Federally Qualified Health Centers provide health care services to underserved communities and vulnerable populations. In Maryland, the burden of chronic disease is high among Federally Qualified ...Health Center patients. Electronic health records (EHRs) are becoming more widely used, and effective use of EHR data may improve chronic disease outcomes. This article describes the process of developing a data aggregation and analytics platform to support health centers in using population health data based on standardized clinical quality measures. This data warehouse, capable of aggregating EHR data across multiple health centers, provides opportunities for benchmarking and elicits a discussion of quality improvement, including identifying and sharing clinical best practices. Phase 1 of the project involved the strategic engagement of health center leadership and staff to get buy-in and to assess readiness. Phase 2 established the technological infrastructure and processes to support data warehouse implementation and began the process of information sharing and collaboration among 4 early adopters. Phase 3 will expand the project to additional health centers and continue quality improvement efforts. The health information technology marketplace is rapidly changing, and staying current will be a priority so that the data warehouse remains a useful quality improvement tool that continues to meet the demands of Maryland health centers. Ongoing efforts will also focus on ways to further add value to the system, such as incorporating new metrics to better inform health center decision making and allocation of resources. The data warehouse can inform and transform the quality of health care delivered to Maryland's most vulnerable populations, and future research should focus on the ability of health centers to translate this potential into actual improvements.
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Background: Schlafen family member 11 (SLFN11) sensitizes tumor cells to DNA-damaging agents and has been investigated as a potential predictive biomarker of response to PLT and ...PARP inhibitors, especially in small cell lung cancer (Lok, CCR 2017; Pietanza, JCO 2018). We aimed to explore the predictive/prognostic role of SLFN11 in PLT-treated CRPC. Methods: We assessed tumor exp of SLFN11 in PLT-treated, metastatic CRPC pts by RNAseq (N=27) and/or CTCs (N=20) (via the Epic Sciences platform). In addition, tumor morphology for neuroendocrine (NE) features and genomic status of select genes (ie, AR, TP53, RB1, BRCA2, BRCA1, ATM) by whole exome sequencing were evaluated. Statistical comparisons used Cox regression analysis and Kaplan Meier method for the association with overall/radiographic progression free survival (OS/rPFS). A dose response curve with PLT was performed in patient-derived organoids using Cell Title Glo according to the manufacturer’s protocol. Results: 41 CRPC (including 20 CRPC-NE) treated with PLT monotherapy (N=3) or PLT combination therapy (N=38) between August 2013 and December 2017 were evaluated. Median age was 67.1 years (range 51-91). Median number of prior therapies was 2 (range 1-7). A longer median rPFS was observed in all SLFN11+ pts treated with PLT (regardless of histology, RB1, TP53, PTEN, or DNA repair status) compared to SLFN11- 5.2 vs 2.3 months, HR 3.5, 95%CI 1.6-7.7, P<0.0001. No association was reported for OS. On multivariable analysis (Table), SLFN11 was an independent factor associated with rPFS. Organoids derived from patient tumors expressing SLFN11 showed sensitivity to PLT in vitro. Conclusions: SLFN11 exp identifies both CRPC and CRPC-NE pts with a better response to PLT. Patient-derived organoids expressing SLFN11 confirmed increased sensitivity to PLT. Larger prospective evaluation of therapy decisions based on SLFN11 exp is now required. Table: see text
BACKGROUND:The 2010 international guidelines for cardiopulmonary resuscitation recently recommended an increase in the minimum compression depth from 38 to 50 mm, although there are limited human ...data to support this. We sought to study patterns of cardiopulmonary resuscitation compression depth and their associations with patient outcomes in out-of-hospital cardiac arrest cases treated by the 2005 guideline standards.
DESIGN:Prospective cohort.
SETTING:Seven U.S. and Canadian urban regions.
PATIENTS:We studied emergency medical services treated out-of-hospital cardiac arrest patients from the Resuscitation Outcomes Consortium Epistry–Cardiac Arrest for whom electronic cardiopulmonary resuscitation compression depth data were available, from May 2006 to June 2009.
MEASUREMENTS:We calculated anterior chest wall depression in millimeters and the period of active cardiopulmonary resuscitation (chest compression fraction) for each minute of cardiopulmonary resuscitation. We controlled for covariates including compression rate and calculated adjusted odds ratios for any return of spontaneous circulation, 1-day survival, and hospital discharge.
MAIN RESULTS:We included 1029 adult patients from seven U.S. and Canadian cities with the following characteristicsMean age 68 yrs; male 62%; bystander witnessed 40%; bystander cardiopulmonary resuscitation 37%; initial rhythmsVentricular fibrillation/ventricular tachycardia 24%, pulseless electrical activity 16%, asystole 48%, other nonshockable 12%; outcomesReturn of spontaneous circulation 26%, 1-day survival 18%, discharge 5%. For all patients, median compression rate was 106 per minute, median compression fraction 0.65, and median compression depth 37.3 mm with 52.8% of cases having depth <38 mm and 91.6% having depth <50 mm. We found an inverse association between depth and compression rate ( p < .001). Adjusted odds ratios for all depth measures (mean values, categories, and range) showed strong trends toward better outcomes with increased depth for all three survival measures.
CONCLUSIONS:We found suboptimal compression depth in half of patients by 2005 guideline standards and almost all by 2010 standards as well as an inverse association between compression depth and rate. We found a strong association between survival outcomes and increased compression depth but no clear evidence to support or refute the 2010 recommendations of >50 mm. Although compression depth is an important component of cardiopulmonary resuscitation and should be measured routinely, the most effective depth is currently unknown. (Crit Care Med 2012; 40:–1198)
Background & Aims Early embryogenesis involves cell fate decisions that define the body axes and establish pools of progenitor cells. Development does not stop once lineages are specified; cells ...continue to undergo specific maturation events, and changes in gene expression patterns lead to their unique physiological functions. Secretory pancreatic acinar cells mature postnatally to synthesize large amounts of protein, polarize, and communicate with other cells. The transcription factor MIST1 is expressed by only secretory cells and regulates maturation events. MIST1-deficient acinar cells in mice do not establish apical-basal polarity, properly position zymogen granules, or communicate with adjacent cells, disrupting pancreatic function. We investigated whether MIST1 directly induces and maintains the mature phenotype of acinar cells. Methods We analyzed the effects of Cre-mediated expression of Mist1 in adult Mist1 –deficient ( Mist1 KO ) mice. Pancreatic tissues were collected and analyzed by light and electron microscopy, immunohistochemistry, real-time polymerase chain reaction analysis, and chromatin immunoprecipitation. Primary acini were isolated from mice and analyzed in amylase secretion assays. Results Induced expression of Mist1 in adult Mist1 KO mice restored wild-type gene expression patterns in acinar cells. The acinar cells changed phenotypes, establishing apical-basal polarity, increasing the size of zymogen granules, reorganizing the cytoskeletal network, communicating intercellularly (by synthesizing gap junctions), and undergoing exocytosis. Conclusions The exocrine pancreas of adult mice can be remodeled by re-expression of the transcription factor MIST1. MIST1 regulates acinar cell maturation and might be used to repair damaged pancreata in patients with pancreatic disorders.
The purpose of this study was to assess the effectiveness of contemporary automatic external defibrillator (AED) use.
In the PAD (Public Access Defibrillation) trial, survival was doubled by focused ...training of lay volunteers to use an AED in high-risk public settings.
We performed a population-based cohort study of persons with nontraumatic out-of-hospital cardiac arrest before emergency medical system (EMS) arrival at Resuscitation Outcomes Consortium (ROC) sites between December 2005 and May 2007. Multiple logistic regression was used to assess the independent association between AED application and survival to hospital discharge.
Of 13,769 out-of-hospital cardiac arrests, 4,403 (32.0%) received bystander cardiopulmonary resuscitation but had no AED applied before EMS arrival, and 289 (2.1%) had an AED applied before EMS arrival. The AED was applied by health care workers (32%), lay volunteers (35%), police (26%), or unknown (7%). Overall survival to hospital discharge was 7%. Survival was 9% (382 of 4,403) with bystander cardiopulmonary resuscitation but no AED, 24% (69 of 289) with AED application, and 38% (64 of 170) with AED shock delivered. In multivariable analyses adjusting for: 1) age and sex; 2) bystander cardiopulmonary resuscitation performed; 3) location of arrest (public or private); 4) EMS response interval; 5) arrest witnessed; 6) initial shockable or not shockable rhythm; and 7) study site, AED application was associated with greater likelihood of survival (odds ratio: 1.75; 95% confidence interval: 1.23 to 2.50; p < 0.002). Extrapolating this greater survival from the ROC EMS population base (21 million) to the population of the U.S. and Canada (330 million), AED application by bystanders seems to save 474 lives/year.
Application of an AED in communities is associated with nearly a doubling of survival after out-of-hospital cardiac arrest. These results reinforce the importance of strategically expanding community-based AED programs.
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. ...Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.
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•Multi-platform study of 150 pancreatic cancers accounting for neoplastic cellularity•Identify KRAS mutational heterogeneity and alternate drivers in KRAS wild-type tumors•Identify proteomic subtypes with prognostic significance and therapeutic implications•Integrated analysis of mRNA and non-coding RNA suggests consensus subtypes
This TCGA study reveals the complex molecular landscape of PDAC, with a small number of tumors carrying multiple KRAS mutations, KRAS wild-type PDACs harboring alterations in other RAS pathway genes or alternate oncogenic drivers, and integrated RNA and protein subtypes indicating clinically significant subsets of disease.
Effective mentorship is likely one of the most important determinants of success in academic medicine and research. Many papers focus on mentoring from the mentor's perspective, but few give guidance ...to mentees forging these critically important relationships. The authors apply "managing up," a corporate concept, to academic medical settings both to promote effective, successful mentoring and to make a mentor's job easier. Managing up requires the mentee to take responsibility for his or her part in the collaborative alliance and to be the leader of the relationship by guiding and facilitating the mentor's efforts to create a satisfying and productive relationship for both parties. The authors review the initiation and cultivation of a mentoring relationship from the perspective of a mentee at any stage (student through junior faculty), and they propose specific strategies for mentee success.
Real-world experience underscores the complexity of interactions among multiple drivers of climate change risk and of how multiple risks compound or cascade. However, a holistic framework for ...assessing such complex climate change risks has not yet been achieved. Clarity is needed regarding the interactions that generate risk, including the role of adaptation and mitigation responses. In this perspective, we present a framework for three categories of increasingly complex climate change risk that focus on interactions among the multiple drivers of risk, as well as among multiple risks. A significant innovation is recognizing that risks can arise both from potential impacts due to climate change and from responses to climate change. This approach encourages thinking that traverses sectoral and regional boundaries and links physical and socio-economic drivers of risk. Advancing climate change risk assessment in these ways is essential for more informed decision making that reduces negative climate change impacts.
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Climate change risk is complex. Multiple drivers of risk and multiple risks interact. We present a framework for climate change risk assessment that includes interactions among multiple risk drivers and among multiple risks. A significant innovation is integrating mitigation and adaptation responses as a determinant of climate change risk. This framework illustrates how risk drivers (hazards, exposures, vulnerabilities, and responses), as well as multiple risks, can aggregate, compound, and cascade to increase or decrease risk severity.
Unplanned bariatric postoperative emergency department (ED) visits occur frequently and may represent inadequate coordination of postdischarge care. Multicenter data on this outcome is limited, as ...this metric has not traditionally been tracked in large clinical databases.
To describe the frequency of and risk factors associated with 90-day postoperative ED visits after bariatric surgery.
Truven Health Analytics MarketScan database.
All patients undergoing primary bariatric operations in the 2012 and 2013 MarketScan database were included. The primary outcome was the presence of an ED visit not resulting in a hospital readmission within 90 days of surgical discharge. Risk factors and demographic characteristics evaluated included age, sex, co-morbidities, insurance type, region, operation type, prior ED visits within 1 year, and index admission length of stay.
Postoperative ED visits not associated with an inpatient admission occurred in 14.6% of patients. The most common diagnoses associated with these visits were abdominal pain (24.4%) and dehydration, nausea, or vomiting (20.8%). On multivariate analysis, younger age, female sex, greater number of co-morbidities, north-central region, open bariatric or laparoscopic gastric bypass operations,≥2 prior ED visits, and increased initial length of stay were all associated with increased odds of an ED visit.
Postoperative ED visits are a frequent and potentially preventable occurrence with several risk factors. Tracking this metric as a quality indicator will allow for targeted interventions to improve the transition of care to the outpatient setting after bariatric surgery.
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