Search

Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700-bed academic medical center. The EWS risk scores were visible in the electronic medical record by bedside clinicians. The EWS risk scores were also monitored remotely 24/7 by critical care trained nurses who actively contacted bedside nurses when a patient's risk levels increased. The primary outcome was inpatient mortality. Secondary outcomes were rapid response team calls and activation of cardiopulmonary arrest (code-4) response teams. The study team conducted a regression discontinuity analysis adjusting for age, gender, insurance, severity of illness, risk of mortality, and hospital occupancy at admission. The analysis included 53,229 hospitalizations. Adjusted analysis showed no significant change in inpatient mortality, rapid response team call, or code-4 activations after implementing the EWS. This study confirms the continued uncertainty in the effectiveness of EWSs and the need for further rigorous examinations of EWSs. [ABSTRACT FROM AUTHOR]

Background: Epigenetic marks (eg, DNA methylation) may capture the effect of gene-environment interactions. DNA methylation is involved in blood pressure (BP) regulation and hypertension development; however, no studies have evaluated its relationship with 24-hour BP phenotypes (daytime, nighttime, and 24-hour average BPs).Methods: We examined the association of whole blood DNA methylation with 24-hour BP phenotypes and clinic BPs in a discovery cohort of 281 Blacks participants using reduced representation bisulfite sequencing. We developed a deep and region-specific methylation sequencing method, Bisulfite ULtrapLEx Targeted Sequencing and utilized it to validate our findings in a separate validation cohort (n=117).Results: Analysis of 38 215 DNA methylation regions (MRs), derived from 1 549 368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour BP phenotypes. No MR was significantly associated with clinic BP. Two to 3 MRs were significantly associated with various 24-hour BP phenotypes after adjustment for age, sex, and body mass index. Together, these MRs explained up to 16.5% of the variance of 24-hour average BP, while age, sex, and BMI explained up to 11.0% of the variance. Analysis of one of the MRs in an independent cohort using Bisulfite ULtrapLEx Targeted Sequencing confirmed its association with 24-hour average BP phenotype.Conclusions: We identified several MRs that explain a substantial portion of variances in 24-hour BP phenotypes, which might be excellent markers of cumulative effect of factors influencing 24-hour BP levels. The Bisulfite ULtrapLEx Targeted Sequencing workflow has potential to be suitable for clinical testing and population screenings on a large scale. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study that investigates the increased proliferative cells in the medullary thick ascending limbs of the loop of Henle isolated from Dahl salt-sensitive rats. The study shows that a week of a high-salt diet resulted to an increase in proliferative medullary thick ascending limb cells. It also shows alterations in the regulatory pathways in Dahl salt-sensitive rats in tissues that were highly enriched for a single cell type.

Previous analysis of 13 overlapping subcongenic strains led to the identification of a 1.37 Mbp region on chromosome 13 (positions 80.92 to 82.29 Mbp in the Rn5 genome assembly) that influenced the mean arterial blood pressure of the Dahl salt-sensitive (SS) rat on a high-salt diet by more than 20 mmHg. The goal of the present study was to identify biological pathways that could mediate the blood pressure effect of this genomic region. RNA-seq analysis was performed for the renal outer medulla tissue in five selected subcongenic strains, the SS, and a congenic strain from which the subcongenic strains were derived. Rats were fed a 0.4% salt diet or switched to a high-salt diet for 7 days. Affymetrix GeneChip data for SS and three additional congenic or consomic strains were obtained from a previous study. The RNA-seq and microarray data were merged using a cross-platform normalization method to generate a transcriptome dataset containing 90 observations for each gene. A Bayesian model analysis was performed for 243 biological pathways to assess their likelihood to discriminate blood pressure levels across experimental groups. Seven pathways showed posterior probabilities greater than 0.4. These pathways involved neuroactive ligand-receptor interaction, phenylalanine, tyrosine and tryptophan biosynthesis, and protein degradation. A Bayesian approach was used to estimate undirected graphical models among the three known genes located in the 1.37 Mbp region (Astn1, Fam5b, and Rfwd2) and genes in each of the 7 pathways identified above and 11 additional pathways known to be involved in blood pressure regulation. The analysis identified several previously unknown relationships between the three candidate genes and genes in pathways that could regulate blood pressure. The study demonstrated a new, unbiased approach for identifying biological pathways mediating the effect of a candidate genomic region on hypertension. [ABSTRACT FROM AUTHOR]

Studies of transcriptome profiles have provided new insights into mechanisms underlying the development of hypertension. Cell type heterogeneity in tissue samples, however, has been a significant hindrance in these studies. We performed a transcriptome analysis in medullary thick ascending limbs (mTALs) of the loop of Henle isolated from Dahl salt-sensitive (SS) rats and salt-insensitive consomic SS.13BN rats on either 0.4% or 7 days of 8% NaCl diet (n=4). The mTAL is a nephron segment importantly implicated in the development of hypertension in SS rats. Pathway analysis was performed based on genes differentially expressed between the two rat strains or by a Bayesian model analysis. The Bayesian model analysis was independent of a priori determination of differential expression and selected pathways by incorporating biological knowledge and expression profiles. Both analytical approaches identified pathways involving cell proliferation, cell cycle regulation, and cytokine signaling. The proliferative state of mTAL cells was analyzed by immunofluorescent staining of Ki-67 and p-H3. Of approximately 4,000 mTAL cells counted in each individual rat, 2.3% to 4.4% were in a proliferative state (positive for Ki-67 staining) when the rats were on the 0.4% salt diet (not significantly different between SS and SS.13BN rats). Exposure to the 8% salt diet for 7 days substantially increased the number of proliferative mTAL cells in both strains. In SS rats on the 8% salt diet, 15.0% of mTAL cells analyzed were in a proliferative state, which was significantly higher than the 10.1% in SS.13BN rats (n=7-9, P<0.05). The total number of cells per mTAL section analyzed was not different between the two strains. The number of cells that were in the G2/M phases (positive for p-H3 staining) tended to be higher in SS rats on the 8% salt diet, but the numbers were small in all treatment groups. The study revealed alterations in regulatory pathways in SS rats in a single cell type, leading to the unexpected finding of a greater increase in the number of proliferative mTAL cells in SS rats on a high-salt diet. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study., Objective: To evaluate the sensitivity and specificity of a combined Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm in defining cervical spine surgery in comparison to patient operative reports in the medical record., Summary of Background Data: Epidemiological studies of spine surgery often use ICD-9-CM billing codes in administrative databases to study trends and outcome of surgery. However, ICD-9-CM codes do not clearly identify specific surgical factors that may be related to outcome, such as instrumentation or number of levels treated. Previous studies have not investigated the sensitivity and specificity of a combined CPT and ICD-9-CM code algorithm for defining cervical spine surgical procedures., Methods: We performed a retrospective study comparing the sensitivity and specificity of a combined CPT and ICD-9-CM code algorithm to the operative note, the gold standard, in a single academic center. We also compared the accuracy of our combined algorithm with our published ICD-9-CM-only algorithm., Results: The combined algorithm has high sensitivity and specificity for defining cervical spine surgery, specific surgical procedures such as discectomy and fusion, and surgical approach. Compared to the ICD-9-CM-only algorithm, the combined algorithm significantly improves identification of discectomy, laminectomy, and fusion procedures and allows identification of specific procedures such as laminaplasty and instrumentation with high sensitivity and specificity. Identification of reoperations has low sensitivity and specificity, but identification of number of levels instrumented, fused, and decompressed has high specificity., Conclusion: The use of our combined CPT and ICD-9-CM algorithm to identify cervical spine surgery was highly sensitive and specific. For categories such as surgical approach, accuracy of our combined algorithm was similar to that of our ICD-9-CM-only algorithm. However, the combined algorithm improves sensitivity, and allows identification of procedures not defined by ICD-9-CM procedure codes, and number of levels instrumented and decompressed. The combined algorithm better defines cervical spine surgery and specific factors that may impact outcome and cost.