Educational content and strategies to support nurses from culturally and linguistically diverse backgrounds caring for patients considering voluntary assisted dying: The Australian experience.

OBJECTIVES: Drawing on findings from a qualitative study that aimed to explore the knowledge and attitudes of nurses from culturally and linguistically diverse (CALD) backgrounds about voluntary assisted dying (VAD). The study also aimed to identify the strategies that assist nurses in their readiness and preparation for exposure to VAD. This paper reports on the educational content and strategies that could assist nurses from CALD backgrounds to be better prepared when they encounter VAD requests. BACKGROUND: Around the world, healthcare professionals have roles to play in caring for patients requesting voluntary assisted dying. Nurses, particularly those from diverse geographic and clinical settings, have voiced inadequate knowledge and understanding about voluntary assisted dying. DESIGN: A qualitative descriptive approach was undertaken. METHODS: Data collection involved one focus group and 16 in-depth interviews. A total of 21 nurses from CALD backgrounds were recruited from one Australian state. Thematic analysis was conducted to interpret the data. FINDINGS: Nurses identified their knowledge gaps and specified the need for education and workplace training on VAD, its legal and ethical aspects, clarity on their role, communication techniques and how VAD intersects with their practice. They suggested various teaching strategies that could prepare nurses to work safely and confidently in a clinical environment where voluntary assisted dying is an option for patients. CONCLUSION: Given the high number of nurses from diverse backgrounds working in the Australian health sector, these nurses need to be fully prepared to care for patients requesting VAD.

NPH Insulin Versus Insulin Glargine Versus NPH Insulin Plus Insulin Glargine for the Treatment of Dexamethasone-Induced Hyperglycemia in Patients With COVID-19: A Retrospective Cohort Study.

Background: Dexamethasone use in patients hospitalized with COVID-19 significantly reduces mortality; however, it commonly results in hyperglycemia. Optimal treatment of dexamethasone-induced hyperglycemia is not well established. Objective: The study purpose was to assess the difference in blood glucose (BG) control between insulin glargine, neutral protamine hagedorn (NPH) insulin, and insulin glargine plus NPH insulin for dexamethasone-induced hyperglycemia in patients with type 2 diabetes (T2DM) and COVID-19 infection. Methods: This retrospective study was conducted in adult inpatients with T2DM and COVID-19 infection who received 6 mg of dexamethasone once daily and insulin during the 5-day study period. The primary outcome was the difference in mean point-of-care (POC) BG levels between study insulins. Secondary outcomes included the incidence of hyperglycemia and hypoglycemia, length of stay, and the percent difference between the mean daily inpatient and home basal insulin doses (for patients who were receiving basal insulin prior to admission in the insulin glargine and insulin glargine and NPH insulin groups only). Results: Ninety-six patients were included in the analysis (67 insulin glargine, 10 NPH insulin, and 19 insulin glargine plus NPH insulin). The difference in mean POC BG level was not different among groups (254 ± 60 mg/dL vs 234 ± 39 mg/dL vs 250 ± 51 mg/dL, respectively; P = 0.548). There were no significant differences in the secondary outcomes. Conclusions: No difference in the mean POC BG level was observed. Dexamethasone-induced hyperglycemia was poorly controlled in patients with T2DM and COVID-19 infection.

Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused Literature Review.

OBJECTIVE: To review the literature describing the use of adjunctive phenobarbital in the treatment of severe alcohol withdrawal syndrome (AWS). DATA SOURCES: PubMed and EMBASE were searched using the following terms: phenobarbital, adjunct, refractory or treatment resistant, severe or complicated, and alcohol withdrawal delirium or alcohol withdrawal seizures. STUDY SELECTION AND DATA EXTRACTION: The search was limited to randomized controlled trials (RCTs) and cohort studies published in English. DATA SYNTHESIS: Seven studies were identified in the emergency department (ED; RCT, n = 1; cohort, n = 2), general medicine ward (cohort, n = 1), and intensive care unit (ICU; cohort, n = 3) settings. For all studies set in the ED and general medicine ward and for 1 ICU study, phenobarbital plus symptom-guided benzodiazepine therapy was compared to symptom-guided benzodiazepine monotherapy. The other 2 ICU studies examined adjunctive phenobarbital before and after implementation of a protocol, meaning patients in both arms could have received phenobarbital. Overall risk of bias across all studies was low to moderate. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The specific role of adjunctive phenobarbital in AWS is not clear because a majority of studies are retrospective cohorts with varying primary outcomes in different patient care settings. CONCLUSIONS: In the ED and general medicine ward, phenobarbital demonstrated benzodiazepine-sparing effects. In the ICU, when a protocol guides phenobarbital use, the need for mechanical ventilation may be reduced. Adjunctive phenobarbital was well tolerated. Because of study limitations, it is challenging to provide specific recommendations for adjunctive phenobarbital use in severe AWS.

Systemic Corticosteroid and Antibiotic Use in Hospitalized Patients With Chronic Obstructive Pulmonary Disease Exacerbation.

BACKGROUND: Effective inpatient chronic obstructive pulmonary disease (COPD) exacerbation management is critical to appropriately manage health care resources. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines provide recommendations on appropriate systemic corticosteroid and antibiotic use, in select patients, for COPD exacerbation. OBJECTIVE: To determine the impact of GOLD guideline-recommended systemic corticosteroid and antibiotic therapy in the hospital setting on clinical outcomes in patients with COPD exacerbation. METHODS: This was a noninterventional, retrospective, single-center study. Adults admitted to a non-intensive care unit internal medicine service with documented COPD exacerbation were included. Two analyses were conducted evaluating systemic corticosteroid and antibiotic therapy. RESULTS: A total of 220 patients were included in the systemic corticosteroid cohort. No difference in 30-day readmission rates was demonstrated for the standard (⩽200 mg prednisone equivalents [PEs] for exacerbation course) and high-dose groups (>200 mg PEs; 20.5% vs 13.1%, respectively; P = 0.15). Hospital length of stay (LOS) was significantly shorter for patients prescribed standard-dose therapy (3 days [2-4.5] vs 4 days [2-6]; P < 0.001). A total of 174 patients were included in the antibiotic cohort. For the appropriate and inappropriate antibiotic use groups, no significant differences were observed between 30-day readmission rates (15% vs 18.4%, respectively; P = 0.57) and hospital LOS (4 days [2-5] in both groups; P = 0.97). Conclusion and Relevance: Hospital LOS was shorter for patients prescribed standard-dose systemic corticosteroids; however, no differences in other clinical outcomes were found in either cohort. Use of guideline-recommended systemic corticosteroid and antibiotic therapy is recommended for hospitalized patients with COPD exacerbation.

Evaluation of Bronchodilator Use During Chronic Obstructive Pulmonary Disease Exacerbation Inpatient Admissions.

Background: It is unknown whether the timing of initiation of a long-acting bronchodilator (LABD) during a chronic obstructive pulmonary disease (COPD) exacerbation or the method of short-acting bronchodilator (SABD) delivery may aid in improving patient outcomes. Objective: The goal of this study was to determine the impact of bronchodilator management in the hospital setting on clinical outcomes in patients with COPD exacerbation. Methods: This retrospective, single-center study evaluated patients admitted to the non-intensive care unit setting with a COPD exacerbation as defined by the International Classification of Diseases, Ninth Revision codes. The primary outcome was difference in 30-day readmission rates for early LABD therapy (<24 hours from hospital admission) versus late/no LABD therapy (>24 hours from hospital admission or not during hospitalization). Secondary objectives included length of stay (LOS) for this group, and 30-day readmission rates and LOS for the SABD via inhaler versus nebulizer groups. Results: Two hundred twenty patients were included. There was no difference in 30-day readmission rate (15.2% vs 18.2%, P = .6) and LOS (median 4 [interquartile range, IQR 3-6]) days for both groups, P = .34) between early versus late/no LABD therapy initiation, respectively. No difference was observed in 30-day readmission rate (16.7% vs 16.6%) and LOS (median 2.5 [IQR 1.1-3.9] days vs median 4 [IQR 2-6] days) between inhaler and nebulizer SABD therapy groups. Conclusions: No difference was observed in 30-day readmission rates or LOS when utilizing early LABD compared with late/no LABD therapy or comparing inhaler and nebulizer SABD delivery methods during COPD exacerbation.

Evidence-Based Review of Smartphone Versus Paper Asthma Action Plans on Asthma Control.

Objective: To summarize and evaluate existing literature regarding the impact of mobile asthma action plans (MAAPs) versus written asthma action plans (WAAPs) on degree of asthma control. Data Sources: PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were searched (2000-January 2019) using the term asthma action plan with each of the following: smartphone, computers, handheld, mobile applications, portable electronic application, portable software application, tablet, or technology. Study Selection and Data Extraction: The search was limited to cohort and randomized controlled trials examining MAAP versus WAAP data. Data extracted included the following: study design, population, intervention, control, outcomes related to asthma control, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool. Data Synthesis: Four of the 41 studies identified were included, each of which were randomized control trials. One study showed significant improvement using a non-asthma-specific assessment tool, 1 study showed improvement only for patients with uncontrolled asthma at baseline, and 2 studies showed no difference in asthma control scores. Overall risk of bias across all studies was low to moderate. Relevance to Patient Care and Clinical Practice: Health care providers should select an asthma action plan (AAP) format based on what the patient is most likely to understand and consistently use. Conclusions: Because of conflicting published data regarding the use of MAAPs versus WAAPs and risk of bias, it is unclear at this time whether one format of AAP is superior to the other for either adolescents or adults.

Evidence Based Review of Pharmacotherapy for Opioid-Induced Constipation in Noncancer Pain.

OBJECTIVE: To summarize and evaluate the existing literature regarding medications to treat opioid-induced constipation (OIC) in patients with chronic noncancer pain (CNCP). DATA SOURCES: PubMed, EMBASE, and Web of Science were searched using the following terms: constipation, opioid, chronic, pain, noncancer, nonmalignant, methylnaltrexone, alvimopan, lubiprostone, naloxegol, and naldemedine. STUDY SELECTION AND DATA EXTRACTION: The search was limited to randomized controlled trials reporting human outcomes. Data extracted included the following: study design, population, intervention, control, outcomes related to OIC and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool. DATA SYNTHESIS: After assessment, 16 of the 190 studies were included: methylnaltrexone (n = 4), naloxegol (n = 3), naldemedine (n = 2), lubiprostone (n = 3), and alvimopan (n = 4). Lubiprostone was the only nonperipherally acting µ-opioid receptor antagonist included. Only 1 study (naloxegol) used "usual care" (nonstudy laxative) rather than placebo as a comparator. Placebo-controlled trials demonstrated benefit for methylnaltrexone, naloxegol, naldemedine, and lubiprostone, with conflicting evidence for alvimopan. No data suggest that one agent is better than another. Overall risk of bias across all studies was low to moderate. CONCLUSIONS: With risk of bias determined to be low to moderate, published data to date suggest that methylnaltrexone, naloxegol, and naldemedine may be appropriate to treat OIC in patients with CNCP.

Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease.

Mutations in mitochondrial DNA (mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births and at least 1 in 10,000 adults in the UK are affected by mtDNA disease. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease. Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has the potential to prevent the transmission of mtDNA disease in humans.

Impact of a Training Program on Pharmacists' Comfort With Pediatric Pharmacy Concepts and Basic Pediatric Knowledge.

Objective: To determine the impact of a training program on pharmacists' comfort with pediatric pharmacy concepts and basic pediatric knowledge. Methods: All pharmacists at our institution were invited to participate in the study. Consenting participants completed a baseline survey of 15 questions on basic knowledge in 5 pediatric topic areas (pharmacokinetics/pharmacodynamics, weight-based dosing, anticoagulation, renal dosing, and common antibiotics) as well as 8 statements rating self-reported comfort with pediatric pharmacy. Following the pretraining survey, a training program combining self-study of handouts on the 5 topics with optional attendance at live education sessions was completed. Participants then completed a posttraining survey of the 5 topics including repeat comfort assessment. The primary outcome was change in self-assigned scores on the comfort-based assessment before and after training. Results: Fifty-two pharmacists consented to participate. Participants reported significant improvement in 6 of 8 comfort questions after training (p < .001). Those without prior pediatric experience had lower comfort ratings at baseline and showed significant improvement after training for 5 of the 8 questions (p < .001). Significant improvement in the proportion of correct answers on the knowledge assessment occurred after training, regardless of prior experience (61% vs 89%, p < .001). Conclusions: Self-study training with optional live education resulted in significant improvement in most self-reported comfort scores for pharmacists, particularly those without recent pediatric pharmacy experience. Pharmacists, regardless of experience, improved basic pediatric knowledge scores after training.

Mitochondrial DNA deletions in muscle satellite cells: implications for therapies.

Progressive myopathy is a major clinical feature of patients with mitochondrial DNA (mtDNA) disease. There is limited treatment available for these patients although exercise and other approaches to activate muscle stem cells (satellite cells) have been proposed. The majority of mtDNA defects are heteroplasmic (a mixture of mutated and wild-type mtDNA present within the muscle) with high levels of mutated mtDNA and low levels of wild-type mtDNA associated with more severe disease. The culture of satellite cell-derived myoblasts often reveals no evidence of the original mtDNA mutation although it is not known if this is lost by selection or simply not present in these cells. We have explored if the mtDNA mutation is present in the satellite cells in one of the commonest genotypes associated with mitochondrial myopathies (patients with single, large-scale mtDNA deletions). Analysis of satellite cells from eight patients showed that the level of mtDNA mutation in the satellite cells is the same as in the mature muscle but is most often subsequently lost during culture. We show that there are two periods of selection against the mutated form, one early on possibly during satellite cell activation and the other during the rapid replication phase of myoblast culture. Our data suggest that the mutations are also lost during rapid replication in vivo, implying that strategies to activate satellite cells remain a viable treatment for mitochondrial myopathies in specific patient groups.

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal expansion of secondary mitochondrial DNA mutations modulating the phenotype, driven by compensatory mitochondrial biogenesis.

Vortioxetine for the treatment of depression.

OBJECTIVE: To evaluate the clinical literature and potential clinical role of vortioxetine (Brintellix) for the treatment of major depressive disorder (MDD). DATA SOURCES: A MEDLINE search (1966-February 2014) was conducted using the search terms vortioxetine, Lu AA21004, and depression. Bibliographies of all articles retrieved were also reviewed. All references included were published between 1999 and 2014. STUDY SELECTION/DATA EXTRACTION: All studies that included humans and were published in English, with data describing vortioxetine for the treatment of MDD, were reviewed. DATA SYNTHESIS: Vortioxetine is a novel multimodal antidepressant agent, which inhibits the 5-HT transporter protein, acts as a 5-HT3 antagonist, 5-HT1A receptor agonist, 5-HT7 receptor antagonist, and a partial agonist of the 5-HT1B receptor. It has been studied in 10 short-term (6-8 weeks), 1 relapse-prevention, and 3 long-term extension trials. Vortioxetine demonstrated efficacy in reducing Montgomery-Asberg Depression Rating Scale or Hamilton Rating Scale for Depression scores in 6 of the short-term trials. The proportion of individuals who responded to treatment and achieved remission increased over time in all 3 long-term trials. The most common adverse effects, consistently reported by >10% of individuals in the clinical trials include nausea and headache. CONCLUSIONS: Vortioxetine is an effective agent for the treatment of MDD, but it does not have any clear advantages over other available treatment options.

Evaluation of education on the appropriate use of vitamin k in warfarin reversal in adult inpatients.

PURPOSE: Vitamin K (phytonadione) is a commonly used first-line reversal agent for vitamin K antagonist (VKA) therapy in patients presenting with a supratherapeutic international normalized ratio (INR) with or without significant bleeding or in patients with a therapeutic INR in need of surgery. The purpose of this study was to determine the impact of education on the appropriate use of vitamin K for VKA reversal. METHODS: Data were collected on patients admitted to a community teaching hospital during February 2010 (pre-education group). These data were analyzed to determine the most common guideline deviations in vitamin K use. Following this analysis, pharmacist education took place in the form of in-service presentations; a protocol, including a guideline-based dosing table, was developed to assist pharmacists in evaluating vitamin K therapy. Data were then collected on patients admitted during February 2011 (post-education group). RESULTS: Forty patients and 47 vitamin K administrations were included in the pre-education group, and 34 patients and 49 vitamin K administrations were included in the post-education group. The number of patients with appropriate vitamin K administrations improved after pharmacist education (25% pre-education vs 55.8% post-education; P = .01). Whereas 27.6% of individual vitamin K administrations were appropriate in the pre-education group, this increased to 63.2% in the post-education group (P = .04). CONCLUSION: Education techniques on the appropriate use of vitamin K for VKA reversal significantly improved compliance with standards of care for proper use of vitamin K. Additional education sessions are necessary to further increase compliance with standards of care and subsequently optimize patient care.

Elevated International Normalized Ratio Due to Apixaban in Patient With End-Stage Renal Disease on Hemodialysis.

Apixaban is known to prolong international normalized ratio (INR) per some observational and in vitro studies. In patients with elevated INR secondary to apixaban use, median INR of 1.4-1.7 has been reported. Extreme elevation in INR is rare with apixaban. In patients with end-stage renal disease (ESRD) on hemodialysis (HD), there are no labeled indications for apixaban use; however, there are some pharmacokinetic data supporting its use in such patients. We present a case of a 68-year-old Hispanic man with ESRD who presented to the emergency room (ER) with INR of 27.42. INR testing was done as a part of routine workup in rehabilitation facility. Medication list was reviewed and included apixaban 2.5 mg twice daily which was recently started for postoperative thromboprophylaxis. INR testing was repeated for confirmation in ER and was reported as >18.5 and prothrombin time >200 seconds. His liver function tests were stable as compared to baseline testing five days ago with normal bilirubin, low normal transaminases, and mild hypoalbuminemia. The patient didn't have any active bleeding. An elevation of INR to >20 with apixaban is a rare event. No other factors including patient characteristics, laboratory results, co-existing conditions, or other medications except the direct oral anticoagulant (DOAC) were found to be responsible for elevated INR. Liver cirrhosis or vitamin K deficiency as cause for INR elevation was ruled out as the baseline INR was normal prior to starting apixaban, liver function tests were stable and INR normalized again shortly after discontinuing the medication. Plasma concentration of DOACs has been found to be correlating with the INR according to a pharmacokinetic study which potentially means that the high INR likely was secondary to high serum concentration of apixaban in this patient. However, INR monitoring is not recommended for monitoring anticoagulant activity of DOACs. As of note, renal clearance accounts for 27% of apixaban clearance. Pharmacokinetic studies have concluded that half dose apixaban, i.e., 2.5 mg twice daily in patients on hemodialysis (dose used in this case) results in drug exposure similar to that of the standard dose of 5 mg twice daily in patients with preserved renal function. Future studies are necessary to address questions about safety of DOACs in patients with ESRD, further elucidate the clinical significance of such high INR values associated with DOACs, and establish appropriate management guidelines. Andexanet alfa has since been approved for apixaban reversal in patients with life-threatening bleeding; however, would not be indicated in such cases when there is no evidence of bleeding.

Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.

Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem cell transplantation (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study of patients who participated in the expanded access program (EAP) of plerixafor and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at 2 centers that participated in the EAP Control patients were matched for age, sex, disease, disease stage, and number of prior therapies. Mobilization costs were defined to be the costs of medical procedures, resource utilization, and medications. Median national CMS reimbursement rates were used to establish the costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell processing and cryopreservation. Average sale price was used for G-CSF, plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of 33 patients from the EAP and 33 matched controls were studied. Two patients in the control group were hospitalized for neutropenic fever during the mobilization period. Apheresis started on the scheduled day in 33 (100%) study patients and in 29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required weekend apheresis. There was no difference in number of CD34(+) cells collected between the groups, and all patients proceeded to HSCT with no difference in engraftment outcomes. Median total cost of mobilization was not different between the plerixafor/G-CSF and control groups ($14,224 versus $18,824; P = .45). In conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization of CD34(-) cells resulted in similar numbers of cells collected, costs of mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization resulted in more predictable days of collection, no weekend apheresis procedures, and no unscheduled hospital admissions.

Inmates Care: Computer-Based Training for Geriatric and End-of-Life Care in Prisons.

The growing aged and dying incarcerated population increases demands on corrections health care. People who are incarcerated can assist in care delivery; however, currently, their training is typically face-to-face, home grown, and variable in content and duration. Six focus groups conducted with peer caregivers (PCs) (n = 12) and staff (n = 15) identified priority training topics. Three prototype modules (Standard Precautions; Loss and Grief; and Role of the Inmate Caregiver in the Final Hours) were developed in consultation with an advisory board. Face-to-face usability testing with (n = 20) PCs and staff confirmed contextual relevance and feasibility of the Inmates Care training. The mean system usability score for all participant segments was 86.5. Inmates Care holds promise to complement nurse-led training with a standardized e-training package.

Estimation of the Prevalence of Antimicrobial Resistance in Badgers (Meles meles) and Foxes (Vulpes vulpes) in Northern Ireland.

Antimicrobial resistant (AMR) bacteria can be shared between humans and animals, through food, water, and the environment. Wild animals are not only potential reservoirs of AMR, but are also sentinels mirroring the presence of AMR zoonotic bacteria in the environment. In Northern Ireland, little is known about levels of AMR in bacteria in wildlife, thus the current study aimed to estimate the prevalence of AMR bacteria in wildlife using wildlife species from two ongoing surveys as a proxy. Nasopharyngeal swabs and faecal samples from European badgers (Meles meles) (146 faecal samples; 118 nasal samples) and red foxes (Vulpes vulpes) (321 faecal samples; 279 nasal samples) were collected throughout Northern Ireland and were used to survey for the presence of extended spectrum beta lactamase resistant and AmpC-type beta lactamases Escherichia coli (ESBL/AmpC), Salmonella spp. (only in badgers) and methicillin resistant Staphylococcus aureus (MRSA). ESBLs were detected in 13 out of 146 badger faecal samples (8.90%) and 37 out of 321 of fox faecal samples (11.53%), all of them presenting multi-drug resistance (MDR). Fourteen out of 146 (9.59%) badger faecal samples carried Salmonella spp. [S. Agama (n = 9), S. Newport (n = 4) and S. enterica subsp. arizonae (n = 1)]. Overall, AMR was found only in the S. enterica subsp. arizonae isolate (1/14, 7.14%). No MRSA were detected in nasopharyngeal swabs from badgers (n = 118) and foxes (n = 279). This is the first attempt to explore the prevalence of AMR in the two common wildlife species in Northern Ireland. These findings are important as they can be used as a base line for further research exploring the origin of the found resistance. These results should encourage similar surveys where environmental samples are included to bring better understanding of AMR dynamics, and the impact on wildlife, domestic livestock and humans.

Mutational and gene expression analysis of mtrDEF, omcA and mtrCAB during arsenate and iron reduction in Shewanella sp. ANA-3.

Arsenate respiration and Fe(III) reduction are important processes that influence the fate and transport of arsenic in the environment. The goal of this study was to investigate the impact of arsenate on Fe(III) reduction using arsenate and Fe(III) reduction deficient mutants of Shewanella sp. strain ANA-3. Ferrihydrite reduction in the absence of arsenate was similar for an arsenate reduction mutant (arrA and arsC deletion strain of ANA-3) compared with wild-type ANA-3. However, the presence of arsenate adsorbed onto ferrihydrite impeded Fe(III) reduction for the arsenate reduction mutant but not in the wild-type. In an Fe(III) reduction mutant (mtrDEF, omcA, mtrCAB null mutant of ANA-3), arsenate was reduced similarly to wild-type ANA-3 indicating the Fe(III) reduction pathway is not required for ferrihydrite-associated arsenate reduction. Expression analysis of the mtr/omc gene cluster of ANA-3 showed that omcA and mtrCAB were expressed under soluble Fe(III), ferrihydrite and arsenate growth conditions and not in aerobically grown cells. Expression of arrA was greater with ferrihydrite pre-adsorbed with arsenate relative to ferrihydrite only. Lastly, arrA and mtrA were simultaneously induced in cells shifted to anaerobic conditions and exposed to soluble Fe(III) and arsenate. These observations suggest that, unlike Fe(III), arsenate can co-induce operons (arr and mtr) implicated in arsenic mobilization.

Impact of the implementation of a pharmacist-driven chronic obstructive pulmonary disease exacerbation orderset in an inpatient setting.

PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines provide recommendations for the management of chronic obstructive pulmonary disease (COPD) exacerbation. Studies have demonstrated shortened hospital length of stay (LOS) with use of guideline-adherent systemic corticosteroid therapy. There are no published studies evaluating the impact of an inpatient orderset on patient-oriented outcomes. METHODS: This institutional review board-approved, retrospective, quasi-experimental, single-center cohort study included adult patients admitted to an internal medicine service for a documented COPD exacerbation from January 2014 through December 2015 (the pre-orderset group) or January 2017 through December 2018 (the post-orderset group). A pharmacy and therapeutics committee-approved orderset recommending guideline-adherent treatment with systemic corticosteroids, scheduled short-acting bronchodilators, and antibiotics was used in the post-orderset group. The primary outcome was hospital LOS. Secondary outcomes included 30-day all-cause and COPD-related readmission rates, systemic corticosteroid-related adverse events, and antibiotic use. RESULTS: A total of 358 unique patient encounters were identified for the pre-orderset group (n = 220) and post-orderset group (n = 138). The mean (SD) hospital LOS was significantly shorter in the post-orderset group (3.4 [2.4] days vs 4.3 [3.0] days; P = 0.004). There were no significant between-group differences in rates of 30-day all-cause and COPD-related readmissions. The overall rate of antibiotic use was lower in the post-orderset group vs the pre-orderset group (71% vs 90.2%; P < 0.001). The rate of occurrence of new blood glucose elevation was significantly lower in the post-orderset group (49.3% vs 79.1%; P < 0.001), with no significant between-group difference in occurrence of new blood pressure elevation. CONCLUSION: A significant reduction in hospital LOS was found with the implementation of a pharmacist-driven COPD exacerbation orderset.