Postacute Care after Pediatric Hospitalizations for a Primary Mental Health Condition.

OBJECTIVES: To determine the proportion of US children hospitalized for a primary mental health condition who are discharged to postacute care (PAC); whether PAC discharge is associated with demographic, clinical, and hospital characteristics; and whether PAC use varies by state. STUDY DESIGN: Retrospective cohort study of a nationally representative sample of US acute care hospitalizations for children ages 2-20 years with a primary mental health diagnosis, using the 2009 and 2012 Kids' Inpatient Databases. Discharge to PAC was used as a proxy for transfer to an inpatient mental health facility. We derived adjusted logistic regression models to assess the association of patient and hospital characteristics with discharge to PAC. RESULTS: In 2012, 14.7% of hospitalized children (n = 248 359) had a primary mental health diagnosis. Among these, 72% (n = 178 214) had bipolar disorder, depression, or psychosis, of whom 4.9% (n = 8696) were discharged to PAC. The strongest predictors of PAC discharge were homicidal ideation (aOR, 24.9; 96% CI, 4.1-150.4), suicide and self-injury (aOR, 15.1; 95% CI, 11.7-19.4), and substance abuse-related medical illness (aOR, 5.0; 95% CI, 4.5-5.6). PAC use varied widely by state, ranging from 2.2% to 36.3%. CONCLUSIONS: The majority of children hospitalized primarily for a mood disorder or psychosis were not discharged to PAC, and safety-related conditions were the primary drivers of the relatively few PAC discharges. There was substantial state-to-state variation. Target areas for quality improvement include improving access to PAC for children hospitalized for mood disorders or psychosis and equitable allocation of appropriate PAC resources across states.

Impact of Chronic Conditions on Emergency Department Visits of Children Using Medicaid.

OBJECTIVE: To assess the impact of chronic conditions on children's emergency department (ED) use. STUDY DESIGN: Retrospective analysis of 1 850 027 ED visits in 2010 by 3 250 383 children ages 1-21 years continuously enrolled in Medicaid from 10 states included in the Truven Marketscan Medicaid Database. The main outcome was the annual ED visit rate not resulting in hospitalization per 1000 enrollees. We compared rates by enrollees' characteristics, including type and number of chronic conditions, and medical technology (eg, gastrostomy, tracheostomy), using Poisson regression. To assess chronic conditions, we used the Agency for Healthcare Research and Quality's Chronic Condition Indicator system, assigning chronic conditions with ED visit rates ≥75th percentile as having the "highest" visit rates. RESULTS: The overall annual ED visit rate was 569 per 1000 enrollees. As the number of the children's chronic conditions increased from 0 to ≥3, visit rates increased by 180% (from 376 to 1053 per 1000 enrollees, P < .001). Rates were 174% higher in children assisted with vs without medical technology (1546 vs 565, P < .001). Sickle cell anemia, epilepsy, and asthma were among the chronic conditions associated with the highest ED visit rates (all ≥1003 per 1000 enrollees). CONCLUSIONS: The highest ED visit rates resulting in discharge to home occurred in children with multiple chronic conditions, technology assistance, and specific conditions such as sickle cell anemia. Future studies should assess the preventability of ED visits in these populations and identify opportunities for reducing their ED use.

Nursing-led Home Visits Post-hospitalization for Children with Medical Complexity.

PURPOSE: Hospital discharge for children with medical complexity (CMC) can be challenging for families. Home visits could potentially benefit CMC and their families after leaving the hospital. We assessed the utility of post-discharge home visits to identify and address health problems for recently hospitalized CMC. DESIGN AND METHODS: A prospective study of 36 CMC admitted to a children's hospital from 4/15/2015 to 4/14/2016 identified with a possible high risk of hospital readmission and offered a post-discharge home visit within 72h of discharge. The visit was staffed by a hospital nurse familiar with the child's admission. The home visit goals were to reinforce education of the discharge plan, assess the child's home environment, and identify and address any problems or issues that emerged post-discharge. RESULTS: The children's median age was 6years [interquartile range (IQR) 2-18]. The median distance from hospital to their home was 38miles (IQR 8-78). All (n=36) children had multiple chronic conditions; 89% (n=32) were assisted with medical technology. The nurse identified and helped with a post-discharge problem during every (n=36) visit. Of the 147 problems identified, 26.5% (n=39) pertained to social/family issues (e.g., financial instability), 23.8% (n=35) medications (e.g., wrong dose), 20.4% (n=30) durable medical equipment (e.g., insufficient supply or faulty function), 20.4% (n=30) child's home environment (e.g., unsafe sleeping arrangement), and 8.8% (n=13) child's health (e.g., unresolved health problem). CONCLUSIONS: Home visits helped identify and address post-discharge issues that occurred for discharged CMC. PRACTICAL IMPLICATIONS: Hospitals should consider home visits when optimizing discharge care for CMC.

Measuring tryptophan dynamics using fast scan cyclic voltammetry at carbon fiber microelectrodes with improved sensitivity and selectivity.

Despite the fact that tryptophan (Trp) is an essential amino acid that humans typically obtain through diet, there are several interesting tryptophan dynamics at play in the body. Quantifying and understanding these dynamics are crucial in studies of depression, autism spectrum disorder, and other disorders that involve neurotransmitters directly synthesized from tryptophan. Here we detail the optimization of waveform parameters in fast scan cyclic voltammetry at carbon fiber microelectrodes to yield four-fold higher sensitivity and six-fold higher selectivity compared to previously reported methods. We demonstrate the utility of our method in measuring (1) exogenous Trp dynamics from administration of Trp to PC-12 cells with and without overexpression of tryptophan hydroxylase-2 and (2) endogenous Trp dynamics in pinealocyte cultures with and without stimulation via norepinephrine. We observed interesting differences in Trp dynamics in both model systems, which demonstrate that our method is indeed sensitive to Trp dynamics in different applications.

Mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal S6 kinase 2 inhibitors.

We previously reported the discovery of a novel ribosomal S6 kinase 2 (RSK2) inhibitor, (R)-5-Methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a] indole-8-carboxylic acid [1-(3-dimethylamino-propyl)-1H-benzoimidazol-2-yl]-amide (BIX 02565), with high potency (IC(50) = 1.1 nM) targeted for the treatment of heart failure. In the present study, we report that despite nanomolar potency at the target, BIX 02565 elicits off-target binding at multiple adrenergic receptor subtypes that are important in the control of vascular tone and cardiac function. To elucidate in vivo the functional consequence of receptor binding, we characterized the cardiovascular (CV) profile of the compound in an anesthetized rat CV screen and telemetry-instrumented conscious rats. Infusion of BIX 02565 (1, 3, and 10 mg/kg) in the rat CV screen resulted in a precipitous decrease in both mean arterial pressure (MAP; to -65 ± 6 mm Hg below baseline) and heart rate (-93 ± 13 beats/min). In telemetry-instrumented rats, BIX 02565 (30, 100, and 300 mg/kg p.o. QD for 4 days) elicited concentration-dependent decreases in MAP after each dose (to -39 ± 4 mm Hg on day 4 at T(max)); analysis by Demming regression demonstrated strong correlation independent of route of administration and influence of anesthesia. Because of pronounced off-target effects of BIX 02565 on cardiovascular function, a high-throughput selectivity screen at adrenergic α(1A) and α(2A) was performed for 30 additional RSK2 inhibitors in a novel chemical series; a wide range of adrenergic binding was achieved (0-92% inhibition), allowing for differentiation within the series. Eleven lead compounds with differential binding were advanced to the rat CV screen for in vivo profiling. This led to the identification of potent RSK2 inhibitors (cellular IC(50) <0.14 nM) without relevant α(1A) and α(2A) inhibition and no adverse cardiovascular effects in vivo.

Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity.

A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were optimized for cellular potency and kinase selectivity. This led to the identification of compound 24, BIX 02565, an attractive candidate for use in vitro and in vivo to explore the role of RSK as a target for the treatment heart failure.

Indole RSK inhibitors. Part 1: discovery and initial SAR.

A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were identified through high throughput screening. An RSK crystal structure and exploratory SAR were used to define the series pharmacophore. Compounds with good cell potency, such as compounds 43, 44, and 55 were identified, and form the basis for subsequent kinase selectivity optimization.

A qualitative evidence synthesis of users' experience of mobile health applications in the self-management of type 2 diabetes.

AIM: The aim of this qualitative evidence synthesis was to identify and synthesise qualitative research relating to experiences of using mobile health (mHealth) applications to aid self-management of Type 2 Diabetes. METHODS: Using a systematic search strategy, 11 databases were searched (Medline, CINAHL, PsychInfo, PubMed, Web of Science, Embase, Cochrane Library, Scopus, ProQuest A&1, ProQuest UK & Ireland, Mednar). "Best fit" framework synthesis was used guided by the Health Information Technology Acceptance Model (HITAM). Assessment of methodological limitations was conducted using Critical Appraisal Skills Programme (CASP) and confidence in the review findings were guided by GRADE-CERQual. RESULTS: Fourteen eligible studies were included in the synthesis (7 qualitative and 5 mixed methods). Key themes identified under the health, information and technology zones of the HITAM revealed the benefits of mHealth apps, barriers to their use, their perceived usefulness and ease of use. DISCUSSION: Most people used the apps for feedback on their self-management and found them helpful in their communication with health care providers. Some embraced the technology and found it easy to use while others found mHealth apps to be counterintuitive.

Wedded to the land? Representations of rural ageing masculinities in Irish culture and society.

This article explores the interactions between social constructions and cultural representations of rural ageing masculinities in Ireland. Constructions of Irish masculinities have historically been linked to rural, farming identities emphasising physicality, self-reliance, patrilineal inheritance and traditional (Catholic) family values. Central to such constructions in many classic works of Irish literature, drama and film has been the powerful role of the father and the imperative of the land. While there is a burgeoning literature on masculinities in Irish literary, cultural and sociological studies, there are however few studies on the intersection of age and masculinities, or across disciplines. This article seeks to address this critical gap in relation to rural masculinities through close readings of significant texts from Irish literature and film, as well as through focus group discussions of men aged 65+ living in Ireland about their views on such images. Taking an intersectional and interdisciplinary approach, it thus offers an overview of cultural constructions of ageing rural masculinities and explores how such representations inform models of ageing in contemporary Ireland.

Disparities in Oral Nutritional Supplement Usage and Dispensing Patterns across Primary Care in Ireland: ONSPres Project.

When treating malnutrition, oral nutritional supplements (ONSs) are advised when optimising the diet is insufficient; however, ONS usage and user characteristics have not been previously analysed. A retrospective secondary analysis was performed on dispensed pharmacy claim data for 14,282 anonymised adult patients in primary care in Ireland in 2018. Patient sex, age, residential status, ONS volume (units) and ONS cost (EUR) were analysed. The categories of 'Moderate' (<75th centile), 'High' (75th-89th centile) and 'Very High' ONS users (≥90th centile) were created. The analyses among groups utilised t-tests, Mann-Whitney U tests and chi-squared tests. This cohort was 58.2% female, median age was 76 years, with 18.7% in residential care. The most frequently dispensed ONS type was very-high-energy sip feeds (45% of cohort). Younger males were dispensed more ONSs than females (<65 years: median units, 136 vs. 90; p < 0.01). Patients living independently were dispensed half the volume of those in residential care (112 vs. 240 units; p < 0.01). 'Moderate' ONS users were dispensed a yearly median of 84 ONS units (median cost, EUR 153), 'High' users were dispensed 420 units (EUR 806) and 'Very High' users 892 yearly units (EUR 2402; p < 0.01). Further analyses should focus on elucidating the reasons for high ONS usage in residential care patients and younger males.

Medication Order Errors at Hospital Admission Among Children With Medical Complexity.

OBJECTIVES: We sought to characterize the nature and prevalence of medication order errors (MOEs) occurring at hospital admission for children with medical complexity (CMC), as well as identify the demographic and clinical risk factors for CMC experiencing MOEs. METHODS: Prospective cohort study of 1233 hospitalizations for CMC from November 1, 2015, to October 31, 2016, at 2 children's hospitals. Medication order errors at admission were identified prospectively by nurse practitioners and a pharmacist through direct patient care. The primary outcome was presence of at least one MOE at hospital admission. Statistical methods used included χ2 test, Fisher exact tests, and generalized linear mixed models. RESULTS: Overall, 6.1% (n = 75) of hospitalizations had ≥1 MOE occurring at admission, representing 112 total identified MOEs. The most common MOEs were incorrect dose (41.1%) and omitted medication (34.8%). Baclofen and clobazam were the medications most commonly associated with MOEs. In bivariable analyses, MOEs at admission varied significantly by age, assistance with medical technology, and numbers of complex chronic conditions and medications (P < 0.05). In multivariable analysis, patients receiving baclofen had the highest adjusted odds of MOEs at admission (odds ratio, 2.2 [95% confidence interval, 1.2-3.8]). CONCLUSIONS: Results from this study suggest that MOEs are common for CMC at hospital admission. Children receiving baclofen are at significant risk of experiencing MOEs, even when orders for baclofen are correct. Several limitations of this study suggest possible undercounting of MOEs during the study period. Further investigation of medication reconciliation processes for CMC receiving multiple chronic, home medications is needed to develop effective strategies for reducing MOEs in this vulnerable population.

The Impact of the COVID-19 Pandemic on the Working Lives and Retirement Timing of Older Nurses in Ireland.

COVID-19 profoundly affected Irish citizens. The effects have been especially pronounced for nurses in front-line, clinical and management roles. This article discusses the national and employer policy context relevant to nurses in Ireland. There have been staff and bed shortages in public hospitals since austerity policies were introduced following the global financial crisis. Government measures responding to the pandemic include initial 'cocooning' of older citizens, travel restrictions, changed working conditions and restricted availability of childcare. This article draws on interviews with 25 older nurses in 2021, sixteen women and nine men, aged 49 or over in Ireland. It explores older nurses' experiences of COVID-19 and asks what are the implications for their working conditions and retirement timing intentions. A gendered political economy of ageing approach and thematic analysis reveals that while some nurses responded positively to the pandemic, some experienced adverse health impacts, stress and exhaustion; some reported a fear of contracting COVID-19 and of infecting their families; several women nurses decided to retire earlier due to COVID-19. The implications of the findings for employer and government policy and for research are discussed.

Pediatric complex care and surgery comanagement: Preparation for spinal fusion.

The aim of this study is to assess the impact of preoperative comanagement with complex care pediatricians (CCP) on children with neuromuscular scoliosis undergoing spinal fusion. We performed chart review of 79 children aged 5-21 years undergoing spinal fusion 1/2014-6/2016 at a children's hospital, with abstraction of clinical documentation from preoperative health evaluations performed regularly by anesthesiologists and irregularly by a CCP. Preoperative referrals to specialists, labs, tests, and care plans needed last minute for surgical clearance were measured. The mean age at surgery was 14 (SD 3) years; cerebral palsy (64%) was the most common neuromuscular condition. Thirty-nine children (49%) had a preoperative CCP evaluation a median 63 days (interquartile range (IQR) 33-156) before the preanesthesia visit. Children with CCP evaluation had more organ systems affected by coexisting conditions than children without an evaluation (median 11 (IQR 9-12) vs. 8 (IQR 5-11); p < .001). The rate of last-minute care coordination activities required for surgical clearance was lower for children with versus without CCP evaluation (1.8 vs. 3.6). A lower percentage of children with CCP evaluation required last-minute development of new preoperative plans (26% vs. 50%, p = .002). Children with CCP involvement were better prepared for surgery, requiring fewer last-minute care coordination activities for surgical clearance.

Identification of pharmacological inhibitors of the MEK5/ERK5 pathway.

We have identified two novel MEK5 inhibitors, BIX02188 and BIX02189, which inhibited catalytic function of purified, MEK5 enzyme. The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. The compounds also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. These inhibitors offer novel pharmacological tools to better characterize the role of the MEK5/ERK5 pathway in various biological systems.

Age trends in 30 day hospital readmissions: US national retrospective analysis.

OBJECTIVE: To assess trends in and risk factors for readmission to hospital across the age continuum. DESIGN: Retrospective analysis. SETTING AND PARTICIPANTS: 31 729 762 index hospital admissions for all conditions in 2013 from the US Agency for Healthcare Research and Quality Nationwide Readmissions Database. MAIN OUTCOME MEASURE: 30 day, all cause, unplanned hospital readmissions. Odds of readmission were compared by patients' age in one year epochs with logistic regression, accounting for sex, payer, length of stay, discharge disposition, number of chronic conditions, reason for and severity of admission, and data clustering by hospital. The middle (45 years) of the age range (0-90+ years) was selected as the age reference group. RESULTS: The 30 day unplanned readmission rate following all US index admissions was 11.6% (n=3 678 018). Referenced by patients aged 45 years, the adjusted odds ratio for readmission increased between ages 16 and 20 years (from 0.70 (95% confidence interval 0.68 to 0.71) to 1.04 (1.02 to 1.06)), remained elevated between ages 21 and 44 years (range 1.02 (1.00 to 1.03) to 1.12 (1.10 to 1.14)), steadily decreased between ages 46 and 64 years (range 1.02 (1.00 to 1.04) to 0.91 (0.90 to 0.93)), and decreased abruptly at age 65 years (0.78 (0.77 to 0.79)), after which the odds remained relatively constant with advancing age. Across all ages, multiple chronic conditions were associated with the highest adjusted odds of readmission (for example, 3.67 (3.64 to 3.69) for six or more versus no chronic conditions). Among children, young adults, and middle aged adults, mental health was one of the most common reasons for index admissions that had high adjusted readmission rates (≥75th centile). CONCLUSIONS: The likelihood of readmission was elevated for children transitioning to adulthood, children and younger adults with mental health disorders, and patients of all ages with multiple chronic conditions. Further attention to the measurement and causes of readmission and opportunities for its reduction in these groups is warranted.

Issues Identified by Postdischarge Contact after Pediatric Hospitalization: A Multisite Study.

BACKGROUND: Many hospitals are considering contacting hospitalized patients soon after discharge to help with issues that arise. OBJECTIVE: To (1) describe the prevalence of contactidentified postdischarge issues (PDI) and (2) assess characteristics of children with the highest likelihood of having a PDI. DESIGN, SETTING, PATIENTS: A retrospective analysis of hospital-initiated follow-up contact for 12,986 children discharged from January 2012 to July 2015 from 4 US children's hospitals. Contact was made within 14 days of discharge by hospital staff via telephone call, text message, or e-mail. Standardized questions were asked about issues with medications, appointments, and other PDIs. For each hospital, patient characteristics were compared with the likelihood of PDI by using logistic regression. RESULTS: Median (interquartile range) age of children at admission was 4.0 years (0-11); 59.9% were nonHispanic white, and 51.0% used Medicaid. The most common reasons for admission were bronchiolitis (6.3%), pneumonia (6.2%), asthma (5.1%), and seizure (4.9%). Twenty-five percent of hospitalized children (n=3263) reported a PDI at contact (hospital range: 16.0%-62.8%). Most (76.3%) PDIs were related to follow-up appointments (eg, difficulty getting one); 20.8% of PDIs were related to medications (eg, problems filling a prescription). Patient characteristics associated with the likelihood of PDI varied across hospitals. Older age (age 10-18 years vs <1 year) was significantly (P<.001) associated with an increased likelihood of PDI in 3 of 4 hospitals. CONCLUSIONS: PDIs were identified often through hospital-initiated follow-up contact. Most PDIs were related to appointments. Hospitals caring for children may find this information useful as they strive to optimize their processes for follow-up contact after discharge.

Glucose-regulated insulin production from genetically engineered human non-beta cells.

In this report we describe development and characterization of four human cell lines that are able to secrete insulin and C-peptide in response to higher concentrations of glucose. These cell lines have been developed by stably and constitutively expressing human proinsulin with a furin-cleavable site, whereas expression of furin is regulated by glucose concentration. These cell lines have been cloned and, therefore, the transgene in each cell is located in an identical location of the genome leading to a uniform expression. Cloning has also allowed us to identify cell lines with more desirable properties such as higher basal insulin secretion and/or better glucose responsiveness. We have further shown that the insulin produced by these cells is biologically active and induces normoglycemia when injected in diabetic animals. Our objective in initiating these studies was to identify a cell line that could serve as a surrogate beta cell line for therapeutic intervention in type I diabetic patients.

Perioperative Spending on Spinal Fusion for Scoliosis for Children With Medical Complexity.

BACKGROUND: Global payment is used with surgeries to optimize health, lower costs, and improve quality. We assessed perioperative spending on spinal fusion for scoliosis to inform how this might apply to children. METHODS: Retrospective analysis of 1249 children using Medicaid and aged ≥5 years with a complex chronic condition undergoing spinal fusion in 2013 from 12 states. From perioperative health services measured 6 months before and 3 months after spinal fusion, we simulated a spending reallocation with increased preoperative care and decreased hospital care. RESULTS: Perioperative spending was $112 353 per patient, with 77.9% for hospitalization, 12.3% for preoperative care, and 9.8% for postdischarge care. Primary care accounted for 0.2% of total spending; 15.4% and 49.2% of children had no primary care visit before and after spinal fusion, respectively. Compared with having no preoperative primary care visit, 1 to 2 visits were associated with a 12% lower surgery hospitalization cost (P = .05) and a 9% shorter length of stay (LOS) (P = .1); ≥3 visits were associated with a 21% lower hospitalization cost (P < .001) and a 14% shorter LOS (P = .01). Having ≥3 preoperative primary care visits for all children would increase total perioperative spending by 0.07%. This increased cost could be underwritten by a 0.1% reduction in hospital LOS or a 1.0% reduction in 90-day hospital readmissions. CONCLUSIONS: Hospital care accounted for most perioperative spending in children undergoing spinal fusion. Multiple preoperative primary care visits were associated with lower hospital costs and shorter hospitalizations. Modestly less hospital resource use could underwrite substantial increases in children's preoperative primary care.

Two-year mortality, complications, and healthcare use in children with medicaid following tracheostomy.

OBJECTIVES/HYPOTHESIS: To assess patient characteristics associated with adverse outcomes in the first 2 years following tracheostomy, and to report healthcare utilization and cost of caring for these children. STUDY DESIGN: Retrospective cohort study. METHODS: Children (0-16 years) in Medicaid from 10 states undergoing tracheostomy in 2009, identified with International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes and followed through 2011, were selected using the Truven Health Medicaid Marketscan Database (Truven Health Analytics, Inc., Ann Arbor, MI). Patient demographic and clinical characteristics were assessed with likelihood of death and tracheostomy complication using chi-square tests and logistic regression. Healthcare use and spending across the care continuum (hospital, outpatient, community, and home) were reported. RESULTS: A total of 502 children underwent tracheostomy in 2009, with 34.1% eligible for Medicaid because of disability. Median age at tracheostomy was 8 years (interquartile range 1-16 years), and 62.7% had a complex chronic condition. Two-year rates of in-hospital mortality and tracheostomy complication were 8.9% and 38.8%, respectively. In multivariable analysis, the highest likelihood of mortality occurred in children age < 1 year compared with 13+ years (odds ratio [OR] 7.3; 95% confidence interval [CI], 3.2-17.1); the highest likelihood of tracheostomy complication was in children with a complex chronic condition versus those without a complex chronic condition (OR 3.3; 95% CI, 1.1-9.9). Total healthcare spending in the 2 years following tracheostomy was $53.3 million, with hospital, home, and primary care constituting 64.4%, 9.4%, and 0.5% of total spending, respectively. CONCLUSION: Mortality and morbidity are high, and spending on primary and home care is small following tracheostomy in children with Medicaid. Future studies should assess whether improved outpatient and community care might improve their health outcomes. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2611-2617, 2016.