A review of the external validity of clinical trials with beta-blockers in heart failure

Beta-blockers (BBs) are the mainstay prognostic medication for all stages of chronic heart failure (CHF). There are many classes of BBs, each of which has varying levels of evidence to support its efficacy in CHF. However, most CHF patients have one or more comorbid conditions such as diabetes, renal impairment, and/or atrial fibrillation. Patient enrollment to randomized controlled trials (RCTs) often excludes those with certain comorbidities, particularly if the symptoms are severe. Consequently, the extent to which evidence drawn from RCTs is generalizable to CHF patients has not been well described. Clinical guidelines also underrepresent this point by providing generic advice for all patients. The aim of this review is to examine the evidence to support the use of BBs in CHF patients with common comorbid conditions.We searched MEDLINE, PubMed, and the reference lists of reviews for RCTs, post hoc analyses, systematic reviews, and meta-analyses that report on use of BBs in CHF along with patient demographics and comorbidities.In total, 38 studies from 28 RCTs were identified, which provided data on six BBs against placebo or head to head with another BB agent in ischemic and nonischemic cardiomyopathies. Several studies explored BBs in older patients. Female patients and non-Caucasian race were underrepresented in trials. End points were cardiovascular hospitalization and mortality. Comorbid diabetes, renal impairment, or atrial fibrillation was detailed; however, no reference to disease spectrum or management goals as a focus could be seen in any of the studies. In this sense, enrollment may have limited more severe grades of these comorbidities.RCTs provide authoritative information for a spectrum of CHF presentations that support guidelines. RCTs may provide inadequate information for more heterogeneous CHF patient cohorts. Greater Phase IV research may be needed to fill this gap and inform guidelines for a more global patient population.Pupalan Iyngkaran, Samia R. Toukhsati, Merlin C. Thomas, Michael V. Jelinek, David L. Hare and John D. Horowit

Effects of long-term exposure to an electronic containment system on the behaviour and welfare of domestic cats

Free-roaming cats are exposed to a variety of risks, including involvement in road traffic accidents. One way of mitigating these risks is to contain cats, for example using an electronic boundary fence system that delivers an electric ‘correction’ via a collar if a cat ignores a warning cue and attempts to cross the boundary. However, concerns have been expressed over the welfare impact of such systems. Our aim was to determine if long-term exposure to an electronic containment system was associated with reduced cat welfare. We compared 46 owned domestic cats: 23 cats that had been contained by an electronic containment system for more than 12 months (AF group); and 23 cats with no containment system that were able to roam more widely (C group). We assessed the cats’ behavioural responses and welfare via four behavioural tests (unfamiliar person test; novel object test; sudden noise test; cognitive bias test) and an owner questionnaire. In the unfamiliar person test, C group lip-licked more than the AF group, whilst the AF group looked at, explored and interacted more with the unfamiliar person than C group. In the novel object test, the AF group looked at and explored the object more than C group. No significant differences were found between AF and C groups for the sudden noise or cognitive bias tests. Regarding the questionnaire, C group owners thought their cats showed more irritable behaviour and AF owners thought that their cats toileted inappropriately more often than C owners. Overall, AF cats were less neophobic than C cats and there was no evidence of significant differences between the populations in general affective state. These findings indicate that an electronic boundary fence with clear pre-warning cues does not impair the long term quality of life of cat

The Perceptions of Dog Intelligence and Cognitive Skills (PoDIaCS) Survey

Dog cognition research is expanding, but few studies have examined people's perceptions of specific cognitive abilities in dogs. The aim of this study was to explore owner perceptions of dog cognitive abilities across different cognitive domains and to determine whether these were associated with the dog-owner relationship. We developed an online questionnaire and analyzed the results from 565 dog owners. Dog owners generally indicated the belief that dogs are socially intelligent and possess the capacity to learn social and general cognitive skills. One quarter of dog owners agreed or strongly agreed that dogs were smarter than most people, and 45.7% indicated the belief that a dog's mental ability is equal to "3-5 year old human children." Perceived emotional owner-dog closeness correlated with all cognition ratings. A better understanding of dog cognitive abilities may help owners interpret dog behavior more appropriately, which may lead to a reduction in the number of dogs relinquished to shelters because of behavioral problems

Auditory stimulus discrimination recorded in dogs, as indicated by mismatch negativity (MMN)

Dog cognition research tends to rely on behavioural response, which can be confounded by obedience or motivation, as the primary means of indexing dog cognitive abilities. A physiological method of measuring dog cognitive processing would be instructive and could complement behavioural response. Electroencephalogram (EEG) has been used in humans to study stimulus processing, which results in waveforms called event-related potentials (ERPs). One ERP component, mismatch negativity (MMN), is a negative deflection approximately 160-200 ms after stimulus onset, which may be related to change detection from echoic sensory memory. We adapted a minimally invasive technique to record MMN in dogs. Dogs were exposed to an auditory oddball paradigm in which deviant tones (10% probability) were pseudo-randomly interspersed throughout an 8 min sequence of standard tones (90% probability). A significant difference in MMN ERP amplitude was observed after the deviant tone in comparison to the standard tone, t5 = -2.98, p = 0.03. This difference, attributed to discrimination of an unexpected stimulus in a series of expected stimuli, was not observed when both tones occurred 50% of the time, t1 = -0.82, p > 0.05. Dogs showed no evidence of pain or distress at any point. We believe this is the first illustration of MMN in a group of dogs and anticipate that this technique may provide valuable insights in cognitive tasks such as object discrimination

Airport ramp safety and intelligent transport systems

The possibilities for intelligent transport systems (ITS) to address safety problems on airport ramps are examined. In addition, a structured approach to aid the safe design and implementation of such systems to aid injury prevention in different industry and transport domains are presented. The work begins by reviewing worldwide ramp accidents and incidents. Thereafter, it presents ramp safety data collected at an Australian international airport. Building on this identification of problems, the research shows that a large number of ITS devices are theoretically possible to address such safety issues, and then proposes criteria upon which decisions to implement such technology could be based. The paper closes by giving general recommendations for which of the identified ITS devices should be further deployed on airport ramps and makes overall conclusions regarding the further development of a structured approach to establish the injury prevention benefits of ITS in different domains

Development of a minimally-invasive protocol for recording mismatch negativity (MMN) in the dog (Canis familiaris) using electroencephalography (EEG)

Mismatch negativity (MMN), observed in event-related potentials (ERPs), constitutes a measurable change in electrophysiological brain activity occurring after exposure to a novel stimulus. In humans, MMN is considered to be related to stimulus discrimination at the cortical level. ERP recording in dogs may present an opportunity to increase understanding of cognitive processes without reliance on observable behaviour, which may be confounded by motivation or training. Preliminary data are presented suggesting the existence of MMN, recorded using a minimally-invasive procedure equivalent to that used in humans, in unrestrained, unanaesthetised dogs. This is the first example of this ERP component in dogs and the method has substantial utility for future research exploring auditory, olfactory, and visual discrimination tasks, development, and breed differences

Sex-specific differences in percutaneous coronary intervention outcomes after a cardiac event : A cohort study examining the role of depression, worry and autonomic function

Background To determine whether differential all-cause hospital readmission exists for men and women 2 years after percutaneous coronary intervention (PCI) treatment for acute coronary syndrome (ACS), and to identify potential autonomic and psychological pathways contributing to this association. Methods Four hundred and sixteen (416) patients admitted with ACS were recruited from coronary care wards. Participants attended the study centre at one (T0) and 12 (T1) months following discharge. Heart rate variability (HRV) was used to assess autonomic functioning measured via a three-lead electrocardiogram. Psychological variables of interest (pathological worry, depression and phobic anxiety) were measured using validated self-report questionnaires. Percutaneous coronary intervention treatment data were collected from hospital records. The primary outcome was 2-year all-cause hospital readmission (yes/no). Logistic regression modelling using both complete case analysis and multiple imputation analysis was applied. Results Men who received PCI had a significant reduction in the odds of being rehospitalised over the following 2 years, relative to women who did not (OR=0.45, 95% CI=0.20, 0.98). No other group benefited to this extent. Adjustment for age, ACS severity and Very Low Frequency (VLF) Power appeared to strengthen the association in both the complete case analysis and multiple imputation analysis models. The inclusion of depression and worry also marginally explained these associations in the multiple imputation analysis model. Conclusions Men who receive PCI after ACS were less likely to be readmitted to hospital over the following 2 years than their female counterparts. The small sample size of women and observational study design limit interpretation of the findings. However, heart rate variability, specifically VLF power, requires further investigation as a driver of such sex-specific outcomes