Polygenic risk scores and the need for pharmacotherapy in neonatal abstinence syndrome.

BACKGROUND: The aim of this study was to identify genetic variants associated with NAS through a genome-wide association study (GWAS) and estimate a Polygenic Risk Score (PRS) model for NAS. METHODS: A prospective case-control study included 476 in utero opioid-exposed term neonates. A GWAS of 1000 genomes-imputed genotypes was performed to identify variants associated with need for pharmacotherapy for NAS. PRS models for estimating genetic predisposition were generated via a nested cross-validation approach using 382 neonates of European ancestry. PRS predictive ability, discrimination, and calibration were assessed. RESULTS: Cross-ancestry GWAS identified one intergenic locus on chromosome 7 downstream of SNX13 exhibiting genome-wide association with need for pharmacotherapy. PRS models derived from the GWAS for a subset of the European ancestry neonates reliably discriminated between need for pharmacotherapy using cis variant effect sizes within validation sets of European and African American ancestry neonates. PRS were less effective when applying variant effect sizes across datasets and in calibration analyses. CONCLUSIONS: GWAS has the potential to identify genetic loci associated with need for pharmacotherapy for NAS and enable development of clinically predictive PRS models. Larger GWAS with additional ancestries are needed to confirm the observed SNX13 association and the accuracy of PRS in NAS risk prediction models. IMPACT: Genetic associations appear to be important in neonatal abstinence syndrome. This is the first genome-wide association in neonates with neonatal abstinence syndrome. Polygenic risk scores can be developed examining single-nucleotide polymorphisms across the entire genome. Polygenic risk scores were higher in neonates receiving pharmacotherapy for treatment of their neonatal abstinence syndrome. Future studies with larger cohorts are needed to better delineate these genetic associations.

Clinical integration of patient-reported outcome measures to enhance the care of patients with SLE: a multi-centre prospective cohort study.

OBJECTIVE: To assess the feasibility and impact of integrating electronic patient-reported outcome measures (PROMs) into the routine outpatient care of patients with SLE. METHODS: We conducted a prospective cohort study, utilizing a mixed-methods sequential explanatory design, of SLE outpatients receiving rheumatology care at two academic medical centres. Participants completed electronic PROMs at enrolment and then prior to their next two routine rheumatology visits. PROM score reports were shared with patients and rheumatologists before visits. Patients and rheumatologists completed post-visit surveys evaluating the utility of PROMs in the clinical encounters. Focus groups of patients and interviews with treating rheumatologists were conducted to further explore their experience utilizing PROMs. RESULTS: A total of 105 SLE patients and 17 rheumatologists participated in the study. Patients completed PROMs in 159 of 184 encounters (86%), with 93% of surveys completed remotely. Patients reported that PROMs were 'quite a bit' or 'very' useful (55% of encounters) and beneficial to communication (55% of encounters). In contrast, physicians found PROMs useful (20%) and beneficial to communication (17%) less frequently. There was no significant change in visit length, health-related quality of life or disease activity after implementation of PROMs; however, patient satisfaction improved slightly. Qualitative analyses revealed that patients felt PROMs provided utility primarily by facilitating communication, particularly when physicians discussed the surveys. CONCLUSION: The remote capture and integration of electronic PROMs into clinical care was feasible in a diverse cohort of SLE outpatients. PROMs were useful to patients and enhanced their clinical experience primarily by facilitating communication.

Effect of Ventral vs Dorsal Spinal Surgery on Patient-Reported Physical Functioning in Patients With Cervical Spondylotic Myelopathy: A Randomized Clinical Trial.

Importance: Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. Objective: To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. Design, Setting, and Participants: Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. Interventions: Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon's discretion. Main Outcomes and Measures: The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. Results: Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, -2.6 to 3.1; P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%; P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). Conclusions and Relevance: Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. Trial Registration: ClinicalTrials.gov Identifier: NCT02076113.

Is insurance instability associated with hypertension outcomes and does this vary by race/ethnicity?

BACKGROUND: Stable health insurance is often associated with better chronic disease care and outcomes. Racial/ethnic health disparities in outcomes are prevalent and may be associated with insurance instability, particularly in the context of health insurance reform. METHODS: We examined whether insurance instability was associated with uncontrolled blood pressure (UBP) and whether this association varied by race/ethnicity. We used a retrospective longitudinal observational cohort study of patients diagnosed with hypertension who obtained care within two health systems in Massachusetts. We measured the UBP, insurance instability, and race of 43,785 adult primary care patients, age 21-64 with visits from 1/2005-12/2013. RESULTS: We found higher rates of UBP for blacks and Hispanics at each time point over the entire 9 years. Insurance instability was associated with greater rates of UBP. Always uninsured black patients fared worst, while white and Hispanic patients with consistent public insurance fared best. CONCLUSIONS: Stable insurance of any type was associated with better hypertension control than no or unstable insurance.

Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis.

BACKGROUND: The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS: In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS: A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS: Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

Racial Differences in Insurance Stability After Health Insurance Reform.

BACKGROUND: One of the potential benefits of insurance reform is greater stability of insurance and reduced coverage disparities by race and ethnicity. OBJECTIVES: We examined the temporal trends in insurance coverage by racial/ethnic group before and after Massachusetts Insurance Reform by abstracting records across 2 urban safety net hospital systems. RESEARCH DESIGN: We examined adjusted odds of being uninsured and incident rate ratios of gaining and losing insurance over time by race and ethnicity. We used billing records to capture the payer for each episode of care. SUBJECTS: We included data from January 2005 through December 2013 on patients with hypertension between the ages of 21 and 64 years. We compared 4 racial and ethnic groups: non-Hispanic white, non-Hispanic Black, non-Hispanic Asian, and Hispanic. MEASURES: We examined individual patients' insurance coverage status in 6-month intervals. We compared odds of being uninsured in the transition and postinsurance reform period to the prereform period, adjusting for age, sex, comorbidities practice location and education, and income by Census tract. RESULTS: Among 48,291 patients with hypertension, reduction in rates of uninsurance with insurance reform was greater for Hispanic (29.7%), non-Hispanic Black (24.8%), and non-Hispanic Asian (26.8%) than non-Hispanic white (14.9%) patients. The odds of becoming uninsured were reduced in all racial and ethnic groups (odds ratio, 0.27-0.41). CONCLUSIONS: Massachusetts Insurance Reform resulted in stable insurance coverage and a reduction in disparities in insurance instability by race and ethnicity.

The role of recombinant human CC10 in the prevention of chronic pulmonary insufficiency of prematurity.

BACKGROUND: Preterm neonates can develop chronic pulmonary insufficiency of prematurity (CPIP) later in infancy. Recombinant human CC10 protein (rhCC10) is an anti-inflammatory agent that could potentially prevent CPIP. METHODS: The safety and efficacy of a single intratracheal dose of rhCC10 in reducing CPIP at 12 months corrected gestational age (CGA) was evaluated in a Phase II double-blind, randomized, placebo-controlled, multisite clinical trial. Eighty-eight neonates were randomized: 22 to placebo and 22 to 1.5 mg/kg rhCC10 in the first cohort and 21 to placebo and 23 to 5 mg/kg rhCC10 in the second cohort. Neonates were followed to 12 months CGA. RESULTS: With CPIP defined as signs/symptoms, medical visits, hospital readmissions, and use of medications for respiratory complications at 12 months CGA, no significant differences were observed between rhCC10 or placebo groups. Only 5% of neonates had no evidence of CPIP at 12 months CGA. CONCLUSIONS: A single dose of rhCC10 was not effective in reducing CPIP at 12 CGA. Since most neonates had evidence of CPIP using these exploratory endpoints, it is essential to develop more robust outcome measures for clinical trials of respiratory medications in high-risk premature neonates.

Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta-analysis.

Patients with resolved hepatitis B virus (HBV) infection who are treated for hematological malignancies remain at risk for HBV reactivation. Because of conflicting studies about whether the antibody to hepatitis B surface antigen (anti-HBs) protects against reactivation in patients with resolved infection (hepatitis B surface antigen negative) receiving chemotherapy for hematological malignancies, we conducted a meta-analysis to determine if anti-HBs reduces HBV reactivation risk. We sought English-language studies through March 1, 2016, in Medline and other sources that examined reactivation in patients with resolved HBV infection receiving chemotherapy for hematologic malignancies. The absolute risks and odds ratio (OR) of reactivation with versus without anti-HBs were estimated in random-effects model meta-analyses. In 20 studies involving 1,672 patients not receiving antiviral prophylaxis, the reactivation risk was 14% (95% confidence interval [CI] 9.4%-19%) in 388 patients who had antibodies to hepatitis B core antigen only versus 5.0% (95% CI 3.0%-7.0%) in 1,284 patients who also had anti-HBs. Anti-HBs reduced reactivation risk with a pooled OR of 0.21 (95% CI 0.14-0.32) versus patients with antibody to hepatitis B core antigen only. Similar results were found when limiting the analysis to rituximab chemotherapy (OR = 0.19, 95% CI 0.11-0.32) and lymphoma (OR = 0.18, 95% CI 0.11-0.28). CONCLUSION: In patients with resolved HBV receiving chemotherapy for hematological malignancies without antiviral prophylaxis, anti-HBs positivity is associated with a decreased risk of reactivation; HBV screening in this patient population should include the routine use of anti-HBs, and those who are anti-HBs-negative should receive antiviral prophylaxis. Future studies should examine the effect of anti-HBs serum titers, the potential role for booster vaccinations, and antiviral prophylaxis prior to chemotherapy in this patient population. (Hepatology 2017;66:379-388).

Three sides to a story: Child, parent, and nurse perspectives on the child's experience during hematopoietic stem cell transplantation.

BACKGROUND: The experience of children undergoing hematopoietic stem cell transplantation (HSCT), including the ways in which different participants (ie, children, parents, and nurses) contribute to the overall picture of a child's experience, is poorly characterized. This study evaluated parent, child, and nurse perspectives on the experience of children during HSCT and factors contributing to interrater differences. METHODS: Participants were enrolled in a multicenter, prospective study evaluating child and parent health-related quality of life over the year after HSCT. Children (n = 165) and their parents and nurses completed the Behavioral, Affective, and Somatic Experiences Scale (BASES) at baseline (before/during conditioning), 7 days after the stem cell infusion (day+7), and 21 days after the stem cell infusion (day+21). The BASES domains included Somatic Distress, Mood Disturbance, Cooperation, and Getting Along. Higher scores indicated more distress/impairment. Repeated measures models by domain assessed differences by raters and changes over time and identified other factors associated with raters' scores. RESULTS: Completion rates were high (≥73% across times and raters). Multivariate models revealed significant time-rater interactions, which varied by domain. For example, parent-rated Somatic Distress scores increased from baseline to day+7 and remained elevated at day+21 (P < .001); children's scores were lower than parents' scores across time points. Nurses' baseline scores were lower than parents' baseline scores, although by day+21 they were similar. Older child age was associated with higher Somatic Distress and Mood Disturbance scores. Worse parent emotional functioning was associated with lower scores across raters and domains except for Cooperation. CONCLUSIONS: Multirater assessments are highly feasible during HSCT. Ratings differ by several factors; considering ratings in light of such factors may deepen our understanding of the child's experience. Cancer 2017;123:3159-66. © 2017 American Cancer Society.

Lower Rates of Promotion of Generalists in Academic Medicine: A Follow-up to the National Faculty Survey.

BACKGROUND: Prior cross-sectional research has found that generalists have lower rates of academic advancement than specialists and basic science faculty. OBJECTIVE: Our objective was to examine generalists relative to other medical faculty in advancement and academic productivity. DESIGN: In 2012, we conducted a follow-up survey (n = 607) of 1214 participants in the 1995 National Faculty Survey cohort and supplemented survey responses with publicly available data. PARTICIPANTS: Participants were randomly selected faculty from 24 US medical schools, oversampling for generalists, underrepresented minorities, and senior women. MAIN MEASURES: The primary outcomes were (1) promotion to full professor and (2) productivity, as indicated by mean number of peer-reviewed publications, and federal grant support in the prior 2 years. When comparing generalists with medical specialists, surgical specialists, and basic scientists on these outcomes, we adjusted for gender, race/ethnicity, effort distribution, parental and marital status, retention in academic career, and years in academia. When modeling promotion to full professor, we also adjusted for publications. KEY RESULTS: In the intervening 17 years, generalists were least likely to have become full professors (53%) compared with medical specialists (67%), surgeons (66%), and basic scientists (78%, p < 0.0001). Generalists had a lower number of publications (mean = 44) than other faculty [medical specialists (56), surgeons (57), and basic scientists (83), p < 0.0001]. In the prior 2 years, generalists were as likely to receive federal grant funding (26%) as medical (21%) and surgical specialists (21%), but less likely than basic scientists (51%, p < 0.0001). In multivariable analyses, generalists were less likely to be promoted to full professor; however, there were no differences in promotion between groups when including publications as a covariate. CONCLUSIONS: Between 1995 and 2012, generalists were less likely to be promoted than other academic faculty; this difference in advancement appears to be related to their lower rate of publication.

Understanding the Relationship Between Child Health-Related Quality of Life and Parent Emotional Functioning in Pediatric Hematopoietic Stem Cell Transplant.

Objective: Explore interrelationships between domains of child health-related quality of life (HRQL) and parent emotional functioning using parent-proxy and child report in the context of hematopoietic stem cell transplant (HSCT). Methods: Data on 258 parent-child dyads were used from two longitudinal studies. Domains of HRQL included physical, emotional, and role functioning, and HSCT-related worry. We used structural equation modeling to model the outcome of parent emotional functioning using primary and alternative conceptual models. Results: Parent-proxy raters reported lower child HRQL than child raters. Structural equation models demonstrated relationships between child emotional functioning, child HSCT-related worry, and parent emotional functioning, with some differences by raters. Conclusions: Relationships between child HRQL and parent emotional functioning within the context of HSCT are complex. To optimize the child's health outcomes, providing psychosocial support for children and their families may be necessary, especially for those experiencing distress or facing treatment complications.

Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of insufficient evidence. PURPOSE: To determine the risk for HBV reactivation with and without antiviral prophylaxis and the effectiveness of prophylaxis in adults with solid tumors and chronic or resolved HBV infection. DATA SOURCES: MEDLINE through 1 July 2015 and Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus through 1 March 2015. STUDY SELECTION: 26 English-language observational studies and randomized, controlled trials in patients with chronic or resolved HBV receiving chemotherapy for solid tumors. DATA EXTRACTION: Study characteristics, quality, and risk of bias were assessed by 1 researcher and verified by another independent researcher. DATA SYNTHESIS: Random-effects model meta-analyses were used to estimate the risk and odds ratio (OR) of reactivation with versus without antiviral prophylaxis. Reactivation in chronic HBV without prophylaxis ranged from 4% to 68% (median, 25%) with substantial heterogeneity. Prophylaxis reduced the risk for HBV reactivation (OR, 0.12 [95% CI, 0.06 to 0.22]), HBV-related hepatitis (OR, 0.18 [CI, 0.10 to 0.32]), and chemotherapy interruption (OR, 0.10 [CI, 0.04 to 0.27]). In 3 studies of patients with resolved HBV infection, none received HBV prophylaxis and reactivation risk ranged from 0.3% to 9.0%. LIMITATIONS: Significant heterogeneity in underlying study populations and treatment regimens, incomplete baseline data, possibility of publication bias, and limited study quality. Most studies were observational and from Asia. CONCLUSION: In patients with chronic HBV receiving solid tumor chemotherapy, the risk for HBV reactivation is similar to the risk with other types of immunosuppressive therapy. Results support HBV screening and antiviral prophylaxis before initiation of chemotherapy for solid tumors. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences and National Institutes of Health.

Joint models for predicting transplant-related mortality from quality of life data.

PURPOSE: To test whether longitudinally measured health-related quality of life (HRQL) predicts transplant-related mortality (TRM) in pediatric hematopoietic stem cell transplant (HSCT). METHODS: The predictors of interest were emotional functioning, physical functioning, role functioning, and global HRQL, as rated by the parent about the child up to 6 times over 12 months of follow-up and measured by the Child Health Ratings Inventories. We used joint models, specifically shared parameter models, with time to TRM as the outcome of interest and other causes of mortality as a competing risk, via the JM software package in R. Choosing shared parameter models instead of standard survival models, such as Cox models with time-dependent covariates, enabled us to address measurement error in the HRQL trajectories and appropriately handle missing data. The nonlinear trajectories for each HRQL domain were modeled by random spline functions. The survival submodels were adjusted for baseline patient, family, and transplant characteristics. RESULTS: Hazard ratios per one-half standard deviation difference in emotional, physical, and role functioning, and global HRQL were 0.61 (95 % CI 0.46-0.81; p < 0.001), 0.70 (0.51-0.96; p = 0.03), 0.54 (0.34-0.85; p = 0.007), and 0.57 (0.41-0.79; p < 0.001), respectively. CONCLUSIONS: HRQL trajectories were predictive of TRM in pediatric HSCT, even after adjusting the survival outcome for baseline characteristics.

Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.

OBJECTIVE: Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants with NAS outcomes. STUDY DESIGN: DNA samples from cord blood or saliva were analyzed for 86 infants who were being treated for NAS according to institutional protocol. Methylation levels at 16 OPRM1 CpG sites were determined and correlated with NAS outcome measures, including need for treatment, treatment with ≥ 2 medications, and length of hospital stay. We adjusted for covariates and multiple genetic testing. RESULTS: Sixty-five percent of infants required treatment for NAS, and 24% required ≥ 2 medications. Hypermethylation of the OPRM1 promoter was measured at the -10 CpG in treated vs nontreated infants (adjusted difference δ = 3.2% [95% CI, 0.3-6.0%], P = .03; nonsignificant after multiple testing correction). There was hypermethylation at the -14 (δ = 4.9% [95% CI, 1.8%-8.1%], P = .003), -10 (δ = 5.0% [95% CI, 2.3-7.7%], P = .0005), and +84 (δ = 3.5% [95% CI, 0.6-6.4], P = .02) CpG sites in infants requiring ≥ 2 medications, which remained significant for -14 and -10 after multiple testing correction. CONCLUSIONS: Increased methylation within the OPRM1 promoter is associated with worse NAS outcomes, consistent with gene silencing.

Emergence and evolution of social self-management of Parkinson's disease: study protocol for a 3-year prospective cohort study.

BACKGROUND: Parkinson's disease affects facial, vocal and trunk muscles. As symptoms progress, facial expression becomes masked, limiting the person's ability to communicate emotions and intentions to others. As people with the disease live and reside in their homes longer, the burden of caregiving is unmitigated by social and emotional rewards provided by an expressive individual. Little is known about how adults living with Parkinson's disease manage their social lives and how an inability to be emotionally expressive can affect social connections and health. Because social networks have been shown to be crucial to the overall well-being of people living with chronic diseases, research is needed on how expressive capacity affects life trajectories and health. METHODS/DESIGN: The overall objective is to understand the emergence and evolution of the trajectories of the self-management of the social lives of people living with Parkinson's disease. The central hypothesis is that expressive capacity predicts systematic change in the pattern of social self-management and quality of life outcomes. The specific aims of this 3-year longitudinal study of 120 people with the disease and a maximum of 120 care partners are: 1) characterize social self-management trajectories over a 3-year period; 2) estimate the degree to which expressive nonverbal capacity predicts the trajectory; and 3) determine the moderating effect of gender on the association between expressive capacity and change in social self-management. Each participant will be assessed 14 times to detect rapid and non-linear changes in social participation and management of social activities; social network; and social comfort, general health and well-being. DISCUSSION: This project will provide evidence to guide the development of interventions for supporting social integration of those living with Parkinson's disease, thus leading to improved overall health. It focuses on the novel construct of social self-management and known factors-expressive capacity and gender-that contribute to stigmatization. The repeated measures design detects triggers of rapid changes in social and health outcomes.

Performance of urinary liver-type fatty acid-binding protein in acute kidney injury: a meta-analysis.

BACKGROUND: Urinary liver-type fatty acid-binding protein (L-FABP) is a proximal tubular injury candidate biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical settings. STUDY DESIGN: Meta-analysis of diagnostic test studies assessing the performance of urinary L-FABP in AKI. SETTING & POPULATION: Literature search in MEDLINE, EMBASE, Scopus, Google Scholar, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov using search terms "liver-type fatty acid-binding protein" and "L-FABP." SELECTION CRITERIA FOR STUDIES: Studies of humans investigating the performance characteristics of urinary L-FABP for the early diagnosis of AKI and AKI-related outcomes, including dialysis requirement and mortality. PREDICTOR: Urinary L-FABP. OUTCOMES: Diagnosis of AKI, dialysis requirement, and in-hospital death. RESULTS: 15 prospective cohort and 2 case-control studies were identified. Only 7 cohort studies could be meta-analyzed. The estimated sensitivity of urinary L-FABP level for the diagnosis of AKI was 74.5% (95% CI, 60.4%-84.8%), and specificity was 77.6% (95% CI, 61.5%-88.2%). The estimated sensitivity of urinary L-FABP level for predicting dialysis requirement was 69.1% (95% CI, 34.6%-90.5%), and specificity was 42.7% (95% CI, 3.1%-94.5%); for in-hospital mortality, sensitivity and specificity were 93.2% (95% CI, 66.2%-99.0%) and 78.8% (95% CI, 27.0%-97.4%), respectively. LIMITATIONS: Paucity and low quality of studies, different clinical settings, and variable definitions of AKI. CONCLUSIONS: Although urinary L-FABP may be a promising biomarker for early detection of AKI and prediction of dialysis requirement and in-hospital mortality, its potential value needs to be validated in large studies and across a broader spectrum of clinical settings.

Measuring global health-related quality of life in children undergoing hematopoietic stem cell transplant: a longitudinal study.

BACKGROUND: Pediatric health-related quality of life (HRQL) measures explore multiple domains of HRQL. To ease administration, burden, and implementation, we created a 7-item unidimensional global HRQL scale for children. This paper evaluates the psychometric properties of the global HRQL scale in children undergoing hematopoietic stem cell transplant (HSCT) and describes the trajectory of global HRQL scores over the 12-month course following HSCT. METHODS: As part of two longitudinal HSCT studies, HRQL was collected on 312 parent-child dyads using the Child Health Ratings Inventories. Parents of children aged 5-18 completed the pediatric global HRQL scale about their child and 117 adolescents completed the scale themselves. Psychometric properties were compared across both raters. Two repeated measures models were built to describe trajectories of (1) global HRQL for all children based on parent proxy report and (2) global HRQL for adolescents based on adolescent self-report and parent proxy report. RESULTS: Internal consistency reliability was high for parent proxy report and adolescent self-report (Cronbach's alpha 0.9, 0.8, respectively). Unidimensionality was verified using principal components analysis. Both models indicated decreased global HRQL in the presence of early complications related to HSCT and Model 1 further indicated decreased HRQL in the presence of later complications. Model 2 showed that parent proxies reported lower global HRQL scores than adolescent self-report. CONCLUSIONS: This study has demonstrated the unidimensionality and strong psychometric properties of a 7-item global HRQL scale in a sample of children undergoing HSCT. Despite its brevity, scale scores vary in clinically meaningful ways. Future applications of this scale are encouraged.

Parental emotional functioning declines with occurrence of clinical complications in pediatric hematopoietic stem cell transplant.

PURPOSE: Parents' stress levels are high prior to their child's hematopoietic stem cell transplant (HSCT) and during transplant hospitalization, usually abating after discharge. Nevertheless, a subgroup of parents continues to experience frequent anxiety and mood disruption, the causes of which are not well understood. The purpose of this study was to assess whether clinical complications of HSCT could explain variation in parents' recovery of emotional functioning. METHODS: Pediatric HSCT recipients (n = 165) aged 5-18 and their parents were followed over the first year post-transplant. Health-related quality of life assessments and medical chart reviews were performed at each time period (baseline, 45 days, 3, 6, and 12 months). We tested the association between clinical complications [acute and chronic graft versus host disease (aGVHD and cGVHD), organ toxicity, and infection] and longitudinally measured parental emotional functioning, as assessed by the Child Health-Ratings Inventories. The models used maximum likelihood estimation with repeated measures. RESULTS: In adjusted analyses covering the early time period (45 days and 3 months), aGVHD grade ≥2, intermediate or poor organ toxicity, and systemic infection were associated with decreases in mean parental emotional functioning of 5.2 (p = 0.086), 5.8 (p = 0.052), and 5.1 (p = 0.023) points, respectively. In the later time period (6 and 12 months), systemic infection was associated with a decrease of 20 points (p < 0.0001). cGVHD was not significantly associated. CONCLUSIONS: When children experience clinical complications after HSCT, parental emotional functioning can be impacted. Intervening at critical junctures could mitigate potential negative consequences for parents and their children.

Performance of the parent emotional functioning (PREMO) screener in parents of children undergoing hematopoietic stem cell transplantation.

PURPOSE: Parents of children undergoing hematopoietic stem cell transplantation (HSCT) may face emotional distress while managing intense treatments with uncertain outcomes. We evaluated a brief parental emotional functioning (PREMO) screener from a health-related quality of life instrument to identify parental emotional distress, as measured by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). METHODS: As part of a longitudinal pediatric HSCT study, parents (N = 165) completed the Child Health Ratings Inventories, which contain the 7-item PREMO screener. Some parents (n = 117) also completed SCID modules for Anxiety, Mood, and Adjustment disorders at baseline and/or 12 months. A composite outcome was created for threshold or subthreshold levels of any of these disorders. Receiver operating characteristic (ROC) analysis assessed how the PREMO screener predicted emotional distress as measured by the SCID. A prediction model was then built. RESULTS: Fifty-two percent of parents completing the SCID had an Axis I disorder at baseline, while 41 % had an Axis I disorder at 12 months. The area under the ROC curve was 0.75 for the PREMO screener and 0.81 for the prediction model. CONCLUSIONS: The PREMO screener may identify parents with, or at risk for, emotional distress and facilitate further evaluation and intervention.

Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome.

IMPORTANCE: Neonatal abstinence syndrome (NAS) caused by in utero opioid exposure is a growing problem; genetic factors influencing the incidence and severity have not been previously examined. Single-nucleotide polymorphisms (SNPs) in the µ-opioid receptor (OPRM1), multidrug resistance (ABCB1), and catechol-o-methyltransferase (COMT) genes are associated with risk for opioid addiction in adults. OBJECTIVE: To determine whether SNPs in the OPRM1, ABCB1, and COMT genes are associated with length of hospital stay and the need for treatment of NAS. DESIGN, SETTING, AND PARTICIPANTS: Prospective multicenter cohort study conducted at 5 tertiary care centers and community hospitals in Massachusetts and Maine between July 2011 and July 2012. DNA samples were genotyped for SNPs, and then NAS outcomes were correlated with genotype. Eighty-six of 140 eligible mother-infant dyads were enrolled. Infants were eligible if they were 36 weeks' gestational age or older and exposed to methadone or buprenorphine in utero . MAIN OUTCOMES AND MEASURES: Primary outcome measure was length of hospital stay, with between-group differences expressed as ß and calculated with linear regression models. Secondary outcome measures included need for any medical treatment for NAS and treatment with 2 or more medications. RESULTS: Infants with the OPRM1 118A>G AG/GG genotype had shortened length of stay (ß = -8.5 days; 95% CI, -14.9 to -2.1 days; P = .009) and were less likely to receive any treatment than AA infants (48% vs 72%; adjusted odds ratio, 0.76; 95% CI, 0.63-0.96; P = .006). The COMT 158A>G AG/GG genotype was associated with shortened length of stay (ß = -10.8 days; 95% CI, -18.2 to -3.4 days; P = .005) and less treatment with 2 or more medications (18% vs 56%; adjusted odds ratio, 0.68; 95% CI, 0.55-0.86; P = .001) than the AA genotype. Associations with the ABCB1 SNPs were not significant. CONCLUSIONS AND RELEVANCE: Among infants with NAS, variants in the OPRM1 and COMT genes were associated with a shorter length of hospital stay and less need for treatment. These preliminary findings may provide insight into the mechanisms underlying NAS.