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The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.
Subject(s)
Dog Diseases , Epilepsy , Placebo Effect , Dogs , Animals , Dog Diseases/drug therapy , Epilepsy/veterinary , Epilepsy/drug therapy , Cross-Over Studies , Female , Male , Anticonvulsants/therapeutic use , Prospective StudiesABSTRACT
BACKGROUND: Two-stage prosthesis exchange is the treatment of choice for chronic periprosthetic joint infection (PJI) of a total hip arthroplasty (THA), especially when the bone and surrounding soft tissues are compromised or difficult-to-treat pathogens are implicated. The aims of our study were as follows: (1) to determine the outcome of 2-stage prosthesis exchange for the treatment of PJI after THA and (2) to determine the risk factors for reinfection leading to subsequent revision surgeries after reimplantation. METHODS: We prospectively enrolled 187 consecutive patients who underwent a 2-stage THA exchange with resection arthroplasty for PJI from 2013 to 2019. The mean (± SD) duration of follow-up was 54.2 ± 24.9 months (range, 36 to 96), and the mean interval until reimplantation was 9.8 ± 8.9 weeks (range, 2 to 38). All patients remained in a spacer-free girdlestone situation between the 2 stages of treatment. Patients who remained infection-free after their 2-stage treatment were considered to have achieved treatment success. RESULTS: The overall success rate was 85.6%. The cumulative probability of reinfection was 11.5% after one year and 14% after 2 years after reimplantation. High virulence or difficult-to-treat pathogens were significant and independent risk factors for reinfection (HR [hazard ratio] = 3.71, 95% CI [confidence interval]: 1.47 to 9.36, P = .006 and HR = 3.85, 95% CI: 1.73 to 8.57, respectively, P = .001), as was previous 2-stage hip prosthesis exchange (HR = 3.58, 95% CI: 1.33 to 9.62, P = .01). Overall reoperation and revision rates were 26.2 and 16.6%, respectively. Re-infected patients had an 80% higher probability of reoperation than noninfected ones (P < .001, log-rank = 102.6), and they were 55% more likely to undergo revision surgery during their follow-up (P < .001, log-rank = 55.4). CONCLUSIONS: Reinfection rates after 2-stage spacer-free THA revision for PJI still remain high but are comparable to those including cement spacers. Patients who have had prior failed 2-stage implant exchanges or are infected by high-grade or difficult-to-treat pathogens are at high risk for treatment failure.
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Prior to undergoing total knee arthroplasty (TKA), surgeons are often confronted with patients with numerous questions regarding the procedure and the recovery process. Due to limited staff resources and mounting individual workload, increased efficiency, e.g., using artificial intelligence (AI), is of increasing interest. We comprehensively evaluated ChatGPT's orthopedic responses using the DISCERN instrument. Three independent orthopedic surgeons rated the responses across various criteria. We found consistently high scores, predominantly exceeding a score of three out of five in almost all categories, indicative of the quality and accuracy of the information provided. Notably, the AI demonstrated proficiency in conveying precise and reliable information on orthopedic topics. However, a notable observation pertains to the generation of non-existing references for certain claims. This study underscores the significance of critically evaluating references provided by ChatGPT and emphasizes the necessity of cross-referencing information from established sources. Overall, the findings contribute valuable insights into the performance of ChatGPT in delivering accurate orthopedic information for patients in clinical use while shedding light on areas warranting further refinement. Future iterations of natural language processing systems may be able to replace, in part or in entirety, the preoperative interactions, thereby optimizing the efficiency, accessibility, and standardization of patient communication.
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BACKGROUND: Studies in people suggest that surface electroencephalography (EEG) electrode positions vary across participants and that the consistency of these positions is electrode-, region-, and examiner-dependent. The aim was to investigate the variability in EEG electrode positions to their underlying cortical regions (CRs) in dogs using a neuronavigation system and evaluate the use of said system in electrode positioning, via a cadaver study with 22 dogs. CT scans and MRI were performed for each dog. These were uploaded onto a neuronavigation system where the desired CRs were annotated. The electrode positions were marked on the heads, which were positioned using only a previously established guide and anatomical landmarks. Using the neuronavigation system, alignment or deviations from the desired CRs were noted. Fifty-three percent of all the marked electrode positions showed an alignment with the desired CRs. Thirty-three percent showed no alignment, and fourteen percent showed partial alignment. Three percent deviated to different cortical lobes. Placement via the neuronavigation system enabled reliable and replicable electrode positioning and CR alignment. The standard for EEG electrode placement in dogs is subjected to a high variance. A neuronavigation system can aid in more precise electrode placements. Specific gyri cannot accurately be evaluated on EEG without imaging-controlled electrode placement.
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Background: Implantable electroencephalography (EEG) recording devices have been used for ultra-long-term epilepsy monitoring both in clinical and home settings in people. Objective and accurate seizure detection and recording at home could be of great benefit in diagnosis, management and research in canine idiopathic epilepsy (IE). Continuous EEG monitoring would allow accurate detection of seizure patterns, seizure cycles, and seizure frequency. An EEG acquisition system usable in an "out of clinic" setting could improve owner and veterinary compliance for EEG diagnostics and seizure management. Objectives: Whether a subcutaneous ultra-long term EEG monitoring device designed for humans could be implanted in dogs. Animals: Cadaver study with 8 medium to large breed dogs. Methods: Comparatively using a subcutaneous and submuscular approach to implant the UNEEG SubQ-Implant in each dog. Positioning was controlled via CT post implantation and cranial measurements were taken. Results: In four of the eight dogs a submuscular implantation without any complications was possible. Complications were close contact to the optic nerve in the first approaches, before the implantation angle was changed and in the smallest dog contact of the implant with the orbital fat body. Cranial measurements of less than 95 mm length proved to be too small for reliable implantation via this approach. The subcutaneous approach showed severe limitations and the implant was prone to dislocation. Conclusion: The UNEEQ SubQ-Implant can be implanted in dogs, via submuscular approach. CT imaging and cranial measurements should be taken prior to implantation.
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Psychiatric and cognitive comorbidities have been known to play a major role in human epilepsy for a long time. People with epilepsy (PWE) frequently express signs of varying psychiatric and cognitive disorders affecting their quality and quantity of life (QoL/QaoL). Over the last few years, research on behavioural comorbidities and their effect on the underlying disease have been performed in canine epilepsy. The following article reviews manifestations of comorbidities in canine epilepsy with an emphasis on patterns of clinical signs and their effects on QoL and QaoL. Cognitive and behavioural alterations in epileptic dogs are mainly represented by fear-/anxiety related behaviour and cognitive impairment (CI). Reduced trainability and altered reactions to daily situations are common results of comorbid changes posing obstacles in everyday life of owners and their dog. In addition, clinical signs similar to attention deficit hyperactivity disorder (ADHD) in humans have been reported. Canine attention-deficit-hyperactivity-disorder-like (c-ADHD-like) behaviour should, however, be evaluated critically, as there are no official criteria for diagnosis of ADHD or ADHD-like behaviour in dogs, and some of the reported signs of c-ADHD-like behaviour could be confused with anxiety-associated behaviour. Many intrinsic and extrinsic factors could potentially influence the development of behavioural and cognitive comorbidities in canine epilepsy. In particular, seizure frequency/severity, signalment and factors concerning disease management, such as pharmacotherapy and nutrition, are closely linked with the presence of the aforementioned comorbid disorders. Further studies of behavioural alterations in epileptic dogs are needed to comprehend the complexity of clinical signs and their multifactorial origin.
Subject(s)
Dog Diseases , Epilepsy , Humans , Dogs , Animals , Quality of Life , Epilepsy/drug therapy , Epilepsy/veterinary , Comorbidity , Anxiety , Cognition , Dog Diseases/epidemiology , Dog Diseases/drug therapyABSTRACT
This review draws connections between the pathogenesis of canine epilepsy and its most commonly recognised comorbidities: cognitive impairment (CI), attention deficit hyperactivity disorder (ADHD)-like behaviour, fear and anxiety. Uni/bidirectional causalities and the possibility of a common aetiology triggering both epilepsy and the associated diseases are considered. Research on this topic is sparse in dogs, so information has been gathered and assessed from human and laboratory animal studies. Anatomical structures, functional connections, disrupted neurotransmission and neuroinflammatory processes collectively serve as a common foundation for epilepsy and its comorbidities. Specific anatomical structures, especially parts of the limbic system, such as the amygdala and the hippocampus, are involved in generating seizures, as well as cognitive- and behavioural disorders. Furthermore, disturbances in inhibitory and excitatory neurotransmission influence neuronal excitability and networks, leading to underlying brain dysfunction. Functional magnetic resonance imaging (fMRI), interictal epileptiform discharges (IEDs), and electroencephalography (EEG) have demonstrated functional brain connections that are related to the emergence of both epilepsy and its various comorbidities. Neuroinflammatory processes can either cause or be a consequence of seizures, and inflammatory mediators, oxidative stress and mitochondrial dysfunction, can equally evoke mood disorders. The extensive relationships contributing to the development and progression of seizures and comorbid cognitive and behavioural conditions illustrate the complexity of the disease that is epilepsy.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Dog Diseases , Epilepsy , Humans , Animals , Dogs , Epilepsy/complications , Epilepsy/veterinary , Attention Deficit Disorder with Hyperactivity/complications , Electroencephalography , Anxiety , Causality , Dog Diseases/etiologyABSTRACT
AIMS: This study aimed to assess the safety and efficacy of microporous polysaccharide hemospheres (MPSHs) in managing blood loss and reducing the risk of postoperative haematoma and early periprosthetic joint infection (PJI) following total hip arthroplasty (THA) for femoral neck fracture (FNF), in the context of the existing treatment challenges. METHODS: A control-matched retrospective analysis of 163 patients undergoing unilateral primary THA for displaced FNF between 2020 and 2023 was performed. The study group consisted of 74 patients who received MPSH administered intraoperatively. The control group consisted of 89 patients who received no topical haemostatics. One-to-one case-control matching between groups was performed. The primary outcome was a perioperative change in the haematologic values (haemoglobin, red blood cell count, haematocrit, platelet concentration) and transfusion rate. The secondary outcomes were the incidence of postoperative local haematoma formation, prolonged wound secretion, surgical site infection (SSI), and PJI within 3 months of surgery. RESULTS: Our analysis found no statistically significant differences in the haematologic parameters between the control and study cohorts. The changes in the haemoglobin concentration were not significant between the control group (3.18 ± 1.0 g/dL) and the treatment group (2.87 ± 1.15 g/dL) (p = 0.3). There were no significant differences (p = 0.24) in the haematocrit and red blood cell concentration (p = 0.15). The platelet levels did not significantly differ (p = 0.12) between the groups. Additionally, we found no significant discrepancy in the incidence of early PJI or blood transfusion rates between the groups. No adverse effects following MPSH use were recorded in the study group. CONCLUSIONS: Routine use of MPSH in THA for FNF management appears to be safe, with no observed adverse events related to Arista® use. Although there was a tendency towards reduced blood loss in the Arista® AH group, MPSH did not significantly impact bleeding complications, local haematoma formation, or subsequent PJI.
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Background: Canine cognitive dysfunction (CCD) is a common, yet underdiagnosed neurodegenerative disease affecting older dogs. Treatment is most effective when started early, so identifying mild cognitive decline in the earlier stages of the disease is considered important. Hypothesis/objective: To compare the results of three different standard screening questionnaires [Canine Dementia Scale (CADES), Canine Cognitive Assessment Scale (CCAS), and Canine Cognitive Dysfunction Rating Scale (CCDR)] for CCD diagnosis. Trainability, pain sensitivity, and fear were additionally assessed with the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) in order to evaluate associations between the three dementia scales and behavior. Methods: An online survey containing all the mentioned questionnaires was designed for and distributed among owners of elderly dogs. Results: Data from 597 dogs were analyzed. Overall, the scores of the three CCD questionnaires correlated well with each other, especially those of the CADES and CCAS. The CADES was more sensitive in identifying dogs with already mild to moderate cognitive impairment, while the others classified them as still undergoing normal aging. CCD scores increased for all questionnaires with age with spatial orientation being a key feature in CCD development. Trainability assessed with the C-BARQ decreased significantly with severity of CCD signs, while pain sensitivity increased. Fear and anxiety was pronounced in animals with mild but not with severe CCD. These associations based on the C-BARQ were more clearly observable in relation to CADES and CCDR than CCAS. Conclusion/clinical relevance: The choice of screening questionnaire impacts the evaluation of cognitive status and severity of CCD. Thresholds for severity classification differ significantly and may have an impact on reliable assessment. Further longitudinal studies are required to determine which of the questionnaires investigated in this study is best suited for early detection of CCD.
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Aims: Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients. Methods: This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline. Results: Overall, several miRNAs in plasma and tissue were identified to be progressively deregulated according to ongoing PJI. When comparing the plasma samples, patients with a high-grade infection showed significantly higher expression levels for hsa-miR-21-3p, hsa-miR-1290, and hsa-miR-4488, and lower expression levels for hsa-miR-130a-3p and hsa-miR-451a compared to the aseptic group. Furthermore, the high-grade group showed a significantly higher regulated expression level of hsa-miR-1260a and lower expression levels for hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-148b-5p, hsa-miR-301a-3p, hsa-miR-451a, and hsa-miR-454-3p compared to the low-grade group. No significant differences were found between the low-grade and aseptic groups. When comparing the tissue samples, the high-grade group showed significantly higher expression levels for 23 different miRNAs and lower expression levels for hsa-miR-2110 and hsa-miR-3200-3p compared to the aseptic group. No significant differences were found in miRNA expression between the high- and low-grade groups, as well as between the low-grade and aseptic groups. Conclusion: With this prospective pilot study, we were able to identify a circulating miRNA signature correlating with high-grade PJI compared to aseptic patients undergoing hip arthroplasty revision. Our data contribute to establishing miRNA signatures as potential novel diagnostic and prognostic biomarkers for PJI.
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Introduction: Alterations in the composition and function of the gut microbiome have been reported in idiopathic epilepsy (IE), however, interactions of gut microbes with the enteric nervous system (ENS) in this context require further study. This pilot study examined how gastrointestinal microbiota (GIM), their metabolites, and nutrients contained in intestinal contents communicate with the ENS. Methods: Fecal supernatants (FS) from healthy dogs and dogs with IE, including drug-naïve, phenobarbital (PB) responsive, and PB non-responsive dogs, were applied to cultured myenteric neurons to test their activation using voltage-sensitive dye neuroimaging. Additionally, the concentrations of short-chain fatty acids (SCFAs) in the FS were quantified. Results: Our findings indicate that FS from all examined groups elicited neuronal activation. Notably, FS from PB non-responsive dogs with IE induced action potential discharge in a higher proportion of enteric neurons compared to healthy controls, which exhibited the lowest burst frequency overall. Furthermore, the highest burst frequency in enteric neurons was observed upon exposure to FS from drug-naïve dogs with IE. This frequency was significantly higher compared to that observed in PB non-responsive dogs with IE and showed a tendency to surpass that of healthy controls. Discussion: Although observed disparities in SCFA concentrations across the various FS samples might be associated with the induced neuronal activity, a direct correlation remains elusive at this point. The obtained results hint at an involvement of the ENS in canine IE and set the basis for future studies.
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Background: Patients access relevant information concerning their orthopaedic surgery resources through multiple information channels before presenting for clinical treatment. Recently, artificial intelligence (AI)-powered chatbots have become another source of information for patients. The currently developed AI chat technology ChatGPT (OpenAI LP) is an application for such purposes and it has been rapidly gaining popularity, including for patient education. This study sought to evaluate whether ChatGPT can correctly answer frequently asked questions (FAQ) regarding periprosthetic joint infection (PJI). Methods: Twelve FAQs about PJI after hip and knee arthroplasty were identified from the websites of fifteen international clinical expert centres. ChatGPT was confronted with these questions and its responses were analysed for their accuracy using an evidence-based approach by a multidisciplinary team. Responses were categorised in four groups: (1) Excellent response that did not require additional improvement; (2) Satisfactory responses that required a small amount of improvement; (3) Satisfactory responses that required moderate improvement; and (4) Unsatisfactory responses that required a large amount of improvement. Results: From the analysis of the responses given by the chatbot, no reply received an 'unsatisfactory' rating; one did not require any correction; and the majority of the responses required low (7 out of 12) or moderate (4 out of 12) clarification. Although a few responses required minimal clarification, the chatbot responses were generally unbiased and evidence-based, even when asked controversial questions. Conclusions: The AI-chatbot ChatGPT was able to effectively answer the FAQs of patients seeking information around PJI diagnosis and treatment. The given information was also written in a manner that can be assumed to be understandable by patients. The chatbot could be a valuable clinical tool for patient education and understanding around PJI treatment in the future. Further studies should evaluate its use and acceptance by patients with PJI.
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Introduction: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy. Methods: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification. Results: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged. Discussion: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.
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BACKGROUND: Dogs with idiopathic epilepsy experience not only the preictal and ictal seizure phases but also the postictal phase. To date, research has primarily focused on the preictal and ictal semiology and therapeutic control of ictal events. Research into the postictal phase's pathophysiology, as a therapeutic target and how it impacts the quality of life, is sparse across different species. Interestingly, even if anecdotally, owners report the postictal period being an impactful negative factor on their quality of life as well as their dog's quality of life. HYPOTHESIS/OBJECTIVES: We aimed to assess the semiology and the impact of postictal signs on the quality of life of owners and dogs. METHOD: This observational study was carried out using surveys of owners of dogs with seizure disorders. RESULTS: The questionnaire was filled out by 432 dog owners, 292 of whom provided complete responses that could be analysed. More than nine out of ten owners (97%) reported the presence of various postictal clinical signs. The dog's and the owner's quality of life was mainly affected by specific postictal signs, i.e., disorientation (dog: 31%; owner: 20%), compulsive walking (dog: 17%; owner: 22%), ataxia (dog: 12%; owner: 6%), and blindness (dog: 17%; owner: 10%). Nearly 61% of the owners felt that the severity of postictal signs was moderate or severe. Rescue antiseizure medications did not have an effect on controlling the postictal signs based on 71% of the responders. In contrast, 77% of the respondents reported that other measures such as rest, physical closeness, and a quiet and dark environment had a positive impact on the postictal phase. CONCLUSIONS AND CLINICAL IMPORTANCE: Overall, this survey shows that specific postictal signs are common and have a notable impact on the perceived quality of life of both dogs and their owners. According to the respondents, antiseizure medication might have no influence on the postictal phase in most cases, in contrast to other nonpharmacological measures. Further research on the management of the postictal phase is vital for improving the quality of life of dogs with seizure disorders and their owners.
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Introduction: In veterinary medicine, abdominal computer tomographic (CT) examinations regularly require a minimum of two scans, with a native scan (true unenhanced, TUE) as a reference for the subsequent contrast-enhanced CT scan (CECT). Spectral detector CT (SDCT) offers the possibility to calculate virtual non-contrast (VNC) images from the post-contrast scan, but this has not yet been investigated in veterinary medicine. The purpose of this study was to assess the reliability of VNC images for abdominal organs in 44 dogs without abdominal pathologies by evaluating their quantitative and qualitative parameters compared to TUE images. We hypothesized that the subtraction of iodine is sufficient in the VNC series compared to the TUE series and that the image quality of the SDCT series is superior to conventional CT images. Methods: Corresponding attenuation values in the VNC and TUE series regarding the regions of interest (ROI) in different parenchymal organs and major vessels of the abdominal cavity were assessed by means of a two one-sided t-test (TOST) and Bland-Altman plots. Additionally, the signal-to-noise ratio (SNR) was calculated for each ROI in the different series. In the second step, two board-certified veterinary radiologists made a qualitative assessment of VNC images vs. TUE images in consensus by rating the iodine subtraction, image noise, and image quality of VNC images based on a specific 5-point Likert scale. Results: The difference in corresponding Hounsfield units (HUs) between TUE and VNC images was less than 10 HU in 78.67% of all ROIs. Regarding the limit of less than 10 HU, in the performed TOST, significant p-values of < 0.05 were reached for the liver, spleen, pancreas, and musculature, implying equivalence of both modalities. The quality of spectral base image (SBI) data was rated equivalent to calculated conventional images in the subjective assessment by reaching an average Likert scale score of 3.2 points. Discussion: VNC images calculated from SDCT data prove a valid alternative to conventional TUE images in the abdominal organs of canine patients without abdominal pathology. VNC offers the possibility to reduce time under general anesthesia and minimize radiation exposure. Future studies are needed to prove the application of this method in clinically diseased patients.