated conservatively with metformin or diet and lifestyle changes only. No statistically significant differences existed in baseline demographic parameters, glucose control, or clinical markers of cardiovascular disease risk between the two T2D groups, which we hypothesized would allow the identification of circulating metabolites independently associated with treatment modality. Over 3000 blank-reduced metabolic features were detected, with the majority of annotated features being lipids or lipid-like molecules. Altered abundance of multiple fatty acids and phospholipids were found in T2D subjects treated with diet and lifestyle changes as compared with nondiabetic subjects, changes that were often reversed by metformin. Our findings provide direct evidence that metformin monotherapy alters the human plasma lipidome independent of T2D disease control and support a potential cardioprotective effect of metformin worthy of future study. SIGNIFICANCE STATEMENT: This work provides important new information on the systemic effects of metformin in type 2 diabetic subjects. We observed significant changes in the plasma lipidome with metformin therapy, with metabolite classes previously associated with cardiovascular disease risk significantly reduced as compared to diet and lifestyle changes. While cardiovascular disease risk was not a primary outcome of our study, our results provide a jumping-off point for future work into the cardioprotective effects of metformin, even in well-controlled type 2 diabetes.

Self-Reported Health Outcomes of Children and Youth with 10 Chronic Diseases.

OBJECTIVES: To identify pediatric patient-reported outcomes (PROs) that are associated with chronic conditions and to evaluate the effects of chronic disease activity on PROs. STUDY DESIGN: Participants (8-24 years old) and their parents were enrolled into 14 studies that evaluated Patient-Reported Outcome Measurement Information System PROs across 10 chronic conditions-asthma, atopic dermatitis, cancer, cancer survivors, chronic kidney disease, Crohn's disease, juvenile idiopathic arthritis, lupus, sickle cell disease, and type 1 diabetes mellitus. PRO scores were contrasted with the US general population of children using nationally representative percentiles. PRO-specific coefficients of variation were computed to illustrate the degree of variation in scores within vs between conditions. Condition-specific measures of disease severity and Cohen d effect sizes were used to examine PRO scores by disease activity. RESULTS: Participants included 2975 child respondents and 2392 parent respondents who provided data for 3409 unique children: 52% were 5-12 years old, 52% female, 25% African American/Black, and 14% Hispanic. Across all 10 chronic conditions, children reported more anxiety, fatigue, pain, and mobility restrictions than the general pediatric population. Variation in PRO scores within chronic disease cohorts was equivalent to variation within the general population, exceeding between-cohort variation by factors of 1.9 (mobility) to 5.7 (anxiety). Disease activity was consistently associated with poorer self-reported health, and these effects were weakest for peer relationships. CONCLUSIONS: Chronic conditions are associated with symptoms and functional status in children and adolescents across 10 different disorders. These findings highlight the need to complement conventional clinical evaluations with those obtained directly from patients themselves using PROs.

Ultrahigh-Resolution Mass Spectrometry-Based Platform for Plasma Metabolomics Applied to Type 2 Diabetes Research.

Metabolomics-the endpoint of the omics cascade-is increasingly recognized as a preferred method for understanding the ultimate responses of biological systems to stress. Flow injection electrospray (FIE) mass spectrometry (MS) has advantages for untargeted metabolic fingerprinting due to its simplicity and capability for high-throughput screening but requires a high-resolution mass spectrometer to resolve metabolite features. In this study, we developed and validated a high-throughput and highly reproducible metabolomics platform integrating FIE with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS for analysis of both polar and nonpolar metabolite features from plasma samples. FIE-FTICR MS enables high-throughput detection of hundreds of metabolite features in a single mass spectrum without a front-end separation step. Using plasma samples from genetically identical obese mice with or without type 2 diabetes (T2D), we validated the intra and intersample reproducibility of our method and its robustness for simultaneously detecting alterations in both polar and nonpolar metabolite features. Only 5 min is needed to acquire an ultra-high resolution mass spectrum in either a positive or negative ionization mode. Approximately 1000 metabolic features were reproducibly detected and annotated in each mouse plasma group. For significantly altered and highly abundant metabolite features, targeted tandem MS (MS/MS) analyses can be applied to confirm their identity. With this integrated platform, we successfully detected over 300 statistically significant metabolic features in T2D mouse plasma as compared to controls and identified new T2D biomarker candidates. This FIE-FTICR MS-based method is of high throughput and highly reproducible with great promise for metabolomics studies toward a better understanding and diagnosis of human diseases.

Considerations to Support Use of Patient-Reported Outcomes Measurement Information System Pediatric Measures in Ambulatory Clinics.

OBJECTIVE: To identify challenges to the use of Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in the ambulatory pediatric setting and possible solutions to these challenges. STUDY DESIGN: Eighteen semistructured telephone interviews of health system leaders, measurement implementers, and ambulatory pediatric clinicians were conducted. Five coders used applied thematic analysis to iteratively identify and refine themes in interview data. RESULTS: Most interviewees had roles in leadership or the implementation of patient-centered outcomes; 39% were clinicians. Some had experience using PROMIS clinically (44%) and 6% were considering this use. Analyses yielded 6 themes: (1) selection of PROMIS measures, (2) method of administration, (3) use of PROMIS Parent Proxy measures, (4) privacy and confidentiality of PROMIS responses, (5) interpretation of PROMIS scores, and (6) using PROMIS scores clinically. Within the themes, interviewees illuminated specific unique considerations for using PROMIS with children, including care transitions and privacy. CONCLUSIONS: Real-world challenges continue to hamper PROMIS use. Ongoing efforts to disseminate information about the integration of PROMIS measures in clinical care is critical to impacting the health of children.

Influences of health and environmental deprivation on family relationships among children with chronic disease.

PURPOSE: Families play a key role in managing chronic illness. Among chronically ill children, we describe the Patient-Reported Outcomes Measurement Information System (PROMIS) Family Relationships measure over time and its associations with sociodemographics, environmental deprivation, and health. METHODS: Parents of children aged 8-18 years with asthma (n = 171), type 1 diabetes (n = 199), or sickle cell disease (n = 135), recruited in pediatric clinics and emergency departments (ED), completed demographic surveys. Every six months for up to three years, children completed PROMIS Family Relationships, Anxiety, and Depressive Symptoms short forms (T-scores; mean 50, SD = 10), and a 5-level health status item. Linear mixed models were fit to estimate associations. RESULTS: Older baseline age was associated with weaker family relationships. For example, for each 3-year higher baseline age, relationships were 3 points weaker for males (- 3.0; 95%CI - 5.7 to - .0.2) and females (- 3.1; 95%CI - 6.0 to - 0.3) with asthma recruited in the ED. For each 1-unit higher mean overall health, relationships were 4.6 points (95%CI 3.2-6.1) stronger for children with diabetes and about 2 points stronger for children with asthma (2.3; 0.7-3.9) and sickle cell disease (2.1; 0.3-3.9). Family relationships were 0.3-0.5 points weaker for each 1-unit increment in mean anxiety or depressive symptoms across all three diseases. Relationships were not significantly associated with environmental deprivation and generally stable over time. CONCLUSIONS: Family relationships were weaker among older children and generally stable over time, yet fluctuated with physical and mental health. Monitoring PROMIS Family Relationships scores may facilitate referrals for chronically ill children who need support.

Reliability and validity of PROMIS® pediatric family relationships short form in children 8-17 years of age with chronic disease.

PURPOSE: Families play a key role in managing pediatric chronic illness. The PROMIS® pediatric family relationships measure was developed primarily within the general pediatric population. We evaluated the Family Relationships short form in the context of pediatric chronic diseases. METHODS: Children aged 8-17 years with asthma (n = 73), type 1 diabetes (n = 122), or sickle cell disease (n = 80) completed the Family Relationships 8a short form and the PROMIS Pediatric Profile-25's six domains representing physical, mental, and social health. Parents (N = 275) of these children completed the parent versions of the same measures. We evaluated reliability of the Family Relationships measure using Cronbach's alpha and IRT-based marginal reliability, and the standard error of measurement (SEM). Convergent/discriminant validity were assessed from correlations between the Family Relationships domain and the PROMIS-25 domains. RESULTS: SEM increased for scores above the normative mean of 50. Cronbach's alpha and IRT-estimated marginal reliabilities exceeded 0.80 for children and parents across diseases, except in asthma, where marginal reliability was 0.75 for parents. Scores displayed small to large correlations in the expected directions with social and mental health domains. The largest correlations occurred with parents' proxy reports of children's depressive symptoms in sickle cell disease and asthma, r = - 0.60 (95% CI - 0.74, - 0.48) and r = - 0.58 (95% CI - 0.68, - 0.48) respectively. CONCLUSIONS: The Family Relationships 8-item short form demonstrated adequate reliability and convergent/discriminant validity for use in pediatric chronic conditions, though scores above the mean displayed greater uncertainty. Evidence of the measure's reliability and validity in multiple contexts furthers the case for its use.

Impact of family-centered tailoring of pediatric diabetes self-management resources.

BACKGROUND: The American Diabetes Association recommends a family-centered approach that addresses each family's specific type 1 diabetes self-management barriers. OBJECTIVE: To assess an intervention that tailored delivery of self-management resources to families' specific self-management barriers. SUBJECTS: At two sites, 214 children 8-16 years old with type 1 diabetes and their parent(s) were randomized to receive tailored self-management resources (intervention, n = 106) or usual care (n = 108). METHODS: Our intervention (1) identified families' self-management barriers with a validated survey, (2) tailored self-management resources to identified barriers, and (3) delivered the resources as four group sessions coordinated with diabetes visits. Mixed effects models with repeated measures were fit to A1c as well as parent and child QOL during the intervention and 1 year thereafter. RESULTS: Participants were 44% youth (8-12 years) and 56% teens (13-16 years). No intervention effect on A1c or QOL was shown, combining data from sites and age groups. Analyzing results by site and age group, post-intervention A1c for teens at one site declined by 0.06 more per month for intervention teens compared to usual care (P < 0.05). In this group, post-intervention A1c declined significantly when baseline A1c was >8.5 (-0.08, P < 0.05), with an even larger decline when baseline A1c was >10 (-0.19, P < 0.05). In addition, for these teens, the significant improvements in A1c resulted from addressing barriers related to motivation to self-manage. Also at this site, mean QOL increased by 0.61 points per month more during the intervention for parents of intervention youth than for usual care youth (P < 0.05). CONCLUSIONS: Tailored self-management resources may improve outcomes among specific populations, suggesting the need to consider families' self-management barriers and patient characteristics before implementing self-management resources.

Testing Young Adults' Reactions to Facebook Cues and Their Associations with Alcohol Use.

Background: Alcohol cues on social media may influence young adults' drinking patterns, these cues may be pro-social or pro-alcohol in nature. The influence of individual Facebook cues on young adults' drinking intentions and behaviors remains unknown. Objectives: The purpose of this study was to assess how Facebook cues influence intention to drink, and how intention was associated with Theory of Reasoned Action constructs including alcohol-related attitudes and norms, and future behavior. Methods: Incoming university students completed a pre-college and a 2-year follow-up phone interview. A vignette presented individual Facebook cues representing "pro-social" or "pro-alcohol" sentiments. Participants indicated intention to drink alcohol and their rationale for this intention after each cue. Additional measures included TRA constructs of alcohol-related attitudes and norms, and problem alcohol use. Analyses included a qualitative approach to examine rationales for intention to drink in response to Facebook cues, and linear mixed effects models. Results: Of 338 participants, 56.1% were female, 74.8% were Caucasian. Alcohol-related attitudes and norms were positively associated with intention to drink in response to pro-social and pro-alcohol Facebook cues. Participants' intention to drink in response to pro-alcohol cues was positively associated with problem alcohol use two years later. Conclusions/importance: Findings illuminate the influence of social media on alcohol-related behaviors and highlight potential future screening approaches.

Content validity of the PROMIS® pediatric family relationships measure for children with chronic illness.

BACKGROUND: Families play a critical role in supporting the health and well-being of children with chronic illnesses, who face a lifetime of responsibility for self-management of their condition. Our goal was to investigate whether the novel Patient-Reported Outcomes Measurement Information System® (PROMIS®) Pediatric Family Relationships measure, developed primarily within the general pediatric population, reflects the experiences of family relationships for chronically ill children and their parents. METHODS: We conducted semi-structured qualitative interviews with children (aged 8-17) with common chronic conditions: asthma (n = 6), type 1 diabetes (n = 5), or sickle cell disease (n = 5), and separately with one of their parents (n = 16). Interviews were recorded, and two team members independently coded the written transcripts facilitated by Nvivo 10. The systematic content analysis used a combination of: 1) pre-specified themes corresponding to the six facets of the domain identified during measure development and reflected in the content of the items (i.e., Sense of Family; Love and Caring; Value and Acceptance; Trust, Dependability, and Support; Communication; Enjoyment), as well as 2) open-coding, allowing participants to define important concepts (i.e., disease impact). RESULTS: Family relationships were conceptualized in a similar way to the general population, as evidenced by child and parent responses to open-ended questions about family relationships and to specific probes that corresponded with the item content in the Family Relationship 8-item short form. Children spontaneously discussed the impact of their disease on family relationships less often than parents did. Although participants described how living with a chronic illness positively and negatively impacted aspects of family relationships, nearly all participants believed their responses to the PROMIS® Family Relationships items would not change if they (or their child) did not have a chronic illness. CONCLUSIONS: Among a sample of families of children with one of 3 chronic illnesses, participants described family relationships in a way that was consistent with the facets of the PROMIS® Family Relationship domain. This study adds to the content validity of the measure for children with chronic illness.

Patient-centred outcomes research: brave new world meets old institutional policies.

Background: Engaging patients across the research trajectory supports research that is generalizable, high quality, timely and actionable. However, this approach comes with challenges and opportunities as investigators and engaged patient stakeholders encounter institutional policies around patient engagement, privacy and research participant protection. Objective: To describe the resolution and impact of quandaries arising when patient stakeholders' values and preferences conflicted with institutional policies. Methods: Case study from a Patient-Centered Outcomes Research Institute-funded trial. Results: The first example focuses on the tension between the health care organization's requirements for background checks for all patient advisors and the funders' requirement to engage hard-to-reach populations. To create an environment of mutual trust and respect with patient stakeholders, the research team decided against imposing background checks. All 53 patient and parent advisors have served continuously for 2 years and meeting attendance exceeds 95%. The second example describes parent stakeholders' role in revising a letter informing patients about a privacy violation. Among 49 families affected by and informed about this violation, 35 (71%) agreed to participate. The third example focuses on how patient stakeholder preferences about study reminders conflict with the 1996 Health Insurance Portability and Accountability Act rules. While patient stakeholders strongly endorsed text message reminders, regulations and technology do not permit reminders with enough detail to ensure clarity. Although retention rates exceeded 90%, attendance at study appointments was below 75% and below 60% for minority and low socio-economic status families. Conclusion: Patient engagement positively impacts research. Resolving conflicts between patient-engaged research and existing institutional policies and regulations would allow this impact to become fully realized.

Family Engagement in Pediatric Sickle Cell Disease Visits.

Adults with sickle cell disease (SCD) report problems in relationship building and information exchange during clinic visits. To explore the origin of these communication challenges, we compare communication in pediatric SCD, diabetes, and asthma visits. We collected visit videos and parent surveys from 78 children ages 9-16 years with SCD, asthma, or diabetes. Coders assessed child, parent, and physician utterances reflecting relationship building, information giving, and information gathering. Associations of engagement with type of chronic disease visit were performed with negative binomial regression. Compared to SCD visits, children in diabetes visits spoke 53% more relationship-building utterances (p < .05) and physicians in asthma visits spoke 48% fewer relationship building utterances to the child (p < .01). In diabetes visits, physicians gave almost twice as much information to children and gave 48% less information to parents (both p < .01) compared to SCD visits. Compared to SCD visits, physicians spoke fewer information-gathering utterances to parents in diabetes and asthma visits (85% and 72% respectively, both p < .001). SCD visits reflect less engagement of the children and greater physician effort to gather information from parents. These differences highlight opportunities to enhance engagement as a mechanism for ultimately improving SCD care.

Long Term Outcomes of a Curriculum on Care for the Underserved.

ACKNOWLEDGEMENTS: This work was funded by HRSA grants D16HP00067 and D08PE50097. BACKGROUND: Evaluations of curricula to enhance ability to care for the underserved are often limited to short-term medical student outcomes. PURPOSE: This study evaluates retention of short-term improvements in outcomes from post-curriculum to graduation. METHODS: Third-year students on 2003-2004 pediatric clerkships were randomized to a curriculum on caring for the underserved in one of three formats: established "readings only", faculty-led, or web-based. Outcomes (knowledge, attitudes, self-efficacy and clinical skills) were assessed at three timepoints-pre- and post-curriculum and at graduation. Analyses, from 2009-2010, included Fisher's exact test to assess the relationship of curriculum group with response patterns, demographics, and outcomes at graduation. Multivariate regression was used to model the longitudinal relationship between outcomes and curriculum groups, adjusting for prior clerkship experiences, baseline scores, and clustering by student. RESULTS: Of 137 students, 135 (99%) completed the pre-curriculum survey, 128 (93%) completed the post-curriculum survey and 88 (64%) completed the graduation survey. Post-curriculum improvements in self-efficacy and clinical skills seen among students receiving the faculty-led or web-based curricula were retained at graduation. At graduation, web-based curriculum students' self-efficacy was significantly greater for "establishing achievable goals with underserved families" compared to established curriculum students. With regard to skills relevant to caring for the underserved, few graduates had facilitated a referral to Women, Infants and Children (33%) or followed up to ensure a patient accessed a needed resource (56%). CONCLUSIONS: Self-efficacy and skills gained through web-based and faculty-led curricula were retained at graduation. Data from items at graduation support targeted curricular improvement.

Application of participatory ergonomics to the redesign of the family-centred rounds process.

Participatory ergonomics (PE) can promote the application of human factors and ergonomics (HFE) principles to healthcare system redesign. This study applied a PE approach to redesigning the family-centred rounds (FCR) process to improve family engagement. Various FCR stakeholders (e.g. patients and families, physicians, nurses, hospital management) were involved in different stages of the PE process. HFE principles were integrated in both the content (e.g. shared mental model, usability, workload consideration, systems approach) and process (e.g. top management commitment, stakeholder participation, communication and feedback, learning and training, project management) of FCR redesign. We describe activities of the PE process (e.g. formation and meetings of the redesign team, data collection activities, intervention development, intervention implementation) and present data on PE process evaluation. To demonstrate the value of PE-based FCR redesign, future research should document its impact on FCR process measures (e.g. family engagement, round efficiency) and patient outcome measures (e.g. patient satisfaction).

Clinicians navigating moral accountability when discussing parental behaviors in the care of the child in the hospital.

OBJECTIVE: The purpose of this study was to explore how moral accountability is navigated when clinicians talk about parental behaviors to support the health of the hospitalized child. METHODS: We conducted a secondary data analysis of 74 conversations during daily rounds video recorded as part of a randomized controlled trial of an intervention to advance family-centered rounds in one children's hospital. Conversations involving children under the age 18 who were cared for by a pediatric hospitalist service, pulmonary service, or hematology/oncology service were recorded. We used conversation analysis to analyze sequences in which physicians engaged in talk that had implications for parent behavior. RESULTS: Two phenomena were apparent in how physicians and parents navigated moral accountability. First, physicians avoided or delayed parental agency in their references to parent behaviors. Second, parents demonstrated and clinicians reassured parental competence of parents caring for their children. CONCLUSION: Physicians appeared to be oriented toward the potential moral implications of asking about parental behavior. PRACTICE IMPLICATIONS: Avoiding attributions of agency and moral accountability as well as providing reassurance for the parents' competence may be useful for clinicians to maintain a good relationship with the parents of children in their care in the hospital setting.

Internet safety education for youth: stakeholder perspectives.

BACKGROUND: Internet use is nearly ubiquitous among US youth; risks to internet use include cyberbullying, privacy violations and unwanted solicitation. Internet safety education may prevent these negative consequences; however, it is unclear at what age this education should begin and what group is responsible for teaching this topic. METHODS: Surveys were distributed to key stakeholders in youth safety education including public school teachers, clinicians, parents and adolescents. Surveys assessed age at which internet safety education should begin, as well as experiences teaching and learning internet safety. Surveys of adults assessed willingness to teach internet safety. Finally, participants were asked to identify a group whose primary responsibility it should be to teach internet safety. RESULTS: A total of 356 participants completed the survey (93.4% response rate), including 77 teachers, 111 clinicians, 72 parents and 96 adolescents. Stakeholders felt the optimal mean age to begin teaching internet safety was 7.2 years (SD = 2.5), range 2-15. Internet safety was regularly taught by some teachers (20.8%), few clinicians (2.6%) and many parents (40.3%). The majority of teachers, clinicians and parents were willing to teach internet safety, but all groups surveyed identified parents as having primary responsibility for teaching this topic. CONCLUSIONS: Findings suggest agreement among key stakeholders for teaching internet safety at a young age, and for identifying parents as primary teachers of this topic. Clinicians have a unique opportunity to support parents by providing resources, guidance and support.

Effect of communication style and physician-family relationships on satisfaction with pediatric chronic disease care.

Over 8% of children have a chronic disease and many are unable to adhere to treatment. Satisfaction with chronic disease care can impact adherence. We examine how visit satisfaction is associated with physician communication style and ongoing physician-family relationships. We collected surveys and visit videos for 75 children ages 9-16 years visiting for asthma, diabetes, or sickle cell disease management. Raters assessed physician communication style (friendliness, interest, responsiveness, and dominance) from visit videos. Quality of the ongoing relationship was measured with four survey items (parent-physician relationship, child-physician relationship, comfort asking questions, and trust in the physician), while a single item assessed satisfaction. Correlations and chi square were used to assess association of satisfaction with communication style or quality of the ongoing relationship. Satisfaction was positively associated with physician to parent (p < 0.05) friendliness. Satisfaction was also associated with the quality of the ongoing parent-physician (p < 0.001) and child-physician relationships (p < 0.05), comfort asking questions (p < 0.001), and trust (p < 0.01). This shows that both the communication style and the quality of the ongoing relationship contribute to pediatric chronic disease visit satisfaction.

Development and validation of the self-management Barriers and Supports Evaluation for working-aged adults with type 1 diabetes mellitus.

INTRODUCTION: To optimize type 1 diabetes mellitus self-management, experts recommend a person-centered approach, in which care is tailored to meet people's needs and preferences. Existing tools for tailoring type 1 diabetes mellitus education and support are limited by narrow focus, lack of strong association with meaningful outcomes like A1c, or having been developed before widespread use of modern diabetes technology. To facilitate comprehensive, effective tailoring for today's working-aged adults with type 1 diabetes mellitus, we developed and validated the Barriers and Supports Evaluation (BASES). RESEARCH DESIGN AND METHODS: Participants 25-64 years of age with type 1 diabetes mellitus were recruited from clinics and a population-based registry. Content analysis of semistructured interviews (n=33) yielded a pool of 136 items, further refined to 70 candidate items on a 5-point Likert scale through cognitive interviewing and piloting. To develop and validate the tool, factor analyses were applied to responses to candidate items (n=392). Additional survey data included demographics and the Diabetes-Specific Quality of Life (QOL) Scale-Revised. To evaluate concurrent validity, hemoglobin A1c (HbA1c) values and QOL scores were regressed on domain scores. RESULTS: Factor analyses yielded 5 domains encompassing 30 items: Learning Opportunities, Costs and Insurance, Family and Friends, Coping and Behavioral Skills, and Diabetes Provider Interactions. Models exhibited good to adequate fit (Comparative Fit Index >0.88 and Root Mean Squared Error of Approximation <0.06). All domains demonstrated significant associations with HbA1c and QOL in the expected direction, except Family and Friends. Coping and Behavioral Skills had the strongest associations with both HbA1c and QOL. CONCLUSIONS: The BASES is a valid, comprehensive, person-centered tool that can tailor diabetes support and education to individuals' needs in a modern practice environment, improving effectiveness and uptake of services. Clinicians could use the tool to uncover patient-specific barriers that limit success in achieving HbA1c goals and optimal QOL.

Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation.

Over half of patients with type 2 diabetes (T2D) are unable to achieve blood glucose targets despite therapeutic compliance, significantly increasing their risk of long-term complications. Discovering ways to identify and properly treat these individuals is a critical problem in the field. The arachidonic acid metabolite, prostaglandin E2 (PGE2), has shown great promise as a biomarker of ß-cell dysfunction in T2D. PGE2 synthesis, secretion, and downstream signaling are all upregulated in pancreatic islets isolated from T2D mice and human organ donors. In these islets, preventing ß-cell PGE2 signaling via a prostaglandin EP3 receptor antagonist significantly improves their glucose-stimulated and hormone-potentiated insulin secretion response. In this clinical cohort study, 167 participants, 35 non-diabetic, and 132 with T2D, were recruited from the University of Wisconsin Hospital and Clinics. At enrollment, a standard set of demographic, biometric, and clinical measurements were performed to quantify obesity status and glucose control. C reactive protein was measured to exclude acute inflammation/illness, and white cell count (WBC), erythrocyte sedimentation rate (ESR), and fasting triglycerides were used as markers of systemic inflammation. Finally, a plasma sample for research was used to determine circulating PGE2 metabolite (PGEM) levels. At baseline, PGEM levels were not correlated with WBC and triglycerides, only weakly correlated with ESR, and were the strongest predictor of T2D disease status. One year after enrollment, blood glucose management was assessed by chart review, with a clinically-relevant change in hemoglobin A1c (HbA1c) defined as ≥0.5%. PGEM levels were strongly predictive of therapeutic response, independent of age, obesity, glucose control, and systemic inflammation at enrollment. Our results provide strong support for future research in this area.

Family Safety Reporting in Hospitalized Children With Medical Complexity.

BACKGROUND AND OBJECTIVES: Hospitalized children with medical complexity (CMC) are at high risk of medical errors. Their families are an underutilized source of hospital safety data. We evaluated safety concerns from families of hospitalized CMC and patient/parent characteristics associated with family safety concerns. METHODS: We conducted a 12-month prospective cohort study of English- and Spanish-speaking parents/staff of hospitalized CMC on 5 units caring for complex care patients at a tertiary care children's hospital. Parents completed safety and experience surveys predischarge. Staff completed surveys during meetings and shifts. Mixed-effects logistic regression with random intercepts controlling for clustering and other patient/parent factors evaluated associations between family safety concerns and patient/parent characteristics. RESULTS: A total of 155 parents and 214 staff completed surveys (>89% response rates). 43% (n = 66) had ≥1 hospital safety concerns, totaling 115 concerns (1-6 concerns each). On physician review, 69% of concerns were medical errors and 22% nonsafety-related quality issues. Most parents (68%) reported concerns to staff, particularly bedside nurses. Only 32% of parents recalled being told how to report safety concerns. Higher education (adjusted odds ratio 2.94, 95% confidence interval [1.21-7.14], P = .02) and longer length of stay (3.08 [1.29-7.38], P = .01) were associated with family safety concerns. CONCLUSIONS: Although parents of CMC were infrequently advised about how to report safety concerns, they frequently identified medical errors during hospitalization. Hospitals should provide clear mechanisms for families, particularly of CMC and those from disadvantaged backgrounds, to share safety concerns. Actively engaging patients/families in reporting will allow hospitals to develop a more comprehensive, patient-centered view of safety.