Evaluation of Pain and Use of Analgesics during Medical Termination of Pregnancy in Real-Life Settings.

INTRODUCTION: Women frequently report pain associated with medical termination of pregnancy (MToP), and its management can differ largely between centres. This study aimed at evaluating in real-life settings pain related to MToP and its management in France. METHODS: This was a non-interventional prospective, longitudinal study run in 23 centres between 2015 and 2016 that included 893 pregnant women. Pain was reported by women prior any curative analgesic intake (CAI) through a five-level Likert scale (absence, mild, moderated, severe, extreme). Modalities of analgesic prophylaxis prescription (APP) and intake (API) and CAI were collected. Risk factors were investigated using ordinal logistic regression (for pain) or logistic regression (for CAI) with stepwise selection of variables. RESULTS: APP was prescribed to 657 (73.7%) women irrespective of the gestational age, among whom 386 (73.7%) took the treatment. Out of 740 women who documented their pain symptoms prior to any CAI, few declared no pain (n = 94, 12.7%) or intense pain (n = 88, 11.9%). The majority reported mild or moderate pain (n = 558, 75.4%). On multivariate analysis adjusted on gestational age, increasing initial [odds ratio (OR) 1.25, 95% confidence interval (CI) 1.06-1.47] or total dose (OR 1.15, 95% CI 1.05-1.26) of misoprostol taken were independent factors associated with risk of more pain. When adjusting for gestational age, initial dose of misoprostol (OR 1.69, 95% CI 1.45-2.66) and pain experienced (OR 3.58, 95% CI 2.82-4.55) were significantly associated with higher risk of CAI while API (OR 0.52, 95% CI 0.36; 0.75) was negatively associated. CONCLUSIONS: Most of the women received an APP, but not all used it. API and gestational age were not related to different risks of more pain following MToP, whereas history of at least one child showed a negative association. Higher doses of misoprostol were strongly associated with both pain and CAI. API was associated with a decreased risk of CAI.

Benefits of Switch from Oral to Subcutaneous Route on Adherence to Methotrexate in Patients with Rheumatoid Arthritis in Real Life Setting.

PURPOSE: The purpose of the APRIM study (for Adherence Polyarthrite Rhumatoïde Injection Methotrexate) was to investigate the change in treatment adherence of patients with rheumatic arthritis (RA) who switched from oral to subcutaneous methotrexate (MTX). PATIENTS AND METHODS: Prospective, observational study in RA patients treated with MTX and switching from oral to subcutaneous (SC) route in real-life conditions. Data on motivations for switch, disease activity (DAS28-CRP), quality of life (AISM-2 SF), disability (HAQ-DI), and adherence to MTX were collected at inclusion (M0) and 6 months later (M6). Adherence was assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8) and defined as high (MMAS-8 = 8), medium (MMAS-8 = 6 or ≤8) or low (MMAS-8 < 6). The primary evaluation criterion was the proportion of patients who maintained strong adherence or improved adherence by at least one category (from low to medium or strong or from medium to strong) between M0 and M6. RESULTS: The analysis involved 207 patients (age 60.4±12.7 years, 75.2% females). 6.7% were in remission and 15.5% had low disease activity (LDA) at baseline. 58.5% reached the primary criterion and strong adherence rate increased from 42.0% to 50.7%. Change of route was combined with increased MTX dose in 34.8% of patients. Switch to SC route increased the proportion of patients with remission or LDA from 22.8% to 52.9% and increased quality of life even in patients with unchanged MTX dose. CONCLUSION: Overall, change from oral to SC route improved adherence to MTX, RA control and quality of life independently of change in MTX dose.

MTX optimization or adding bDMARD equally improve disease activity in rheumatoid arthritis: results from the prospective study STRATEGE.

OBJECTIVES: The STRATEGE (Therapeutic Strategy in Patients Treated With Methotrexate for Rheumatoid Arthritis) study aimed to describe treatment strategies in current practice in RA biologic DMARD (bDMARD)-naïve patients with an inadequate response to MTX therapy, and to compare clinical efficacy of the different therapeutic strategies on disease activity after 6 months. METHODS: The main inclusion criteria of this prospective, observational, multicentre study were confirmed RA diagnosis, treatment by MTX monotherapy and need for therapeutic management modification. RESULTS: The 722 patients included had a mean (s.d.) RA duration of 5.3 (6.7) years, a mean DAS28 of 4.0 (1.1); they were all receiving MTX monotherapy, 68% oral, at a mean dose of 15.0 (4.1) mg/week. Two major strategies were identified: (i) MTX monotherapy dose and/or route optimization (72%) and (ii) bDMARD initiation ± MTX (16%). MTX dosing was modified for 70% of patients, maintained (dose and route) for 28% of patients and interrupted for 2%. bDMARDs were started when the MTX mean dose was 17.4 mg/week, 56% parenterally; MTX was maintained concomitantly for 96% of patients. Six-month follow-up results adjusted by propensity score showed that both options were equally successful in improving disease activity and physical function, with 63 and 68% of good-to-moderate EULAR responses, respectively. CONCLUSION: The STRATEGE study shows the importance of initial MTX treatment optimization before initiation of a biological treatment and emphasizes the importance of treat-to-target strategy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02288520.

Efficacy of mifepristone - Prostaglandin analogue combination in medical termination of pregnancy up to and beyond 7 weeks of amenorrhea: The RYMMa study.

OBJECTIVE: To assess, in real-life conditions, the success rate of the protocol mifepristone 600 mg / prostaglandin analogue (PG) in women requesting medical termination of pregnancy (MToP) either up to or beyond 7 weeks of amenorrhea (WA). STUDY DESIGN: The study was performed between 2015 and 2016. This was a non-interventional prospective, multicentre, longitudinal study conducted in France, among a sample of public and/or private centres dealing with MToP. Characteristics of women, term of Mtop, modality of PG used were reported. The primary outcome was success of MToP, defined as complete abortion without surgical procedure. RESULTS: A total of 893 pregnant women with less than the legal term of 14 WA were included in this study: 490 (54.9 %) ≤7 WA and 403 (45.1 %) >7 WA comprising 29 > 9 WA. The mean age of women was 28.1 ± 6.8 years and the one of pregnancy was 7.0 WA ± 1.3 WA. The most frequently used PG combined to mifepristone 600 mg was misoprostol 400 µg (57.0 % ≤7 WA and 35.1 % >7 WA) or 800 µg per os (oral or oral transmucosal) (27.5 % ≤7 WA and 40.1 % >7 WA). Vaginal misoprostol (6.4 %, N = 48) and gemeprost (5.2 %, N = 39) were less used. In women ≤7 WA (N = 422) and women >7 WA (N = 354) for whom result of the MToP was collected, success rates were 94.5 % (95 %CI 91.9 %-96.5 %) and 92.4 % (95 %CI 89.1 %-94.9 %), respectively (p = 0.219). In multivariate regression analysis, three factors were significantly associated with a higher risk of MToP failure: increased number of previous pregnancies (OR = 1.233; 95 %CI 1.086-1.401 for one pregnancy), increased number of previous surgical ToPs (OR = 1.563; 95 %CI 1.036-2.359 for one ToP) and increased interval between mifepristone and PG intake (OR = 1.061; 95 %CI 1.012-1.112 for one hour). Term of pregnancy (OR = 1.497; 95 %CI 0.833-2.690 for ≤7 WA vs >7WA), administration route (OR = 1.553; 95 %CI 0.488-4.936 for oral vs oral transmucosal; and OR = 1.216; 95 %CI 0.625-2.366 for vaginal vs oral transmucosal), and dose of misoprostol (OR = 1.000; 95 %CI 0.999-1.001), were not associated with the risk of failure. Overall, tolerance was good. CONCLUSION: This study showed, in real-life settings, a high rate of success for MToP using mifepristone 600 mg, independent of the pregnancy term and the therapeutic protocol used. MToP was safe and well tolerated however only a small number of women beyond 9 WA have been included.

Impact of Chloroprocaine on the Eligibility for Hospital Discharge in Patients Requiring Ambulatory Surgery Under Spinal Anesthesia: An Observational Multicenter Prospective Study.

INTRODUCTION: This observational study was designed to assess the use of spinal anesthesia with chloroprocaine in the context of ambulatory surgery. METHODS: A prospective, multicenter, observational study was carried out among 33 private or public centers between May 2014 and January 2015 and adult patients, scheduled for a short ambulatory surgery under spinal anesthesia with chloroprocaine. The primary outcomes were anesthetic effectiveness, defined as performance of the whole surgical procedure without any additional anesthetic agent, and the time to achieve eligibility for hospital discharge. Secondary outcomes were the effect of chloroprocaine on motor and sensory blocks, patients' satisfaction, and the use of analgesics in the first 24 h after surgery. RESULTS: Among the 615 enrolled patients, 56% were male, the mean age was 47.2 ± 15.2 years, and most patients had an ASA (American Society of Anesthesiologists) status of 1 (63.7%). Main surgical procedures performed were orthopedic (62.6%) and gynecologic (16.1%), and the mean duration of surgery was 26.7 ± 16.7 min. The overall anesthetic success rate was 93.8% (95% CI [91.5%; 95.6%]) for the 580 patients with available data for primary criteria. The failure rate was lower than 7% for all surgical procedures, except for gynecologic surgery (14.8%; 95% CI [8.1%; 23.9%]). The average times of eligibility for hospital discharge and effective discharge were 252.7 ± 82.7 min and 313.8 ± 109.9 min, respectively. The time of eligibility for hospital discharge is defined as the recovery of the patient's normal clinical parameters and the time of effective discharge is defined as the time for the patient to leave the hospital after surgery. Eligibility for patient's discharge was achieved more rapidly in private than public hospitals (236.3 ± 77.2 min vs. 280.9 ± 80.7 min, respectively, p < 0.001). CONCLUSIONS: This study showed positive results on the effectiveness of chloroprocaine as a short-duration anesthetic and could be used to reduce the time to achieve eligibility for hospital discharge. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02152293. Registered on May 6, 2014. Date of enrollment of the first participant in the trial May 7, 2014.

Factors Determining the Choice of Spinal Versus General Anesthesia in Patients Undergoing Ambulatory Surgery: Results of a Multicenter Observational Study.

INTRODUCTION: Available short-acting intrathecal anesthetic agents (chloroprocaine and prilocaine) offer an alternative to general anesthesia for short-duration surgical procedures, especially ambulatory surgeries. Factors determining the choice of anesthesia for short-duration procedures have not been previously identified. METHODS: This observational, prospective, multicenter, cohort study was conducted between July 2015 and July 2016, in 33 private or public hospitals performing ambulatory surgery. The primary objective was to determine the factors influencing the choice of anesthetic technique (spinal or general anesthesia). Secondary outcomes included efficacy of the anesthesia, time to hospital discharge, and patient satisfaction. RESULTS: Among 592 patients enrolled, 309 received spinal anesthesia and 283 underwent general anesthesia. In both study arms, the most frequently performed surgical procedures were orthopedic and urologic (43.3% and 30.7%, respectively); 66.1% of patients were free to choose their type of anesthesia, 21.8% chose one of the techniques because they were afraid of the other, 16.8% based their choice on the expected ease of recovery, 19.2% considered their degree of anxiety/stress, and 16.9% chose the technique on the basis of its efficacy. The median times to micturition and to unassisted ambulation were significantly shorter in the general anesthesia arm compared with the spinal anesthesia arm (225.5 [98; 560] min vs. 259.0 [109; 789] min; p = 0.0011 and 215.0 [30; 545] min vs. 240.0 [40; 1420]; p = 0.0115, respectively). The median time to hospital discharge was equivalent in both study arms. In the spinal anesthesia arm, patients who received chloroprocaine and prilocaine recovered faster than patients who received bupivacaine. The time to ambulation and the time to hospital discharge were shorter (p < 0.001). The overall success rate of spinal anesthesia was 91.6%, and no significant difference was observed between chloroprocaine, prilocaine, and bupivacaine. The patients' global satisfaction with anesthesia and surgery was over 90% in both study arms. CONCLUSIONS: Patient's choice, patient fear of the alternative technique, patient stress/anxiety, the expected ease of recovery, and the efficacy of the technique were identified as the main factors influencing patient choice of short-acting local anesthesia or general anesthesia. Spinal anesthesia with short-acting local anesthetics was preferred to general anesthesia in ambulatory surgeries and was associated with a high degree of patient satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02529501. Registered on June 23, 2015. Date of enrollment of the first participant July 21, 2015.

Use of Auto-Injector for Methotrexate Subcutaneous Self-Injections: High Satisfaction Level and Good Compliance in SELF-I Study, a Randomized, Open-Label, Parallel Group Study.

INTRODUCTION: The objective of the study was to compare compliance and acceptability of a new auto-injector (AI) versus syringe for administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: We conducted a randomized, open-label, parallel group study comparing AI to pre-filled syringe (PFS). Adult patients with RA (ACR/EULAR 2010) receiving MTX (orally or by injection) for at least 3 months were allocated to AI or PFS for 6 months and then were allocated to AI for 6 further months. Two co-primary endpoints were defined at M6: percentage of patients with compliance at least 80%; change in functional capacity assessed by Health Assessment Questionnaire (HAQ). Secondary endpoints included quality of life (RaQoL), RA activity (DAS28), and acceptability. Local safety at injection site was assessed at each visit. RESULTS: Two-hundred and sixty-five patients were randomized. The main analysis was conducted on per protocol set (99 AI and 98 PFS). Compliance was 96.2% in AI and 98.9% in PFS. Good complier rates were 89.9% and 94.9%, thus a difference of - 5.0% (- 18.9%; 8.9%). HAQ remained stable in both groups. No difference was found on RaQoL, change in RA activity, and safety profile. Autonomy, acceptability, and patient satisfaction were better with AI, and patients having had the experience of both AI and PFS preferred AI (p < 0.001). CONCLUSIONS: Although this study did not demonstrate non-inferiority of AI versus PFS, compliance was excellent in the two groups, and AI, which was preferred by patients, is a valuable alternative to PFS for administration of MTX. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02553018. FUNDING: Nordic Pharma SAS.

Evaluation of Usability and Acceptance of a New Autoinjector Intended for Methotrexate Subcutaneous Self-Administration in the Management of Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, for which the introduction of injectable treatments has had a major impact on quality of life directly related to the disease. The purpose of this descriptive study was to evaluate the usability of a new autoinjector, intended for methotrexate self-administration, based on the device's design and instructions for use (IFU). METHODS: This multicenter trial included three user groups: a group of patients with established RA subdivided into two groups according to their hand disability, and a group of caregivers or nurses. Each subject performed three simulated injections with a water-filled device on a foam pad. The first injection was made just after reading the IFU without further instructions (first phase). The second phase consisted of two injections made after explanations provided upon request of the subject in an optimum environment and in a "worst-case" home environment. The usability of the autoinjector was assessed by a questionnaire (success: ≥75% of positive responses) and by a score card reflecting injection performances (success: execution of ≥75% of handling steps). RESULTS: Forty-two subjects were enrolled in the study. During the first phase, the great majority of subjects succeeded in the usability questionnaire (90.5%) and in the injection performance (95.2%) with no major differences between the user groups. In the Second phase, all subjects from all three user groups succeeded in the usability questionnaire and had a positive rate of device handling, regardless of the environment and of the user group. No safety concerns were raised during the study. CONCLUSIONS: This study found a very high level of usability and subject acceptance of the autoinjector, intended for methotrexate self-administration, regardless of the hand disability and environmental conditions. FUNDING: Nordic Group. TRIAL REGISTRATION: EudraCT reference number: 2014-A0141245.