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Abstract Introduction and Aim Small fibre neuropathy (SFN) is a peripheral neuropathy, leading to neuropathic pain and autonomic dysfunction. An evidence‐based standardized patient diagnostic SFN service has been implemented in the Netherlands for improving patient‐centred SFN care. However, the quality of care of this diagnostic SFN service has never been assessed from a patient perspective. The aim of this study was to develop and validate an SFN‐Patient Satisfaction Questionnaire (SFN‐PSQ) to measure the quality performance of a standardized diagnostic SFN service. Methods A descriptive qualitative study to create the SFN‐PSQ was performed using the (COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. For item generation and content development, domains and/or items from validated PSQs were selected. The content development and content validity were performed using a Delphi method with SFN expert caregivers with different backgrounds. By using the three‐step‐test method in individual cognitive interviews, the content validity by patients was finalized. Results In one online Delphi panel round, the content of the first concept of the SFN‐PSQ was validated, which resulted in the second concept of the SFN‐PSQ. From July 2019 till March 2020, nine patients consented to participate in the individual cognitive interviews. The most significant changes of the new questionnaire were adding domains and items concerning the waiting list, the diagnostic services and consultation by the hospital psychiatrist. Also, a differentiation was made for both an inpatient and outpatient diagnostic SFN service. Furthermore, the clarity and intelligibility of the domains/items were improved, resulting in an increased comprehension of the SFN‐PSQ. Ultimately, the new developed SFN‐PSQ consisted of 10 domains and 51 items, suitable for measuring patient satisfaction of the neurological analysis in patients with SFN. Conclusion Through item generation, expert opinions and interviews with patients, the SFN‐PSQ was developed and validated, and feasibility was confirmed. The structure of the questionnaire, based on the logistic and diagnostic SFN pathway, could be used as a model in other hospitals to improve the quality, continuity and access of SFN care and other chronic diseases taking into account potential cross‐cultural differences. Patient or Public Contribution Caregivers were involved in the item generation and content development of the questionnaire. Patients were directly involved in testing the content validity and feasibility of the SFN‐PSQ. Clinical Trial Registration Not applicable.

Horses can distinguish sweet, salty, sour, and bitter tastes, but little is known about their preferences for various tastants. Understanding horse taste preferences can aid in increasing water intake by adding a preferred tastant or by masking an unpleasant taste to encourage administration of medications, for example. The quantity of water intake by horses was examined over five separate trials involving a two-choice preference test between tap water and water containing varying concentrations of sucrose (0-50g/100ml), citric acid (0-2.43mg/100ml), quinine (0-30mg/100ml) or a mix of sucrose (10mg/100ml)/citric acid (1.31mg/100ml) and sucrose (10mg/100ml)/quinine (20mg/100ml). Horses (n = 5) showed a weak preference for sweetened water up to 10mg/100ml (p < .001), with a rejection at higher concentrations. Horses rejected all concentrations of both sour (n = 12 horses; p < .001) and bitter (n = 6 horses; p < .001) solutions. In the mixed tastant trials, sucrose mixed with citric acid was only weakly rejected compared to the sucrose solution alone, which was moderately rejected (n = 5 horses; p < .001). Similarly, mixed sucrose/quinine solution intake increased over the quinine solution alone (n = 9 horses; p < .001). There was a large variation among individual horses within each trial, with some horses strongly rejecting sucrose solutions and others strongly preferring citric acid solutions. No horse indicated a preference for bitter solution in any trial. Age (p < .001), breed (p < .001), and exercise (p = .004) all influenced total fluid intake in the sour trial, not dependent on treatment (p = .063). These preliminary results show that some horses appear to prefer sweet and a preferred tastant can mask a less preferred tastant.

Horses employ a range of subtle to overt behaviours to communicate their current affective state. Humans who are more cognisant of their own bodily sensations may be more attuned to recognising affective states in horses (Equus caballus) thereby promoting positive human-horse interactions. This study investigated human ability to categorise human-horse interactions depicted in media relative to equine behaviour experts and compared participant scores to their level of interoception. Using an online survey, participants (n = 534) categorised 31 photographs and videos as (overt) positive, likely (subtle) positive, neutral, likely (subtle) negative or (overt) negative human-horse interactions from the horse’s point of view and completed the Multidimensional Assessment of Interoceptive Awareness questionnaire (MAIA-2) to assess their level of interoception. Demographic information was also collected (age, gender, education, level of experience with horses, location). Participants differed from expert categorisations of horse affective states across all categories, exactly matching experts only 52.5% of the time and approximately matching experts for positive and negative valence 78.5% of the time. The MAIA-2 did not predict participant ability to accurately categorise human-horse interactions. Women outperformed men in categorising overt positive, overt negative and subtle negative human-horse interactions. Increased levels of education and greater experience with horses were associated with improved categorisation of certain human-horse interactions. More training or awareness is needed to recognise behavioural indicators of horse affect to guide appropriate human-horse activities that impact horse welfare.

IntroductionSmall fiber neuropathy (SFN) is a common cause of neuropathic pain in peripheral neuropathies. Good accessibility of diagnostics and treatment is necessary for an accurate diagnosis and treatment of SFN. Evidence is lacking on the quality performance of the diagnostic SFN service in the Netherlands. Our aim was to determine the patient satisfaction and -accessibility of the diagnostic SFN service, and to identify areas for improvement.MethodsIn a single-center, prospective, survey-based cohort study, 100 visiting patients were asked to fill in the SFN patient satisfaction questionnaire (SFN-PSQ), with 10 domains and 51 items. Cut-off point for improvement was defined as ≥ 25% dissatisfaction on an item. A chi-square test and linear regression analyses was used for significant differences and associations of patient satisfaction.ResultsFrom November 2020 to May 2021, 98 patients with SFN-related complaints filled in the online SFN-PSQ within 20 minutes. In 84% of the patients SFN was confirmed, average age was 55.1 (52.5-57.8) years and 67% was female. High satisfaction was seen in the domains 'Waiting List Period', Chest X-ray', 'Consultation with the Doctor or Nurse Practitioner (NP)', 'Separate Consultation with the Doctor or NP about Psychological Symptoms', and 'General' of the SFN service. Overall average patient satisfaction score was 8.7 (IQR 8-10) on a 1-to-10 rating scale. Main area for improvement was shortening the 8-week period for receiving the results of the diagnostic testing (p < 0.05). General health status was statistically significant associated with patient satisfaction (p < 0.05).ConclusionA good reflection of the high patient satisfaction and -accessibility of the SFN-service is shown, with important points for improvement. These results could help hospitals widely to optimize the logistic and diagnostic pathway of SFN analysis, benchmarking patient satisfaction results among the hospitals, and to improve the quality of care of comparable SFN services.

Horse obesity is a growing concern that can result in negative welfare. The role horse owners play in horse weight management is not well understood. This study aimed to: (1) explore the attitudes, beliefs, and perceptions of owners with overweight or obese horses regarding their horses’ weight; and (2) understand the motivators and barriers for owners to implement, improve and maintain weight management-related strategies. A semi-structured interview guide based on the Theoretical Domains Framework was developed. Qualitative interviews were conducted with 24 owners in Prince Edward Island, Canada whose horse(s) were previously classified as overweight or obese by a veterinarian. Interviews were analysed using template analysis, organising patterns in the data into a codebook and overarching themes. Owners believed horse weight management was important, however, their perceived complexity of the issue made the implementation of the weight management practices difficult. Owners held conflicting perceptions, viewing overweight horses as well cared for, yet recognised these horses were at increased risk for negative health outcomes. Ultimately, participants felt emotionally torn about compromising their horse’s mental well-being to address weight issues. Owners considered the practicality of weight-management strategies, the strategies’ effectiveness, and whether recommended strategies aligned with their beliefs regarding good horse care practices. Knowledge was embedded into owners’ understanding of horse weight, however, some highlighted that traditional knowledge dominates the equine industry hindering systemic industry change. Increased understanding of the effectiveness and impacts of weight management strategies on horses and fostering a society that recognises and accepts horses within a healthy weight range are warranted.

Summary: The quality of evidence leading to new oncological treatments suffers shortcomings, as has recently been addressed for drug approvals. In this 'Personal view', we evaluate the unintended effects of adopting stereotactic radiosurgery as the standard of care for patients with limited number of symptomatic brain metastases and favourable prognostic factors in international guidelines in view of the limitations in the evidence of efficacy and effectiveness, with special focus on countries with relatively limited resources.

Objective: Stimulated skin wrinkling test (SSW) has been launched as a non-invasive diagnostic procedure. However, no normative age dependent values have been reported that can be applied in clinical practice. The objectives of the study were to (1) collect age-dependent normative values according to the 5-point scale assessment for the SSW, to (2) determine reliability scores for the obtained norm values, and to (3) introduce a new digital method for SSW assessment, the Digit Wrinkle Scan© (DWS©) for detection of wrinkles in a more quantitative manner. Methods: Firstly, 82 healthy participants were included, divided in 5 age groups. The participants underwent SSW using lidocaine and prilocaine topical cream. Secondly, 35 healthy participants were included to test whether the DWS© could be a novel manner to assess the grade of wrinkling quantitatively. We determined the inter-observer reliability of both methods. Also, the intra-observer reliability was calculated for the DWS©. Results: We found a decrease in normative values over age. The inter-observer reliability of assessment by the 5-point scale method was moderate after SSW (Cohen’s k: 0.53). Results of the DWS© indicate that total wrinkle length per mm2 showed moderate to good agreement for the 4th and 5th digits after SSW, and a low agreement for the other digits. Conclusions: Age-dependent normative values were obtained according to the 5-point scale, but its clinical application is doubtful since we found a moderate inter-observer reliability. We introduced the DWS© as a possible new method in order to quantify the grade of wrinkling. Significance: We found unsatisfactory reliability scores, which hampers its usefulness for clinical practice.

Abstract Background Voltage‐gated sodium channels are essential for the generation and conduction of electrical impulses in excitable cells. Sodium channel Nav1.7, encoded by the SCN9A‐gene, has been of special interest in the last decades because missense gain‐of‐function mutations have been linked to a spectrum of neuropathic pain conditions, including inherited erythermalgia (IEM), paroxysmal extreme pain disorder (PEPD), and small fiber neuropathy (SFN). Methods In this case report, we present a 61‐year‐old woman who was referred to our tertiary referral center in a standard day care setting with suspicion of SFN. We performed additional investigations: skin biopsy to determine the intra‐epidermal nerve fiber density (IENFD), quantitative sensory testing (QST), and blood examination (including DNA analysis) for possible underlying conditions. Results The patient showed a clinical picture that fulfilled the criteria of IEM, PEPD, and SFN. DNA analysis revealed the heterozygous variant c.554G > A in the SCN9A‐gene (OMIM 603415). This variant has already been described in all three human pain conditions separately, but never in one patient having symptoms of all three conditions. Because its pathogenicity has never been functionally confirmed, the variant is classified as a variance of unknown significance (VUS)/risk factor. This suggests that another genetic and/or environmental substrate plays a role in the development of neuropathic conditions like described. Conclusion We have described this as the SCN9A‐pain triangle phenomenon. Treatment should focus on pain management, genetic counseling, and improving/maintaining quality of life by treating symptoms and, if indicated, starting a rehabilitation program.

Abstract The two main objectives of this analysis were to (i) characterize the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra®) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG pharmacokinetic (PK) parameters, including those from a previous population PK model, were used to predict individual IgG profile and exposure metrics. Treatment‐related changes in Inflammatory Neuropathy Cause and Treatment (INCAT) scores were best described by a maximum effect (Emax) model as a function of ΔIgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilization). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.

Background and Purpose: Chemotherapy‐induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient‐reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision‐making. Methods: Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE), Total Neuropathy Scale–clinical version (TNSc) items, and the disease‐specific quality of life ‐ Chemotherapy‐Induced Peripheral Neuropathy questionnaire (QLQ‐CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k‐means clustering and internally validated by discriminant functional analysis. Results: Both NCI‐CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ‐CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ‐CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ‐CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. Conclusions: Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well‐differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ‐CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation. [ABSTRACT FROM AUTHOR]

Abstract Background Outcome prediction in critically ill patients under invasive ventilation remains extremely challenging. The driving pressure (ΔP) and the mechanical power of ventilation (MP) are associated with patient-centered outcomes like mortality and duration of ventilation. The objective of this study was to assess the predictive validity for mortality of the ΔP and the MP at 24 h after start of invasive ventilation. Methods This is a post hoc analysis of an observational study in intensive care unit patients, restricted to critically ill patients receiving invasive ventilation for at least 24 h. The two exposures of interest were the modified ΔP and the MP at 24 h after start of invasive ventilation. The primary outcome was 90-day mortality; secondary outcomes were ICU and hospital mortality. The predictive validity was measured as incremental 90-day mortality beyond that predicted by the Acute Physiology, Age and Chronic Health Evaluation (APACHE) IV score and the Simplified Acute Physiology Score (SAPS) II. Results The analysis included 839 patients with a 90-day mortality of 42%. The median modified ΔP at 24 h was 15 [interquartile range 12 to 19] cm H2O; the median MP at 24 h was 206 [interquartile range 145 to 298] 10−3 J/min/kg predicted body weight (PBW). Both parameters were associated with 90-day mortality (odds ratio (OR) for 1 cm H2O increase in the modified ΔP, 1.05 [95% confidence interval (CI) 1.03 to 1.08]; P

Limited research has assessed the “human dimension” of horse care. The aims of this study were to (1) understand horse owner attitudes toward horse welfare when kept outdoors versus indoors and in groups versus individually, (2) compare horse owner attitudes toward horse welfare with the ways in which they house their horses, and (3) explore horse owner reasons for and challenges with their horses’ housing. Seventy-six horse owners in Prince Edward Island, Canada completed a questionnaire. Non-parametric tests and quantitative content analysis were used for data analysis. Consistent with the way horses were kept, most (82–96%) owners agreed that horses’ physical health, mental well-being, and natural living were better when kept outdoors and in groups. Fewer (64–68%) participants agreed that the horses’ standard of care was better when kept outdoors or in groups. Results show associations between owners whose attitudes suggest indoor and/or individual housing is better for horse welfare and keeping their horses indoors part-time and/or individually. Two overarching themes were developed from owners’ responses regarding their reasons and challenges related to the ways in which horses were housed: horse-centered and owner-centered care. The results indicate that horse owners’ choices about their horses’ housing correspond to beliefs about improved horse welfare.

Recent concerns regarding horse welfare during competition has highlighted the occurrence of overtightened nosebands on competition horses. Current rules are often vague—e.g., “nosebands may never be so tightly fixed as to harm the horse.” To investigate the need and acceptance prior to any rule changes Equestrian Canada (EC) launched a pilot noseband measuring project. Nineteen officiating stewards measured noseband fit using the ISES taper gauge (TG) at 32 equestrian events of various disciplines in 2021. Additionally, stakeholder surveys collected data from 1528 EC members and 27 stewards regarding opinions and perceptions on noseband use, fit, measurement and rules. Descriptive and qualitative statistics along with Pearson chi-squared examined relationships between specific variables. Of the 551 horses tested with the TG, 71% passed the 1.5 cm (two-fingers) measurement and an additional 19% passed the 1 cm (one-finger) measurement. Stewards unanimously agreed that overtightened nosebands present a welfare issue although 63% believed this to represent only a small subset of riders. While 60% of stewards believed the current rules were sufficient, 40% did not. Despite the fact that 84% of stewards believe there should be a standardized fit across disciplines, 52% felt the use of the TG should be at their discretion. The top three reasons riders indicated for using nosebands were discipline expectation (41%), requirement for competition (39%) or for control/safety (32%). Open comments referred to an option to not wear a noseband in competition. Professional riders believed overtightened nosebands were less of a welfare issue than amateur riders (76% vs. 88% respectively; p < 0.025) and correspondingly did not feel the TG was a fair method (44% vs. 68% respectively; p < 0.001). Slightly more than half of the respondents (51.5%) believed that measuring noseband fit on the frontal nasal plane was the appropriate location. To advance equestrian practice, more education is needed to inform stakeholders of the reasons for noseband measurements and appropriate fit.

Communication within a species is essential for access to resources, alerting to dangers, group facilitation and social bonding; human facial expressions are considered to be an important factor in one’s ability to communicate with others. Evidence has shown that dogs and horses are able to distinguish positive and negative facial expressions by observing photographs of humans, however there is currently no research on how facial expressions from a live human are perceived by horses. This study investigated how ponies distinguish facial expressions presented by live actors. Trained actors (n = 2), using the human Facial Action Coding System, displayed four facial expressions (anger, sadness, joy and neutral) individually to twenty ponies. Heart rate and behaviors of the ponies including first monocular eye look, eye look duration (right and left side bias) and latency to approach were observed. A generalized linear mixed model (GLIMMIX) using Sidak’s multiple comparisons of least squared means determined that when exposed to anger expressions ponies looked more often with their left eye first and when exposed to joy, looked more often with their right eye first (p = 0.011). The ponies spent more time looking at angry expressions (p = 0.0003) in comparison to other expressions. There was no variation in heart rate across expressions (p > 0.89). Regardless of human facial expression, ponies looked longer (p = 0.0035), took longer to approach (p = 0.0297) and displayed more oral behaviours (p < 0.0001) with one actor than the other indicating increased arousal or negative valence. Ponies with more experience as a lesson mount had lower heart rates (p < 0.0001) carried their head lower (p < 0.0001), kept their left ear on the actor (p < 0.03) and exhibited more oral behaviours (p < 0.0001) than ponies with less experience. This study demonstrates that ponies are able to distinguish facial expressions presented by a live human, but other factors also contribute to their responses to humans.

Introduction and Aim: Small fibre neuropathy (SFN) is a peripheral neuropathy, leading to neuropathic pain and autonomic dysfunction. An evidence‐based standardized patient diagnostic SFN service has been implemented in the Netherlands for improving patient‐centred SFN care. However, the quality of care of this diagnostic SFN service has never been assessed from a patient perspective. The aim of this study was to develop and validate an SFN‐Patient Satisfaction Questionnaire (SFN‐PSQ) to measure the quality performance of a standardized diagnostic SFN service. Methods: A descriptive qualitative study to create the SFN‐PSQ was performed using the (COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. For item generation and content development, domains and/or items from validated PSQs were selected. The content development and content validity were performed using a Delphi method with SFN expert caregivers with different backgrounds. By using the three‐step‐test method in individual cognitive interviews, the content validity by patients was finalized. Results: In one online Delphi panel round, the content of the first concept of the SFN‐PSQ was validated, which resulted in the second concept of the SFN‐PSQ. From July 2019 till March 2020, nine patients consented to participate in the individual cognitive interviews. The most significant changes of the new questionnaire were adding domains and items concerning the waiting list, the diagnostic services and consultation by the hospital psychiatrist. Also, a differentiation was made for both an inpatient and outpatient diagnostic SFN service. Furthermore, the clarity and intelligibility of the domains/items were improved, resulting in an increased comprehension of the SFN‐PSQ. Ultimately, the new developed SFN‐PSQ consisted of 10 domains and 51 items, suitable for measuring patient satisfaction of the neurological analysis in patients with SFN. Conclusion: Through item generation, expert opinions and interviews with patients, the SFN‐PSQ was developed and validated, and feasibility was confirmed. The structure of the questionnaire, based on the logistic and diagnostic SFN pathway, could be used as a model in other hospitals to improve the quality, continuity and access of SFN care and other chronic diseases taking into account potential cross‐cultural differences. Patient or Public Contribution: Caregivers were involved in the item generation and content development of the questionnaire. Patients were directly involved in testing the content validity and feasibility of the SFN‐PSQ. Clinical Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

[This corrects the article DOI: 10.1371/journal.pone.0238467.].

Resolving the genetic architecture of painful neuropathy will lead to better disease management strategies. We aimed to develop a reliable method to re-sequence multiple genes in a large cohort of painful neuropathy patients at low cost. In this study, we compared sensitivity, specificity, targeting efficiency, performance and cost effectiveness of Molecular Inversion Probes-Next generation sequencing (MIPs-NGS) and TruSeq® Custom Amplicon-Next generation sequencing (TSCA-NGS). Capture probes were designed to target nine sodium channel genes (SCN3A, SCN8A-SCN11A, and SCN1B-SCN4B). One hundred sixty-six patients with diabetic and idiopathic neuropathy were tested by both methods, 70 patients were validated by Sanger sequencing. Sensitivity, specificity and performance of both techniques were comparable, and in agreement with Sanger sequencing. The average targeted regions coverage for MIPs-NGS was 97.3% versus 93.9% for TSCA-NGS. MIPs-NGS has a more versatile assay design and is more flexible than TSCA-NGS. The cost of MIPs-NGS is >5 times cheaper than TSCA-NGS when 500 or more samples are tested. In conclusion, MIPs-NGS is a reliable, flexible, and relatively inexpensive method to detect genetic variations in a large cohort of patients. In our centers, MIPs-NGS is currently implemented as a routine diagnostic tool for screening of sodium channel genes in painful neuropathy patients.