The effect of a pharmacist-led multidisciplinary transitions-of-care pilot for patients at high risk of readmission.

OBJECTIVES: To evaluate the feasibility and effect of a pharmacist-led transitions-of-care (TOC) pilot targeted to patients at high risk of readmission on process measures, hospital readmissions, and emergency department (ED) visits. SETTING: Academic medical center in Colorado. PRACTICE DESCRIPTION: Pharmacists enrolled patients identified as high risk for readmission in a TOC pilot from July 2014 to July 2015. The pilot included medication reconciliation, medication counseling, case management or social work evaluation, a postdischarge telephone call, and an expedited primary care follow-up appointment. PRACTICE INNOVATION: Implementation and evaluation of the pharmacist-led TOC pilot program with risk score embedded into the electronic health record. EVALUATION: Comparison of TOC-related process measures and clinical outcomes between pilot patients and randomly matched control patients included readmissions or ED visits at 30 and 90 days. RESULTS: We enrolled 34 pilot patients and randomly matched them to 34 control patients. The intervention took an average of 57.1 minutes for pharmacists to deliver. More pilot patients had a case management or social work note compared with control patients (88% vs. 59%; P = 0.006 [statistically significant]). Readmission rates in pilot versus nonpilot patients, respectively, were 18% versus 24% (P = 0.547) at 30 days and 27% versus 39% (P = 0.296) at 90 days. The composite outcome of a readmission or ED visit in pilot versus nonpilot patients was 24% versus 30% (P = 0.580) at 30 days and 36% versus 49% (P = 0.319) at 90 days. CONCLUSION: A pharmacist-led TOC pilot demonstrates potential for reducing hospital readmissions. The intervention was time intensive and led to creation of a TOC pharmacist role to implement medication-related transitional care.

Phosphoketolase overexpression increases biomass and lipid yield from methane in an obligate methanotrophic biocatalyst.

Microbial conversion of methane to high-value bio-based fuels, chemicals, and materials offers a path to mitigate GHG emissions and valorize this abundant-yet -underutilized carbon source. In addition to fermentation optimization strategies, rational methanotrophic bacterial strain engineering offers a means to reach industrially relevant titers, carbon yields, and productivities of target products. The phosphoketolase pathway functions in heterofermentative bacteria where carbon flux through two sugar catabolic pathways to mixed acids (lactic acid and acetic acid) increases cellular ATP production. Importantly, this pathway also serves as an alternative route to produce acetyl-CoA that bypasses the CO2 lost through pyruvate decarboxylation in the Embden-Meyerhof-Parnas pathway. Thus, the phosphoketolase pathway can be leveraged for carbon efficient biocatalysis to acetyl-CoA-derived intermediates and products. Here, we show that the industrially promising methane biocatalyst, Methylomicrobium buryatense, encodes two phosphoketolase isoforms that are expressed in methanol- and methane-grown cells. Overexpression of the PktB isoform led to a 2-fold increase in intracellular acetyl-CoA concentration, and a 2.6-fold yield enhancement from methane to microbial biomass and lipids compared to wild-type, increasing the potential for methanotroph lipid-based fuel production. Off-gas analysis and metabolite profiling indicated that global metabolic rearrangements, including significant increases in post-translational protein acetylation and gene expression of the tetrahydromethanopterin-linked pathway, along with decreases in several excreted products, coincided with the superior biomass and lipid yield observed in the engineered strain. Further, these data suggest that phosphoketolase may play a key regulatory role in methanotrophic bacterial metabolism. Given that acetyl-CoA is a key intermediate in several biosynthetic pathways, phosphoketolase overexpression offers a viable strategy to enhance the economics of an array of biological methane conversion processes.

The NO-responsive hemoglobins of Campylobacter jejuni: concerted responses of two globins to NO and evidence in vitro for globin regulation by the transcription factor NssR.

Campylobacter jejuni possesses NO-responsive and -detoxifying mechanisms to survive NO during transmission and pathogenesis. C. jejuni possesses two hemoglobins. The first (Cgb) is a single-domain (non-flavo)hemoglobin encoded by gene Cj1586 (cgb), mutation of which leads to hypersensitivity to S-nitrosoglutathione and NO. Transcription of cgb is induced by nitrosative stress and confers resistance to NO, presumably via a Cgb-catalyzed dioxygenase or denitrosylase reaction that converts NO and oxygen to nitrate. Expression of Cgb in response to NO is mediated via the positively-acting transcription factor NssR, which regulates expression of a small regulon that includes cgb and ctb (Cj0465c), the latter encoding the truncated hemoglobin, Ctb. The role of Ctb is unclear: it is not directly involved in NO detoxification but is implicated in oxygen delivery or metabolism. Here, we describe attempts to define a function for Ctb by examining the effects of a ctb mutation on the NO transcriptome and cgb gene expression during normoxia and hypoxia. Mutation of ctb does not elicit major compensatory transcriptomic changes but relatively minor changes in genes involved in intermediary metabolism, solute transport and signal transduction. We present and test the hypothesis that, by binding NO or O(2), Ctb dampens the response to NO under hypoxic conditions and limits cgb expression, perhaps because Cgb function (i.e. NO detoxification) requires O(2)-dependent chemistry. We report the purification of NssR and specific binding to the ctb promoter. GSNO does not affect the high affinity of NssR for the ctb promoter.

CRISPR-Cas, a highly effective tool for genome editing in Clostridium saccharoperbutylacetonicum N1-4(HMT).

The solventogenic clostridia have long been known for their ability to convert sugars from complex feedstocks into commercially important solvents. Although the acetone-butanol-ethanol process fell out of favour decades ago, renewed interest in sustainability and 'green' chemistry has re-established our appetite for reviving technologies such as these, albeit with 21st century improvements. As CRISPR-Cas genome editing tools are being developed and applied to the solventogenic clostridia, their industrial potential is growing. Through integration of new pathways, the beneficial traits and historical track record of clostridial fermentation can be exploited to generate a much wider range of industrially relevant products. Here we show the application of genome editing using the endogenous CRISPR-Cas mechanism of Clostridium saccharoperbutylacetonicum N1-4(HMT), to generate a deletion, SNP and to integrate new DNA into the genome. These technological advancements pave the way for application of clostridial species to the production of an array of products.

Oxygen- and NssR-dependent globin expression and enhanced iron acquisition in the response of campylobacter to nitrosative stress.

Pathogenic bacteria experience nitrosative stress from NO generated in the host and from nitrosating species such as S-nitrosoglutathione. The food-borne pathogen Campylobacter jejuni responds by activating gene expression from a small regulon under the control of the NO-sensitive regulator, NssR. Here, we describe the full extent of the S-nitrosoglutathione response using transcriptomic and proteomic analysis of batch- and chemostat-cultured C. jejuni. In addition to the NssR regulon, which includes two hemoglobins (Cgb and Ctb), we identify more than 90 other up-regulated genes, notably those encoding heat shock proteins and proteins involved in oxidative stress tolerance and iron metabolism/transport. Up-regulation of a subset of these genes, including cgb, is also elicited by NO-releasing compounds. Mutation of the iron-responsive regulator Fur results in insensitivity of growth to NO, suggesting that derepression of iron-regulated genes and augmentation of iron acquisition is a physiological response to nitrosative damage. We describe the effect of oxygen availability on nitrosative stress tolerance; cells cultured at higher rates of oxygen diffusion have elevated levels of hemoglobins, are more resistant to inhibition by NO of both growth and respiration, and consume NO more rapidly. The oxygen response is mediated by NssR. Thus, in addition to NO detoxification catalyzed by the hemoglobins Cgb and possibly Ctb, C. jejuni mounts an extensive stress response. We suggest that inhibition of respiration by NO may increase availability of oxygen for Cgb synthesis and function.

Obstacles to the prescribing of growth hormone in children with chronic kidney disease.

Despite its effectiveness, recombinant human growth hormone (rhGH) is under-utilized in short children with chronic kidney disease (CKD). We conducted a multicenter study to explore the obstacles preventing children with CKD from receiving rhGH. We investigated the use of rhGH in 307 children with CKD from seven pediatric nephrology centers. Among the 110 patients who fell below the 5th percentile, 56 (51%) had not received rhGH. The most common reasons given for these children not receiving rhGH were family refusal, secondary hyperparathyroidism, and non-compliance. However, no explanation was apparent for 25% of the short children with CKD. Boys were more likely than girls to receive rhGH (65% vs 31%; P = 0.002). Use of rhGH was similar in African Americans and non-Hispanic Whites. Children who had received rhGH achieved a 0.5 increase in height z-score in the first year after the initiation of rhGH therapy. Children who had not received rhGH achieved a 0.03 increase in height z-score during the first year after falling below the 5th percentile (P = 0.005 vs the children who had received rhGH). Waiting for insurance company approval led to a significant delay in the initiation of rhGH treatment in 18% of patients. The fact that more than 50% of short children with CKD did not receive rhGH is secondary to multiple factors, many of which may be amenable to intervention efforts.

The prevalence of laryngeal disease in a large population of competition draft horses.

OBJECTIVES: (1) To determine the effect of age, height, weight, breed, sex, and specific use on the prevalence of idiopathic left laryngeal hemiplegia (ILH) in a population of draft performance horses; (2) to determine the association between tracheal mucus and laryngeal dysfunction, and the prevalence of exercise-induced pulmonary hemorrhage (EIPH) in a population of draft performance horses. STUDY DESIGN: Cross-sectional. ANIMALS: Draft horses competing at the 2005 Michigan Great Lakes Draft Horse Show. METHODS: Endoscopic examinations were performed on horses competing at the 2005 Michigan Great Lakes Draft Horse Show. Signalment, height, and weight were obtained from the owners and trainers. RESULTS: Belgian, Percheron, and Clydesdale horses (n=183) were studied. Prevalence of ILH was 35%. Horse height was significantly associated with the risk of ILH in Belgian and Percheron horses but not Clydesdales. There was a significantly different prevalence of ILH among the breeds such that 42% Belgians, 31% Percherons, and 17% Clydesdales were affected. Laryngeal disease was a risk factor for increased tracheal mucus. None of the horses had acute evidence of EIPH. CONCLUSIONS: The prevalence of ILH in draft horses has increased or is higher in competition horses compared with previously studied groups. Tracheal and/or pulmonary inflammation may be more common in draft horses with ILH based on our findings that horses with ILH have more tracheal mucus than horses with normal laryngeal function. CLINICAL RELEVANCE: Selection pressure for large, taller, longer-necked horses may be responsible for a seemingly increased incidence of ILH in competitive draft horses.