Using the ecology model to describe the impact of asthma on patterns of health care

BACKGROUND: Asthma changes both the volume and patterns of healthcare of affected people. Most studies of asthma health care utilization have been done in selected insured populations or in a single site such as the emergency department. Asthma is an ambulatory sensitive care condition making it important to understand the relationship between care in all sites across the health service spectrum. Asthma is also more common in people with fewer economic resources making it important to include people across all types of insurance and no insurance categories. The ecology of medical care model may provide a useful framework to describe the use of health services in people with asthma compared to those without asthma and identify subgroups with apparent gaps in care. METHODS: This is a case-control study using the 1999 U.S. Medical Expenditure Panel Survey. Cases are school-aged children (6 to 17 years) and young adults (18 to 44 years) with self-reported asthma. Controls are from the same age groups who have no self-reported asthma. Descriptive analyses and risk ratios are placed within the ecology of medical care model and used to describe and compare the healthcare contact of cases and controls across multiple settings. RESULTS: In 1999, the presence of asthma significantly increased the likelihood of an ambulatory care visit by 20 to 30% and more than doubled the likelihood of making one or more visits to the emergency department (ED). Yet, 18.8% of children and 14.5% of adults with asthma (over a million Americans) had no ambulatory care visits for asthma. About one in 20 to 35 people with asthma (5.2% of children and 3.6% of adults) were seen in the ED or hospital but had no prior or follow-up ambulatory care visits. These Americans were more likely to be uninsured, have no usual source of care and live in metropolitan areas. CONCLUSION: The ecology model confirmed that having asthma changes the likelihood and pattern of care for Americans. More importantly, the ecology model identified a subgroup with asthma who sought only emergent or hospital services

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787–0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576–0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556–0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620–1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818–0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383–1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449–0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475–1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD

Multistakeholder Collaborative Effort to Enhance Long-Term Follow-Up in the Abdominal Core Health Quality Collaborative

Objective:. To determine the effectiveness of a clinical call center in performing focused long-term patient reported outcome (PRO)-based follow-up for ventral hernia patients in routine practice. Background:. Long-term follow-up remains the mainstay of assessing quality of care in hernia management. Achieving acceptable rates of long-term follow-up outside of clinical trials in the routine care of patients has been very difficult to achieve. Methods:. A prospective quality improvement intervention using a clinical call center in 1000 random patients eligible for long-term (1 year or greater) follow-up after ventral hernia repair in the Abdominal Core Health Quality Collaborative was performed. The primary outcome measure was the proportion of patients with successfully completed PRO-based long-term follow-up. Results:. Between 2013 and 2017, the baseline long-term follow-up PRO completion rate was 2167/13,950 (15.5%). For the Focus on Follow-Up initiative, 890 patients were eligible for contact; a completion rate of 450/890 (50.6%, P < 0.001) was achieved. Conclusions:. Clinical call center-based patient contact can greatly facilitate the completion of PROs utilized for long-term follow-up in ventral hernia repair. This has important implications for quality improvement programs and postmarket device surveillance