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Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
Children breast-fed during infancy consume more fruits and vegetables than formula-fed children. This pattern is likely due, in part, to infant learning from flavours of the mother’s diet transmitted through breast milk, but more research is needed to understand associations between early flavour exposures and later dietary patterns. We examined whether breast-feeding and maternal fruit and vegetable consumption during nursing were synergistically associated with higher child fruit and vegetable consumption.
Prospective cohort study of breast-feeding duration, maternal diet postpartum and child diet. Complete breast-feeding and maternal diet data were available for 1396 mother–child dyads; multiple imputation was used for missing data in other variables. In separate multivariable logistic regression models, we estimated the adjusted odds of high child fruit or vegetable consumption at 12 months or 6 years as a function of breast-feeding duration, maternal fruit or vegetable consumption during nursing, and their interaction.
The Infant Feeding Practices Study II and Year 6 Follow-Up.
Mother–child dyads followed from birth to 6 years during 2005–2012 in the USA.
Longer breast-feeding duration was associated with high child fruit and vegetable consumption at 12 months. At 6 years, the interaction between breast-feeding duration and maternal vegetable consumption was associated with high child vegetable consumption.
Higher maternal vegetable consumption and longer breast-feeding duration were synergistically associated with high child vegetable consumption at 6 years, independent of sociodemographic characteristics and fruit and vegetable availability. Exposures to vegetable flavours through breast milk may promote later child vegetable consumption.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Background: Chronic intravenous immunoglobulin (IVIg) is used to treat refractory myasthenia gravis (MG). This subgroup analysis evaluated response to eculizumab in patients receiving chronic IVIg before entry to REGAIN, a phase 3, randomized, double-blind, placebo-controlled study of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized MG. Methods: IVIg was only permitted during REGAIN as rescue therapy; previously treated patients underwent a 4-week washout before randomization. Patients included in this analysis had received chronic IVIg ≥4 times in 1 year, with ≥1 dose within 6 months before REGAIN entry. Exacerbations and MG status changes were assessed. Results: Eighteen patients were evaluated; four experienced exacerbations (eculizumab-treated, 1/9; placebo-treated, 3/9). Clinically relevant improvements were larger with eculizumab than placebo, respectively (mean change, standard deviation [SD]: MG Activities of Daily Living score [MG-ADL], -5.3 [4.0] vs -2.1 [2.8]; Quantitative MG score [QMG], -4.1 [6.1] vs -1.3 [3.5]). More patients receiving eculizumab (7/9) had clinically meaningful responses (MG-ADL ≥3 and/or QMG ≥5 points) than those receiving placebo (3/9). Eculizumab safety was consistent with previous reports. Interim data from the open-label extension of REGAIN will be presented. Conclusions: In patients previously receiving chronic IVIg, eculizumab showed a trend toward meaningful clinical improvements and fewer exacerbations compared with placebo. (NCT01997229, NCT02301624).
Background: Patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (MG) unresponsive to conventional treatment experience greater disease burden than responsive patients. This is partly due to exacerbations, which may result in significant healthcare resource utilization. Eculizumab is well tolerated and gives clinically meaningful benefits in these patients. We evaluated the effect of long-term eculizumab treatment on exacerbations, hospitalizations and rescue therapy in the REGAIN study and its open-label extension. Methods: Exacerbations were defined as clinical worsening/deterioration, MG crises or rescue therapy usage; pre-study exacerbations/hospitalizations were defined from patient records. Event rates adjusted for patient-years were calculated for all patients in the pre-study year, patients receiving placebo during REGAIN, and patients receiving eculizumab during REGAIN and its open-label extension (median exposure, 27.5 months [range, 22 days–42.8 months]); rates were compared using a Poisson regression model. Results: Eculizumab treatment reduced exacerbations by 65% (p=0.0057), hospitalizations by 71% (p=0.0316) and rescue therapy use by 66% (p=0.0072) versus placebo. Eculizumab treatment reduced exacerbations by 74% and hospitalizations by 83% (both p<0.0001) versus the pre-study year. Conclusions: Long-term eculizumab treatment reduces disease burden and healthcare resource utilization, demonstrating continuing improvements in clinical endpoints that lead to additional meaningful outcomes for patients with AChR+ generalized MG. (NCT01997229, NCT02301624).
To determine the best nursing home facility characteristics for aggregating antibiotic susceptibility testing results across nursing homes to produce a useful annual antibiogram that nursing homes can use in their antimicrobial stewardship programs.
Derivation cohort study.
Center for Medicare and Medicaid Services (CMS) certified skilled nursing facilities in Georgia (N = 231).
All residents of eligible facilities submitting urine culture specimens for microbiologic testing at a regional referral laboratory.
Crude and adjusted metrics of antibiotic resistance prevalence (percent of isolates testing susceptible) for 5 bacterial species commonly recovered from urine specimens were calculated using mixed linear models to determine which facility characteristics were predictive of testing antibiotic susceptibility.
In a single year, most facilities had an insufficient number of isolates tested to create facility-specific antibiograms: 49% of facilities had sufficient Escherichia coli isolates tested, but only about 1 in 10 had sufficient isolates of Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, or Pseudomonas aeruginosa. After accounting for antibiotic tested and age of the patient, facility characteristics predictive of susceptibility were: E. coli, region, year, average length of stay; K. pneumoniae, region, bed size; P. mirabilis, region; and for E. faecalis or P. aerginosa no facility parameter remained in the model.
Nursing homes often have insufficient data to create facility-specific antibiograms; aggregating data across nursing homes in a region is a statistically sound approach to overcoming data shortages in nursing home stewardship programs.
Culturally modified trees (CMTs) provide tangible evidence of long-term forest use by Indigenous peoples. In Northwest Coast cedar forests, this record rarely spans beyond the last three centuries because older bark-harvest scars have been obscured through taphonomic processes such as natural healing and decay. Thus, archaeological visibility and identification are hindered. Here, I recover chronologies of ancient forest harvesting using a post-impact assessment methodology of targeting old-growth clear-cuts in southern Nuu-chah-nulth territories on the west coast of Vancouver Island, British Columbia, Canada. Bark-peeling scars are identified and dated in cross section by growth-ring patterns of recently logged trees. Approximately half of all bark-peeling scars are “embedded” inside healing lobes, suggesting at least half of all such CMTs are effectively invisible in standing forests. Features in these post-impact surveys predated those discovered in conventional archaeological impact assessments by a mean of almost a century. Additionally, one of the oldest continually used cultural forests ever recorded, dating to AD 908, is found in the Toquaht Nation traditional territory. These findings uncover measurable frequencies of cedar-bark harvesting generations prior to the contact period and reveal the inadequacy of heritage protections for old-growth cedar stands.
To estimate the burden of Clostridium difficile infections (CDIs) due to interfacility patient sharing at regional and hospital levels.
Retrospective observational study.
We used data from the Healthcare Cost and Utilization Project California State Inpatient Database (2005–2011) to identify 26,878,498 admissions and 532,925 patient transfers. We constructed a weighted, directed network among the hospitals by defining an edge between 2 hospitals to be the monthly average number of patients discharged from one hospital and admitted to another on the same day. We then used a network autocorrelation model to study the effect of the patient sharing network on the monthly average number of CDI cases per hospital, and we estimated the proportion of CDI cases attributable to the network.
We found that 13% (95% confidence interval [CI], 7.6%–18%) of CDI cases were due to diffusion through the patient-sharing network. The network autocorrelation parameter was estimated at 5.0 (95% CI, 3.0–6.9). An increase in the number of patients transferred into and/or an increased CDI rate at the hospitals from which those patients originated led to an increase in the number of CDIs in the receiving hospital.
A minority but substantial burden of CDI infections are attributable to hospital transfers. A hospital’s infection control may thus be nontrivially influenced by its neighboring hospitals. This work adds to the growing body of evidence that intervention strategies designed to minimize HAIs should be done at the regional rather than local level.
Quantitative phase analysis by XRD requires the attainment of (1) random crystallite orientation and (2) homogeneous and intimate mixing of the constituent phases in the samples. These two requirements must also be met in the preparation of random composite materials, particularly those containing randomly-oriented fibers or whiskers.
The two most common methods for producing random crystallite orientation are spray drying and the air suspension method. In the latter, an air suspension of the crystallites is rapidly collected onto a glass fiber filter. The crystallites then assume the random orientation of the filter fibers on which they are deposited.
Formation of a low barrier back contact plays a critical role in improving the photoconversion efficiency of the CdTe solar cells. Incorporating a buffer layer to minimize the band bending at the back of the CdTe device can significantly lower the barrier for the hole current, improving open circuit voltage (VOC) and the fill factor. Over the past years, researchers have incorporated the both ZnTe and Te as buffer layers to improve CdTe device performance. Here we compare device performance using these two materials as buffer layers at the back of CdTe devices. We show that using Te in contact to CdTe results in higher performance than using ZnTe in contact to the CdTe. Low temperature current density-voltage measurements show that Te results is a lower barrier with CdTe than ZnTe, indicating that Te has better band alignment, resulting in less downward bending in the CdTe at the back interface, than ZnTe does.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement.
Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified.
Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9–5.7) and 5.7 kg (5.5–6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5–100%). Digoxin was used by 11/14 centres in 25% of patients (23–31%), and 81% had some oral feeds (68–84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75–113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8–32%). Seven centres extubated 5% of patients (2–40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0–5.3) and total length of stay was 7.5 days (6–10).
In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.