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Purpose Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs). Materials and methods We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and identified 619 proteins composing the core ESFT sEV proteome. We compared these core proteins to databases of common plasma-based proteins and sEV-associated proteins found within healthy plasma to identify proteins unique or enriched within ESFT. Results From these analyses, two membrane bound proteins with biomarker potential were selected, CD99/MIC2 and NGFR, to develop a liquid-based assay enriching of ESFT-associated sEVs and detection of sEV mRNA cargo (i.e., EWS-ETS transcripts). We employed this immuno-enrichment approach to diagnosis of ESFT utilizing plasma (250 μl) from both localized and metastatic ESFT pediatric patients and cancer-free controls, and showed significant diagnostic power [AUC = 0.92, p = 0.001 for sEV numeration, with a PPV = 1.00, 95% CI = (0.63, 1.00) and a NPV = 0.67, 95% CI = (0.30, 0.93)]. Conclusions In this study, we demonstrate utilization of circulating ESFT-associated sEVs in pediatric patients as a source of minimally invasive diagnostic and potentially prognostic biomarkers.

The ultrafiltrate flow over the major processes and cell body generates fluid flow shear stress (FFSS) on podocytes. Hyperfiltration-associated increase in FFSS can lead to podocyte injury and detachment. Previously, we showed that FFSS-induced upregulation of the cyclooxygenase 2 (COX2)-PGE2-prostaglandin E receptor 2 (EP2) axis in podocytes activates Akt-glycogen synthase kinase-3β-β-catenin and MAPK/ERK signaling in response to FFSS. Integrative MultiOmics Pathway Resolution (IMPRes) is a new bioinformatic tool that enables simultaneous time-series analysis of more than two groups to identify pathways and molecular connections. In the present study, we used previously characterized COX2 [prostaglandin-endoperoxide synthase 2 ( Ptgs2)], EP2 ( Ptger2), and β1-catenin ( Ctnnb1) as “seed genes” from an array data set of four groups analyzed over a time course. The 3 seed genes shared 7 pathways and 50 genes of 14 pathways and 89 genes identified by IMPRes. A composite of signaling pathways highlighted the temporal molecular connections during mechanotransduction signaling in FFSS-treated podocytes. We investigated the “proteoglycans in cancer” and “galactose metabolism” pathways predicted by IMPRes. A custom-designed PCR array validated 60.7% of the genes predicted by IMPRes analysis, including genes for the above-named pathways. Further validation using Western blot analysis showed increased expression of phosho-Erbb2, phospho-mammalian target of rapamycin (mTOR), CD44, and hexokinase II (Hk2); decreased total Erbb2, galactose mutarotase (Galm), and β-1,4-galactosyltransferase 1 (B4galt1); and unchanged total mTOR and AKT3. These findings corroborate our previously reported results. This study demonstrates the potential of the IMPRes method to identify novel pathways. Identifying the “proteoglycans in cancer” and “galactose metabolism” pathways has generated a lead to study the significance of FFSS-induced glycocalyx remodeling and possible detachment of podocytes from the glomerular matrix.

Objective Our study examines how consistently fall prevention practices and implementation strategies are used by U.S. hospitals. Methods We conducted a cross-sectional, descriptive study of 60 general adult hospital units.We administered a survey measuring 5 domains of fall prevention practices: visibility and identification, bed modification, patient monitoring, patient safety, and education. We measured 4 domains of implementation strategies including quality management (e.g., providing data and support for quality improvement), planning (e.g., designating leadership), education (e.g., providing consultation and training), and restructuring (e.g., revising staff roles and modifying equipment). Results Of 60 units, 43% were medical units and 57% were medical-surgical units. The hospital units varied in fall prevention practices, with practices such as keeping a patient's bed in a locked position (73% strongly agree) being used more consistently than other practices, such as scheduled toileting (15% strongly agree). Our study observed variation in fall prevention implementation strategies. For example, publicly posting fall rates (60% strongly agree) was more consistently used than having a multidisciplinary huddle after a fall event (12% strongly agree). Conclusions There is substantial variation in the implementation of fall prevention practices and implementation strategies across inpatient units. Our study found that resource-intensive practices (e.g., scheduled toileting) are less consistently used than less resource-intensive practices and that interdisciplinary approaches to fall prevention are limited. Future studies should examine how units tailor fall prevention practices based on patient risk factors and how units decide, based on their available resources, which implementation strategies should be used.

This study investigated the impact of SLCO1B1 genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 13; 521CC, n = 2) and wild type controls (521TT, n = 13) completed a single oral dose pharmacokinetic study. The variability contributed by SLCO1B1 c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration-time curve from 0-24 hours (AUC0-24 ) was 1.4-fold and 2.2-fold higher in participants with c.521TC and c.521CC genotype compared 521TT participants, respectively. Interindividual variability of RVA exposure within SLCO1B1 genotype groups exceeded the ~ 1.5-fold to 2-fold difference in mean RVA exposure observed among SLCO1B1 genotype groups, suggesting that other factors also contribute to interindividual variability in the rosuvastatin dose-exposure relationship. A multivariate model performed confirmed SLCO1B1 c.521T>C genotype as the primary factor contributing to RVA systemic exposure in this pediatric cohort, accounting for ~ 30% of the variability RVA AUC0-24 . However, of the statins investigated to date in the pediatric population, RVA has the lowest magnitude of variability in systemic exposure.

Purpose To test the validity of the Ecological Video Identification of Physical Activity (EVIP) computer vision algorithms for automated video-based ecological assessment of physical activity in settings such as parks and schoolyards. Methods Twenty-seven hours of video were collected from stationary overhead video cameras across 22 visits in nine sites capturing organized activities. Each person in the setting wore an accelerometer, and each second was classified as moderate-to-vigorous physical activity or sedentary/light activity. Data with 57,987 s were used to train and test computer vision algorithms for estimating the total number of people in the video and number of people active (in moderate-to-vigorous physical activity) each second. In the testing data set (38,658 s), video-based System for Observing Play and Recreation in Communities (SOPARC) observations were conducted every 5 min (130 observations). Concordance correlation coefficients (CCC) and mean absolute errors (MAE) assessed agreement between (1) EVIP and ground truth (people counts+accelerometry) and (2) SOPARC observation and ground truth. Site and scene-level correlates of error were investigated. Results Agreement between EVIP and ground truth was high for number of people in the scene (CCC = 0.88; MAE = 2.70) and moderate for number of people active (CCC = 0.55; MAE = 2.57). The EVIP error was uncorrelated with camera placement, presence of obstructions or shadows, and setting type. For both number in scene and number active, EVIP outperformed SOPARC observations in estimating ground truth values (CCC were larger by 0.11–0.12 and MAE smaller by 41%–48%). Conclusions Computer vision algorithms are promising for automated assessment of setting-based physical activity. Such tools would require less manpower than human observation, produce more and potentially more accurate data, and allow for ongoing monitoring and feedback to inform interventions.

Purpose:Dismissal of families who refuse mandated childhood vaccines from pediatric practices has become more common among US pediatricians over the past 2 decades. While nurses (registered nurses [RNs] and advanced practice registered nurses [APRNs]) often are the first health-care professional to encounter parents’ vaccine hesitancy and serve as a primary source of information, there are no published data on nurses’ perspectives on dismissal as a response to vaccine refusal. This study examined nurses’ perspectives on dismissal of vaccine-refusing families from primary care practices.Design:Cross-sectional survey administered electronically from February to September 2018. Data analysis was conducted from November 2018 to March 2019.Setting:Data were collected electronically from a national sample of nurses.Subjects:A convenience sample of 488 primary care nurses (74% APRNs) was recruited and enrolled in the study through collaboration with 4 professional nursing associations.Measure and Analysis:A cross-sectional survey was conducted from February to September 2018. We explored correlates of nurses’ (n = 488) attitudes toward dismissal by modeling attitude scores as a function of practice and respondent characteristics. We also modeled odds of encountering vaccine refusal and odds of reporting dismissal of a vaccine-refusing family in the last 12 months, each as a function of respondents’ practice characteristics.Results:Eighty-four percent of respondents encountered vaccine refusal in the previous 12 months, and 22% reported that their practice had dismissed a vaccine-refusing family within the previous 12 months. Twenty-eight percent agreed/strongly agreed that they would dismiss or support a decision to dismiss families who refuse all vaccines, and 12% supported dismissal of families for refusal of some but not all vaccines. Thirty-nine percent of respondents disagreed/strongly disagreed with dismissing families who refuse all vaccines, and 50% disagreed/strongly disagreed with dismissal for refusal of some but not all.Conclusion:Almost all nurses working in primary care encounter vaccine refusal, and most consider all Centers for Disease Control and Prevention–recommended childhood vaccines to be important to public health. There is significant polarization of nurses’ attitudes toward the appropriateness of dismissal as a response to vaccine refusal. We recommend the development of professional nursing guidelines for responding to vaccine refusal. However, because there are no data on the community health impact of dismissal policies, we recommend further research on outcomes of dismissal policies to inform such guidelines.

Objective Lumbar mobilization is a standard intervention for the management of low back pain, yet ways to quantify lumbar mobilization are limited. An inertial measurement unit (IMU) is a small and inexpensive device that can be used to quantify lumbar mobilization. The objective of this study was to determine the validity and reliability of an IMU in measuring the amplitude of displacement of a clinician's hand movement during oscillatory lumbar mobilization. Methods An IMU was secured on a clinician's hand during application of mobilization forces at the L4 segment of 16 healthy participants. The validity of the IMU was tested against common laboratory methods of measurements (force plate and motion capture system). The reliability of the IMU measurements was determined between 2 clinicians (inter-rater reliability) and between 2 sessions (intra-rater reliability) by calculating percent error of measurement (%e) and limits of agreement (LOA). The reliability was considered high when |%e| ≤ 10% and |LOA| ≤ 20%; moderate when |%e| 10% to 20% and |LOA| 21% to 40%; and non-acceptable when |%e| > 20% and |LOA| > 40%. Results The IMU measurements had high correlation with the force plate measurements (rs = 0.94) and high agreement with the motion capture system measurements (%e = 4%, LOA = -11% and 20%). Both the inter-rater reliability (%e = 6%, LOA = -25% and 37%) and the intrarater reliability (%e = -1%, LOA = -29% and 27%) of IMU measurements were moderate. Conclusion The IMU seems to be a valid device to measure the amplitude of a clinician's hand movement. The moderate reliability found in this study may not reflect poor reliability of the IMU as much as inconsistency in reapplication of lumbar mobilization.

Early infant diagnosis (EID) involves age-specific tracking and testing of HIV-exposed infants during the first 18 months of life and rapid initiation of life-saving treatment for those infected. In Kenya, pre-2013 data estimate EID lost to follow-up (LTFU) at 39–65%, yet no study has documented LTFU rates and predictors throughout the EID cascade since Option B+ fundamentally changed services by placing all HIV-positive expectant mothers on lifelong treatment. Using an explanatory mixed-method design, we assessed LTFU rates and predictors among 870 mother–infant dyads enrolled in EID in six urban/peri-urban Kenyan government hospitals. Mothers completed baseline surveys, and dyads were tracked through EID. We selected 12 baseline variables and modeled odds of LTFU at 9 and 18 months using mixed logistic regression. Qualitative interviews were conducted with 61 mothers to assess barriers and facilitators to completing EID. Thematically coded transcripts were used to interpret quantitative predictors of LTFU. By the 18-month test, 145 dyads (22%) were LTFU, with three-quarters of LTFU occurring between 9- and 18-month tests. Odds of LTFU at 18 months decreased by 10% for each additional year of maternal age and by 66% with HIV status disclosure. Qualitative data revealed how disclosure facilitated essential social support for EID completion and how older mothers attributed maturity and life experience to successful engagement in care. Findings suggest LTFU rates in Kenya have declined, but gaps remain in ensuring universal coverage. Efforts to improve retention should focus on increasing support for younger mothers and those who have not disclosed their HIV status.

BACKGROUND Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for pediatric FGIDs remains rare. The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic (APC) would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement. AIM To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related FGIDs and identify patient characteristics that predicted clinical outcomes. METHODS Participants were 392 children, ages 8-18 [M = 13.8; standard deviation (SD) = 2.7], seen between August 1, 2013 and June 15, 2016 in an interdisciplinary APC housed within the Division of Gastroenterology in a medium-sized Midwestern children’s hospital. To be eligible, patients had to be 8 years of age or older and have had abdominal pain for ≥ 8 wk at the time of initial evaluation. Medical and psychosocial data collected as part of standard of care were retrospectively reviewed and analyzed in the context of the observational study. Logistic regression was used to model odds of reporting vs never reporting improvement, as well as to differentiate rapid from slower improvers. RESULTS Nearly 70% of patients followed during the study period achieved resolution on at least one of the employed outcome indices. Among those who achieved resolution during follow up, 43% to 49% did so by the first follow up (i.e., within roughly 2 mo after initial evaluation and initiation of interdisciplinary treatment). Patient age, sleep, ease of relaxation, and depression all significantly predicted the likelihood of resolution. More specifically, the odds of clinical resolution were 14% to 16% lower per additional year of patient age (P < 0.001 to P = 0.016). The odds of resolution were 28% to 42% lower per 1-standard deviation (SD) increase on a pediatric sleep measure (P = 0.006 to P < 0.040). Additionally, odds of clinical resolution were 58% lower per 1-SD increase on parent-reported measure of depression (P = 0.006), and doubled in cases where parents agreed that their children found it easy to relax (P = 0.045). Furthermore, sleep predicted the rapidity of clinical resolution; that is, the odds of achieving resolution by the first follow up visit were 47% to 60% lower per 1-SD increase on the pediatric sleep measure (P = 0.002). CONCLUSION Outcomes for youth with FGIDs may be significantly improved by paying specific attention to sleep, ensuring adequate skills for relaxation, and screening of and referral for treatment of comorbid depression.

Ewing sarcoma (ES) are aggressive pediatric bone and soft tissue tumors driven by EWS-ETS fusion oncogenes, most commonly EWS-FLI1. Treatment of ES patients consists of up to 9 months of alternating courses of 2 chemotherapeutic regimens. Furthermore, EWS-ETS-targeted therapies have yet to demonstrate clinical benefit, thereby emphasizing a clinical responsibility to search for new therapeutic approaches. Our previous in silico drug screening identified entinostat as a drug hit that was predicted to reverse the ES disease signatures and EWS-FLI1-mediated gene signatures. Here, we establish preclinical proof of principle by investigating the in vitro and in vivo efficacy of entinostat in preclinical ES models, as well as characterizing the mechanisms of action and in vivo pharmacokinetics of entinostat. ES cells are preferentially sensitive to entinostat in an EWS-FLI1 or EWS-ERG-dependent manner. Entinostat induces apoptosis of ES cells through G0/G1 cell cycle arrest, intracellular reactive oxygen species (ROS) elevation, DNA damage, homologous recombination (HR) repair impairment, and caspase activation. Mechanistically, we demonstrate for the first time that HDAC3 is a transcriptional target of EWS-FLI1 and that entinostat inhibits growth of ES cells through suppressing a previously unexplored EWS-FLI1/HDAC3/HSP90 signaling axis. Importantly, entinostat significantly reduces tumor burden by 97.4% (89.5 vs. 3397.3 mm3 of vehicle, p

BACKGROUND Hepatic sinusoidal obstruction syndrome (SOS) is a potentially fatal complication after hematopoietic stem cell transplantation (HSCT). Current clinical guidelines state that spectral Doppler changes occur late in the disease, and imaging is only useful for confirming SOS diagnosis. OBJECTIVE Our primary objective was to examine abdominal ultrasound variables as predictors of development of SOS in pediatric HSCT patients. MATERIALS AND METHODS A single-center cohort retrospective study was conducted on patients aged 0 to 21 years who underwent HSCT between September 2001 and May 2017 at our institution. Patients were excluded if they did not have abdominal ultrasounds after HSCT. Clinical, demographic, grayscale, and spectral Doppler liver ultrasound findings were evaluated. We modeled the odds of SOS diagnosis within 100 days after HSCT as a function of each of the 15 ultrasound variables. RESULTS A total of 333 patients received an HSCT. One hundred forty subjects had ultrasound data available. Thirty-two patients developed SOS, and 9 of these patients died. Sinusoidal obstruction syndrome odds more than double per 1-SD increase in peak systolic velocity in common hepatic artery or left hepatic artery and more than triple per 1-SD decrease in main portal vein velocity or change in ascites severity. Several ultrasound variables were statistically significant predictors in the Cox models for time to SOS diagnosis. CONCLUSION Several ultrasound variables can be used as predictors for a patient's risk of developing SOS. The strongest predictors are ascites severity, main portal vein velocity, common hepatic artery peak systolic velocity, and left hepatic artery peak systolic velocity.

Ductal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.

Background Safer conception counseling (SCC) to promote the use of safer conception methods (SCM) is not yet part of routine family planning or HIV care. Guidelines for the use of SCM have been published, but to date there are no published controlled evaluations of SCC. Furthermore, it is unknown whether standard methods commonly used in resource constrained settings to integrate new services would be sufficient, or if enhanced training and supervision would result in a more efficacious approach to implementing SCC. Methods In a hybrid, cluster randomized controlled trial, six HIV clinics were randomly assigned to implement the SCC intervention Our Choice using either a high (SCC1) or low intensity (SCC2) approach (differentiated by amount of training and supervision), or existing family planning services (usual care). Three hundred eighty-nine HIV clients considering childbearing with an HIV-negative partner enrolled. The primary outcome was self-reported use of appropriate reproductive method (SCM if trying to conceive; modern contraceptives if not) over 12 months or until pregnancy. Results The combined intervention groups used appropriate reproductive methods more than usual care [20.8% vs. 6.9%; adjusted OR (95% CI)=10.63 (2.79, 40.49)], and SCC1 reported a higher rate than SCC2 [27.1% vs. 14.6%; OR (95% CI)=4.50 (1.44, 14.01)]. Among those trying to conceive, the intervention arms reported greater accurate use of SCM compared to usual care [24.1% vs. 0%; OR (95% CI)=91.84 (4.94, 1709.0)], and SCC1 performed better than SCC2 [34.6% vs. 11.5%; OR (95% CI)=6.43 (1.90, 21.73)]. The arms did not vary on modern contraception use among those not trying to conceive. A cost of $631 per person was estimated to obtain accurate use of SCM in SCC1, compared to $1014 in SCC2. Conclusions More intensive provider training and more frequent supervision leads to greater adoption of complex SCM behaviors and is more cost-effective than the standard low intensity implementation approach. Trial registration Clinicaltrials.gov, NCT03167879; date registered May 23, 2017.

We conducted a novel pilot randomized controlled trial of the Treatment Ambassador Program (TAP), an 8-session, peer-based, behavioral intervention for people with HIV (PWH) in South Africa not on antiretroviral therapy (ART). PWH (43 intervention, 41 controls) completed baseline, three- and six-month assessments. TAP was highly feasible (90% completion), with peer counselors demonstrating good intervention fidelity. Post-intervention interviews showed high acceptability of TAP and counselors, who supported autonomy, assisted with clinical navigation, and provided psychosocial support. Intention-to-treat analyses indicated increased ART initiation by three months in the intervention vs. control arm (12.2% [5/41] vs. 2.3% [1/43], Fisher exact p-value = 0.105; Cohen’s h = 0.41). Among those previously on ART (off for >6 months), 33.3% initiated ART by three months in the intervention vs. 14.3% in the control arm (Cohen’s h = 0.45). Results suggest that TAP was highly acceptable and feasible among PWH not on ART.

Introduction Tracheostomy in children is often performed to alleviate airway obstruction (AO) or to facilitate long-term ventilator support due to respiratory failure of various etiologies, such as heart failure, and postoperative respiratory failure. Although many of these pathologies are common among trisomy 21 patients, tracheostomy rates among this population have not previously been reported. The aim of our study was to determine the incidence of trisomy 21 patients undergoing tracheostomy. Secondary objectives include decannulation rates and mortality associated with tracheostomy. Materials and methods A retrospective cohort study was conducted on pediatric trisomy 21 patients undergoing tracheostomy between 2004 and 2013. Results Twenty patients underwent tracheostomy at a median age of 7.1 months (interquartile range [IQR] = 3.5,21.3). The estimated incidence of tracheostomy in trisomy 21 patients among our tracheostomy population was 1.7% (20/1173) over 10 years. The most common indications were airway obstruction (AO) (55%), cardiac/pulmonary respiratory failure (CRF) (25%), or both (20%). Overall mortality was 30%, much lower among AO patients (9%) than CRF (40%) or both (60%), (P = 0.029). Nine patients (45%) were successfully decannulated, with median duration of cannulation of 2.2 years (IQR = 1.7,3). Conclusions This study suggests a rate of tracheostomy in the pediatric trisomy 21 population approximately 3 times that of the general pediatric population. Over half in this cohort underwent tracheostomy for isolated AO, while the general pediatric tracheostomy population demonstrates a much higher prevalence of prematurity-related CRF. Overall mortality rate and decannulation rate approximated that of the general pediatric tracheostomy population, although outcomes were significantly poorer among patients trisomy 21 patients undergoing tracheostomy for CRF.

Bed and chair alarms are widely used in hospitals, despite lack of effectiveness and unintended negative consequences. In this cross-sectional, observational study, we examined alarm prevalence and contributions of patient- and unit-level factors to alarm use on 59 acute care nursing units in 57 U.S. hospitals participating in the National Database of Nursing Quality Indicators®. Nursing unit staff reported data on patient-level fall risk and fall prevention measures for 1,489 patients. Patient-level propensity scores for alarm use were estimated using logistic regression. Expected alarm use on each unit, defined as the mean patient propensity-for-alarm score, was compared to the observed rate of alarm use. Over one-third of patients assessed had an alarm in the “on” position. Patient characteristics associated with higher odds of alarm use included recent fall, need for ambulation assistance, poor mobility judgment, and altered mental status. Observed rates of unit alarm use ranged from 0%-100% (median 33%, 10(th) percentile 5%, 90(th) percentile 67%). Expected alarm use varied less (median 31%, 10(th) percentile 27%, 90(th) percentile 45%). Only 29% of variability in observed alarm use was accounted for by expected alarm use. Unit assignment was a stronger predictor of alarm use than patient-level fall risk variables. Alarm use is common, varies widely across hospitals, and cannot be fully explained by patient fall risk factors; alarm use is driven largely by unit practices. Alarms are used too frequently and too indiscriminately, and guidance is needed for optimizing alarm use to reduce noise and encourage mobility in appropriate patients.

Rejection is responsible for just under 50% of graft loss in the pediatric kidney transplant population. Early identification and treatment of allograft injury, specifically modifiable pathologies such as subclinical rejection (SCR), calcineurin inhibitor toxicity, and BK virus nephropathy, may improve allograft survival. Protocol surveillance biopsy (SB) currently offers the earliest opportunity for targeted interventions. This is a single-center retrospective review of 215 kidney SBs obtained from 2008 to 2016 in 97 pediatric kidney transplant recipients. SBs were obtained at 6, 12, and 24 months post-transplantation. Frequency of abnormal histologic findings, estimated glomerular filtration rate at time of SB, and SB-related complications were recorded. Data were analyzed to investigate possible time trends and the presence of demographic or clinical associations with abnormal histologic findings. Potentially modifiable histologic findings were seen in 38.1% of all SBs. SCR was found with increasing frequency across all time points with an estimated 49% increase in the odds of a SCR finding per additional 6 months post-transplantation (aOR 1.49, 95% CI 1.06–2.09, p = 0.022). Among follow-up biopsies in patients who underwent treatment for SCR, 50% had no SCR and 18.8% showed histologic improvement. The complication rate associated with SB was 1.9% (4/215 SBs) and consisted of only minor complications. SBs are safe and offer the opportunity to identify and treat modifiable histologic changes in the pediatric kidney transplant population. The performance of SBs for up to 2 years after transplantation can have meaningful clinical impact.

Contains fulltext : 220573.pdf (Publisher’s version ) (Open Access) The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age-dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus-adolescents). Twenty-seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with age, and overlap with an adjacent gene. Two splice variants code for reference OATP1B1 protein, and eight code for truncated proteins. The expression of eight isoforms was associated with age. We conclude that alternative splicing of SLCO1B1 occurs frequently in children; although the functional consequences remain unknown, the data raise the possibility of a regulatory role for alternative splicing in mediating developmental changes in drug disposition.

High rates of fertility desires, childbearing and serodiscordant partnerships among people living with HIV (PLHIV) in Uganda underscore the need to promote use of safer conception methods (SCM). Effective SCM exist but few PLHIV benefit from provider-led safer conception counseling (SCC) and comprehensive national SCC guidelines are still lacking. Providers' self-efficacy, intentions and attitudes for SCC impact provision and should inform development of services, but there are no longitudinal studies that assess these important constructs. This study reports on changes in providers' knowledge, attitudes, motivation and confidence to provide SCC among a 24-month observational cohort of Ugandan HIV providers. Compared to baseline, providers evidenced increased awareness of SCM, perceived greater value in providing SCC, saw all SCM but sperm washing as likely to be acceptable to clients, reported consistently high interest in and peer support for providing SCC, and perceived fewer barriers at the 24-month follow-up. Providers' intentions for providing SCC stayed consistently high for all SCM except manual self-insemination which decreased at 24 months. Self-efficacy for providing SCC increased from baseline with the greatest improvement in providers' confidence in advising serodiscordant couples where the man is HIV-infected. Providers consistently cite the lack of established guidelines, training, and their own reluctance to broach the issue with clients as significant barriers to providing SCC. Despite providers being more interested and open to providing SCC than ever, integration of SCC into standard HIV services has not happened. Concerted efforts are needed to address remaining barriers by establishing national SCC guidelines and implementing quality provider training.

To test the hypothesis that our motivational sexual health intervention (SexHealth) would increase health service uptake when compared with control.In a randomized controlled trial at a pediatric emergency department, sexually active adolescents received either the SexHealth intervention or printed materials (control). SexHealth, delivered by a health educator, was a tablet-based, interactive intervention that included motivational techniques to promote sexual health, condom skills training, and tailored service recommendations. We assessed feasibility (eg, intervention completion, recommendations discussed, intervention duration), acceptability (ie, proportion enrolled and rating intervention as satisfactory), and efficacy; secondary outcomes were sexual and care-seeking behaviors at 6 months. The efficacy outcome was completion of ≥1 service at the index visit (ie, counseling, condoms, emergency contraception for immediate or future use, pregnancy/sexually transmitted infection/HIV testing, sexually transmitted infection treatment, and clinic referral).We enrolled 91 participants (intervention = 44; control = 47). The intervention demonstrated high feasibility: 98% completed the intervention; 98% of recommendations were discussed; duration was 24.6 minutes, and acceptability: 87% of eligible adolescents enrolled and 93% rated the intervention as fairly to very satisfactory. Compared with controls, intervention participants were more likely to complete ≥1 service (98% vs 70%, P .001) including HIV testing (33% vs 6%, P = .02) and emergency contraception (80% vs 0%, P = .01). There were no meaningful differences between arms in behaviors at follow-up.SexHealth was feasible to implement, acceptable to youth, and resulted in increased uptake of health services during the emergency department visit. Additional strategies may be needed to extend intervention effects over time.ClinicalTrials.gov; NCT03341975.

Background Executive function (EF) is considered an important mediator of health outcomes. It is hypothesized that those with better EF are more likely to succeed in turning their intentions into actual health behaviors. Prior studies indicate EF is associated with smoking cessation. Experimental and longitudinal studies, however, have yielded mixed results. Few studies have examined whether EF predicts post-treatment smoking behavior. Fewer still have done so prospectively in a large trial. We sought to determine if EF predicts quit attempts and cessation among community smokers in a large randomized trial evaluating the efficacy of motivational interventions for encouraging cessation. Methods Participants (N = 255) completed a baseline assessment that included a cognitive battery to assess EF (Oral Trail Making Test B, Stroop, Controlled Oral Word Association Test). Participants were then randomized to 4 sessions of Motivational Interviewing or Health Education or one session of Brief Advice to quit. Quit attempts and cessation were assessed at weeks 12 and 26. Results In regression analyses, none of the EF measures were statistically significant predictors of quit attempts or cessation (all ps > 0.20). Conclusions Our data did not support models of health behavior that emphasize EF as a mediator of health outcomes. Methodological shortcomings weaken the existing support for an association between EF and smoking behavior. We suggest methodological improvements that could help move this potentially important area of research forward.

Many individuals with type 1 diabetes (T1D) upload and review blood glucose data between clinic visits. Mobile phone applications that receive data from a "connected" glucometer and that support pattern management are available and have the capacity to make data upload and review less burdensome. Whether mobile apps can improve diabetes self-management among individuals with type 1 diabetes remains unknown.We analyzed retrospective data on 81 youths with T1D who were trained to use a glucometer-connected mobile app in their self-management. To assess the effect of glucometer synchronization ("sync") rate on hemoglobin A1c (HbA1c), mean blood glucose (mBG), and daily frequency of SMBG, we regressed those clinical outcomes on the frequency of glucometer syncs with the mobile app after controlling for other clinical care variables.Median age was 14.0 (IQR 10.4-15.9) years, median duration of diabetes was 4.9 (2.7, 7.5) years, and median baseline HbA1c was 8.6% (7.9, 9.8). The sample was 49% male and 86% white. Youths with T1D synchronized glucometer data with the mobile app an average of 0.22 times per week (range 0-2.25). The glucometer sync rate did not have a statistically significant association with HbA1c or mean BG; in contrast, data sync frequency was associated with the frequency of self-monitoring of blood glucose (SMBG) such that each additional sync was associated with a 2.3-fold increase in SMBG frequency ( P.01).A glucometer-connected mobile app may increase an individual's engagement with other aspects of care (eg, SMBG frequency). Whether diabetes device-connected mobile apps can improve glycemic control remains to be determined.

Introduction Hyperfiltration is a major contributor to progression of chronic kidney disease (CKD) in diabetes, obesity and in individuals with solitary functioning kidney (SFK). We have proposed hyperfiltration-induced injury as a continuum of overlapping glomerular changes caused by increased biomechanical forces namely, fluid flow shear stress (FFSS) and tensile stress. We have shown that FFSS is elevated in animals with SFK and, it upregulates prostaglandin E2 (PGE2), cyclooxygenase-2 and PGE2 receptor EP2 in cultured podocytes and in uninephrectomized mice. We conceptualized urinary PGE2 as a biomarker of early effects of hyperfiltration-induced injury preceding microalbuminuria in individuals with SFK. We studied children with SFK to validate our hypothesis. Methods Urine samples from children with SFK and controls were analyzed for PGE2, albumin (glomerular injury biomarker) and epidermal growth factor (EGF, tubular injury biomarker). Age, gender, and Z-scores for height, weight, BMI, and blood pressure were obtained. Results Children with SFK were comparable to controls except for lower BMI Z-scores. The median values were elevated in SFK compared to control for urine PGE2 [9.1 (n = 57) vs. 5.7 (n = 72), p = 0.009] ng/mgCr and albumin [7.6 (n = 40) vs. 7.0 (n = 41), p = 0.085] μg/mgCr, but not for EGF [20098 (n = 44) vs. 18637 (n = 44), p = 0.746] pg/mgCr. Significant increase in urinary PGE2 (p = 0.024) and albumin (p = 0.019) but not EGF (p = 0.412) was observed using additional regression modeling. These three urinary analytes were independent of each other. Conclusion Increased urinary PGE2 from elevated SNGFR and consequently increased FFSS during early stage of CKD precedes overt microalbuminuria and is a biomarker for early hyperfiltration-induced injury in individuals with SFK.

Background The Centers for Medicare & Medicaid Services (CMS) implemented the Hospital-Acquired Conditions (HACs) Initiative in October 2008; the CMS no longer reimbursed hospitals for fall injury. The effects of this payment change on fall and fall injury rates are not well described, nor its effect on physical restraint use. Objective The aim of this study was to examine the effects of the 2008 HACs Initiative on the rates of falls, injurious falls, and physical restraint use. Design/setting This was a nine-year retrospective cohort study (July 2006-December 2015) involving 2,862 adult medical, medical-surgical, and surgical nursing units from 734 hospitals. Measurements Annual rates of change in falls, injurious falls, and physical restraint use during the two years before the payment rule went into effect were compared with one-, four-, and seven-year rates of annual change after implementation, adjusting for unit- and facility-level covariates. Stratified analyses were conducted according to bed size and teaching status. Results Compared with prior to the payment change, there was stable acceleration in the one-, four-, and seven-year annual rates of decline in falls as follows: -2.1% (-3.3%, -0.9%), -2.2% (-3.2%, -1.1%), and -2.2% (-3.4%, -1.0%) respectively. For injurious falls, there was an increasing acceleration in the annual declines, achieving statistical significance only at seven years post CMS change as follows: -3.2% (-5.5%, -1.0%). Physical restraint use prevalence decreased from 1.6% to 0.6%. Changes in the rates of falls, injurious falls, and restraint use varied according to hospital bed size and teaching status. Conclusions and relevance Since the HACs Initiative, there was at best a modest decline in the rates of falls and injurious falls observed primarily in larger, major teaching hospitals. An increase in restraint use was not observed. Falls remain a difficult patient safety problem for hospitals, and further research is required to develop cost-effective, generalizable strategies for their prevention.

BACKGROUND:Substantial variability exists in the care of febrile, well-appearing infants. We aimed to assess the impact of a national quality initiative on appropriate hospitalization and length of stay (LOS) in this population.METHODS:The initiative, entitled Reducing Variability in the Infant Sepsis Evaluation (REVISE), was designed to standardize care for well-appearing infants ages 7 to 60 days evaluated for fever without an obvious source. Twelve months of baseline and 12 months of implementation data were collected from emergency departments and inpatient units. Ill-appearing infants and those with comorbid conditions were excluded. Participating sites received change tools, run charts, a mobile application, live webinars, coaching, and a LISTSERV. Analyses were performed via statistical process control charts and interrupted time series regression. The 2 outcome measures were the percentage of hospitalized infants who were evaluated and hospitalized appropriately and the percentage of hospitalized infants who were discharged with an appropriate LOS.RESULTS:In total, 124 hospitals from 38 states provided data on 20 570 infants. The median site improvement in percentages of infants who were evaluated and hospitalized appropriately and in those with appropriate LOS was 5.3% (interquartile range = −2.5% to 13.7%) and 15.5% (interquartile range = 2.9 to 31.3), respectively. Special cause variation toward the target was identified for both measures. There was no change in delayed treatment or missed bacterial infections (slope difference 0.1; 95% confidence interval, −8.3 to 9.1).CONCLUSIONS:Reducing Variability in the Infant Sepsis Evaluation noted improvement in key aspects of febrile infant management. Similar projects may be used to improve care in other clinical conditions.

The present study describes the development and initial validation of a newly developed measure of child and caregiver knowledge of the child's own IBD and treatment, called IBD KNOW-IT. One hundred and fifty-five children and their caregivers completed the IBD KNOW-IT as well as a scale designed to compare each dyad's perceived knowledge to their actual knowledge. Initial psychometric evaluation of IBD KNOW-IT was completed by conducting factor analysis and determining internal consistency, convergent validity, and associations with demographic and medical characteristics. Results supported the validity of a 12-item measure with 4 subscales including Symptoms, Medication Regimen, Disease Monitoring, and Medical Team. Support for the internal consistency of IBD KNOW-IT was obtained. Evidence of validity was demonstrated by significant correlations between child and caregiver scales, and high congruence between perceived and actual knowledge across all subscales. The reliability of the measure was demonstrated by good internal consistency and test-retest reliability. Preliminary psychometric evaluation suggests that IBD KNOW-IT is reliable and valid.

The purpose of this study was to examine national trends and variation in nurse staffing on inpatient psychiatric units in US general hospitals from 2005-2017. The National Database of Nursing Quality Indicators® provided data on nurse staffing from 1,143 psychiatric units in 610 US hospitals. A weighted linear mixed model was fitted for each of two staffing measures: Registered nurse (RN) hours per patient day (HPPD) and non-RN HPPD. Monthly staffing levels were modeled as a function of study year, unit type, and hospital bed size, teaching status, government ownership, for-profit status, metropolitan location, and US census division. Very gradual upward trends in staffing were observed. Compared with adult units, child/adolescent units had lower RN staffing and higher non-RN staffing. Levels of both types of staffing were lower in for-profit facilities. The Pacific census division had higher RN staffing than every other census division by an estimated margin of 0.52-1.54 HPPD, and census divisions with the lowest levels of RN staffing had the highest levels of non-RN staffing. Despite concerns expressed over the past 15 years about patient violence, staffing levels, and use of seclusion and restraint on psychiatric units, average staffing levels have apparently increased only modestly since 2005, and increases in RN staffing on psychiatric units have not kept pace with increases in general care units. Marked regional differences in staffing merit further investigation.

Background: Resting energy expenditure (REE) is a valuable measure in clinical management of obesity and other chronic illnesses. Gold standard methods for measuring REE (e.g., Douglas bags and metabolic cart) are too expensive and cumbersome for an outpatient clinical setting. The purpose of this study was to determine the accuracy of a handheld indirect calorimeter (HHIC) and prediction equations (PEs) for measurement of REE in youth with and without obesity. Methods: Fifty-three children and adolescents (12.8 ± 4.3 years, 50.9% female) had REE measured first with a MedGem™ HHIC for 10 minutes, followed by a reference indirect calorimeter system (ParvoMedics TrueOne 2400™) with hood canopy and dilution pump for 30 minutes. REE was also estimated using nine PEs as follows: Henry-1, Henry-2, Schofield, World Health Organization, Molnar, Muller, Herrmann, Schmelzle, and Harris–Benedict. Concordance correlation coefficients and Bland–Altman analyses were used for comparisons among PEs, MedGem HHIC, and metabolic cart. Results: The observed correlation between the HHIC and the reference system was r(c) = 0.89 with a mean bias of 2.27 ± 3.41 kcal/(kg·d) (9.1% ± 14.7%). Regarding PE, Molnar had the highest agreement with the reference system [r(c) = 0.93, bias of 2.17 ± 2.04 kcal/(kg·d); 9.8% ± 8.1%], followed by Harris–Benedict (r(c) = 0.89; 13.8% ± 8.9%), Henry-2 (r(c) = 0.89; 15% ± 7.6%), and Henry-1 (r(c) = 0.86; 16.7% ± 7.3%). All PEs were less accurate for children with overweight/obesity. Conclusions: Compared to PE, the HHIC provided more accurate REE estimates for children across the age and BMI spectrum, although positive bias was present throughout. Difference in positive bias between the HHIC and the Molnar equation may be clinically significant for youth with overweight/obesity.

Psychiatric mental health clinicians often rely on proxy and self-report evaluations to determine the cognitive function of older adults however, performance measures have greater accuracy and predictive ability for everyday function. This study tested physical and cognitive predictors of functional abilities in fifty-one community residing older adults. We administered a computerized battery of executive function tasks, a performance-based measure of instrumental activities of daily living (IADL), and three physical function measures (grip strength, 30-second Chair Stand Test, and 8-foot Up and Go). Regression models assessed the associations of three components of executive function (updating, shifting, and inhibition) with IADLs and physical functions. Updating was a significant predictor of the Medications and Financial DAFS scores and of grip strength. Shifting also predicted grip strength. In conclusion, different executive functions predict different domains of IADL functioning. Working memory was a robust predictor of IADL functioning in older adults, especially medication management skills.

Objective Estimate the impact on clinical practice of using a mobile device–based electronic clinical decision support (mECDS) tool within a national standardization project. Materials and Methods An mECDS tool (app) was released as part of a change package to provide febrile infant management guidance to clinicians. App usage was analyzed using 2 measures: metric hits per case (metric-related screen view count divided by site-reported febrile infant cases in each designated market area [DMA] monthly) and cumulative prior metric hits per site (DMA metric hits summed from study month 1 until the month preceding the index, divided by sites in the DMA). For each metric, a mixed logistic regression model was fit to model site performance as a function of app usage. Results An increase of 200 cumulative prior metric hits per site was associated with increased odds of adherence to 3 metrics: appropriate admission (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.18), appropriate length of stay (OR, 1.20; 95% CI, 1.12-1.28), and inappropriate chest x-ray (OR, 0.82; 95% CI, 0.75-0.91). Ten additional metric hits per case were also associated: OR were 1.18 (95% CI, 1.02-1.36), 1.36 (95% CI, 1.14-1.62), and 0.74 (95% CI, 0.62-0.89). Discussion mECDS tools are increasingly being implemented, but their impact on clinical practice is poorly described. To our knowledge, although ecologic in nature, this report is the first to link clinical practice to mECDS use on a national scale and outside of an electronic health record. Conclusions mECDS use was associated with changes in adherence to targeted metrics. Future studies should seek to link mECDS usage more directly to clinical practice and assess other site-level factors.

Background In recent years several authors have documented common problems in the use of statistics in nursing research, including failure to consider the effects of multiple testing, inattention to clinical significance, and under-reporting of effect sizes and confidence intervals. More subtle forms of multiple testing are not as widely recognized, and abuse of researcher degrees of freedom has received little attention in the nursing research literature. These and other unsound practices in applying and interpreting statistics are problematic in themselves, and they arguably reflect an insufficiently clear understanding of statistical inference as a method for dealing with randomness among many researchers. Objectives The goal of this educational paper is to improve the understanding and practice of inferential statistics among nursing researchers. An accessible explanation of hypothesis testing is provided, including discussion of the crucial concept of repeated sampling. Several pervasive mistakes and misconceptions in statistical inference are examined in detail, including misinterpretation of “non-significant” p-values as evidence for the null hypothesis, failure to account for forms of multiple testing that arise in model selection, abuse of researcher degrees of freedom, and hypothesis testing for baseline differences between arms in randomized trials. Recommendations for better statistical practice are offered. Conclusion For the foreseeable future classical methods of statistical inference based on the idea of repeated sampling will be the primary tools for quantifying randomness in nursing research. The hypothesis testing framework, despite its limitations, can be helpful in ruling out chance as an explanation for observed effects. Nursing researchers who use quantitative methods, as well as journal reviewers and editors, should understand this framework well. Those involved in educating nursing researchers and those who teach statistics would do well to ask what changes need to be made to raise the level of statistical practice in nursing research.

Reliability-the extent to which multiple measurements of a target yield similar results-is critical in comparing healthcare provider quality. Hospital unit fall rates are widely tracked and used for benchmarking, but their reliability is not well-studied. Our twofold purpose was to estimate fall rate reliability, both in terms of signal (between-unit variability) relative to noise (within-unit variability) and in terms of the accuracy with which units can be classified as high-fall units; and to assess reliability as a function of the number of quarters of data used to compute fall rates. Using year 2013 data from 11,765 critical care, step-down, medical, surgical, medical-surgical, and rehabilitation units in 1,552 US hospitals, we identified high-fall-rate units, computed units' signal-noise reliability, and simulated data to assess accuracy of high-fall-rate unit classification as a function of quarters of data. When critical care units were excluded, median unit type signal-noise reliabilities for annual total and injurious fall rates, respectively, ranged from .74 to .82 and from .53 to .68. In simulation, seven quarters of data were sufficient to achieve top-decile misclassification rates at or below 10% for all unit types except critical care. Top-quartile misclassification rates were higher; even 12 quarters of data did not consistently yield top-quartile misclassification rates below 10%. In the absence of long-term data, and for units with low patient volume and unit types with very low fall rates, comparison with a unit's own historical data may be more helpful for quality monitoring than attempting to rank it among its peers. © 2016 Wiley Periodicals, Inc.

Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n=427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR=7.51 P=0.007) was associated with a greater hazard than cancer stage (HR=2.45, P=0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.

It is widely thought that low staffing levels are associated with higher risk of psychiatric inpatient violence. The purpose of this study was to determine whether odds of an injurious assault are higher in months in which unit staffing levels are higher or lower relative to unit average, using a design allowing each unit to serve as its own control. Using 2011-2013 National Database of Nursing Quality Indicators data from 480 adult and 90 geriatric units in 361 US hospitals, monthly assault odds were modeled as functions of unit staffing. Monthly RN and non-RN staffing (hours per patient day) were categorized as very low, low, average, high, or very high, based on deviation from the unit's average staffing across study months. Endpoints were binary indicators for one or more injurious assaults against staff during the month and for one or more injurious assaults against patients during the month. Despite large sample sizes, neither RN nor non-RN staffing was a statistically significant predictor of odds of assault, nor was there a consistent trend of odds of assault being higher at below- or above-average staffing levels. There was little evidence that monthly deviation in unit staffing is associated with the odds of an injurious assault on a unit. This suggests that staffing-assault rate associations in previous studies of monthly data are largely attributable to between-unit rather than within-unit staffing differences. Hospitals may need to look beyond below- or above-average nurse staffing as a cause of assaults. © 2016 Wiley Periodicals, Inc.

Hospital performance reports often include rankings of unit pressure ulcer rates. Differentiating among units on the basis of quality requires reliable measurement. Our objectives were to describe and apply methods for assessing reliability of hospital‐acquired pressure ulcer rates and evaluate a standard signal‐noise reliability measure as an indicator of precision of differentiation among units. Quarterly pressure ulcer data from 8,199 critical care, step‐down, medical, surgical, and medical‐surgical nursing units from 1,299 US hospitals were analyzed. Using beta‐binomial models, we estimated between‐unit variability (signal) and within‐unit variability (noise) in annual unit pressure ulcer rates. Signal‐noise reliability was computed as the ratio of between‐unit variability to the total of between‐ and within‐unit variability. To assess precision of differentiation among units based on ranked pressure ulcer rates, we simulated data to estimate the probabilities of a unit's observed pressure ulcer rate rank in a given sample falling within five and ten percentiles of its true rank, and the probabilities of units with ulcer rates in the highest quartile and highest decile being identified as such. We assessed the signal‐noise measure as an indicator of differentiation precision by computing its correlations with these probabilities. Pressure ulcer rates based on a single year of quarterly or weekly prevalence surveys were too susceptible to noise to allow for precise differentiation among units, and signal‐noise reliability was a poor indicator of precision of differentiation. To ensure precise differentiation on the basis of true differences, alternative methods of assessing reliability should be applied to measures purported to differentiate among providers or units based on quality. © 2016 The Authors. Research in Nursing & Health published by Wiley Periodicals, Inc.

This study determined if a SystemCHANGE™ intervention was more efficacious than attention control in increasing immunosuppressive medication adherence and improving outcomes in adult kidney transplant recipients during a 6-month intervention phase and subsequent 6-month (no intervention) maintenance phase. The SystemCHANGE™ intervention taught patients to use person-level quality improvement strategies to link adherence to established daily routines, environmental cues, and supportive people. Eighty-nine patients (average age 51.8 years, 58% male, 61% African American) completed the 6-month intervention phase. Using an intent-to-treat analysis, at 6 months, medication adherence for SystemCHANGE™ (median 0.91, IQR 0.76-0.96) and attention control (median 0.67, IQR 0.52-0.72) patients differed markedly (difference in medians 0.24, 95% CI 0.13-0.30, P < .001). At the conclusion of the subsequent 6-month maintenance phase, the gap between medication adherence for SystemCHANGE™ (median 0.77, IQR 0.56-0.94) and attention control (median 0.60, IQR 0.44-0.73) patients remained large (difference in medians 0.17, 95% CI 0.06-0.33, P = .004). SystemCHANGE™ patients evidenced lower mean creatinine and BUN at 12 months and more infections at 6 and 12 months. This first fully powered RCT testing SystemCHANGE™ to improve and maintain medication adherence in kidney transplant recipients demonstrated large, clinically meaningful improvements in medication adherence. Clinical Trial Registration: NCT02416479.

Objective Data on early miscarriage incidence is limited due to various social and methodological barriers. We report on 24-month pregnancy outcomes of 299 female Ugandan HIV clients in committed relationships with an intention to conceive. Miscarriage data are reported as auxiliary findings to a larger study (5R01HD072633). Results 127 (42%) participants reported a pregnancy during the study; among the remaining 172, 82 indicated they stopped trying to conceive, and 16 dropped out prior to month 24. Of the 127 pregnancies, 55 (43%) resulted in live births, 67 (53%) in spontaneous miscarriage, 1 (

Background Despite the recognized importance of human milk (HM) use, breastfeeding is often discouraged for infants with cleft lip and/or palate because of their anatomical abnormalities. Poor weight gain may require formula for calorie supplementation. Stresses associated with caring for infants with cleft lip/palate may decrease rates of HM provision to these infants. Purpose This study investigates the experiences of mothers of infants with cleft lip/palate (CL/P) to determine choices and factors associated with providing HM to their infants. Methods A retrospective telephone survey was administered to a cohort of mothers of infants with CL/P. Results Fifty mothers agreed to participate in the survey. Most (78%) initiated use of HM for a median duration of 4 months, 32% provided HM for 6 months or more, and 79% exclusively expressed their HM. Poor supply was the most frequent challenge to providing HM and led to cessation in 46% of the mothers. Formula was used to supplement for poor supply or poor infant weight gain in 90% of the mothers. The best predictors of a mother's use of HM were child not in day care, genetic diagnosis, and gestational age at birth. Only 36% of mothers reported individual encouragement to provide HM, and 18% reported they were specifically discouraged from providing HM for their infants. Implications for practice Although initiation rates were high, there are opportunities to improve support for mothers to increase duration of HM provision in children with CL/P. Implications for research This study establishes a baseline for future prospective studies looking at the impact of active encouragement and provision of lactation support within the cleft team setting.

This study investigated the impact of SLCO1B1 genotype on pravastatin systemic exposure in children and adolescents with hypercholesterolemia. Participants (8-20 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 15; 521CC, n = 2) and wild-type controls (521TT, n = 15) completed a single oral dose pharmacokinetic study. Interindividual variability of pravastatin acid (PVA) exposure within SLCO1B1 genotype groups exceeded the approximately twofold difference in mean PVA exposure observed between SLCO1B1 genotype groups (P > 0.05, q > 0.10). The 3'α-iso-pravastatin acid and lactone isomer formation in the acidic environment of the stomach prior to absorption also was variable and affected PVA exposure in all genotype groups. The SLCO1B1 c.521 gene variant contributing to variability in systemic exposure to PVA in our pediatric cohort was comparable to previous studies in adults. However, other demographic and physicochemical factors seem to also contribute to interindividual variability in the dose-exposure relationship.

With data from 400 HIV clients with fertility intentions and 57 HIV providers in Uganda, we evaluated the psychometrics of new client and provider scales measuring constructs related to safer conception methods (SCM) and safer conception counselling (SCC). Several forms of validity (i.e., content, face, and construct validity) were examined using standard methods including exploratory and confirmatory factor analysis. Internal consistency was established using Cronbach's alpha correlation coefficient. The final scales consisted of measures of attitudes towards use of SCM and delivery of SCC, including measures of self-efficacy and motivation to use SCM, and perceived community stigma towards child-bearing. Most client and all provider measures had moderate to high internal consistency (alphas 0.60–0.94), most had convergent validity (associations with other SCM or SCC-related measures), and client measures had divergent validity (poor associations with depression). These findings establish preliminary psychometric properties of these scales and should facilitate future studies of SCM and SCC.

Technological advances provide opportunities for automating direct observations of physical activity, which allow for continuous monitoring and feedback. This pilot study evaluated the initial validity of computer vision algorithms for ecological assessment of physical activity. The sample comprised 6630 seconds per camera (three cameras in total) of video capturing up to nine participants engaged in sitting, standing, walking, and jogging in an open outdoor space while wearing accelerometers. Computer vision algorithms were developed to assess the number and proportion of people in sedentary, light, moderate, and vigorous activity, and group-based metabolic equivalents of tasks (MET)-minutes. Means and standard deviations (SD) of bias/difference values, and intraclass correlation coefficients (ICC) assessed the criterion validity compared to accelerometry separately for each camera. The number and proportion of participants sedentary and in moderate-to-vigorous physical activity (MVPA) had small biases (within 20% of the criterion mean) and the ICCs were excellent (0.82–0.98). Total MET-minutes were slightly underestimated by 9.3–17.1% and the ICCs were good (0.68–0.79). The standard deviations of the bias estimates were moderate-to-large relative to the means. The computer vision algorithms appeared to have acceptable sample-level validity (i.e., across a sample of time intervals) and are promising for automated ecological assessment of activity in open outdoor settings, but further development and testing is needed before such tools can be used in a diverse range of settings.

Background: Youth are active in multiple locations, but it is unknown whether more physical activity in one location is associated with less in other locations. This cross-sectional study examines whether on days with more physical activity in a given location, relative to their typical activity in that location, youth had less activity in other locations (i.e., within-person associations/compensation). Methods: Participants were 528 adolescents, ages 12 to 16 (M = 14.12, SD = 1.44, 50% boys, 70% White non-Hispanic). Accelerometer and Global Positioning System devices were used to measure the proportion of time spent in moderate-to-vigorous physical activity (MVPA) in five locations: home, home neighborhood, school, school neighborhood, and other locations. Mixed-effects regression was used to examine within-person associations of MVPA across locations and moderators of these associations. Results: Two of ten within-participant associations tested indicated small amounts of compensation, and one association indicated generalization across locations. Higher at-school MVPA (relative to the participant’s average) was related to less at-home MVPA and other-location MVPA (Bs = −0.06 min/day). Higher home-neighborhood MVPA (relative to the participant’s average) was related to more at-home MVPA (B = 0.07 min/day). Some models showed that compensation was more likely (or generalization less likely) in boys and non-whites or Hispanic youth. Conclusions: Consistent evidence of compensation across locations was not observed. A small amount of compensation was observed for school physical activity, suggesting that adolescents partially compensated for high amounts of school activity by being less active in other locations. Conversely, home-neighborhood physical activity appeared to carry over into the home, indicating a generalization effect. Overall these findings suggest that increasing physical activity in one location is unlikely to result in meaningful decreases in other locations. Supporting physical activity across multiple locations is critical to increasing overall physical activity in youth.

Objective The purpose of this study was to investigate the effect of grade IV lumbar mobilization on the activity/contraction of erector spinae (ES) and lumbar multifidus (LM) muscles in healthy people. Methods A randomized, repeated-measures design was used. Sixteen healthy subjects attended 3 testing sessions with a different intervention in each session (no intervention, grade IV central lumbar mobilization at L4, and placebo/light touch). Lying in a prone position, subjects lifted a light weight with their right arm while ultrasound images of LM and surface electromyography signals of ES were captured before and immediately after application of the intervention in the session. The contraction of LM was calculated from US images, and the root mean square was calculated from the electromyography signals of ES and used as outcome measures. Results A significant difference was found in LM contraction between the placebo and mobilization intervention (difference = 0.04, P = .02). There was no difference for the root mean square of electromyography signals between the interventions. Conclusion The significant difference in LM contraction was small and may not have clinical significance. Lumbar mobilization did not change the activity of ES in healthy people. Future studies with larger samples are needed to confirm our findings and to investigate the effect of mobilization on back muscles in people with low back pain.

Background Time trends and seasonal patterns have been observed in nurse staffing and nursing-sensitive patient outcomes in recent years. It is unknown whether these changes were associated. Methods Quarterly unit-level nursing data in 2004–2012 were extracted from the National Database of Nursing Quality Indicators® (NDNQI®). Units were divided into groups based on patterns of missing data. All variables were aggregated across units within these groups and analyses were conducted at the group level. Patient outcomes included rates of inpatient falls and hospital-acquired pressure ulcers. Staffing variables included total nursing hours per patient days (HPPD) and percent of nursing hours provided by registered nurses (RN skill-mix). Weighted linear mixed models were used to examine the associations between nurse staffing and patient outcomes at trend and seasonal levels. Results At trend level, both staffing variables were inversely associated with all outcomes (p

Background Although it is plausible that nurse staffing is associated with use of physical restraints in hospitals, this has not been well established. This may be due to limitations in previous cross-sectional analyses lacking adequate control for unmeasured differences in patient-level variables among nursing units. Objective To conduct a longitudinal study, with units serving as their own control, examining whether nurse staffing relative to a unit’s long-term average is associated with restraint use. Design We analyzed 17 quarters of longitudinal data using mixed logistic regression, modeling quarterly odds of unit restraint use as a function of quarterly staffing relative to the unit’s average staffing across study quarters. Subjects 3101 medical, surgical, and medical-surgical units in US hospitals participating in the National Database of Nursing Quality Indicators during 2006–2010. Units had to report at least one quarter with restraint use and one quarter without. Main Measures We studied two nurse staffing variables: staffing level (total nursing hours per patient day) and nursing skill mix (proportion of nursing hours provided by RNs). Outcomes were any use of restraint, regardless of reason, and use of restraint for fall prevention. Key Results Nursing skill mix was inversely correlated with restraint use for fall prevention and for any reason. Compared to average quarters, odds of fall prevention restraint and of any restraint were respectively 16 % (95 % CI: 3–29 %) and 18 % (95 % CI: 8–29 %) higher for quarters with very low skill mix. Conclusions In this longitudinal study there was a strong negative correlation between nursing skill mix and physical restraint use. Ensuring that skill mix is consistently adequate should reduce use of restraint.

The purpose of this study was to develop methods for assessing the reliability of scores on a widely disseminated hospital quality measure based on nursing unit fall rates. Poisson regression interactive multilevel modeling was adapted to account for clustering of units within hospitals. Three signal-noise reliability measures were computed. Squared correlations between the hospital score and true hospital fall rate averaged 0.52 ± 0.18 for total falls (0.68 ± 0.18 for injurious falls). Reliabilities on the other two measures averaged at least 0.70 but varied widely across hospitals. Parametric bootstrap data reflecting within-unit noise in falls were generated to evaluate percentile-ranked hospital scores as estimators of true hospital fall rate ranks. Spearman correlations between bootstrap hospital scores and true fall rates averaged 0.81 ± 0.01 (0.79 ± 0.01). Bias was negligible, but ranked hospital scores were imprecise, varying across bootstrap samples with average SD 11.8 (14.9) percentiles. Across bootstrap samples, hospital-measure scores fell in the same decile as the true fall rate in about 30% of cases. Findings underscore the importance of thoroughly assessing reliability of quality measurements before deciding how they will be used. Both the hospital measure and the reliability methods described can be adapted to other contexts involving clustered rates of adverse patient outcomes.

Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult smokers with low motivation to quit. Over 15 months, 33% of smokers who inquired about the study were enrolled. Common recruitment methods included word-of-mouth, print advertisements and clinic referrals. Frequently mentioned reasons for participating included to: gain financial incentives (44.7%), learn about research or help others quit (43%), learn about smoking and risks (40%) and help with future quits (i.e. Quit Assistance, 23.9%). Separate regression models predicting study outcomes at 26 weeks indicated that smokers who said they participated for Quit Assistance reported higher motivation to quit (B 1.26) and were more likely to have made a quit attempt (OR 2.03) compared to those not mentioning this reason, when baseline characteristics were controlled. Understanding reasons for unmotivated smokers' interest in treatment can help practitioners and researchers design effective strategies to engage this population.

Our purpose was to compare frequentist, empirical Bayes, and Bayesian hierarchical model approaches to estimating reliability of health care quality measures, including construction of credible intervals to quantify uncertainty in reliability estimates, using data on inpatient fall rates on hospital nursing units. Precision of reliability estimates and Bayesian approaches to estimating reliability are not well studied. We analyzed falls data from 2372 medical units; the rate of unassisted falls per 1000 inpatient days was the measure of interest. The Bayesian methods “shrunk” the observed fall rates and frequentist reliability estimates toward their posterior means. We examined the association between reliability and precision in fall rate rankings by plotting the length of a 90% credible interval for each unit’s percentile rank against the unit’s estimated reliability. Precision of rank estimates tended to increase as reliability increased but was limited even at higher reliability levels: Among units with reliability >0.8, only 5.5% had credible interval length 0.9, only 31.9% had credible interval length

Background Composite indices are single measures that combine the strengths of two or more individual measures and provide broader, easy-to-use measures for evaluation of provider performance and comparisons across units and hospitals to support quality improvement. Objective The study objective was to develop a unit-level inpatient composite nursing care quality performance index—the Pressure Ulcer and Fall Rate Quality Composite Index. Design Two-phase measure development study. Settings 5144 patient care units in 857 United States hospitals participating in the National Database of Nursing Quality Indictors ® during the year 2013. Methods The Pressure Ulcer and Fall Rate Quality Composite Index was developed in two phases. In Phase 1 the formula was generated using a utility function and generalized penalty analysis. Experts with experience in healthcare quality measurement provided the point of indicator equivalence. In Phase 2 initial validity evidence was gathered based on hypothesized relationships between the Pressure Ulcer and Fall Rate Quality Composite Index and other variables using two-level (unit, hospital) hierarchical linear mixed modeling. Results The Pressure Ulcer and Fall Rate Quality Composite Index = 100 − PUR − FR , where PUR is pressure ulcer rate and FR is total fall rate. Higher scores indicate better quality. Bland-Altman plots demonstrated agreement between pairs of experts and provided evidence for inter-rater reliability of the formula. The validation process demonstrated that higher registered nurse skill mix, higher percent of registered nurses with a baccalaureate in nursing or higher degree, higher percent of registered nurses with national specialty certification, and lower percent of hours supplied by agency staff were significantly associated with higher Pressure Ulcer and Fall Rate Quality Composite Index scores. Higher percentages of unit patients at risk for a hospital-acquired pressure ulcer and higher unit rates of physical restraint use were not associated with higher Pressure Ulcer and Fall Rate Quality Composite Index scores. Conclusions The Pressure Ulcer and Fall Rate Quality Composite Index is a step toward providing a more holistic perspective of unit level nursing quality than individual measures and may help nurses nursing administrators obtain a broader view of which patient care units are the higher and lower performers. Further study is needed to examine the usability of the Pressure Ulcer and Fall Rate Quality Composite Index.

Despite the importance of early detection to signal lifesaving treatment initiation for HIV+ infants, early infant diagnosis (EID) services have received considerably less attention than other aspects of prevention of mother to child transmission care. This study draws on baseline data from an on-going cluster randomized study of an intervention to improve EID services at six government hospitals across Kenya. Two logistic regressions examined potential predictors of “on time” (infant ≤6 weeks of age) vs. “late” (≥7 weeks) and “on time” versus “very late” (≥12 weeks) EID engagement among 756 mother-infant pairs. A quarter of the infants failed to get “on time” testing. Predictors of “on time” testing included being informed about EID by providers when pregnant, perceiving less HIV stigma, and mother’s level of education. Predictors of “very late” testing (≥12 weeks of age) included not being informed about EID by providers when pregnant and living farther from services. Findings highlight the importance of ensuring that health care providers actively and repeatedly inform HIV+ mothers of the availability of EID services, reduce stigma by frequently communicating judgment free support, and assisting mothers in early planning for accessing EID services. Extra care should be focused on engaging mothers with less formal education who are at increased risk for seeking “late” EID testing. This study offers clear targets for improving services so that all HIV-exposed infants can be properly engaged in EID services, thus increasing the potential for the best possible outcomes for this vulnerable population.