Caseworker Visitation After Reunification and Children's Reentry Into Foster Care: A Survival Analysis.

To prevent children from reentering the welfare system, it is crucial to understand the role of caseworker visits after reunification on reentry and identify the factors related to reentry. Utilizing the administrative data of one Mid-Atlantic state, children who reunified with their families between July 2016 and June 2020 were selected as the study sample (N = 3,510). Reentry rates were higher for children who did not have caseworker visits after reunification than for those who did. The survival analysis revealed that male children, living in metropolitan areas, having a prior history of removal, having a behavioral issue, and court-ordered return increased the risk of reentry, while Black children, older children, having a last placement as trial home visit, and caseworker visits after reunification decreased the risk of reentry. The study suggests formally outlining policies for post-reunification caseworker visits and increasing collaboration between the child welfare system and court system.

Family outcomes in alternative response: A multilevel analysis of recurrence.

Alternative response (AR) is preventative, family-centered, strengths-based approach within child protective services (CPS). When AR is offered it typically creates a two-track system where low- to moderate-risk families are not subjected to a traditional, fact-finding response that concludes with a determination of child abuse/neglect. One area that continues to concern child welfare administrators and researchers is recurrence, or when a family returns to CPS. Yet, it is unclear whether AR families have the same or different predictors of recurrence than TR families. Using a multilevel analytic approach, the present study followed 17,741 families in one mid-Atlantic state for 18-months post-response to determine what child, family, and county-level predicted a reported re-investigation and a substantiated re-investigation. We found few differences in predictors at the child and family level but found distinct differences at the county level for AR families. Recommendations are provided for policy, practice, and research, including a suggestion for further inquiry on what makes an optimal AR track.

Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate.

Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson's disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative 18 (LRRK2 G2019S cKi 0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18/CHK1 10-pt. mutant showing the 2-methyl substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of 18 gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] derivative 32. Optimization of 32 afforded diastereomeric oxolan-3-yl derivatives 44 and 45, which demonstrated a favorable in vitro PK profile, although they displayed species disconnects in the in vivo PK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds 44 and 45 demonstrated high potency and exquisite selectivity for LRRK2 and utility as chemical probes for the study of LRRK2 inhibition.

Neighborhood disorder and child behavioral problems among kinship children: Mediated by social support and moderated by race/ethnicity?

BACKGROUND: Children in kinship care may be placed in similar neighborhoods as their birth families, which are predominantly characterized as distressed neighborhoods with high poverty and crime rates, poor-quality housing conditions, and few social resources. Disordered neighborhoods are negatively correlated to social support, but this dynamic may vary by race or ethnicity. However, children's previously established attachment and social bonding may offset the negative effects of distressed neighborhoods on child behavioral health. OBJECTIVES: This study examined the relation between neighborhood disorder and children's internalizing and externalizing problems among children in kinship care and tested caregivers' social support as a potential mediator. Moreover, this study examined if race/ethnicity moderated the pathway from neighborhood disorder to social support, and from social support to children's internalizing and externalizing problems. PARTICIPANTS AND SETTING: This study used NSCAW II wave 3 data for a sample of children in kinship care. METHODS: Univariate, bivariate, and moderated mediation analyses were conducted using STATA 15. RESULTS: Neighborhood disorder was indirectly associated with children's internalizing and externalizing problems through a mediator of social support. No racial/ethnic differences were identified. CONCLUSIONS: Implications for improving social support for kinship caregivers to ameliorate the effects of neighborhood disorder on children's behavioral health are discussed. Implementing effective neighborhood-level interventions could promote positive outcomes for children in kinship care.

Children and youth in out-of-home care: What can predict an initial change in placement?

BACKGROUND: A significant proportion of children placed in out of-home care experience placement disruptions in the United States. Placement instability has deleterious effects on children's well-being. OBJECTIVES: (a) To measure the time-to-initial placement change in different types of settings, including non-relative foster homes, kinship care, residential treatment centers (RTC), group homes and other types of settings; and (b) To identify predictors of the initial placement change. PARTICIPANTS AND SETTING: Data were obtained from the State Automated Child Welfare Information System operated by the child welfare agency in a Mid-Atlantic state. The sample included 4177 children who entered into the foster care and were followed over three years. METHOD: Descriptive, bivariate, and survival Cox regression models were conducted. RESULTS: More than half (53%) of the children had experienced placement change within 3 years. The mean length for an initial change in placement was longer for children in RTC and kinship care compared to children in foster and group homes, and other placements (χ2 = 322.31, p < 0.001). Several factors significantly increased the likelihood of an initial change, including: older children (p < 0.001, HR = 1.01), children with behavioral problems (p < 0.001, HR = 1.26), parental substance abuse (p < 0.05, HR = 1.12), and cases in which the parents voluntarily gave up their parental rights (p < 0.05, HR = 1.12). The type of placement also increased the risk for placement change. CONCLUSIONS: Providing early interventions and services to these children and their families is essential to increase placement stability.

Impact of Inpatient Harms on Hospital Finances and Patient Clinical Outcomes.

OBJECTIVE: The aim of this study was to determine the impact of all-cause inpatient harms on hospital finances and patient clinical outcomes. RESEARCH DESIGN: A retrospective analysis of inpatient harm from 24 hospitals in a large multistate health system was conducted during 2009 to 2012 using the Institute of Healthcare Improvement Global Trigger Tool for Measuring Adverse Events. Inpatient harms were detected and categorized into harm (F-I), temporary harm (E), and no harm. RESULTS: Of the 21,007 inpatients in this study, 15,610 (74.3%) experienced no harm, 2818 (13.4%) experienced temporary harm, and 2579 (12.3%) experienced harm. A patient with harm was estimated to have higher total cost ($4617 [95% confidence interval (CI), $4364 to 4871]), higher variable cost ($1774 [95% CI, $1648 to $1900]), lower contribution margin (-$1112 [95% CI, -$1378 to -$847]), longer length of stay (2.6 d [95% CI, 2.5 to 2.8]), higher mortality probability (59%; odds ratio, 1.4 [95% CI, 1.0 to 2.0]), and higher 30-day readmission probability (74.4%; odds ratio, 2.9 [95% CI, 2.6 to 3.2]). A patient with temporary harm was estimated to have higher total cost ($2187 [95% CI, $2008 to $2366]), higher variable cost ($800 [95% CI, $709 to $892]), lower contribution margin (-$669 [95% CI, -$891 to -$446]), longer length of stay (1.3 d [95% CI, 1.2 to 1.4]), mortality probability not statistically different, and higher 30-day readmission probability (54.6%; odds ratio, 1.2 [95% CI, 1.1 to 1.4]). Total health system reduction of harm was associated with a decrease of $108 million in total cost, $48 million in variable cost, an increase of contribution margin by $18 million, and savings of 60,000 inpatient care days. CONCLUSIONS: This all-cause harm safety study indicates that inpatient harm has negative financial outcomes for hospitals and negative clinical outcomes for patients.

Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1).

Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified, and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors. Fragment hit-derived arylpyrrolo[2,3-b]pyridine LRRK2 inhibitors underwent structure-guided optimization using this crystallographic surrogate. LRRK2-pSer935 HEK293 IC50 data for 22 were consistent with binding to Ala2016 in LRRK2 (equivalent to Ala147 in CHK1 10-point mutant structure). Compound 22 was shown to be potent, moderately selective, orally available, and brain-penetrant in wild-type mice, and confirmation of target engagement was demonstrated, with LRRK2-pSer935 IC50 values for 22 in mouse brain and kidney being 1.3 and 5 nM, respectively.

Foster Care Reentry: A survival analysis assessing differences across permanency type.

Foster care reentry is an important factor for evaluating the overall success of permanency. Rates of reentry are typically only measured for 12-months and are often evaluated only for children who exit foster care to reunification and not across exit types, also known as 'permanency types'. This study examined the odds of reentry across multiple common permanency types for a cohort of 8107 children who achieved permanency between 2009 and 2013. Overall, 14% of children reentered care within 18-months with an average time to reentry of 6.36 months. A Kaplan-Meier survival analysis was used to assess differences in reentry across permanency types (including reunification, relative guardianship and non-relative guardianship). Children who achieved guardianship with kin had the lowest odds of reentry overall, followed by guardianship with non-kin, and reunification with family of origin. Children reunifying against the recommendations of Children and Family Services had the highest odds of reentry. A Cox regression survival analysis was conducted to assess odds of reentry across permanency type while controlling for demographics, services, and other risk factors. In the final model, only permanency type and cumulative risk were found to have a statistically significant impact on odds of reentry.

Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase.

Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro.

Child welfare outcomes for youth in care as a result of parental death or parental incarceration.

Every day, in the United States, children are removed from their homes and placed into state supervised out-of-home care because of concerns around their safety. These children enter care as a result of child abuse, child neglect, abandonment or some other reasons. Lost in most discussions of out-of-home care is the role that parental incarceration and parental death have on the trajectory of children through the child welfare system. In order to address this gap in the literature, the present study aims to compare youth in foster care as a result of parental death or youth in foster care as a result of parental incarceration with youth in care because of child maltreatment in terms of the length of time to achieve permanency. Holding all other variables constant, entering care as a result of parental death more than doubled the average time to exit (HR=2.32, SE=0.22), and these youth were significantly less likely to exit to permanency when compared to children entering care for other maltreatment reasons (OR=0.35, SE=0.24). Entering care as a result of parental incarceration led to a 24% longer time to exit (HR=1.24, SE=0.09) compared to children entering care for other maltreatment reasons. Findings suggest that a one-size-fits-all approach to policy and practice may not be useful to identifying permanent placements for children entering care as a result of parental death or incarceration.

Age-related trends in psychotropic medication use among very young children in foster care.

OBJECTIVES: The specific objectives were to investigate changes in the prevalence of psychotropic medication use for each year increase in age from three to six years old among children in foster care and to examine time-varying odds of longer duration of use by each year of age. METHODS: A retrospective analysis of data on mental health and pharmacy services was conducted for 1,491 children age six and younger who were in foster care in 2010 and had at least 365 days in foster care during 2009-2011. A total of 178 children received at least one psychotropic medication from 2009 through 2011. Psychotropic prevalence and average days of use were calculated for each therapeutic class. Longitudinal regression models assessed the time-varying relationship between year of age and duration of use, controlling for demographic and clinical covariates. RESULTS: Approximately 12% of children age six and younger in foster care for 365 days or more received at least one psychotropic medication over the three-year study period. Prevalence of ADHD medication and antipsychotic medication and duration increased with each year of age (p<.001). In adjusted longitudinal models, each year increase in age was associated with a nearly twofold higher likelihood of longer duration of antipsychotic and ADHD medication use. CONCLUSIONS: Young children who initiated antipsychotic and ADHD medications before the age of six continued to receive them for longer periods of time. There is a critical need for long-term studies to evaluate the effect of chronic exposure on children's health and well-being.

The effect of deployment, distress, and perceived social support on Army spouses' weight status.

UNLABELLED: This study examined the relationship between deployment status, psychological distress, perceived social support, age, rank, and gender with Army spouses' (N=1863) weight status. We posited that spouses of deployed Soldiers have a higher body mass index (BMI) than spouses of nondeployed Soldiers; spouses with higher psychological distress scores have a higher BMI than those with lower distress scores; and spouses with low social support scores have higher BMIs than those with higher social support scores. METHOD: Secondary analysis of data from the 2008 Active Duty Spouse Survey was used to examine the relationship between weight status (health versus overweight or obese) and Army spouses' deployment status, demographic characteristics, psychological distress, and perceived social support. RESULTS: Deployment status and weight status were not related (P=.097). Male spouses were significantly more likely than female spouses to be overweight or obese. Psychological distress increased in direct correlation with increased age, and as perceived social support decreased, the incidents of being overweight or obese increased. CONCLUSIONS: Findings suggest several risk factors are associated with being overweight or obese: male spouse, noncommissioned officers in the ranks of E5 through E9, older age, higher psychological distress scores, and lower perceived social support scores. The risk factors support the use of the Army Surgeon General's Performance Triad of sleep, activity, and nutrition as a tool to assist Army personnel and Department of the Army civilians in teaching spouses awareness and methods of changing behaviors that may result in choosing healthy options.

Estimating staffing needs for in-home child welfare services with a weighted caseload formula.

State child welfare risk and safety assessment data were analyzed to determine three levels of in-home service that correspond to the Child Welfare League of America's (CWLA) national caseload standards and to evaluate the number of staff needed to provide services at each level. The analysis revealed that 50% additional case-carrying in-home services staff were needed to provide appropriate risk- and safety-based services to children in their own homes. Findings from this study were used by the state child welfare services agency to allocate vacant worker positions to local jurisdictions.

Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.

78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K(D) = 80 nM and 14 with K(D) = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.

Diagnostic utility of the structured inventory of malingered symptomatology to detect malingering in a forensic sample.

The Structured Inventory of Malingered Symptomatology (SIMS) is a 75-item, self-report measure to be used with individuals at least 18 years of age, which may be utilized to assess potential malingering of psychosis, neurologic impairment, amnesia, low intelligence, or affective disorder. However, no studies in the literature have examined the diagnostic validity of this instrument in a known-groups design involving medicolegal referrals diagnosed as malingering using the criteria outlined by Slick and colleagues [Slick, D. J., Sherman, E. M. S., & Iverson, G. L. (1999). Diagnostic criteria for malingered neurocognitive dysfunction: Proposed standards for clinical practice and research. The Clinical Neuropsychologist, 13, 545-561]. The current known-groups, archival study was designed to examine the effectiveness of the SIMS at identifying malingering in patients involved in personal injury lawsuits or disability claims. Findings indicate that a higher cut score on the SIMS for identification of malingering may be appropriate for use with this population. Limitations, clinical implications, and suggestions for further research are discussed.

A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells.

PURPOSE: The anti-apoptotic function of the 70 kDa family of heat shock proteins and their role in cancer is well documented. Dual targeting of Hsc70 and Hsp70 with siRNA induces proteasome-dependent degradation of Hsp90 client proteins and extensive tumor specific apoptosis as well as the potentiation of tumor cell apoptosis following pharmacological Hsp90 inhibition. METHODS: We have previously described the discovery and synthesis of novel adenosine-derived inhibitors of the 70 kDa family of heat shock proteins; the first inhibitors described to target the ATPase binding domain. The in vitro activity of VER-155008 was evaluated in HCT116, HT29, BT474 and MDA-MB-468 carcinoma cell lines. Cell proliferation, cell apoptosis and caspase 3/7 activity was determined for VER-155008 in the absence or presence of small molecule Hsp90 inhibitors. RESULTS: VER-155008 inhibited the proliferation of human breast and colon cancer cell lines with GI(50)s in the range 5.3-14.4 microM, and induced Hsp90 client protein degradation in both HCT116 and BT474 cells. As a single agent, VER-155008 induced caspase-3/7 dependent apoptosis in BT474 cells and non-caspase dependent cell death in HCT116 cells. VER-155008 potentiated the apoptotic potential of a small molecule Hsp90 inhibitor in HCT116 but not HT29 or MDA-MB-468 cells. In vivo, VER-155008 demonstrated rapid metabolism and clearance, along with tumor levels below the predicted pharmacologically active level. CONCLUSION: These data suggest that small molecule inhibitors of Hsc70/Hsp70 phenotypically mimic the cellular mode of action of a small molecule Hsp90 inhibitor and can potentiate the apoptotic potential of a small molecule Hsp90 inhibitor in certain cell lines. The factors determining whether or not cells apoptose in response to Hsp90 inhibition or the combination of Hsp90 plus Hsc70/Hsp70 inhibition remain to be determined.

Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.

The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.

Measuring racial disparity in child welfare.

Overrepresentation of certain racial/ethnic groups in the foster care system is one of the most troubling and challenging issues in child welfare today. In response, many states have started reporting outcomes by race and ethnicity to identify disproportionately high rates of system contact. The identification of disproportional representation is the first step in developing targeted strategies to address disproportionality--highlighting where resources should be directed and guiding future research. However, present and future efforts to address disproportionality must be accompanied by statistically sound and meaningful methods of measurement. In this article, we argue for the adoption of a relative rate measure of representation--a "Disparity Index"--as the primary instrument for assessing racial disparity in child welfare.

Children ever in care: an examination of cumulative disproportionality.

Most studies of ethnic disproportionality in child welfare examine data in one of two ways: a point in time approach or an entry cohort approach. While each provides insight into disproportionality, neither gives a full picture of the differences among ethnic groups in the experience of the child welfare system over time. This study uses longitudinal administrative child welfare data to examine ethnic disproportionality in involvement with the child welfare system during the first seven years of life at three levels of contact: (1) initial referrals, (2) substantiated referrals, and (3) first entries. Findings suggest the experience of African American families, and probably Native American families, with the child welfare system is much different from other families.

The National Health Service Corps and Medicaid inpatient care: experience in a southern state.

BACKGROUND: Since 1970, the National Health Service Corps (NHSC) has worked to increase primary care access among underserved groups. This study examined whether NHSC alumni physicians were likely to treat a high proportion of Medicaid patients in their practices. METHODS: Using licensure files and hospital discharge data, we identified all physicians practicing in South Carolina who attended at least one discharge in 1998, excluding physicians who graduated before 1969, residents, and current NHSC-obligated physicians. The outcome studied was ranking in the highest quartile for Medicaid participation. RESULTS: Former NHSC participants, after adjustment for personal characteristics, education, and specialty, were nearly twice as likely to fall into the category of high Medicaid participation. NHSC physicians were more likely to practice in community health centers and to locate in areas with a health professions shortage and counties with high percentages of minorities and people living in poverty. CONCLUSION: NHSC alumni make career choices leading them to serve low-income patients.