Which advanced treatment should be used following the failure of a first-line anti-TNF in patients with rheumatoid arthritis? 15 years of evidence from the Quebec registry RHUMADATA.

BACKGROUND: Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe rheumatoid arthritis (RA). Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first Tumor Necrosis Factor inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA. METHODS: Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up, or November 25, 2022. Kaplan-Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted, and propensity score-adjusted imputed data analyses were produced. RESULTS: 611 patients (320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)) were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44-0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18-0.84) had better retention than TNFi after adjusting for patient characteristics. CONCLUSION: Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy.

Intravenous dexmedetomidine for the treatment of shivering during Cesarean delivery under neuraxial anesthesia: a randomized-controlled trial.

PURPOSE: About 55% of patients undergoing a Cesarean delivery under spinal or epidural anesthesia will experience shivering, which may interfere with the monitoring of vital signs. Recent studies have shown that dexmedetomidine could potentially help to alleviate shivering associated with anesthesia. We investigated whether dexmedetomidine, an alpha 2-adrenergic agonist, reduces the duration of shivering associated with neuraxial anesthesia during Cesarean delivery. METHODS: Eighty parturients undergoing Cesarean delivery under neuraxial anesthesia and experiencing shivering were enlisted in this prospective, randomized, double-blind trial. After childbirth, the intervention group (n = 40) received a single intravenous bolus of dexmedetomidine (30 µg) while the control group (n = 40) received saline. Randomization and allocation were based on a computer-generated list. The primary outcome measure was the time required for an observable decrease in shivering after the intervention. RESULTS: One hundred fifty-five patients were recruited, 80 of whom presented with shivering and were randomized. Our study showed that dexmedetomidine reduced the mean (standard deviation) duration of shivering after a single intravenous bolus to 2.6 (2.1) min after dexmedetomidine from 17.9 (12.6) min after saline (difference in means, -15.3 min; 95% confidence interval [CI], -11.2 to -19.4). The effect of dexmedetomidine persisted 15 min after the bolus was administered, as shivering had completely stopped in 90% of the patients in the intervention group vs 22.5% in the control group (relative risk, 4.0; 95% CI, 2.2 to 7.2). No adverse effects, including bradycardia, were observed. CONCLUSION: A single intravenous bolus of dexmedetomidine decreased the duration of shivering for up to 15 min during Cesarean delivery under neuraxial anesthesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02384343); registered 10 March, 2015.

RéSUMé: OBJECTIF: Environ 55 % des patientes subissant un accouchement par césarienne sous anesthésie rachidienne ou épidurale vont manifester des frissons, lesquels peuvent interférer avec la mesure des signes vitaux. Des études récentes ont démontré que la dexmédétomidine a le potentiel de réduire les frissons associés à l'anesthésie. Nous avons cherché à démontrer si la dexmédétomidine, un agoniste des récepteurs alpha-2-adrénergiques, peut réduire la durée des frissons associés à l'anesthésie neuraxiale lors d'un accouchement par césarienne. MéTHODE: Quatre-vingts parturientes subissant un accouchement par césarienne sous anesthésie neuraxiale et manifestant des frissons ont été recrutées pour cette étude prospective, randomisée et à double insu. Après la naissance, le groupe intervention (n = 40) a reçu un bolus intraveineux unique de dexmédétomidine (30 µg) alors que le groupe témoin (n = 40) a reçu une solution saline. La randomisation et l'attribution ont suivi une liste générée par ordinateur. Le critère d'évaluation principal était le temps nécessaire avant d'observer une réduction des frissons après l'intervention. RéSULTATS: Cent cinquante-cinq patientes ont été recrutées, dont 80 ont présenté des frissons et ont été randomisées. Notre étude a montré que la dexmédétomidine réduisait la durée moyenne (écart type) des frissons après un bolus intraveineux unique à 2,6 (2,1) min après l'administration de dexmédétomidine par rapport à une durée moyenne de 17,9 (12,6) min après la solution saline (différence de moyennes, -15,3 min; intervalle de confiance [IC] 95 %, -11,2 à -19,4). L'effet de la dexmédétomidine persistait 15 min après l'administration du bolus, où les frissons avaient complètement cessé chez 90 % des patientes du groupe intervention vs 22,5 % du groupe témoin (risque relatif, 4,0; IC 95 %, 2,2 à 7,2). Aucun effet secondaire néfaste, y compris la bradycardie, n'a été observé. CONCLUSION: Un bolus intraveineux unique de dexmédétomidine réduit la durée des frissons jusqu'à 15 min lors d'un accouchement par césarienne sous anesthésie neuraxiale. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02384343); enregistrée le 10 mars 2015.

Distraction Kits for Pain Management of Children Undergoing Painful Procedures in the Emergency Department: A Pilot Study.

To assess the feasibility, usefulness, and acceptability of using distraction kits, tailored to age, for procedural pain management of young children visiting the emergency department and requiring a needle-related procedure. A pre-experimental design was piloted. A kit, tailored to age (infants-toddlers: 3 months-2 years; preschoolers: 3-5 years), was provided to parents before their child's needle-related procedure. Data was collected to assess feasibility, usefulness, and acceptability of the kits by parents and nurses. Pain was measured pre-, peri-, and postprocedure using the Face, Legs, Activity, Cry, Consolability scale. A total of 25 infants and toddlers (mean age: 1.4 ± .7 years) and 25 preschoolers (mean age: 4.0 ± .9) participated in the study. Parents and nurses considered the kits useful and acceptable for distraction in the emergency department, especially in the postprocedural period. Addition of more animated and interactive toys to the kits was suggested. In the infants-toddlers group, mean pain scores were 1.6 ± 2.5 preprocedure, 7.1 ± 3.0 periprocedure, and 2.5 ± 2.5 postprocedure. In the preschoolers group, mean pain scores were 1.6 ± 3.0 preprocedure, 4.8 ± 3.4 periprocedure, and 2.0 ± 3.2 postprocedure. Distraction kits were deemed useful and acceptable by parents and emergency nurses. They are an interesting nonpharmacologic option for nurses to distract children, giving them a sense of control over their pain and improving their hospital experience. Future research should address the feasibility of distraction kits for a broader population of patients and a variety of painful procedures.

Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study.

OBJECTIVES: To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. METHODS: Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values. RESULTS: Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007). CONCLUSION: When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX. TRIAL REGISTRATION: EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

Fast-track recovery after day case surgery.

BACKGROUND: Fast-track recovery processes are implemented for pediatric day case surgery. We conducted a prospective study to evaluate postoperative comfort and parental satisfaction of children included in this process to improve quality of care. METHODS: We included all children scheduled for superficial procedures or dental treatment outside the operating room. A questionnaire was explained to parents before hospital discharge to evaluate the first night at home. Postoperative comfort evaluation included postoperative pain score (FLACC scale), incidence of postoperative nausea and vomiting, and postoperative behavior disorders. Incidence of posthospital behavior disturbance was evaluated measuring postoperative agitation at home, and disinterest with toys and games. Parental satisfaction was evaluated with a four-point Likert scale (1 = not satisfied at all, 2 = not satisfied, 3 = satisfied, 4 = very satisfied). RESULTS: One hundred and forty-three questionnaires were returned to hospital. Despite reduced length of stay in short-stay unit after anesthesia (28 ± 34 min), we did not report serious complications, and global parental satisfaction was good about the care process. Pain scores (FLACC >3) were higher in the group scheduled for dental procedures, but were very low for the other superficial surgery. With an odd ratio of 5.8 (95% confidence interval 2-17; P = 0.001), postoperative behavior modification (agitation or disinterest with toys or games) was the strongest variable that can predict parental dissatisfaction. CONCLUSION: Optimal pain management, better parental information about risks of postoperative behavior disturbances, and program integrating parent and child preparation should improve quality of care and global satisfaction in the fast-track recovery process.

Guided Imagery for Adolescent Post-spinal Fusion Pain Management: A Pilot Study.

Orthopedic surgery for adolescent idiopathic scoliosis entails anxiety and severe postoperative pain. The aim of this pilot study was to investigate an intervention for adolescent post-spinal fusion pain management in patients from a tertiary care hospital in Montreal, Canada. Participants were adolescents and young adults ages 11 to 20 years undergoing spinal fusion. Participants were randomized to standard care or standard care with adjunct intervention. The intervention consisted of a DVD with information and guided imagery/relaxation exercises to practice at least three times a week at home. A nurse screened the DVD with the patient preoperatively and at discharge (T1) and telephoned 2 weeks post-discharge (T2) to reinforce the technique. Both groups completed questionnaires at T1, T2, and T3 (1-month postoperative follow-up). Outcome measures included pain intensity, anxiety, coping mechanisms, and daily activities. From March 2010 to June 2011, we enrolled 40 of 45 eligible participants (n = 20 per group), average age 15 ± 2.1 years, 7 participants were male. Compared with the control group, the experimental group experienced significantly less overall pain at all time points, with moderate to large effect sizes at T2, T3 (p ≤ .007). Worst pain in 24 hours was moderately decreased at T2 (p = .01). State-trait anxiety remained high. On a 10-point scale, a median 2.5-point benefit was seen in eating and sleeping (Mann-Whitney test, p = .002), and 2 points in walking (Mann-Whitney test, p = .003). Coping strategies showed no significant differences. Addition of a guided imagery and relaxation exercise DVD for home use was more effective than standard care alone for postoperative pain. Our nonpharmacologic adjunct looks promising. Larger sample size and longer (6-9 months) follow-up will permit refinement.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.