Feasibility study of hospital antimicrobial stewardship analytics using electronic health records

Background: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimise the use of antimicrobials. Most hospitals depend on time-consuming manual audits to monitor clinicians’ prescribing. But much of the information needed could be sourced from electronic health records (EHRs). Objectives: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records. Methods: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialties at Queen Elizabeth Hospital, Birmingham, UK (September 2017–August 2018). The study involved: (1) a review of antimicrobial stewardship standards of care; (2) their translation into concepts measurable from commonly available EHRs; (3) pilot application in an EHR cohort study (n=61,679 admissions). Results: We developed data modelling methods to characterise the use of antimicrobials (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy of 5.8 days) enabling production of several actionable findings. For example, 22% of therapy episodes for low-severity community acquired pneumonia were congruent with prescribing guidelines, with a tendency to use antibiotics with a broader spectrum. Analysis of therapy changes revealed a delay in switching from intravenous to oral therapy by an average 3.6 days [95% CI: 3.4; 3.7]. Performance of microbial cultures prior to treatment initiation occurred in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice all the way down to specialties, wards, and individual clinical teams by case mix, enabling more meaningful peer comparison. Conclusions: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimising prescribing, and AMS impact evaluation studies

Emergence of beta/gamma oscillations: ING, PING, and what about RING?

Poster presentation from Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011. Background: Oscillatory activity in high-beta and gamma bands (20-80Hz) is known to play an important role in cortical processing being linked to cognitive processes and behavior. Beta/gamma oscillations are thought to emerge in local cortical circuits via two mechanisms: the interaction between excitatory principal cells and inhibitory interneurons – the pyramidal-interneuron gamma (PING) [1], and in networks of coupled inhibitory interneurons under tonic excitation – the interneuronal gamma (ING) [2]. Experimental evidence underlines the important role of inhibitory interneurons and especially of the fast spiking (FS) interneurons [3,4]. We show in simulation that an important property of FS neurons, namely the membrane resonance (frequency preference), represents an additional mechanism – the resonance induced gamma (RING), i.e. modulation of oscillatory discharge by resonance. RING promotes frequency stability and enables oscillations in purely excitatory networks. Methods: Local circuits were modeled with small world networks of 80% excitatory and 20% inhibitory neuron populations interconnected in small-world topology by realistic conductance-based synapses. Neuron populations were leaky integrate and fire (LIF) or Izhikevich resonator (RES) neurons. We also tested networks of purely inhibitory and purely excitatory RES neurons. Networks were stimulated with miniature postsynaptic potentials (MINIs) [5] and with low frequency sinusoidal (0.5 Hz) input that mimics the effect of gratings passing trough the visual field. The activity was calibrated to match recordings from cat visual cortex (firing rate, oscillatory activity). Results: Sinusoidal input modulates network oscillation frequency. This effect is most prominent in IF excitatory and IF inhibitory (IF-IF) networks and less prominent (about 4 times) in IF-RES or RES-IF networks where frequency remains relatively stable. The most stable frequency was observed in networks of pure resonators (RES-RES, None-RES, RES-None). Interestingly, purely excitatory RES networks (RES-None) were also able to exhibit oscillations through RING. By contrast purely excitatory or inhibitory IF networks (IF-None, None-IF) were not able to express oscillations under these conditions, matching experimental parameters. Conclusions: In both PING and ING, adding membrane resonance to principal cells or inhibitory interneurons stabilizes network oscillation frequency via the RING mechanism. Notably, in networks of purely excitatory networks, where ING and PING are not defined, oscillations can emerge via the RING mechanism if membrane resonance is expressed. Thus, RING appears as a potentially important mechanism for promoting stable network oscillations

Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease

© 2018 The Author(s). Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD

Investigating the association between early years foundation stage profile scores and subsequent diagnosis of an autism spectrum disorder: a retrospective study of linked healthcare and education data

Objective: We set out to test whether the early years foundation stage profile (EYFSP) score derived from 17 items assessed by teachers at the end of reception school year had any association with autism spectrum disorder (ASD) diagnosis in subsequent years. This study tested the feasibility of successfully linking education and health data. Design: A retrospective data linkage study. Setting and participants: The Born in Bradford longitudinal cohort of 13, 857 children. Outcome measures: We linked the EYFSP score at the end of reception year with subsequent diagnosis of an ASD, using all ASD general practitioner Read codes. We used the total EYFSP score and a subscore consisting of five key items in the EYFSP, prospectively identified using a panel of early years autism experts. Results: This study demonstrated the feasibility of linking education and health data using ASDs as an exemplar. A total of 8,935 children had linked primary care and education data with 20.7% scoring <25 on the total EYFSP and 15.2% scoring <10 on a EYFSP subscore proposed by an expert panel prospectively. The rate of diagnosis of ASDs at follow-up was just under 1% (84 children), children scoring <25 on the total EYFSP had a 4.1% chance of ASD compared with 0.15% of the remaining children. Using the prospectively designed subscore, this difference was greater (6.4% and 0.12%, respectively). Conclusions: We demonstrate the feasibility of linking education and health data. Performance on teacher ratings taken universally in school reception class can flag children at risk of ASDs. Further research is warranted to explore the utility of EYFSP as an initial screening tool for ASD in early school years

Oxygen supplementation facilitating successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease following trans-tibial amputation: a case report

Abstract Introduction Dysvascular amputations are increasingly performed in patients with underlying cardiac and pulmonary disorders. A limb prosthesis is rarely offered to patients with severe chronic obstructive pulmonary disease because of their inability to achieve the high energy expenditure required for prosthetic ambulation. We describe a case of successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease with the aid of oxygen supplementation. Case presentation A 67-year-old aboriginal woman with severe chronic obstructive pulmonary disease and hypercapnic respiratory failure underwent right trans-tibial (below the knee) amputation for severe foot gangrene. An aggressive rehabilitation program of conditioning exercises and gait training utilizing oxygen therapy was initiated. She was custom-fitted with a right trans-tibial prosthesis. A rehabilitation program improved her strength, endurance and stump contracture, and she was able to walk for short distances with the prosthesis. The motion analysis studies showed a cadence of 73.5 steps per minute, a velocity of 0.29 meters per second and no difference in right and left step time and step length. Conclusion This case report illustrates that patients with significant severe chronic obstructive pulmonary disease can be successfully fitted with limb prostheses and undergo rehabilitation using supplemental oxygen along with optimization of their underlying comorbidities. Despite the paucity of published information in this area, prosthesis fitting and rehabilitation should be considered in patients who have undergone amputation and have severe chronic obstructive disease.</p

Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al

Implementing complete smokefree policies in mental health inpatient settings Results from a before and after mixed-methods evaluation : results from a before and after mixed-methods evaluation

Abstract Background Tobacco smoking is extremely prevalent in people with severe mental illness (SMI) and has been recognised as the main contributor to widening health inequalities in this population. Historically, smoking has been deeply entrenched in the culture of mental health settings in the UK, and until recently, smokefree policies tended to be only partially implemented. However, recent national guidance and the government’s tobacco control plan now call for the implementation of complete smokefree policies. Many mental health Trusts across the UK are currently in the process of implementing the new guidance, but little is known about the impact of and experience with policy implementation. Methods This paper reports findings from a mixed-methods evaluation of policy implementation across 12 wards in a large mental health Trust in England. Quantitative data were collected and compared before and after implementation of NICE guidance PH48 and referred to 1) identification and treatment of tobacco dependence, 2) smoking-related incident reporting, and 3) prescribing of psychotropic medication. A qualitative exploration of the experience of inpatients was also carried out. Descriptive statistical analyses were performed, and the feasibility of collecting relevant and complete data for each quantitative component was assessed. Qualitative data were analysed using thematic framework analysis. Results Following implementation of the complete smokefree policy, increases in the numbers of patients offered smoking cessation advice (72% compared to 38%) were identified. While incident reports demonstrated a decrease in challenging behaviour during the post-PH48 period (6% compared to 23%), incidents relating to the concealment of smoking materials increased (10% compared to 2%). Patients reported encouraging changes in smoking behaviour and motivation to maintain change after discharge. However, implementation issues challenging full policy implementation, including covert facilitation of smoking by staff, were reported, and difficulties in collecting relevant and complete data for comprehensive evaluation purposes identified. Conclusions Overall, the implementation of complete smokefree policies in mental health settings may currently be undermined by partial support. Strategies to enhance support and the establishment of suitable data collection pathways to monitor progress are required

Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats

Abstract Rationale Tiagabine is an anticonvulsant drug which may also have sleep-enhancing properties. It acts by inhibiting reuptake at the gamma-aminobutyric acid (GABA) transporter (GAT-1). Objectives The aim of the study was to determine whether tiagabine acted as a discriminative stimulus and, if so, whether other GABAergic compounds would generalise to it. Materials and methods Rats were trained to discriminate tiagabine (30 mg/kg p.o.) from vehicle, and generalisation to drugs that modulate GABA was assessed. Results Gaboxadol (5-20 mg/kg p.o.), a selective extrasynaptic GABA A agonist, generalised to tiagabine, although the extent of the generalisation was inconclusive. Indiplon (1 mg/kg p.o.), a benzodiazepine-like hypnotic, also partially generalised to tiagabine, although zolpidem and S-zopiclone did not. Baclofen, a GABA B receptor agonist, and gabapentin, which increases synaptic GABA, did not generalise to tiagabine. (+)-Bicuculline (3 mg/kg i.p.), a GABA A receptor antagonist, blocked the tiagabine cue, but the less brainpenetrant salt form, bicuculline methochloride, had no effect. Conclusions These data suggest that tiagabine generates a discriminative stimulus in rats, and provides a central GABA-mediated cue, but is distinct from the other GABAergic compounds tested