Efficacy of a Psychologically-Informed Physiotherapy Intervention in Patients with Chronic Low Back Pain at High Risk of Poor Prognosis: A Pilot and Feasibility Randomized Controlled Trial.

Purpose: To determine the feasibility of a randomized controlled trial (RCT) testing the efficacy of psychologically-informed physiotherapy (PIPT), which includes usual physiotherapy (UP) interventions, compared with UP, and to explore the preliminary effectiveness of the interventions. Method: People with chronic low back pain at high risk of poor prognosis (using the STarT Back screening tool) were recruited and allocated to PIPT or UP. Effectiveness of recruitment strategies, adherence to intervention, risk of contamination, and specific challenges were assessed. Functional capacity, pain, quality of life, kinesiophobia, catastrophization, central sensitization, and self-efficacy were measured at baseline, 6-, 12- and 24-week follow-ups. Results: Forty participants were recruited mainly by diffusing through Laval University's email list, and 10 physiotherapists treated the participants recruited. The retention rate of participants at 24 weeks was 72.5%. Adherence to treatment by participants and physiotherapists was very good. The risk of contamination was low, and the specific challenges identified were modifiable. Significant improvement over time in all clinical variables of interest, except self-efficacy, was observed with no difference between groups. Conclusions: As most success criteria were met, conducting an RCT evaluating PIPT and PU is feasible with modifications. PIPT and UP appear to be similarly effective.

Objectif: déterminer la faisabilité d'une étude randomisée et contrôlée (ÉRC) évaluant l'efficacité de la physiothérapie fondée sur la psychologie (PTFP), qui inclut les interventions de physiothérapie conventionelle (PC), par rapport à la PC, et explorer l'efficacité préliminaire des interventions. Méthodologie: les chercheurs ont recruté des personnes qui souffrent de douleurs lombaires chroniques, ayant une probabilité élevée de mauvais pronostic (au moyen de l'outil de dépistage STarT Back) et les ont réparties entre la PTFP et la PC. Ils ont évalué l'efficacité des stratégies de recrutement, l'adhésion à l'intervention, le risque de contamination et les difficultés particulières. Ils ont également mesuré la capacité fonctionnelle, la douleur, la qualité de vie, la kinésiophobie, la catastrophisation, la sensibilisation centrale et l'autoefficacité en début d'étude ainsi que lors des suivis à six, 12 et 24 semaines. Résultats: les chercheurs ont recruté 40 participants, principalement en diffusant le projet par courriel à la communauté de l'Université Laval, et dix physiothérapeutes les ont traités. Le taux de rétention des participants était de 72,5 % à 24 semaines. Les participants et les physiothérapeutes ont démontré une très bonne adhésion au traitement. Le risque de contamination était faible, et les difficultés particulières constatées pouvaient être modifiées. Les chercheurs ont observé une amélioration considérable au fil du temps pour toutes les variables cliniques d'intérêt, sauf l'autoefficacité, sans différence entre les groupes. Conclusions: puisque la plupart des critères de succès étaient respectés, il est faisable de réaliser une ÉRC pour évaluer la PTFP et la PU, sous réserve de modifications. La PTFP et la PC semblent avoir une efficacité similaire.

Assessing the Feasibility and Preliminary Effects of a Web-Based Self-Management Program for Chronic Noncancer Pain: Mixed Methods Study.

BACKGROUND: In Canada, adults with chronic noncancer pain face a persistent insufficiency of publicly funded resources, with the gold standard multidisciplinary pain treatment facilities unable to meet the high clinical demand. Web-based self-management programs cost-effectively increase access to pain management and can improve several aspects of physical and emotional functioning. Aiming to meet the demand for accessible, fully automated resources for individuals with chronic noncancer pain, we developed a French web- and evidence-based self-management program, Agir pour moi (APM). This program includes pain education and strategies to reduce stress, practice mindfulness, apply pacing, engage in physical activity, identify and manage thinking traps, sleep better, adapt diet, and sustain behavior change. OBJECTIVE: This study aims to assess the APM self-management program's feasibility, acceptability, and preliminary effects in adults awaiting specialized services from a center of expertise in chronic pain management. METHODS: We conducted a mixed methods study with an explanatory sequential design, including a web-based 1-arm trial and qualitative semistructured interviews. We present the results from both phases through integrative tables called joint displays. RESULTS: Response rates were 70% (44/63) at postintervention and 56% (35/63) at 3-month follow-up among the 63 consenting participants who provided self-assessed information at baseline. In total, 46% (29/63) of the participants completed the program. We interviewed 24% (15/63) of the participants. The interview's first theme revolved around the overall acceptance, user-friendliness, and engaging nature of the program. The second theme emphasized the differentiation between microlevel and macrolevel engagements. The third theme delved into the diverse effects observed, potentially influenced by the macrolevel engagements. Participants highlighted the features that impacted their self-efficacy and the adoption of self-management strategies. We observed indications of improvement in self-efficacy, pain intensity, pain interference, depression, and catastrophizing. Interviewees described these and various other effects as potentially influenced by macrolevel engagement through behavioral change. CONCLUSIONS: These findings provided preliminary evidence that the APM self-management program and research methods are feasible. However, some participants expressed the need for at least phone reminders and minimal support from a professional available to answer questions over the first few weeks of the program to engage. Recruitment strategies of a future randomized controlled trial should focus on attracting a broader representation of individuals with chronic pain in terms of gender and ethnicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT05319652; https://clinicaltrials.gov/study/NCT05319652.

Codéveloppement d'un programme d'autogestion de la douleur chronique en ligne: un projet de recherche basé sur la conception et axé sur l'engagement des patients.

Introduction: L'autogestion est une approche privilégiée pour gérer la douleur chronique. Jusqu'à tout récemment, aucun programme d'autogestion en français, en ligne et codéveloppé avec des patients partenaires atteints de douleur n'était accessible gratuitement. Pourtant, la littérature pointe vers l'inclusion de ces partenaires aux équipes de développement, permettant une meilleure considération de leurs besoins et préférences. Objectif: Cette étude visait le codéveloppement d'un tel programme d'autogestion de la douleur chronique, réalisable sans le soutien d'un professionnel de la santé. Méthode: La démarche s'inscrit dans la recherche basée sur la conception et est réalisée dans le cadre d'un partenariat étroit entre chercheurs, partenaires atteints de douleur chronique, professionnels de la santé, étudiants en médecine et graphiste. Nous avons principalement basé le contenu du programme sur une revue systématique de la littérature, des guides de pratique, l'expérience clinique et l'expertise expérientielle des patients. Le codéveloppement a été réalisé en plusieurs cycles itératifs, dont trois mises à l'essai. Résultats: Grâce à l'apport des parties prenantes, nous avons codéveloppé le programme « Agir pour moi ¼. L'identité du programme, son contenu, sa structure et les modalités d'apprentissage proposées soutiennent pas à pas le développement de compétences et l'application de stratégies d'autogestion par soi-même. Ces démarches sont favorisées par l'intégration de témoignages positifs, d'un contenu empreint de bienveillance et d'une utilisation accrue de techniques de changement de comportement. Conclusion: L'approche de recherche choisie a permis de créer un environnement d'apprentissage jugé bienveillant, susceptible de soutenir le sentiment d'auto-efficacité et la motivation.

The Medication Quantification Scale 4.0: An Updated Index Based on Prescribers' Perceptions of the Risk Associated With Chronic Pain Medications.

To quantify risks associated with drug utilization in the real world for the treatment of chronic pain (CP), an index called the Medication Quantification Scale (MQS) was developed in 1992 in the United States and last updated in 2003. This study aimed to update, adapt to the contemporary Canadian context, and validate a revised version of the MQS (the MQS-4.0). Step 1: An expert committee adapted the MQS to the Canadian clinical practice context. Step 2: An update of risk weights given to medication subclasses was achieved using a prescriber survey (weights were derived from median 0-10 scores given to each subclass). Step 3: Construct validity of the MQS-4.0 was assessed after applying risk weights to the medication use profile of persons living with CP covered by public drug insurance plan. Thirty-six medication subclasses were included in the MQS-4.0. A total of 207 prescribers (physicians, pharmacists, and nurse practitioners) participated in the perception survey; 10.63% identified as pain specialists. When risk weights were applied to prescription claims (n = 9,122), the MQS-4.0 score was associated (P < .05) with the MQS-III score and variables associated with polypharmacy (eg, Charlson Comorbidity Index, number of prescribers or health care visits). This study provides an updated index intended for adult populations based on prescribers' perceptions of the risk associated with CP medications that can be useful for clinical practice and research among persons living with CP in Canada. It will, however, be relevant to verify whether similar risk weights are obtained in future pain specialist surveys. PERSPECTIVE: The MQS-4.0 is an update of the MQS used for quantifying the risk associated with the use of analgesics/coanalgesics. Adequate psychometrics properties were found.

Pain Medications Used by Persons Living With Fibromyalgia: A Comparison Between the Profile of a Quebec Sample and Clinical Practice Guidelines.

Background: Pharmacological management of fibromyalgia is complex. Chronic pain management is characterized by off-label prescribing and use, multimorbidity, and polypharmacy. Aims: This study aimed to describe pain medications use and perceived risk among people living with fibromyalgia and compare this use to evidence-based recommendations. Methods: Directive telephone interviews were conducted with 63 individuals self-reporting a diagnosis of fibromyalgia (Quebec, Canada). The questionnaire addressed specific questions about their pain and pharmacological treatments currently used for pain management (prescribed and over-the-counter). Collected data were compared to the Canadian Fibromyalgia Clinical Practice Guidelines and to evidence reports published by recognized organizations. Results: Despite a lack of robust scientific evidence to support opioids use to manage pain in fibromyalgia, 33% of our sample reported using them. Nonsteroidal anti-inflammatory drugs were used by 54.0% of participants, although this medication is not recommended due to lack of efficacy. Tramadol, which is recommended, was used by 23.8% of participants. Among the medications strongly recommended, anticonvulsants were used by 36.5%, serotonin norepinephrine reuptake inhibitor antidepressants by 55.6%, and tricyclic antidepressants by 22.2%. Cannabinoids (17.5%) and medical cannabis (34.9%) use were also reported. For all of these medication subclasses, no differences were found between participants not reporting (n = 35) or reporting (n = 28) more than one pain diagnosis (P < 0.05). Medication subclasses considered most at risk of adverse effects by participants were the least used. Conclusions: Results reveal discordance between evidence-based recommendations and medications use, which highlights the complexity of pharmacological treatment of fibromyalgia.

Contexte: La prise en charge pharmacologique de la fibromyalgie est complexe. La prise en charge de la douleur chronique est caractérisée par la prescription et l'utilisation non conforme de médicaments, la multimorbidité et la polypharmacothérapie.Objectifs: Cette étude visait à décrire l'utilisation de médicaments contre la douleur et le risque perçu chez les personnes atteintes de fibromyalgie, et à comparer cette utilisation aux recommandations fondées sur des données probantes.Méthodes: Des entretiens téléphoniques directifs ont été menés auprès de 63 personnes ayant déclaré avoir reçu un diagnostic de fibromyalgie (Québec, Canada). Le questionnaire abordait des questions précises sur leur douleur et les traitements pharmacologiques actuellement utilisés pour la prise en charge de leur douleur (prescrits et vendus sans ordonnance). Les données recueillies ont été comparées aux Lignes directrices canadiennes sur la fibromyalgie et aux rapports de données probantes publiés par des organisations reconnues.Résultats: Malgré l'absence de données probantes robustes à l'appui de l'utilisation des opioïdes pour la prise en charge la douleur chez les personnes atteintes de fibromyalgie, 33 % de notre échantillon a déclaré les utiliser. Les anti-inflammatoires nonstéroïdiens étaient pour leur part utilisés par 54,0 % des participants, bien que ce médicament ne soit pas recommandé en raison d'un manque d'efficacité. Le tramadol, recommandé, était utilisé par 23,8 % des participants. Parmi les médicaments fortement recommandés, les anticonvulsivants étaient utilisés par 36,5 % desparticipants, les antidépresseurs inhibiteurs de la recapture de la sérotonine et de la noradrénaline par 55,6 % des participants, et les antidépresseurs tricycliques par 22,2 % d'entre eux. La consommation de cannabinoïdes (17,5 %) et de cannabis médical (34,9 %) ont également été signalées. Pour toutes ces sous-classes de médicaments, aucune différence n'a été trouvée entre les participants ne signalant pas (n = 35) ou signalant (n = 28) plus d'un diagnostic de douleur (P < 0,05). Les sous-classes de médicaments considérées par les participants comme les plus à risque d'effets indésirables étaient les moins utilisées.Conclusions: Les résultats révèlent une discordance entre les recommandations fondées sur des données probantes et l'utilisation de médicaments, ce qui met en évidence la complexité du traitement pharmacologique de la fibromyalgie.

A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver.

BACKGROUND: Hepatitis E virus (HEV) is a zoonotic virus transmitted by pig meat and responsible for chronic hepatitis E in immunocompromised patients. It has proved challenging to reproduce this disease in its natural reservoir. We therefore aimed to develop a pig model of chronic hepatitis E to improve the characterization of this disease. METHODS: Ten pigs were treated with a tacrolimus-based regimen and intravenously inoculated with HEV. Tacrolimus trough concentration, HEV viremia, viral diversity, innate immune responses, liver histology, clinical disease and biochemical markers were monitored for 11 weeks post-infection (p.i.). RESULTS: HEV viremia persisted for 11 weeks p.i. HEV RNA was detected in the liver, small intestine, and colon at necropsy. Histological analysis revealed liver inflammation and fibrosis. Several mutations selected in the HEV genome were associated with compartmentalization in the feces and intestinal tissues, consistent with the hypothesis of extrahepatic replication in the digestive tract. Antiviral responses were characterized by a downregulation of IFN pathways in the liver, despite an upregulation of RIG-I and ISGs in the blood and liver. CONCLUSIONS: We developed a pig model of chronic hepatitis E that reproduced the major hallmarks of this disease. This model revealed a compartmentalization of HEV genomes in the digestive tract and a downregulation of innate immune responses in the liver. These original features highlight the relevance of our model for studies of the pathogenesis of chronic hepatitis E and for validating future treatments.

Behavioral and Electrocortical Response to a Sensorimotor Conflict in Individuals with Fibromyalgia.

People with fibromyalgia have been shown to experience more somatosensory disturbances than pain-free controls during sensorimotor conflicts (i.e., incongruence between visual and somatosensory feedback). Sensorimotor conflicts are known to disturb the integration of sensory information. This study aimed to assess the cerebral response and motor performance during a sensorimotor conflict in people with fibromyalgia. Twenty participants with fibromyalgia and twenty-three pain-free controls performed a drawing task including visual feedback that was either congruent with actual movement (and thus with somatosensory information) or incongruent with actual movement (i.e., conflict). Motor performance was measured according to tracing error, and electrocortical activity was recorded using electroencephalography. Motor performance was degraded during conflict for all participants but did not differ between groups. Time-frequency analysis showed that the conflict was associated with an increase in theta power (4-8 Hz) at conflict onset over the left posterior parietal cortex in participants with fibromyalgia but not in controls. This increase in theta suggests a stronger detection of conflict in participants with fibromyalgia, which was not accompanied by differences in motor performance in comparison to controls. This points to dissociation in individuals with fibromyalgia between an altered perception of action and a seemingly unaltered control of action.

"It feels like an endless fight": a qualitative study exploring healthcare utilization of persons with rheumatic conditions waiting for pain clinic admission.

BACKGROUND: Individuals living with a rheumatic pain condition can face delays in accessing pain clinics, which prevents them from receiving timely treatment. Little is known regarding their specific healthcare utilization in order to alleviate pain while waiting to obtain services in pain clinics. Hence, the aim of this study was to explore the perceptions and experiences of persons living with rheumatic conditions regarding healthcare utilization while waiting to access a pain clinic. METHODS: In this qualitative descriptive study, semi-structured interviews were conducted with adults living with a painful rheumatic condition that reported either being waiting for admission in a pain clinic, having been referred but then denied pain clinic services, or having received services during the previous six months, in the province of Quebec, Canada. The interviews were transcribed verbatim, and an inductive thematic analysis was performed. RESULTS: Twenty-six individuals were interviewed (22 women and 4 men; mean age 54 ± 10 years). Three themes were identified: 1) lacking guidance in identifying solutions to their complex and multidimensional needs, 2) struggling to obtain and maintain services due to systemic access barriers, and 3) displaying resilience through a search for accessible and sustainable self-management strategies. CONCLUSIONS: The current approaches and structures of health services fail to adequately answer the service needs of individuals experiencing painful rheumatic conditions. Important shifts are required in pain education, in increasing access to multidisciplinary approaches at the primary care level and in breaking down barriers individuals with chronic pain face to receive appropriate and timely care.

Development of a Mixed Hypnosis and Music Intervention Program for the Management of Pain, Anxiety, and Wellbeing in End-of-Life Palliative Care.

Background: The palliative care people present needs that can be partially met by complementary intervention. Approaches based on the use of hypnosis and music are increasingly being studied and have shown potential benefits on pain, anxiety, and wellbeing for many populations including those in palliative care. Objective: This study aims to present the initial process of creating and refining a hypnosis and music intervention program intended for persons in palliative care, with a panel of experts of diverse relevant backgrounds. It also aims to evaluate its feasibility, preliminary acceptability, and content. Methods: To achieve the objectives, we followed ORBIT recommendations for the development and redesign of behavioral interventions (phase I a-b). Based on a meta-analysis, reference interventions were identified and then adapted to the target population. Twenty-two experts from different backgrounds were consulted to obtain their evaluation on the acceptability, feasibility, and content of the interventions. Result: The various components of the program were deemed appropriate or very appropriate by over 80% of the experts. However, possible risks were raised related to some uncertainty about the reactions of individuals to the intervention. Several experts (32%) indicated potential adverse effects consisting of negative emotional experiences during the sessions. Modifications were proposed specifically to reduce or mitigate this risk. Over 90% of the experts considered that the revised program provides a safer and more appropriate intervention for palliative care persons. Conclusion: A mixed intervention program with hypnosis and music has been developed and attained a high level of consensus by the experts. The proposed intervention is ready to be assessed for clinical efficacy in a pilot study (ORBIT Phase II).

In Vivo Tracking of Bacterial Colonization in Different Murine Models Using Bioluminescence: The Example of Salmonella.

Applications of bioluminescence for the in vivo study of pathogenic microorganisms are numerous, ranging from the quantification of virulence gene expression to measuring the effect of antimicrobial molecules on the colonization of tissues and organs by the pathogen. Most studies are performed in mice, but recent works demonstrate that this technique is applicable to larger animals like fish, guinea pigs, ferrets, and chickens. Here, we describe the construction and the utilization of a constitutively luminescent strain of Salmonella Typhimurium to monitor in vivo and ex vivo the colonization of mice in the gastroenteritis, typhoid fever, and asymptomatic carriage models of Salmonella infection.

Hypnosis and music interventions for anxiety, pain, sleep and well-being in palliative care: systematic review and meta-analysis.

BACKGROUND: Maintaining quality of life is a primary goal of palliative care (PC). Complementary interventions can help meet the needs of patients at the end of life. OBJECTIVES: This meta-analysis aims to (1) evaluate the feasibility, acceptability and fidelity of music and hypnosis interventions designed for patients in PC and (2) evaluate the impact of these interventions on pain, anxiety, sleep and well-being. METHODS: Relevant studies were sourced from major databases. We selected both randomised controlled trials (RCTs) and studies relying on pre-post design with details of the intervention(s). RESULTS: Four RCT and seven non-randomised pre-post studies met the inclusion criteria. Overall, the feasibility and acceptability of the interventions reached an adequate level of satisfaction. However, only three studies reported using a written protocol. The meta-analysis of RCT indicated a significant decrease in pain with an effect size of -0.42, p=0.003. The small number of RCT studies did not allow us to quantify the effects for other variables. Analyses of data from pre-post designs indicated a favourable outcome for pain, anxiety, sleep and well-being. CONCLUSION: Despite the limited number of studies included in our meta-analysis, hypnosis and music intervention in the context of PC shows promising results in terms of feasibility and acceptability, as well as improvements on pain, anxiety, sleep and well-being. The available studies are insufficient to compare the efficacy across interventions and assess the potential benefits of their combinations. These results underscore the importance of further research on well-described complementary interventions relying on hypnosis and music. PROSPERO REGISTRATION NUMBER: CRD-42021236610.

Strategies to reduce waiting times in outpatient rehabilitation services for adults with physical disabilities: A systematic literature review.

OBJECTIVE: Identifying effective strategies to reduce waiting times is a crucial issue in many areas of health services. Long waiting times for rehabilitation services have been associated with numerous adverse effects in people with disabilities. The main objective of this study was to conduct a systematic literature review to assess the effectiveness of service redesign strategies to reduce waiting times in outpatient rehabilitation services for adults with physical disabilities. METHODS: We conducted a systematic review, searching three databases (MEDLINE, CINAHL and EMBASE) from their inception until May 2021. We identified studies with comparative data evaluating the effect of rehabilitation services redesign strategies on reducing waiting times. The Mixed Methods Appraisal Tool was used to assess the methodological quality of the studies. A narrative synthesis was conducted. RESULTS: Nineteen articles including various settings and populations met the selection criteria. They covered physiotherapy (n = 11), occupational therapy (n = 2), prosthetics (n = 1), exercise physiology (n = 1) and multidisciplinary (n = 4) services. The methodological quality varied (n = 10 high quality, n = 6 medium, n = 3 low); common flaws being missing information on the pre-redesign setting and characteristics of the populations. Seven articles assessed access processes or referral management strategies (e.g. self-referral), four focused on extending/modifying the roles of service providers (e.g. to triage) and eight changed the model of care delivery (e.g. mode of intervention). The different redesign strategies had positive effects on waiting times in outpatient rehabilitation services. CONCLUSIONS: This review highlights the positive effects of many service redesign strategies. These findings suggest that there are several effective strategies to choose from to reduce waiting times and help better respond to the needs of persons experiencing physical disabilities.

Enhanced Pathogenesis Caused by Influenza D Virus and Mycoplasma bovis Coinfection in Calves: a Disease Severity Linked with Overexpression of IFN-γ as a Key Player of the Enhanced Innate Immune Response in Lungs.

Bovine respiratory disease (BRD) is a major disease of young cattle whose etiology lies in complex interactions between pathogens and environmental and host factors. Despite a high frequency of codetection of respiratory pathogens in BRD, data on the molecular mechanisms and pathogenesis associated with viral and bacterial interactions are still limited. In this study, we investigated the effects of a coinfection with influenza D virus (IDV) and Mycoplasma bovis in cattle. Naive calves were infected by aerosol with a French IDV strain and an M. bovis strain. The combined infection shortened the incubation period, worsened the disease, and led to more severe macroscopic and microscopic lesions compared to these parameters in calves infected with only one pathogen. In addition, IDV promoted colonization of the lower respiratory tract (LRT) by M. bovis and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The gamma interferon (IFN-γ) gene was shown to be the gene most statistically overexpressed after coinfection at 2 days postinfection (dpi) and at least until 7 dpi, which correlated with the high level of lymphocytes in the LRT. Downregulation of the PACE4 and TMPRSS2 endoprotease genes was also highlighted, being a possible reason for the faster clearance of IDV in the lungs of coinfected animals. Taken together, our coinfection model with two respiratory pathogens that when present alone induce moderate clinical signs of disease was shown to increase the severity of the disease in young cattle and a strong transcriptomic innate immune response in the LRT, especially for IFN-γ. IMPORTANCE Bovine respiratory disease (BRD) is among the most prevalent diseases in young cattle. BRD is due to complex interactions between viruses and/or bacteria, most of which have a moderate individual pathogenicity. In this study, we showed that coinfection with influenza D virus (IDV) and Mycoplasma bovis increased the severity of the respiratory disease in calves in comparison with IDV or M. bovis infection. IDV promoted M. bovis colonization of the lower respiratory tract and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The IFN-γ gene in particular was highly overexpressed after coinfection, correlated with the disease severity, immune response, and white cell recruitment in the lungs. In conclusion, we showed that IDV facilitates coinfections within the BRD complex by modulating the local innate immune response, providing new insights into the mechanisms involved in severe respiratory diseases.

Establishment of a Newborn Lamb Gut-Loop Model to Evaluate New Methods of Enteric Disease Control and Reduce Experimental Animal Use.

Enteric infectious diseases are not all well controlled, which leads to animal suffering and sometimes death in the most severe cases, in addition to economic losses for farmers. Typical symptoms of enteric infections include watery diarrhea, stomach cramps or pain, dehydration, nausea, vomiting, fever and weight loss. Evaluation of new control methods against enteric infections requires the use of many animals. We aimed to develop a new method for an initial in vivo screen of promising compounds against neonatal diseases such as cryptosporidiosis while limiting experimental animal use. We therefore adapted an in vivo method of multiple consecutive but independent intestinal loops to newborn lambs delivered by cesarean section, in which endotoxin responsiveness is retained. This new method allowed for the screening of natural yeast fractions for their ability to stimulate immune responses and to limit early Cryptosporidium parvum development. This model may also be used to investigate host-pathogen interactions and immune responses in a neonatal controlled environment.

Transmission of Bluetongue Virus Serotype 8 by Artificial Insemination with Frozen-Thawed Semen from Naturally Infected Bulls.

Transmission of bluetongue (BT) virus serotype 8 (BTV-8) via artificial insemination of contaminated frozen semen from naturally infected bulls was investigated in two independent experiments. Healthy, BT negative heifers were hormonally synchronized and artificially inseminated at oestrus. In total, six groups of three heifers received semen from four batches derived from three bulls naturally infected with BTV-8. Each experiment included one control heifer that was not inseminated and that remained BT negative throughout. BTV viraemia and seroconversion were determined in 8 out of 18 inseminated heifers, and BTV was isolated from five of these animals. These eight heifers only displayed mild clinical signs of BT, if any at all, but six of them experienced pregnancy loss between weeks four and eight of gestation, and five of them became BT PCR and antibody positive. The other two infected heifers gave birth at term to two healthy and BT negative calves. The BT viral load varied among the semen batches used and this had a significant impact on the infection rate, the time of onset of viraemia post artificial insemination, and the gestational stage at which pregnancy loss occurred. These results, which confirm unusual features of BTV-8 infection, should not be extrapolated to infection with other BTV strains without thorough evaluation. This study also adds weight to the hypothesis that the re-emergence of BTV-8 in France in 2015 may be attributable to the use of contaminated bovine semen.

Single-Shot Vaccines against Bovine Respiratory Syncytial Virus (BRSV): Comparative Evaluation of Long-Term Protection after Immunization in the Presence of BRSV-Specific Maternal Antibodies.

The induction of long-lasting clinical and virological protection is needed for a successful vaccination program against the bovine respiratory syncytial virus (BRSV). In this study, calves with BRSV-specific maternally derived antibodies were vaccinated once, either with (i) a BRSV pre-fusion protein (PreF) and MontanideTM ISA61 VG (ISA61, n = 6), (ii) BRSV lacking the SH gene (ΔSHrBRSV, n = 6), (iii) a commercial vaccine (CV, n = 6), or were injected with ISA61 alone (n = 6). All calves were challenged with BRSV 92 days later and were euthanized 13 days post-infection. Based on clinical, pathological, and proteomic data, all vaccines appeared safe. Compared to the controls, PreF induced the most significant clinical and virological protection post-challenge, followed by ΔSHrBRSV and CV, whereas the protection of PreF-vaccinated calves was correlated with BRSV-specific serum immunoglobulin (Ig)G antibody responses 84 days post-vaccination, and the IgG antibody titers of ΔSHrBRSV- and CV-vaccinated calves did not differ from the controls on this day. Nevertheless, strong anamnestic BRSV- and PreF-specific IgG responses occurred in calves vaccinated with either of the vaccines, following a BRSV challenge. In conclusion, PreF and ΔSHrBRSV are two efficient one-shot candidate vaccines. By inducing a protection for at least three months, they could potentially improve the control of BRSV in calves.

The burden of waiting to access pain clinic services: perceptions and experiences of patients with rheumatic conditions.

BACKGROUND: Extensive waiting times before receiving services is a major barrier to adequate pain management. Waiting times may have a detrimental impact on patients' conditions and quality of life. However, there remains a lack of knowledge on the actual experiences of patients waiting to receive services, especially for those with rheumatic conditions. The present study aimed to gain an in-depth understanding of perceptions and experiences of patients with rheumatic conditions regarding access to pain clinic services. The secondary objective was to identify possible solutions to improve this access according to patients' perspectives. METHODS: This qualitative study based on semi-structured interviews was conducted with adults with rheumatic conditions waiting to access pain clinics in the province of Quebec, Canada. Interviews were transcribed verbatim and analyzed using thematic content analysis. RESULTS: Twenty-six participants were interviewed (22 women and 4 men; mean age 54 ± 10 years). Four main themes were identified: 1) the perception that waiting time is unacceptably long; 2) how the lack of information affects patients' experiences of waiting; 3) patients' various expectations towards the pain clinic, from high hopes to disillusionment and 4) carrying an emotional, physical and financial burden resulting from the wait. Participants reported several solutions to improve the experience of waiting, including providing information to patients, increasing resources, improving prioritization processes and care coordination, and providing alternative interventions to patients during the wait. CONCLUSIONS: For patients with rheumatic conditions, access to pain clinic services is challenging due to extensive waiting times. The burden it imposes on them adds to the existing challenge of living with a chronic rheumatic condition. The solutions identified by participants could serve as building blocks to develop and implement measures to improve patients' experience of accessing pain-related services.

Tactile Detection in Fibromyalgia: A Systematic Review and a Meta-Analysis.

Fibromyalgia is a chronic pain syndrome characterized by sensorimotor deficits and distortions of body representation, that could both be caused by alterations in sensory processing. Several studies suggest a hypersensitivity to various sensory stimulations in fibromyalgia but results on detection of both noxious and non-noxious tactile stimulation, which are particularly relevant for body representation and motor control, remain conflicting. Therefore, the aim of this study is to systematically review and quantify the detection thresholds to noxious and non-noxious tactile stimuli in individuals with fibromyalgia compared to pain-free controls. A systematic review and a meta-analysis were performed in the MEDLINE, EMBASE, CINAHL, Cochrane, PsycInfo and Web of Science databases using keywords related to fibromyalgia, tactile pain detection threshold, tactile detection threshold and quantitative sensory testing. Nineteen studies were included in the review, with 12 in the meta-analysis. Despite the heterogeneity of the results, the data from both the review and from the meta-analysis suggest a trend toward hyperalgesia and no difference of sensitivity to non-noxious tactile stimuli in participants with fibromyalgia compared to healthy controls. This contradicts the hypothesis of a general increase in responsiveness of the central nervous system to noxious and non-noxious stimulations in fibromyalgia. This study shows no alteration of the sensitivity to non-noxious tactile stimulation in fibromyalgia, suggesting that an altered unimodal processing is not sufficient to explain symptoms such as sensorimotor impairments and body representation distortions. Future research should investigate whether alterations in multisensory integration could contribute to these symptoms.

The association between waiting time and multidisciplinary pain treatment outcomes in patients with rheumatic conditions.

BACKGROUND: Access to multidisciplinary pain treatment facilities (MPTF) is limited by extensive waiting time in many countries. However, there is a lack of knowledge about the impact of waiting time on clinical outcomes, particularly for patients with rheumatic conditions. This study examined the association between waiting time for MPTF and clinical outcomes in patients with rheumatic conditions. METHODS: Data were extracted from the Quebec Pain Registry, a large database of patients who received services in MPTF. The associations between waiting time (classified as < 2 months, 2-6 months and >  6 months) and change in pain interference, pain intensity and health-related quality of life, from the initial visit at the MPTF to the 6-month follow-up, were tested using generalized estimating equations. RESULTS: A total of 3230 patients with rheumatic conditions (mean age: 55.8 ± 14.0 years; 66% were women) were included in the analysis. Small significant differences in improvement between waiting time groups were revealed, with patients waiting less than 2 months having a larger improvement in all clinical outcomes compared to patients who waited 2-6 months or over 6 months before their initial visit (adjusted time X group effect p ≤ 0.001). Only patients waiting less than 2 months reached a clinically important improvement in pain interference (1.12/10), pain intensity (1.3/10) and physical and mental quality of life (3.9 and 3.7/100). CONCLUSIONS: Longer delays experienced by patients before receiving services in MPTF were associated with statistically significant smaller improvements in pain interference, pain intensity and health-related quality of life; these differences were, however, not clinically significant. Based on these results, we advise that strategies are developed not only to reduce waiting times and mitigate their impacts on patients with rheumatic conditions, but also to improve treatment effectiveness in MPTF.

Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain: A Systematic Review and Meta-analysis.

BACKGROUND: Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the analgesic effect and adverse events with the perioperative use of gabapentinoids in adult patients. METHODS: Randomized controlled trials studying the use of gabapentinoids in adult patients undergoing surgery were included. The primary outcome was the intensity of postoperative acute pain. Secondary outcomes included the intensity of postoperative subacute pain, incidence of postoperative chronic pain, cumulative opioid use, persistent opioid use, lengths of stay, and adverse events. The clinical significance of the summary estimates was assessed based on established thresholds for minimally important differences. RESULTS: In total, 281 trials (N = 24,682 participants) were included in this meta-analysis. Compared with controls, gabapentinoids were associated with a lower postoperative pain intensity (100-point scale) at 6 h (mean difference, -10; 95% CI, -12 to -9), 12 h (mean difference, -9; 95% CI, -10 to -7), 24 h (mean difference, -7; 95% CI, -8 to -6), and 48 h (mean difference, -3; 95% CI, -5 to -1). This effect was not clinically significant ranging below the minimally important difference (10 points out of 100) for each time point. These results were consistent regardless of the type of drug (gabapentin or pregabalin). No effect was observed on pain intensity at 72 h, subacute and chronic pain. The use of gabapentinoids was associated with a lower risk of postoperative nausea and vomiting but with more dizziness and visual disturbance. CONCLUSIONS: No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients.