Genome sequencing of the mpox virus 2022 outbreak with amplicon-based Oxford Nanopore MinION sequencing.

We present an amplicon-based assay for MinION Nanopore sequencing of mpox virus (MPXV) genomes from clinical specimens, obtaining high-quality results with an average genome coverage of 99% for Ct values of up to 25, and a genome coverage of 97.1% for Ct values from 25 to 30 which are challenging to sequence. This assay is easy to implement in PCR-based workflows and provides accurate genomic data within a short time.

Mental imagery and visual attentional templates: A dissociation.

There is a growing interest in the relationship between mental images and attentional templates as both are considered pictorial representations that involve similar neural mechanisms. Here, we investigated the role of mental imagery in the automatic implementation of attentional templates and their effect on involuntary attention. We developed a novel version of the contingent capture paradigm designed to encourage the generation of a new template on each trial and measure contingent spatial capture by a template-matching visual feature (color). Participants were required to search at four different locations for a specific object indicated at the start of each trial. Immediately prior to the search display, color cues were presented surrounding the potential target locations, one of which matched the target color (e.g., red for strawberry). Across three experiments, our task induced a robust contingent capture effect, reflected by faster responses when the target appeared in the location previously occupied by the target-matching cue. Contrary to our predictions, this effect remained consistent regardless of self-reported individual differences in visual mental imagery (Experiment 1, N = 216) or trial-by-trial variation of voluntary imagery vividness (Experiment 2, N = 121). Moreover, contingent capture was observed even among aphantasic participants, who report no imagery (Experiment 3, N = 91). The magnitude of the effect was not reduced in aphantasics compared to a control sample of non-aphantasics, although the two groups reported substantial differences in their search strategy and exhibited differences in overall speed and accuracy. Our results hence establish a dissociation between the generation and implementation of attentional templates for a visual feature (color) and subjectively experienced imagery.

Lapses in the Person Radar: ADHD Symptoms Predict Difficulty in Interpersonal Distancing.

OBJECTIVE: Across contexts, from social cognition to the COVID-19 pandemic response, individual variation in the regulation of interpersonal distance has typically been viewed as a voluntary choice. Here we examine the frequency of unintentional lapses in interpersonal distancing, and their relationship with childhood ADHD symptoms. METHOD: We administered a novel measure of difficulty with interpersonal distancing across three undergraduate samples (total N = 1,225), in addition to measures of recalled childhood ADHD symptoms, mind wandering, and hyperfocus. RESULTS: Almost all (>97%) participants reported unintentional lapses in maintaining interpersonal distance, with 16% experiencing such lapses frequently. Thirty percent of the variance in these reports was accounted for by attentional traits: Inattentive and hyperactive/impulsive ADHD symptoms jointly predicted difficulties with interpersonal distancing, with the former relationship fully mediated by hyperfocus and spontaneous mind wandering. CONCLUSION: Both inattentive and hyperactive/impulsive ADHD symptoms confer vulnerability to frequent unintentional lapses in interpersonal distancing.

Irrelevant sights and sounds require spatial suppression: ERP evidence.

Both real-world experience and behavioral laboratory research suggest that entirely irrelevant stimuli (distractors) can interfere with a primary task. However, it is as yet unknown whether such interference reflects competition for spatial attention - indeed, prominent theories of attention predict that this should not be the case. Whilst electrophysiological indices of spatial capture and spatial suppression have been well-investigated, experiments have primarily utilized distractors which share a degree of task-relevance with targets, and are limited to the visual domain. The present research measured behavioral and ERP responses to test the ability of salient yet entirely task-irrelevant visual and auditory distractors to compete for spatial attention during a visual task, while also testing for potentially enhanced competition from multisensory distractors. Participants completed a central letter search task, while ignoring lateralized visual (e.g., image of a dog), auditory (e.g., barking), or multisensory (e.g., image + barking) distractors. Results showed that visual and multisensory distractors elicited a PD component indicative of active lateralized suppression. We also establish for the first time an auditory analog of the PD component, the PAD , elicited by auditory and multisensory distractors. Interestingly, there was no evidence to suggest enhanced ability of multisensory distractors to compete for attentional selection, despite previous proposals of a "special" saliency status for such items. Our findings hence suggest that irrelevant multisensory and unisensory distractors are similarly capable of eliciting a spatial "attend-to-me" signal - a precursor of spatial attentional capture - but at least in the present data set did not elicit full spatial attentional capture.

RespiCoV: Simultaneous identification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and 46 respiratory tract viruses and bacteria by amplicon-based Oxford-Nanopore MinION sequencing.

Since December 2019 the world has been facing the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Identification of infected patients and discrimination from other respiratory infections have so far been accomplished by using highly specific real-time PCRs. Here we present a rapid multiplex approach (RespiCoV), combining highly multiplexed PCRs and MinION sequencing suitable for the simultaneous screening for 41 viral and five bacterial agents related to respiratory tract infections, including the human coronaviruses NL63, HKU1, OC43, 229E, Middle East respiratory syndrome coronavirus, SARS-CoV, and SARS-CoV-2. RespiCoV was applied to 150 patient samples with suspected SARS-CoV-2 infection and compared with specific real-time PCR. Additionally, several respiratory tract pathogens were identified in samples tested positive or negative for SARS-CoV-2. Finally, RespiCoV was experimentally compared to the commercial RespiFinder 2SMART multiplex screening assay (PathoFinder, The Netherlands).

Faces are not always special for attention: Effects of response-relevance and identity.

Research over the past 25 years indicates that stimulus processing is diminished when attention is engaged in a perceptually demanding task of high 'perceptual load'. These results have generalized across a variety of stimulus categories, but a controversy evolved over the question of whether perception of distractor faces (or other categories of perceptual expertise) can proceed irrespective of the level of perceptual load in the attended task. Here we identify task-relevance, and in particular identity-relevance, as a potentially important factor in explaining prior inconsistencies. In four experiments, we tested whether perceptual load in an attended letter or word task modulates the processing of famous face distractors, while varying their task-relevance. Distractor interference effects on task RTs was reduced by perceptual load not only when the faces were entirely task-irrelevant, but also when the face gender was task relevant, within a name gender classification response-competition task, using famous female or male distractor faces. However, when the identity associated with the famous faces was primed by the task using their names, as in prior demonstrations that face distractors are immune to the effects of perceptual load, we were able to replicate these prior findings. Our findings demonstrate a role for identity-priming by the relevant task in determining attentional capture by faces under high perceptual load. Our results also highlight the importance of considering even relatively subtle forms of task-relevance in selective attention research.

Clinical safety of robenacoxib in cats with chronic musculoskeletal disease.

BACKGROUND: Evaluate the clinical safety of robenacoxib in cats with chronic musculoskeletal disease (CMSD). ANIMALS: Four hundred forty-nine client-owned cats with CMSD. METHODS: Pooled analysis of safety variables from 4 prospective randomized blinded clinical trials of robenacoxib (n = 222) versus placebo (n = 227), administered orally once daily for 4 to 12 weeks. Safety was evaluated from reported adverse events (AEs) and abnormalities detected on hematology and serum and urine chemistry analyses. RESULTS: The number of cats with at least 1 AE was not significantly different (P = .15) with robenacoxib (n = 106, 47.8%) compared to placebo (n = 93, 41.0%). The relative risk of at least 1 AE (incidence robenacoxib/placebo) was 1.15 (95% confidence interval 0.93-1.43). There was no significant difference between groups in the number of clinical signs (range, 0-9) per cat (P = .23). Serum creatinine concentrations were higher during robenacoxib administration compared to placebo (+4.36 µmol/L, 95% confidence interval 0.21-8.50), but no related adverse clinical effects were detected. In the subgroup of 126 cats with evidence of chronic kidney disease, the relative risk of at least 1 AE (robenacoxib/placebo) was 1.09 (95% confidence interval 0.78-1.52, P = .61). CONCLUSIONS AND CLINICAL IMPORTANCE: Robenacoxib was not associated with increased risk of AEs compared to placebo when administered for 4 to 12 weeks to cats with CMSD. The generalizability of the results to general practice is limited by the fact that cases with severe and uncontrolled concomitant diseases were not included.

AmpliCoV: Rapid Whole-Genome Sequencing Using Multiplex PCR Amplification and Real-Time Oxford Nanopore MinION Sequencing Enables Rapid Variant Identification of SARS-CoV-2.

Since the emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in December 2019, the scientific community has been sharing data on epidemiology, diagnostic methods, and whole-genomic sequences almost in real time. The latter have already facilitated phylogenetic analyses, transmission chain tracking, protein modeling, the identification of possible therapeutic targets, timely risk assessment, and identification of novel variants. We have established and evaluated an amplification-based approach for whole-genome sequencing of SARS-CoV-2. It can be used on the miniature-sized and field-deployable sequencing device Oxford Nanopore MinION, with sequencing library preparation time of 10 min. We show that the generation of 50,000 total reads per sample is sufficient for a near complete coverage (>90%) of the SARS-CoV-2 genome directly from patient samples even if virus concentration is low (Ct 35, corresponding to approximately 5 genome copies per reaction). For patient samples with high viral load (Ct 18-24), generation of 50,000 reads in 1-2 h was shown to be sufficient for a genome coverage of >90%. Comparison to Illumina data reveals an accuracy that suffices to identify virus mutants. AmpliCoV can be applied whenever sequence information on SARS-CoV-2 is required rapidly, for instance for the identification of circulating virus mutants.

Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) against natural flea and tick infestations on dogs presented as veterinary patients in Europe.

BACKGROUND: A pivotal randomised, blinded, positive-controlled, multicentre, European field study was conducted to evaluate the effectiveness and safety of a novel combination tablet of lotilaner and milbemycin oxime (Credelio® Plus) administered orally to client-owned dogs naturally infested with fleas and/or ticks. METHODS: In this field study, households with flea- or tick-infested dog(s) were enrolled on Day 0 into the study to provide data for either the tick or flea infestation cohorts. Households were randomised in a 2:1 ratio to receive either the combination investigational product (IP, Credelio Plus® tablets) or the control product (CP: Nexgard Spectra® tablets). Dogs were administered IP (flea cohort n = 135; tick cohort: n = 147) or CP (flea cohort: n = 67; tick cohort: n = 74) once every 4 weeks for a total of three times at a dose rate of 20.0-41.5 mg/kg bodyweight lotilaner and 0.75-1.53 mg/kg bodyweight milbemycin oxime (IP) or as recommended (CP). Percentage reduction was calculated by comparing individual dog flea and tick counts at each assessed post-treatment time point to their respective baseline (pre-treatment) infestation. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea-allergic dogs on the days that flea counts were performed. RESULTS: Flea effectiveness of Credelio Plus® after 3 consecutive monthly treatments was 100% against Ctenocephalides felis, C. canis and Pulex irritans. Tick effectiveness of Credelio Plus® over the same time frame was 99.3% for Ixodes ricinus and 100% against Rhipicephalus sanguineus (s.l.). Flea effectiveness of the CP after three consecutive monthly treatments was 100% against C. felis, C. canis and P. irritans. Tick effectiveness of the CP over the same time frame was 99.8% for I. ricinus and 100% against R. sanguineus. Credelio Plus® was well tolerated based on the safety assessments in all treated dogs in this field study. Within both treatment groups there was a reduction in total FAD scores from baseline. CONCLUSIONS: This pivotal European field study demonstrated the excellent effectiveness and safety of a combination of lotilaner and milbemycin oxime (Credelio Plus®) administered orally to dogs naturally infested with fleas and/or ticks.

Resource-efficient internally controlled in-house real-time PCR detection of SARS-CoV-2.

BACKGROUND: The reliable detection of SARS-CoV-2 has become one of the most important contributions to COVID-19 crisis management. With the publication of the first sequences of SARS-CoV-2, several diagnostic PCR assays have been developed and published. In addition to in-house assays the market was flooded with numerous commercially available ready-to-use PCR kits, with both approaches showing alarming shortages in reagent supply. AIM: Here we present a resource-efficient in-house protocol for the PCR detection of SARS-CoV-2 RNA in patient specimens (RKI/ZBS1 SARS-CoV-2 protocol). METHODS: Two duplex one-step real-time RT-PCR assays are run simultaneously and provide information on two different SARS-CoV-2 genomic regions. Each one is duplexed with a control that either indicates potential PCR inhibition or proves the successful extraction of nucleic acid from the clinical specimen. RESULTS: Limit of RNA detection for both SARS-CoV-2 assays is below 10 genomes per reaction. The protocol enables testing specimens in duplicate across the two different SARS-CoV-2 PCR assays, saving reagents by increasing testing capacity. The protocol can be run on various PCR cyclers with several PCR master mix kits. CONCLUSION: The presented RKI/ZBS1 SARS-CoV-2 protocol represents a cost-effective alternative in times of shortages when commercially available ready-to-use kits may not be available or affordable.

Intact Goal-Driven Attentional Capture in Autistic Adults.

BACKGROUND: Autistic individuals have been found to show increased distractibility by salient irrelevant information, yet reduced distractibility by information of personal motivational salience. Here we tested whether these prior discrepancies reflect differences in the automatic guidance of attention by top-down goals. METHODS: Autistic (self-reported diagnoses, confirmed with scores on the Social Responsiveness Scale) and non-autistic adults, without intellectual disability (IQ > 80 on Wechsler Abbreviated Scale of Intelligence), searched for a color-defined target object (e.g., red) among irrelevant color objects. Spatially uninformative cues, matching either the target color or a nontarget/irrelevant color, were presented prior to each display. RESULTS: Replicating previous work, only target color cues reliably captured attention, delaying responses when invalidly versus validly predicting target location. Crucially, this capture was robust for both autistic and neurotypical participants, as confirmed by Bayesian analysis. Limitations: While well powered for our research questions, our sample size precluded investigation of the automatic guidance of attention in a diverse group of autistic people (e.g. those with a range of cognitive abilities). CONCLUSIONS: Our findings imply that key mechanisms underlying the automatic implementation of top-down attentional goals are intact in autism, challenging theories of reduced top-down control.

Ingested but not perceived: Response to satiety cues disrupted by perceptual load.

Selective attention research has shown that when perceptual demand is high, unattended sensory information is filtered out at early stages of processing. We investigated for the first time whether the sensory and nutrient cues associated with becoming full (satiety) would be filtered out in a similar manner. One-hundred and twenty participants consumed either a low-satiety (75 kcal) or high-satiety (272 kcal plus thicker texture) beverage, delivered via an intra-oral infusion device while participants simultaneously completed a task which was either low or high in perceptual demand. Among participants who performed the low perceptual load task, ingestion of the high-satiety beverage increased rated satiety and reduced consumption at a subsequent snack test. However, both effects were eliminated by the high perceptual load task. Therefore, the processing of satiety cues was dependent on the availability of attention, identifying a novel perceptual load mechanism of inattentive eating and supporting more recent cognitive models of appetite control.

Testing a load theory framework for food-related cognition.

The way we process rewarding stimuli is widely held to play a key role in normal and abnormal behavior. Biased processing of food-arguably the most primal form of reward-has been strongly implicated in the obesity crisis. Paradoxically, however, existing evidence suggests that both too much and too little attention can potentially lead to overeating. Here we sought to explain this contradiction within the framework of the load theory of attention, while also elucidating the relatively understudied role of memory biases. In 3 experiments, we presented food and nonfood images as irrelevant distractors during a letter search task with high and low levels of perceptual load, followed by a forced choice recognition task. As predicted, increasing perceptual load consistently powerfully reduced distraction by food and nonfood images alike. Similarly, food images encountered under high perceptual load were less likely to be recognized in a surprise memory test. Unexpectedly, however, there was a striking absence of attentional bias to food above and beyond salient nonfood stimuli, either within-subjects or in relation to traits implicated in food-biases. By contrast, a food memory bias was consistently observed across participants, and appeared independent of attentional biases. Food memory was consistently heightened in individuals with high levels of trait disinhibition (a measure of opportunistic eating). Our findings suggest that attention and memory for food and nonfood are similarly impacted by perceptual load. We discuss implications of the load theory framework for the wider literature on food-related cognition and for real world eating behaviors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

A high perceptual load task reduces thoughts about chocolate, even while hungry.

Intrusive thoughts about food can trigger cravings and result in unhealthy eating behaviour. Here we tested whether Load Theory of attention can be applied to the eating behaviour literature and reduce intrusive appetitive-related thoughts. Load Theory predicts that high levels of perceptual load in a task exhaust attentional capacity and so reduces interference from a range of stimuli, including intrusive thoughts. Therefore, this study aimed to test whether perceptual load reduced appetitive-related intrusive thoughts about chocolate. Sixty female participants were first given a chocolate bar to interact with for 2 min, before rating their levels of hunger, craving and liking for chocolate. They were then asked to avoid thinking about chocolate and instead focus attention on a visual search task. Perceptual load was manipulated within-subjects by varying the search set size. Appetitive-related thoughts were measured using both self-caught and probe-caught measures, allowing us to index load effects at varying levels of meta-awareness. Across subjects, the level of appetitive-related thoughts seen in the high load condition was significantly reduced, to less than half the level seen in the low load condition, on both probe and self-caught measures. Furthermore, self-reported hunger, craving and liking for the chocolate were positively correlated with appetitive-related thoughts under low load, but high perceptual load eliminated these state individual differences. Therefore, engaging in perceptually demanding tasks may be a worthwhile strategy for those wanting to disrupt the cycle of craving at the earliest stage.

Testing a goal-driven account of involuntary attentional capture by threat.

Attention has long been characterized within prominent models as reflecting a competition between goal-driven and stimulus-driven processes. It remains unclear, however, how involuntary attentional capture by affective stimuli, such as threat-laden content, fits into such models. Although such effects were traditionally thought to reflect stimulus-driven processes, recent research has increasingly implicated a critical role of goal-driven processes. Here we test an alternative goal-driven account of involuntary attentional capture by threat using an experimental manipulation of goal-driven attention. To this end we combined the classic contingent capture and emotion-induced blink paradigms in an RSVP task with both positive or threatening target search goals. Across 6 experiments, positive and threat distractors were presented in peripheral, parafoveal, and central locations. Across all distractor locations we found that involuntary attentional capture by irrelevant threat distractors could be induced via the adoption of a search goal for a threatening category; adopting a goal for a positive category conversely led to capture only by positive stimuli. Our findings provide direct experimental evidence for a causal role of voluntary goals in involuntary capture by irrelevant threat stimuli, and hence demonstrate the plausibility of a top-down account of this phenomenon. We discuss the implications of these findings in relation to current cognitive models of attention and clinical disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Not looking for any trouble? Purely affective attentional settings do not induce goal-driven attentional capture.

It is well established that directing goal-driven attention to a particular stimulus property (e.g., red), or a conceptual category (e.g., toys) can induce powerful involuntary capture by goal-matching stimuli. Here, we tested whether broad affective search goals (e.g., for anything threat-related) could similarly induce a generalized capture to an entire matching affective category. Across four experiments, participants were instructed to search for threat-related images in a Rapid Serial Visual Presentation (RSVP) stream, while ignoring threat-related distractors presented in task-irrelevant locations. Across these experiments we found no evidence of goal-driven attentional capture by threat distractors when participants adopted a general 'threat detection' goal encompassing multiple subcategories of threat (Experiments 1a, 1b). This was true even when there was partial overlap between the threat distractors and the search goal (i.e., subset of the targets matched the distractor; Experiment 2). However, when participants adopted a more specific goal for a single subcategory of threat (e.g., fearful faces), robust goal-driven capture occurred by distractors matching this subcategory (Experiment 3). These findings suggest that while affective criteria can be used in the guidance of attention, attentional settings based on affective properties alone may not induce goal-driven attentional capture. We discuss implications for recent goal-driven accounts of affective attentional biases.

"What Smell?" Temporarily Loading Visual Attention Induces a Prolonged Loss of Olfactory Awareness.

The human sense of smell is highly sensitive, often conveying important biological signals. Yet anecdotal evidence suggests that we commonly fail to notice suprathreshold environmental olfactory stimuli. The determinants of olfactory awareness are, as yet, unknown. Here, we adapted the inattentional-blindness paradigm to test whether olfactory awareness is dependent on attention. Across three experiments, participants performed a visual search task with either a high or low perceptual load (a well-established attentional manipulation) while exposed to an ambient coffee aroma. Consistent with our hypothesis, results showed that task load modulated olfactory awareness: 42.5% fewer participants in the high- than in the low-load condition reported noticing the coffee aroma. Our final experiment demonstrates that because of unique characteristics of olfactory habituation, the consequences of inattentional anosmia can persist even once attention becomes available. These findings establish the phenomenon of inattentional anosmia and have applied implications for predicting when people may miss potentially important olfactory information.

Goal-driven attentional capture by appetitive and aversive smoking-related cues in nicotine-dependent smokers.

BACKGROUND: Conventionally, involuntary attentional capture by tobacco cues in smokers are seen as an implicit bias, operating independently of current search goals. Prominent attention research, however, has suggested that search goals can induce an involuntary attentional capture. In the current investigation, we tested whether appetitive and aversive smoking images affected attention through such a mechanism and whether there were group differences based on nicotine dependence. METHODS: We instructed non-smokers (NS), occasional smokers (OS; low dependence), and nicotine-dependent smokers (NDS; moderate-high dependence), to hold search goals for either an aversive or appetitive smoking category, or a category of non-smoking images. These images were presented in a stream of briefly appearing filler images, while task-irrelevant distractors were presented outside the stream. Distractors could be aversive or appetitive smoking images or a category of non-smoking images. Therefore, in some conditions, the distractors matched the current category being searched for, while in others it was incongruent. RESULTS: Task-irrelevant smoking distractors reduced target detection, compared to the non-smoking distractors, only when they were congruent with the specific category being searched for. There was no effect of either aversive or appetitive smoking distractors on performance when participants were searching for the non-smoking targets. Distractor interference did not differ between smokers and non-smokers. CONCLUSIONS: The results support a goal-driven mechanism underpinning involuntary attentional capture by smoking cues. These findings can be used to inform models of addiction and attention, and the display of health warnings.

Attentional capture by alcohol-related stimuli may be activated involuntarily by top-down search goals.

Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol-related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here, we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be congruent or incongruent with the current search goal. Applying a meta-analysis, we combined the results across the three experiments and found consistent evidence of goal-driven attentional capture, whereby alcohol distractors impeded target detection when the search goal was for alcohol. By contrast, alcohol distractors did not interfere with target detection, whilst participants were searching for a non-alcoholic category. A separate experiment revealed that the goal-driven capture effect was not found when participants held alcohol features active in memory but did not intentionally search for them. These findings suggest a strong goal-driven account of attentional capture by alcohol cues in social drinkers.

Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with congestive heart failure: a randomized non-inferiority clinical trial.

A fixed-dose combination tablet of benazepril and pimobendan (Fortekor Plus; Elanco Animal Health) was tested in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD) in a three-arm, masked, randomized, non-inferiority clinical trial in Japan. The test group (n = 34) received Fortekor Plus twice daily. Two control groups received registered formulations of benazepril (Fortekor; Elanco Animal Health) and pimobendan (Vetmedin; Boehringer Ingelheim Vetmedica) with administration of Vetmedin twice daily and Fortekor twice (Control I, n = 14) or once (Control II, n = 19) daily. Diuretics were used in 22 dogs (32.8%). Global clinical scores decreased significantly from baseline in all groups; there were no significant differences between groups, and non-inferiority of Fortekor Plus compared to Control I, Control II, and combined Control I + II groups was demonstrated. There were no significant differences between groups for relevant clinical chemistry and hematology variables or frequency of all adverse events. Frequency of emesis was significantly (p = 0.0042) lower in the Fortekor Plus (8.8%) group than in the Control I + II (39.4%) group. In conclusion, Fortekor Plus had non-inferior efficacy and was associated with significantly less emesis compared to Fortekor and Vetmedin in dogs with CHF caused by MMVD.