Compounds commonly used in equine medicine inhibits the voltage-gated potassium channel Kv11.1.

BACKGROUND: The voltage-gated K+-channel Kv11.1 has a central role in cardiac repolarization. Blockage of Kv11.1 has been linked to severe cardiovascular side effects, such as acquired long QT syndrome (aLQTS), torsade de pointes arrhythmia and sudden cardiac death (SCD). Kv11.1 is susceptible to unspecific drug interactions due to the presence of two aromatic amino acids residing in the inner vestibule of the pore. These aromatic residues are also present in the equine orthologue of Kv11.1. This suggests that equine Kv11.1 may also be prone to high-affinity block by a range of different chemical entities, which potentially could cause severe cardiac side effects and SCD in horses. AIM: To screen a series of commonly used drugs in equine medicine for interaction with Kv11.1. METHODS: High-throughput screening of selected compounds on human Kv11.1 expressed in a mammalian cell line was performed using an automated patch clamp system, the SyncroPatch 384PE (Nanion Technologies, Munich, Germany). Results were validated on equine Kv11.1 expressed in CHO-K1 cells by manual patch clamp. RESULTS: Acepromazine maleat (IC50 = 0.5 µM) trimethoprim (IC50 = 100 µM), diphenhydramine hydrochloride (IC50 = 2 µM) and cyproheptadine hydrochloride (IC50 = 1.84 µM) inhibited equine Kv11.1 current at clinically relevant drug concentrations. CONCLUSION: The results suggest that drug interaction with Kv11.1 can occur in horses and that some drugs potentially may induce repolarization disorders in horses.

Evaluating antibiotic stewardship in a tertiary care hospital in Kerala, India: a qualitative interview study.

OBJECTIVES: To determine what barriers and facilitators to antibiotic stewardship exist within a healthcare facility. SETTING: 1300-bed tertiary care private hospital located in the state of Kerala, India. PARTICIPANTS: 31 semistructured interviews and 4 focus groups with hospital staff ranging from physicians, nurses, pharmacists and a clinical microbiologist. RESULTS: Key facilitators of antibiotic stewardship (AS) at the hospital included a dedicated committee overseeing appropriate inpatient antibiotic use, a prompt microbiology laboratory, a high level of AS understanding among staff, established guidelines for empiric prescribing and an easily accessible antibiogram. We identified the following barriers: limited access to clinical pharmacists, physician immunity to change regarding stewardship policies, infrequent antibiotic de-escalation, high physician workload, an incomplete electronic medical record (EMR), inadequate AS programme (ASP) physical visibility and high antibiotic use in the community. CONCLUSIONS: Opportunities for improvement at this institution include increasing accessibility to clinical pharmacists, implementing strategies to overcome physician immunity to change and establishing a more accessible and complete EMR. Our findings are likely to be of use to institutions developing ASPs in lower resource settings.

Characterising the gut microbiome in veterans with Gulf War Illness: a protocol for a longitudinal, prospective cohort study.

INTRODUCTION: Approximately 25%-35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI), a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for Gulf War Veterans, and there remains a critical need to identify innovative, novel therapies.Gut microbiota perturbation plays a key role in the symptomatology of other chronic multi-symptom illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given similarities between ME/CFS and GWI and the presence of gastrointestinal disorders in GWI patients, Veterans with GWI may also have gut abnormalities like those seen with ME/CFS. In this longitudinal cohort study, we are comparing the diversity (structure) and the metagenomes (function) of the gut microbiome between Gulf War Veterans with and without GWI. If we find differences in Veterans with GWI, the microbiome could be a target for therapeutic intervention to alleviate GWI symptoms. METHODS AND ANALYSIS: Participants answer questions about diet, exercise and lifestyle factors. Participants also complete a questionnaire (based on the Kansas case definition of GWI) regarding their medical history and symptoms; we use this questionnaire to group participants into GWI versus healthy control cohorts. We plan to enrol 52 deployed Gulf War Veterans: 26 with GWI and 26 healthy controls. Participants provide stool and saliva samples weekly for an 8-week period for microbiome analyses. Participants also provide blood samples at the beginning and end of this period, which we will use to compare measures of inflammation markers between the groups. ETHICS AND DISSEMINATION: The protocol was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board and the William S. Middleton Memorial Veterans Hospital Research and Development Committee. Results of this study will be submitted for publication in a peer-reviewed journal.

Effectiveness of a multisite personal protective equipment (PPE)-free zone intervention in acute care.

OBJECTIVE: Determine the effectiveness of a personal protective equipment (PPE)-free zone intervention on healthcare personnel (HCP) entry hand hygiene (HH) and PPE donning compliance in rooms of patients in contact precautions. DESIGN: Quasi-experimental, multicenter intervention, before-and-after study with concurrent controls. SETTING: All patient rooms on contact precautions on 16 units (5 medical-surgical, 6 intensive care, 5 specialty care units) at 3 acute-care facilities (2 academic medical centers, 1 Veterans Affairs hospital). Observations of PPE donning and entry HH compliance by HCP were conducted during both study phases. Surveys of HCP perceptions of the PPE-free zone were distributed in both study phases. INTERVENTION: A PPE-free zone, where a low-risk area inside door thresholds of contact precautions rooms was demarcated by red tape on the floor. Inside this area, HCP were not required to wear PPE. RESULTS: We observed 3,970 room entries. HH compliance did not change between study phases among intervention units (relative risk [RR], 0.92; P = .29) and declined in control units (RR, 0.70; P = .005); however, the PPE-free zone did not significantly affect compliance (P = .07). The PPE-free zone effect on HH was significant only for rooms on enteric precautions (P = .008). PPE use was not significantly different before versus after the intervention (P = .15). HCP perceived the zone positively; 65% agreed that it facilitated communication and 66.8% agreed that it permitted checking on patients more frequently. CONCLUSIONS: HCP viewed the PPE-free zone favorably and it did not adversely affect PPE or HH compliance. Future infection prevention interventions should consider the complex sociotechnical system factors influencing behavior change.