Current Role at Stanford
Assisting Researchers in Stanford School of Medicine to help materialize their research projects with STRIDE and EMR data.
Assisting Researchers in Stanford School of Medicine to help materialize their research projects with STRIDE and EMR data.
It has been posited that high workload and long work hours for trainees could affect the quality and efficiency of patient care. Duty hour restrictions seek to balance patient care and resident education by limiting resident work hours. Through a retrospective cohort study, we investigate whether patient care on an inpatient general medicine service at a large academic medical center is impacted when housestaff work greater than eighty hours per week METHODS: We identified all admissions to a housestaff-run general medicine service between June 25, 2013 and June 29, 2014. Each hospitalization was classified by whether or not the patient was admitted by housestaff who have worked more than eighty hours a week during their hospitalization. Housestaff computer activity and duty hours were calculated by institutional electronic heath record audit, as well as length of stay and a composite of in-hospital mortality, ICU transfer rate, and 30-day readmission rate.We identified 4,767 hospitalizations by 3,450 unique patients; of which 40.9% of hospitalizations were managed by housestaff who worked more than eighty hours that week during their hospitalization. There was a significantly higher rate of the composite outcome (19.2% vs. 16.7%, p = 0.031) for patients admitted by housestaff working more than eighty hours a week during their hospitalization. We found a statistically significant higher length of stay (5.12 vs. 4.66 days, p = 0.048) and rate of ICU transfer (3.18% vs. 2.38%, p = 0.029). There was no statistically significant difference in 30-day readmission rate (13.7% vs. 12.8%, p = 0.395), or in-hospital mortality rate (3.18% vs. 2.42%, p = 0.115).There was no correlation with team census on admission and patient outcomes.Patients taken care of by housestaff working more than eighty hours a week had increased length of stay and number of ICU transfers. There was no association between resident work-hours and patient in-hospital mortality or 30-day readmission rate.
View details for DOI 10.1016/j.amjmed.2016.03.023
View details for PubMedID 27103047
Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. This study investigated the clinical importance of RRVD by assessing its relationship with clot burden and biomarkers. We identified consecutive patients admitted to the emergency department between 1999 and 2014 who underwent computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV assessment included measurements of ventricular dimensions, fractional area change, free-wall longitudinal strain and tricuspid annular plane systolic excursion. Clot burden was assessed using the modified Miller score. Of 82 patients identified, 51 had acute PE (mean age 66 ± 17 years, 43 % male). No patient had RV myocardial infarction. RRVD was present in 41 % of PEs and absent in all patients without PE. Among patients with PE, 86 % of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81 vs. 30 %, p < 0.01) and dysfunction (86 vs. 23 %, p < 0.01). There was a strong trend for higher troponin level in PE patients with RRVD (38 vs. 13 % in PE patients without RRVD, p = 0.08), while there was no significant difference for NT-proBNP (67 vs. 73 %, p = 0.88). RRVD showed good concordance between readers (87 %). RRVD is associated with an increased clot burden in acute PE and is more prevalent among patients with moderate-to-severe RV enlargement and dysfunction.
View details for DOI 10.1007/s10554-015-0780-1
View details for PubMedID 26428674
To evaluate whether the administration of hypotonic fluids compared with isotonic fluids is associated with a greater risk for hyponatremia in hospitalized children.Informatics-enabled cohort study of all hospitalizations at Lucile Packard Children's Hospital between April 2009 and March 2011. Extraction and analysis of electronic medical record data identified normonatremic hospitalized children who received either hypotonic or isotonic intravenous maintenance fluids upon admission. The primary exposure was the administration of hypotonic maintenance fluids, and the primary outcome was the development of hyponatremia (serum sodium <135 mEq/L).A total of 1048 normonatremic children received either hypotonic (n = 674) or isotonic (n = 374) maintenance fluids upon admission. Hyponatremia developed in 260 (38.6%) children who received hypotonic fluids and 104 (27.8%) of those who received isotonic fluids (unadjusted OR 1.63; 95% CI 1.24-2.15, P < .001). After we controlled for intergroup differences and potential confounders, patients receiving hypotonic fluids remained more likely to develop hyponatremia (aOR 1.37, 95% CI 1.03-1.84). Multivariable analysis identified additional factors associated with the development of hyponatremia, including surgical admission (aOR 1.44, 95% CI 1.09-1.91), cardiac admitting diagnosis (aOR 2.08, 95% CI 1.34-3.20), and hematology/oncology admitting diagnosis (aOR 2.37, 95% CI 1.74-3.25).Hyponatremia was common regardless of maintenance fluid tonicity; however, the administration of hypotonic maintenance fluids compared with isotonic fluids was associated with a greater risk of developing hospital-acquired hyponatremia. Additional clinical characteristics modified the hyponatremic effect of hypotonic fluid, and it is possible that optimal maintenance fluid therapy now requires a more individualized approach.
View details for DOI 10.1016/j.jpeds.2013.07.020
View details for PubMedID 23998517
Social networks have been used in the study of outbreaks of infectious diseases, including in small group settings such as individual hospitals. Collecting the data needed to create such networks, however, can be time consuming, costly, and error prone. We sought to create a social network of hospital inpatients using electronic medical record (EMR) data already collected for other purposes, for use in simulating outbreaks of nosocomial infections.We used the EMR data warehouse of a tertiary academic hospital to model contact among inpatients. Patient-to-patient contact due to shared rooms was inferred from admission-discharge-transfer data, and contact with healthcare workers was inferred from clinical documents. Contacts were used to generate a social network, which was then used to conduct probabilistic simulations of nosocomial outbreaks of methicillin-resistant Staphylococcus aureus and influenza.Simulations of infection transmission across the network reflected the staffing and patient flow practices of the hospital. Simulations modeling patient isolation, increased hand hygiene, and staff vaccination showed a decrease in the spread of infection.We developed a method of generating a social network of hospital inpatients from EMR data. This method allows the derivation of networks that reflect the local hospital environment, obviate the need for simulated or manually collected data, and can be updated in near real time.Inpatient social networks represent a novel secondary use of EMR data, and can be used to simulate nosocomial infections. Future work should focus on prospective validation of the simulations, and adapting such networks to other tasks.
View details for DOI 10.1136/amiajnl-2012-001401
View details for Web of Science ID 000317477500005
View details for PubMedID 23467473
View details for PubMedCentralID PMC3628065
Both the activated partial thromboplastin time (aPTT) and anti-Xa assay can be used to monitor unfractionated heparin (UFH). Following implementation of an anti-Xa method for heparin dosing protocols in our hospital, we became aware of many patients with discordant aPTT and anti-Xa values.To determine the frequency of discordant aPTT and anti-Xa values in a large cohort of hospitalized patients treated with UFH, as well as the demographics, coagulation status, indication for UFH, and clinical outcomes in this population.All aPTT and anti-Xa values from adults hospitalized between February and August 2009 at Stanford Hospital who were treated with UFH were analyzed. All samples were drawn simultaneously. A polynomial fit correlating aPTT and anti-Xa with a 99% confidence limit was designed. Paired aPTT/anti-Xa values were grouped according to whether the paired values fell within or outside of the concordant area. Patients were placed into groups based on concordance status, and clinical outcomes were assessed.A total of 2321 paired values from 539 patients were studied; 42% of data pairs had a high aPTT value relative to the anti-Xa value. Patients with elevated baseline prothrombin time/international normalized ratio or aPTT frequently demonstrated disproportionate relative prolongation of the aPTT. Patients with at least 2 consecutive high aPTT to anti-Xa values had increased 21-day major bleeding (9% vs 3%; p = 0.0316) and 30-day mortality (14% dead vs 5% dead at 30 days; p = 0.0202) compared with patients with consistently concordant values.aPTT and anti-Xa values are frequently discordant when used to measure UFH in hospitalized patients. A disproportionate prolongation of the aPTT relative to the anti-Xa was the most common discordant pattern in our study. Patients with relatively high aPTT to anti-Xa values appear to be at increased risk of adverse outcomes. Monitoring both aPTT and Xa values may have utility in managing such patients.
View details for DOI 10.1345/aph.1R635
View details for PubMedID 23386070
The lipid-lowering agent pravastatin and the antidepressant paroxetine are among the most widely prescribed drugs in the world. Unexpected interactions between them could have important public health implications. We mined the US Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) for side-effect profiles involving glucose homeostasis and found a surprisingly strong signal for comedication with pravastatin and paroxetine. We retrospectively evaluated changes in blood glucose in 104 patients with diabetes and 135 without diabetes who had received comedication with these two drugs, using data in electronic medical record (EMR) systems of three geographically distinct sites. We assessed the mean random blood glucose levels before and after treatment with the drugs. We found that pravastatin and paroxetine, when administered together, had a synergistic effect on blood glucose. The average increase was 19 mg/dl (1.0 mmol/l) overall, and in those with diabetes it was 48 mg/dl (2.7 mmol/l). In contrast, neither drug administered singly was associated with such changes in glucose levels. An increase in glucose levels is not a general effect of combined therapy with selective serotonin reuptake inhibitors (SSRIs) and statins.
View details for DOI 10.1038/clpt.2011.83
View details for Web of Science ID 000291853800023
View details for PubMedID 21613990
View details for PubMedCentralID PMC3216673
The dose-response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy.We have generated 3 lines of transgenic mice, expressing low, mid, and high levels of full-length human dysferlin from a muscle-specific promoter. Transgenic skeletal muscle was analyzed and scored for morphological and functional deficits.Overexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait, and reduced muscle mass and strength. Moreover, protein dosage correlated with phenotype severity. In contrast to dysferlin-null skeletal muscle, no evidence of sarcolemmal impairment was revealed. Rather, increased levels of Ca(2+)-regulated, dysferlin-binding proteins and endoplasmic reticulum stress chaperone proteins were observed in muscle lysates from transgenic mice as compared with controls.Expression levels of dysferlin are important for appropriate function without deleterious or cytotoxic effects. As a corollary, we propose that future endeavors in gene replacement for correction of dysferlinopathy should be tailored to take account of this.
View details for DOI 10.1002/ana.21926
View details for Web of Science ID 000276216800014
View details for PubMedID 20373350
Spinal cord injury (SCI) results in muscle weakness but the degree of impairment at the level of single fibers is not known. The purpose of this study was to examine the effects of T9-level SCI on single muscle fibers from the tibialis anterior of rats. Significant decreases in cross-sectional area (CSA), maximal force (Po), and specific force (SF = Po/CSA) were noted at 2 weeks. Atrophy and force-generating capacity were reversed at 4 weeks, but SF remained impaired. Maximum shortening velocity (Vo) did not change after injury. SCI thus appears to affect various contractile properties of single muscle fibers differently. Normal cage activity may partially restore function but new interventions are needed to restore muscle fiber quality.
View details for DOI 10.1002/mus.20530
View details for Web of Science ID 000238688000012
View details for PubMedID 16518854
Five patients with untreated dermatomyositis, five with inclusion body myositis, and 16 healthy elderly volunteer subjects (controls) underwent open (dermatomyositis and inclusion body myositis) or percutaneous (controls) muscle biopsy. Biopsied muscles included deltoid, biceps and vastus lateralis. Chemically skinned single muscle fibers were activated with Ca(+2); the slack test was performed to determine maximal unloaded shortening velocity (Vo). Parameters measured include single fiber cross sectional area, maximal force, specific force and Vo. 429 Type I and 94 Type IIA fibers were studied. Cross sectional area and maximal force were greater in inclusion body myositis than dermatomyositis or control for Type I and IIA fibers. Specific force of Type I fibers was similar in inclusion body myositis and dermatomyositis but greater than in controls. Vo was greater in Type I, but not IIA, fibers in dermatomyositis compared with inclusion body myositis and controls. The force and velocity generating capacity of single muscle fibers is preserved in patients with dermatomyositis and inclusion body myositis suggesting that dysfunction of the contractile proteins does not contribute to clinical muscle weakness.
View details for DOI 10.1016/j.nmd.2005.01.011
View details for Web of Science ID 000228893000004
View details for PubMedID 15833427
View details for DOI 10.1016/j.apmr.2004.07.230
View details for DOI 10.1016/j.apmr.2004.07.003
The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 infects both plants and animals. Previously, using plants to screen directly for P. aeruginosa virulence-attenuated mutants, we identified a locus, pho34B12, relevant in mammalian pathogenesis. Here, nonsense point mutations in the two opposing ORFs identified in the pho34B12 locus revealed that one of them, mvfR (multiple virulence factor Regulator), is able to control all of the phenotypes that mutant phoA34B12 displays. Both genetic and biochemical evidence demonstrate that the mvfR gene encodes a LysR-like transcriptional factor that positively regulates the production of elastase, phospholipase, and of the autoinducers, 3oxo-dodecanoyl homoserine lactone (PAI I) and 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as the expression of the phnAB operon, involved in phenazine biosynthesis. We demonstrate that the MvfR protein is membrane-associated and acts as a transcriptional activator until cells reach stationary phase, when a unique negative feedback mechanism is activated to signal the down-regulation of the MvfR protein. This work reveals an unprecedented virulence mechanism of P. aeruginosa and identifies a unique indispensable player in the P. aeruginosa quorum-sensing cascade.
View details for Web of Science ID 000172576900077
View details for PubMedID 11724939
Saxiphilin is a plasma protein from the bullfrog (Rana catesbiana) that binds saxitoxin (STX), a causative agent of paralytic shellfish poisoning. Saxiphilin is homologous to transferrin and consists of two internally homologous domains called the N-lobe and the C-lobe. STX binds to a single site in the C-lobe of saxiphilin. In this study, cloned genes coding for recombinant saxiphilin and C-lobe saxiphilin were modified to contain two tandemly located affinity tags, Flag epitope (DYKDDDDK) and His(6) (HHHHHH), at the protein C-terminus and were expressed in cultured insect cells using baculovirus vectors. Both tagged proteins are readily detected on immunoblots by anti-Flag monoclonal antibody. Flag-His(6)-tagged saxiphilin was purified to homogeneity using Ni(2+)-chelate affinity chromatography and Heparin Sepharose chromatography. Equilibrium analysis of [3H]STX binding to tagged saxiphilin and tagged C-lobe saxiphilin gave K(D) values of 0.75 and 2.7 nM, respectively. Flag-His(6)-tagged saxiphilin was also utilized in a microtiter well solid-phase assay with Reacti-bind metal chelate plates to measure [3H]STX binding and binding competition by unlabeled STX. Such Flag-His(6)-tagged derivatives of saxiphilin have many possible applications in the assay of STX and related toxinological research.
View details for Web of Science ID 000089441800016
View details for PubMedID 10978747
The type 1 domain of thyroglobulin is a protein module (Thyr-1) that occurs in a variety of secreted and membrane proteins. Several examples of Thyr-1 modules have been previously identified as inhibitors of the papain family of cysteine proteinases. Saxiphilin is a neurotoxin-binding protein from bullfrog and a homolog of transferrin with a pair of such Thyr-1 modules located in the N-lobe. Saxiphilin is now characterized as a potent inhibitor of three cysteine proteinases as follows: papain, human cathepsin B, and cathepsin L. The stoichiometry of enzyme inhibition reveals that both Thyr-1 domains of saxiphilin inhibit papain (apparent K(i) = 1. 72 nm), but only one of these domains inhibits cathepsin B (K(i) = 1. 67 nm) and cathepsin L (K(i) = 0.02 nm). Physical association of saxiphilin and papain blocked from turnover at the active-site cysteine residue can be detected by cross-linking with glutaraldehyde. The rate of association of saxiphilin and cathepsin B is strongly pH-dependent with an optimum at pH 5.2, reflecting control by at least two H(+)-titratable groups. These results further demonstrate that various Thyr-1 domains are selective inhibitors of cysteine proteinases with utility in the study of protein interactions and degradation.
View details for Web of Science ID 000087128300107
View details for PubMedID 10748022
The binding of 125I-labeled apocytochrome c to human erythrocytes was determined for free apocytochrome c concentrations at 10(-10)-10(-6) M. At about 2 x 10(-9) M, maximum cell association of apocytochrome c occurs at 50 mM NaCl and at 22 degrees C. Intact erythrocytes at 22 degrees C have three classes of apocytochrome c binding sites: one high-affinity noncooperative site (n1 = 728 per cell, Kd1 = 1.5 x 10(-9) M) and two positively cooperative sites (n2 = 3.7 x 10(4) per cell, Kd2 = 1.2 x 10(-7) M, alpha 2 = 2.0, and n3 = 2.5 x 10(5) per cell, Kd3 = 7.1 x 10(-7) M, alpha 3 = 12). Erythrocytes at 37 degrees C, and erythrocyte ghosts at 22 degrees C, also have three classes of apocytochrome c binding sites, and most sites are positively cooperative.
View details for Web of Science ID A1994PJ24800012
View details for PubMedID 8092129
Aldolase and glyceraldehyde-3-phosphate dehydrogenase from the extremely halophilic archaebacterium Haloarcula vallismortis are stable only in high concentrations of KCl present within the physiological environment. Data concerning the structural changes in the two enzymes as a result of lowering of salt concentration and changes in pH were obtained by monitoring the intrinsic protein fluorescence in the presence of quenchers. When the KCl concentrations were lowered below 2 M or in the presence of 6 M guanidine hydrochloride, the emission maximum shifted to a longer wavelength, indicating enhanced exposure of tryptophyl residues to the solvent. The spectral characteristics of the two proteins in guanidine hydrochloride and 0.4 M KCl were identical. However, these denatured states appear to be different than those observed after acid denaturation. Further perturbation of fluorescence was observed due to I-, and application of the Stern-Volmer law showed that the total fluorescence was available to the quenchers only in 0.4 M KCl solutions. The unfolding of proteins in 0.4 M KCl was a gradual process which was accompanied by a time-dependent loss in enzyme activity. The activity loss was complete within 30 min for aldolase whereas in the case of GAPDH nearly 3 h was required for the destruction of activity. For both enzymes, inactivation and protein denaturation were strongly correlated. The data on activity and thermostability measurements of the two enzymes in varying concentrations of KCl and potassium phosphate revealed that though both proteins are halophilic, the forces in the maintenance of their stability could be different.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1993KJ64400008
View details for PubMedID 8422383
View details for Web of Science ID A1991GJ93100060
An electrophoretically homogeneous class I (Schiff base) alsolase has been isolated for the first time from the archaebacterial halophile Haloarcula (Halobacterium) vallismortis. The aldolase was characterized with respect to its molecular mass, amino acid composition, salt dependency, immunological cross-reactivity and kinetic properties. The subunit mass of aldolase is 27 kDa, which is much smaller than other class I aldolases. By the gel filtration method, the molecular mass of the halobacterial enzyme was estimated as 280 +/- 10 kDa, suggesting a decameric nature. In contrast to many halobacterial proteins, the H. vallismortis aldolase, though a halophilic enzyme, did not show an excess of acidic residues. Unlike the eukaryotic aldolases, the activity of the halobacterial enzyme was not affected by carboxypeptidase digestion. The general catalytic features of the enzyme were similar to its counterparts from other sources. No antigenic similarity could be detected between the H. vallismortis aldolase and class I aldolase from eubacteria and eukaryotes or class II halobacterial aldolases.
View details for Web of Science ID A1991EW78300007
View details for PubMedID 1900049
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