Ten CEO Imperatives for Healthcare Transformation: Lessons From Top-Performing Academic Medical Centers.

EXECUTIVE SUMMARY: The transition from a delivery model based on volume to a model based on value is underpinning an unprecedented rate of change in healthcare. Our research identifies academic medical centers that have successfully moved their organizations from a volume-based care delivery model to a model that is based on value, achieving top decile performance in the transition. We asked senior leaders about their key imperatives in achieving system-wide healthcare transformations.Major teaching hospitals were sampled using data envelopment analysis to identify hospitals that produced the best value-based purchasing process of care, Hospital Consumer Assessment of Healthcare Providers and Systems scores, and mortality scores with the most efficient utilization of human and financial organizational resources. On-site interviews were conducted with the CEOs of the top-performing hospitals. Content analysis of the transcribed interviews revealed 10 clear imperatives that our sample of CEOs said were essential.

Value-Based Purchasing: The Effect of Hospital Ownership and Size.

This research tests the effect of hospital ownership and size on value-based purchasing scores. Representative samples were randomly selected of short-term acute-care hospitals from across the nation and grouped into 3 categories of both ownership and size. The ownership categories are as follows: (1) for-profit, (2) nonprofit, and (3) government. The size categories are as follows: (1) small, 99 beds or fewer; (2) medium, 100 to 249 beds; (3) large, 250 beds or more. Value-based purchasing scores for the 12 process-of-care (PC) measures and the 8 patient experience-of-care (Hospital Consumer Assessment of Healthcare Providers and System [HCAHPS]) measures were calculated and combined into their single total performance score (TPS). The results reveal that for-profit controlled hospitals outperform both nonprofit and government-controlled hospitals in PC measures, HCAHPS measures, and value-based purchasing TPSs. The results also reveal that small hospitals (≤99 beds) outperform both medium hospitals (100-249 beds) and large hospitals (≥250 beds) in PC measures, HCAHPS measures, and TPS. Results are discussed.

First Report of Impatiens Downy Mildew Caused by Plasmopara obducens in Ohio.

Single and double flowered impatiens (Impatiens walleriana Hook.f.) plants with symptoms of downy mildew were found in commercial greenhouses in Delaware, Wayne, and Holmes counties, Ohio, in April 2012. Plants were stunted and defoliated. Symptoms on remaining leaves included general chlorosis without discrete spots and downward curling of leaves. A downy white growth was observed on the lower surface of infected leaves. The disease was widespread in affected greenhouses and incidence in cvs. Shimmer Coral, Accent Mix, and Super Elfin was nearly 90%. The downy growth consisted of coenocytic mycelia, monopodial sporangiophores, and ovoid, hyaline sporangia typical of Plasmopara obducens (J. Schröt.) J. Schröt in Cohn (1,2,4). Sporangia were borne on branchlets measuring 5 to 15 µm long (average 10 µm) at right angles to the main axis of the sporangiophore. Sporangia were 9.4 to 17.5 × 12.8 to 16.3 µm. No oospores were observed. Total DNA was extracted directly from plant tissue with the Wizard SV Genomic DNA Purification System (Promega, Madison, WI) following the manufacturer's instructions. Large ribosomal subunit DNA was amplified by PCR using primers NL-1 and NL-4 (3). Amplicons of 690 bp and 834 bp were produced from each diseased sample, while only the 690-bp amplicon was produced from healthy tissue. DNA from each amplicon of sample IDM041712 was purified using the Wizard SV Gel and PCR Clean-Up System (Promega), sequenced, and the sequence of the diagnostic 834-bp amplicon was deposited in GenBank (JX142134). The sequence of the 834-bp amplicon was 99% similar to those of P. obducens isolates from Serbia (HQ246451) (1), the UK (AY587558), and Austria (EF196869). The sequence of the 690-bp amplicon (JX142135) was 99% similar to that of I. walleriana (HQ223336). Twelve young impatiens 'Shimmer Coral' plants were inoculated with sporangia washed from infected leaves (1 × 104 sporangia/ml). Plants were incubated at room temperature for 24 h in a moist chamber and then maintained in a greenhouse (21 to 23°C) until symptoms appeared. Control plants were sprayed with sterile water and maintained in the same environment. After 12 to 14 days, typical symptoms of downy mildew developed on the inoculated plants and microscopic examination revealed the same pathogen morphology as the original isolate. All non-inoculated control plants remained disease free. To our knowledge, this is the first report of downy mildew on impatiens in Ohio. This disease caused considerable economic losses in Ohio in 2012 and is likely to be a recurring problem requiring intensive preventative management. References: (1) A. Bulajic et al. Plant Dis. 95:491, 2011. (2) O. Constantinescu. Mycologia 83:473, 1991. (3) W. Maier et al. Can. J. Bot. 81:12, 2003. (4) S. N. Wegulo et al. Plant Dis. 88:909, 2004.

Disposition of sulfadimethoxine in camels (Camelus dromedarius) following single intravenous and oral doses.

Single-dose pharmacokinetics of sulfadimethoxine were determined in six adult camels (Camelus dromedarius) following administration of a mean dosage of 17.5 +/- 2.7 mg/kg both i.v. and p.o. Serial blood samples were collected through an indwelling jugular catheter intermittently for 5 days for both routes. Sulfadimethoxine was assayed using high-performance liquid chromatography. Serum drug concentration versus time data for each animal was subjected to linear regression, with the best-fit model selected based on residual analysis. The data fit best into a two-compartment open model, with first-order input for oral administration. For orally administered drug, mean maximum serum concentration of 19.3 +/- 1.7 microg/ml was reached at 11.41 +/- 2.59 hr, with an elimination rate constant of 0.09/hr +/- 0.05/hr and an elimination half-life of 11.7 +/- 3 hr. Mean peak serum concentration following i.v. administration was 223 +/- 48 microg/ml. Mean volume of distribution at steady state was 0.393 +/- 0.049 L/kg. Elimination rate constants differed with i.v. and oral administration, suggesting a flip-flop model. Oral bioavailability was 103% +/- 38%. Comparison of maximum serum concentrations to the microbial breakpoint concentration reported for sulfadimethoxine (512 microg/ml) suggests that the dose used in this study, 17.5 +/- 2.7 mg/kg, is insufficient for achieving therapeutic serum levels.

Dacryocystorhinostomy in south west England.

PURPOSE: To assess the pre-operative management, surgical technique employed, success rate and patient satisfaction following surgery in patients undergoing dacryocystorhinostomy (DCR) in South West England. METHOD: Two hundred and forty-two patients who underwent DCR were retrospectively studied. A telephone questionnaire was used to assess patient satisfaction in 100 patients. RESULTS: One hundred and thirteen (46%) patients had nasolacrimal duct obstruction, half of whom had a history of dacryocystitis, 70 (29%) had canalicular obstruction and 8 (3%) had mixed blockage. The site of blockage was not known or recorded in 51 patients (22%). Seventy-five (31%) patients underwent DCR, 151 (62%) DCR with insertion of silicon tubes, 9 (4%) DCR and Lester Jones tube, and 7 (3%) canaliculodacryocystorhinostomy (CDCR). Overall an 83.5% success rate was reported by the surgeons. The success rate for patients with a history of dacryocystitis was 98%, for nasolacrimal duct obstruction 96% and for canalicular obstruction 82%. When the site of blockage was not known or recorded the success rate was 60%. Where the name of the surgeon was not recorded there was a 15% successful outcome. Eighty per cent of patients reported some improvement in their symptoms following surgery. CONCLUSIONS: DCR is an effective surgical procedure with a high rate of patient satisfaction. Pre-operative identification of the site of the blockage is likely to improve surgical outcome.

Antioxidant defenses in the peripheral cell layers of legume root nodules.

Ascorbate peroxidase (AP) is a key enzyme that scavenges potentially harmful H2O2 and thus prevents oxidative damage in plants, especially in N2-fixing legume root nodules. The present study demonstrates that the nodule endodermis of alfalfa (Medicago sativa) root nodules contains elevated levels of AP protein, as well as the corresponding mRNA transcript and substrate (ascorbate). Enhanced AP protein levels were also found in cells immediately peripheral to the infected region of soybean (Glycine max), pea (Pisum sativum), clover (Trifolium pratense), and common bean (Phaseolus vulgaris) nodules. Regeneration of ascorbate was achieved by (homo)glutathione and associated enzymes of the ascorbate-glutathione pathway, which were present at high levels. The presence of high levels of antioxidants suggests that respiratory consumption of O2 in the endodermis or nodule parenchyma may be an essential component of the O2-diffusion barrier that regulates the entry of O2 into the central region of nodules and ensures optimal functioning of nitrogenase.

Heterologous expression and characterization of soybean cytosolic ascorbate peroxidase.

Ascorbate peroxidase is a widespread plant enzyme that catalyzes the removal of potentially harmful H2O2. This enzyme is particularly important in legume root nodules due to their high potential for generating activated forms of oxygen. A cDNA clone of soybean nodule ascorbate peroxidase was used to construct an expression system in Escherichia coli. The recombinant protein had an N-terminal tag of six consecutive histidine residues to allow for purification by Ni(2+)-agarose affinity chromatography. Large amounts of recombinant peroxidase (about 27% of total soluble protein) were produced but most of the peroxidase was present in the apo-form (without heme). Addition of delta-aminolevulinic acid to the growth media resulted in an increase in production of holoprotein. Apoprotein was easily converted to the holo-form by in vitro reconstitution with hemin. The reconstituted protein was catalytically, spectrally, and immunologically indistinguishable from native ascorbate peroxidase.

Alternative mRNA splicing generates the two ribulosebisphosphate carboxylase/oxygenase activase polypeptides in spinach and Arabidopsis.

Sequence analysis of ribulosebisphosphate carboxylase/oxygenase (rubisco) activase cDNA and genomic clones isolated from spinach and Arabidopsis thaliana indicates that the two polypeptides of rubisco activase arise from alternative splicing of a common pre-mRNA. In spinach, two 5' splice sites are used in processing a single 137-nucleotide intron near the 3' end of the primary transcript. This intron was either removed completely or, alternatively, the first 22 nucleotides of the intervening sequence were retained in the mature rubisco activase mRNA. The 22-nucleotide auxiliary exon contains an in-frame ochre termination codon and leads to the synthesis of a 41-kilodalton polypeptide. Removal of the entire 137-nucleotide intervening sequence results in the synthesis of a larger 45-kilodalton polypeptide. Thus, alternative splicing of the spinach rubisco activase mRNA results in the synthesis of two polypeptides that are identical except for 37 additional amino acids at the C terminus of the 45-kilodalton polypeptide. This conclusion was confirmed by Cleveland peptide mapping and by N-terminal and C-terminal amino acid sequence analyses of both purified polypeptides. This method of producing the two rubisco activase polypeptides may be an evolutionarily conserved feature in higher plants because a nearly identical process occurs in the production of the two rubisco activase polypeptides in Arabidopsis. In Arabidopsis, an alternatively spliced intron resides at precisely the same position as the alternatively spliced intron in spinach and results in the synthesis of 44-kilodalton and 47-kilodalton rubisco activase polypeptides. In contrast to spinach, however, the retained portion of the intervening sequence does not contain an in-frame termination codon. Rather, a shift in reading frame leads to termination of translation of the smaller polypeptide within the coding region of the larger polypeptide.

Purification and assay of rubisco activase from leaves.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) activase protein was purified from spinach leaves by ammonium sulfate precipitation and ion exchange fast protein liquid chromatography. This resulted in 48-fold purification with 70% recovery of activity and yielded up to 18 milligrams of rubisco activase protein from 100 grams of leaves. Based on these figures, the protein comprised approximately 2% by weight of soluble protein in spinach (Spinacia oleracea L.) leaves. The preparations were at least 95% pure and were stable when frozen in liquid nitrogen. Addition of ATP during purification and storage was necessary to maintain activity. Assay of rubisco activase was based on its ability to promote activation of rubisco in the presence of ribulose-1,5-bisphosphate. There was an absolute requirement for ATP which could not be replaced by other nucleoside phosphates. The initial rate of increase of rubisco activity and the final rubisco specific activity achieved were both dependent on the concentration of rubisco activase. The initial rate was directly proportional to the rubisco activase concentration and was used as the basis of activity. The rate of activation of rubisco was also dependent on the rubisco concentration, suggesting that the activation process is a second order reaction dependent on the concentrations of both rubisco and rubisco activase. It is suggested that deactivation of rubisco occurs simultaneously with rubisco activase-mediated activation, and that rubisco activation state represents a dynamic equilibrium between these two processes.

Cytokinin Oxidase from Phaseolus vulgaris Callus Cultures : Affinity for Concanavalin.

Cytokinin oxidase activity from Phaseolus vulgaris cv Great Northern callus cultures exhibited affinity for the lectin concanavalin A. Over 80% of the activity extracted from the callus tissue bound to a concanavalin A-Sepharose 4B column. The bound activity was eluted from the column by the addition of methylmannose to the eluting buffer. On the basis of this result, it appears that most of the cyokinin oxidase activity present in Great Northern callus cultures exists in the form of a glycoprotein. The apparent pI of this enzyme, as estimated by chromatofocusing, is approximately 5.0.

Catalysis of Ribulosebisphosphate Carboxylase/Oxygenase Activation by the Product of a Rubisco Activase cDNA Clone Expressed in Escherichia coli.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) activase activity was obtained from a partially purified extract of Escherichia coli transformed with a 1.6-kilobase spinach (Spinacia oleracea L.) cDNA clone. This activity was ATP-dependent. Catalysis of rubisco activation by spinach and cloned rubisco activase was accompanied by the same extent of carboxyarabinitol bisphosphate-trapped (14)CO(2) as occurred in spontaneous activation, indicating that rubisco carbamylation is one facet of the rubisco activase reaction. The CO(2) concentration required for one-half maximal rubisco activase activity was about 8 micromolar CO(2). These observations are consistent with the postulated role of rubisco activase in regulating rubisco activity in vivo.

Cytokinin Oxidase from Phaseolus vulgaris Callus Tissues : Enhanced in Vitro Activity of the Enzyme in the Presence of Copper-Imidazole Complexes.

The effects of metal ions on cytokinin oxidase activity extracted from callus tissues of Phaseolus vulgaris L. cv Great Northern have been examined using an assay based on the oxidation of N(6)-(Delta(2)-isopentenyl)-adenine-2,8-(3)H (i(6) Ade) to adenine (Ade). The addition of cupric ions to reaction mixtures containing imidazole buffer markedly enhanced cytokinin oxidase activity. In the presence of optimal concentrations of copper and imidazole, cytokinin oxidase activity was stimulated more than 20-fold. The effect was enzyme dependent, specific for copper, and observed only in the presence of imidazole. The substrate specificity of the copper-imidazole enhanced reaction, as judged by substrate competition tests, was the same as that observed in the absence of copper and imidazole. Similarly, in tests involving DEAE-cellulose chromatography, elution profiles of cytokinin oxidase activity determined using a copper-imidazole enhanced assay were identical to those obtained using an assay without copper and imidazole. On the basis of these results, the addition of copper and imidazole to reaction mixtures used to assay for cytokinin oxidase activity is judged to provide a reliable and specific assay of greatly enhanced sensitivity for the enzyme. The mechanism by which copper and imidazole enhance cytokinin oxidase activity is not certain, but the reaction catalyzed by the enzyme was not inhibited by anaerobic conditions when these reagents were present. This observation suggests that copper-imidazole complexes are substituting for oxygen in the reaction mechanism by which cytokinin oxidase effects cleavage of the N(6)-side chain of i(6)Ade.

Regulation of Cytokinin Oxidase Activity in Callus Tissues of Phaseolus vulgaris L. cv Great Northern.

The regulation of cytokinin oxidase activity in callus tissues of Phaseolus vulgaris L. cv Great Northern has been examined using an assay based on the oxidation of N(6)-(Delta(2)-isopentenyl)adenine-8-(14)C (i(6) Ade-8-(14)C) to adenine. Solutions of exogenous cytokinins applied directly to the surface of the callus tissues induced relatively rapid increases in cytokinin oxidase activity. The increase in activity was detectable after 1 hour and continued for about 8 hours, reaching values two- to three-fold higher than the controls. The cytokinin-induced increase in cytokinin oxidase activity was inhibited in tissues pretreated with cordycepin or cycloheximide, suggesting that RNA and protein synthesis may be required for the response. Rifampicin and chloramphenicol, at concentrations that inhibited the growth of Great Northern callus tissues, were ineffective in inhibiting the increase in activity. All cytokinin-active compounds tested, including both substrates and nonsubstrates of cytokinin oxidase, were effective in inducing elevated levels of the enzyme in Great Northern callus tissue. The cytokinin-active urea derivative, Thidiazuron, was as effective as any adenine derivative in inducing this response. The addition of Thidiazuron to the reaction volumes used to assay cytokinin oxidase activity resulted in a marked inhibition of the degradation of the labeled i(6) Ade-8-(14)C substrate. On the basis of this result, it is possible that Thidiazuron may serve as a substrate for cytokinin oxidase, but other mechanisms of inhibition have not yet been excluded.