Embracing a New Evidence-Based Thought Paradigm of Sepsis.

ABSTRACT: In 1991, sepsis was first defined by the Society of Critical Care Medicine as the systemic inflammatory response syndrome, in the presence of infection. Systemic inflammatory response syndrome is an adaptive host response to infection, as well as to other insults like trauma and stress. Research pertaining to sepsis was guided by this adaptive definition for 25 years. After established guidelines for sepsis management were challenged in 2014, sepsis was redefined in 2016 as a dysregulated host response to infection. However, there still remains no consensus on which immunologic or metabolic mechanisms have become dysregulated. We sought to examine sepsis literature published after the 2016 consensus definition and compare it to the original systemic inflammatory response syndrome paradigm proposed in 1991. The purpose of this intensive analysis was to recommend a new sepsis archetype, with consideration to dysregulated immunologic and metabolic mechanisms that have recently been identified in sepsis. Nurses and other clinicians must shift their thought paradigm toward an evidence-based dysregulated model, in order to improve on sepsis recognition and management.

In vivo peripheral nerve activation using sinusoidal low-frequency alternating currents.

BACKGROUND: The sinusoidal low-frequency alternating current (LFAC) waveform was explored recently as a novel means to evoke nerve conduction block. In the present work, we explored whether increasing the amplitude of the LFAC waveform results in nerve fiber activation in autonomic nerves. In-silico methods and preliminary work in somatic nerves indicated a potential frequency dependency on the threshold of activation. The Hering-Breuer (HB) reflex was used as a biomarker to detect cervical vagus nerve activation. METHODS: Experiments were conducted in isoflurane-anesthetized swine (n = 5). Two stimulating bipolar cuff electrodes and a tripolar recording cuff electrode were implanted on the left vagus nerve. To ensure the electrical stimulation affects only the afferent pathways, the nerve was crushed caudal to the electrodes to eliminate cardiac effects. (1) Standard pulse stimulation (Vstim) using a monophasic train of pulses was applied through the caudal electrode to elicit HB reflex and to identify the activated nerve fiber type. (2) Continuous sinusoidal LFAC waveform with a frequency ranging from 5 through 20 Hz was applied to the rostral electrode without Vstim to explore the activation thresholds at each LFAC frequency. In both cases, the activation of nerve fibers was detected by a HB reflex-induced reduction in the breathing rate. RESULTS: LFAC was found to be capable of eliciting an HB response. The LFAC activation thresholds were found to be frequency-dependent. The HB threshold was 1.02 ± 0.3 mAp at 5 Hz, 0.66 ± 0.3 mAp at 10 Hz, and 0.44 ± 0.2 mAp at 20 Hz. In comparison, it was 0.7 ± 0.47 mA for a 100 µs pulse. The LFAC amplitude was within the linear limits of the electrode interface. Damage to the cuff electrodes or the nerve tissues was not observed. Analysis of Vstim-based compound nerve action potentials (CNAP) indicated that the decrease in breathing rate was found to be correlated with the activation of slower components of the CNAP suggesting that LFAC reached and elicited responses from these slower fibers associated with afferents projecting to the HB response. CONCLUSIONS: These results suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic nerve fibers and potentially provide a new modality to the neurorehabilitation field.

Cognitive Testing During Mild Acute Ischemic Stroke Predicts Long-Term Return to Work.

OBJECTIVES: Many survivors of a mild ischemic stroke do not return to work or driving. Cognitive testing is commonly done to assess long-term cognitive impairment after stroke. Inpatient cognitive testing during the acute period of ischemic stroke may also be a predictor for workforce reengagement and functional outcome. MATERIALS AND METHODS: At our comprehensive stroke center, we prospectively enrolled previously working adults < 65 years old who were diagnosed with first-ever ischemic stroke, had a prestroke modified Rankin Scale (mRS) ≤ 1 and NIHSS ≤ 3. Testing performed within 1 week of stroke included the Montreal Cognitive Assessment (MOCA), Clock Drawing Test (CDT), Trail Making Tests A and B, Backward Digit Span Test, and Hospital Anxiety and Depression Scale (HADS). Other data obtained included age, gender, years of education, occupation, stroke location, stroke laterality, and presence of white matter disease on imaging. Outcome measures assessed at 3 months, 6 months, and 12 months post-stroke included return to work, return to driving, and mRS. In a logistic regression analysis, we performed both univariate and multivariate analyses. Multivariate analysis was completed on variables with p-value ≤ 0.05 in the univariate analysis. RESULTS: Of 39 total stroke patients enrolled and tested (median [IQR] age 55 [46-60] years; 77.5% male; 22.5% female), 36 completed 3-month follow up, of which 58% returned to work, 78% returned to driving, and 72% had mRS of 0-1. In multivariate analysis, a single point increase in the clock drawing task score increased the odds of return to work by 3.79 (95% CI, 1.10-14.14) and return to driving by 6.74 (95% CI, 1.22-37.23) at 3 months. MOCA and HADS were both associated with mRS ≤ 1. MOCA was associated with return to work at 6 months and CDT was associated with return to work at 12 months. CONCLUSION: Cognitive testing with CDT and MOCA in the acute period after ischemic stroke may predict common patient goals post stroke, including return to work, driving, and independence. These tools can potentially be used for prognosis and identifying those who may benefit from further interventions.

In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block.

BACKGROUND: This paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5). METHODS: Two bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. RESULTS: LFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mAp (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP. CONCLUSION: These novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.

The effectiveness of NHS smoking cessation services: a systematic review.

OBJECTIVES: To analyse evidence on the effectiveness of intensive NHS treatments for smoking cessation in helping smokers to quit. METHODS: A systematic review of studies published between 1990 and 2007. Electronic databases were searched for published studies. Unpublished reports were identified from the national research register and experts. RESULTS: Twenty studies were included. They suggest that intensive NHS treatments for smoking cessation are effective in helping smokers to quit. The national evaluation found 4-week carbon monoxide monitoring validated quit rates of 53%, falling to 15% at 1 year. There is some evidence that group treatment may be more effective than one-to-one treatment, and the impact of 'buddy support' varies based on treatment type. Evidence on the effectiveness of in-patient interventions is currently very limited. Younger smokers, females, pregnant smokers and more deprived smokers appear to have lower short-term quit rates than other groups. CONCLUSION: Further research is needed to determine the most effective models of NHS treatment for smoking cessation and the efficacy of those models with subgroups. Factors such as gender, age, socio-economic status and ethnicity appear to influence outcomes, but a current lack of diversity-specific analysis of results makes it impossible to ascertain the differential impact of intervention types on particular subpopulations.

Preventing smoking in young people: a systematic review of the impact of access interventions.

AIMS: To examine existing evidence on the effectiveness of interventions that are designed to prevent the illegal sale of tobacco to young people. The review considers specific sub-questions related to the factors that might influence effectiveness, any differential effects for different sub-populations of youth, and barriers and facilitators to implementation. METHODS: A review of studies on the impact of interventions on young people under the age of 18 was conducted. It included interventions that were designed to prevent the illegal sale of tobacco to children and young people. The review was conducted in July 2007, and included 20 papers on access restriction studies. The quality of the papers was assessed and the relevant data was extracted. RESULTS: The evidence obtained from the review indicates that access restriction interventions may produce significant reductions in the rate of illegal tobacco sales to youth. However, lack of enforcement and the ability of youth to acquire cigarettes from social sources may undermine the effectiveness of these interventions. CONCLUSIONS: When access interventions are applied in a comprehensive manner, they can affect young people's access to tobacco. However, further research is required to examine the effects of access restriction interventions on young people's smoking behaviour.

Location restrictions on smoking: assessing their differential impacts and consequences in the workplace.

OBJECTIVES: To analyze existing evidence on the impact of two types of location restrictions on smoking: workplace bans and bans in hospitality settings, and to assess the extent to which they differentially affect subpopulations. METHODS: A review of international studies on location restrictions on smoking published between 1990-2007. RESULTS: Although workplace smoking bans reduce exposure to second-hand smoke (SHS) at work, their effects on overall cigarette consumption and smoking prevalence may be uneven across the population. Bans in hospitality settings reduce SHS exposure among workers, but have potentially uneven effects based on the interactions between gender, socio-economic status (SES) and ethnicity. The unintended consequences of smoking bans are also more likely to be experienced by low SES groups. CONCLUSIONS: Although location restrictions on smoking reduce SHS exposure and may serve to positively impact smoking behaviours, there is preliminary evidence that they may have a reduced impact on subpopulations such as low-income groups, although further research is needed.

Tobacco use, women, gender, and chronic obstructive pulmonary disease: are the connections being adequately made?

This article reflects on a multidisciplinary workshop addressing the evidence pertaining to tobacco use, sex, gender, and chronic obstructive pulmonary disease (COPD). In preparation, a literature review was conducted that examined the academic and gray literature on tobacco, COPD, and gender and women, with a view to assessing if and how these literatures spoke to each other. These materials were discussed in a sponsored workshop (Toward a Research Agenda on Gender and Chronic Obstructive Pulmonary Disease) held in Vancouver, Canada, in 2007, engaging a variety of scientists and stakeholders in assessing the issues and emergent questions. The goal of this workshop was to foster the advancement of a research agenda that more tightly links tobacco, COPD, and lung health and that reflects and investigates sex and gender issues, especially in reference to the growing rates of COPD among women. A research agenda for consideration by researchers in the fields of women's health, medicine, tobacco use, COPD, and related fields is offered.