-
1.
Improvement in wound healing, pain, and quality of life after 12 weeks of SNF472 treatment: a phase 2 open-label study of patients with calciphylaxis.
Brandenburg, VM, Sinha, S, Torregrosa, JV, Garg, R, Miller, S, Canals, AZ, Bahr, D, Joubert, PH, Salcedo, C, Carroll, KJ, et al
Journal of nephrology. 2019;(5):811-821
Abstract
BACKGROUND Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification. METHODS In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations. RESULTS Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (- 8.1; P < 0.001), pain VAS (- 23.6 mm; P = 0.015) and wound-QoL global score (- 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related. CONCLUSIONS SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.
-
2.
Randomised crossover trial showed that using breast milk or sucrose provided the same analgesic effect in preterm infants of at least 28 weeks.
Collados-Gómez, L, Ferrera-Camacho, P, Fernandez-Serrano, E, Camacho-Vicente, V, Flores-Herrero, C, García-Pozo, AM, Jiménez-García, R
Acta paediatrica (Oslo, Norway : 1992). 2018;(3):436-441
Abstract
AIM: Repeated, ongoing exposure to pain influences the growth, cognitive and motor functions, behaviour, personality and neurodevelopment of preterm infants. We compared the analgesic effects of expressed breast milk (EBM) and 24% oral sucrose on preterm neonates during venipuncture. METHODS This multicentre randomised, noninferiority, crossover trial focused on five neonatal university units in Madrid, Spain, from October 2013 to October 2014. It comprised 66 preterm infants born at less than 37 weeks and randomly split into two groups. They received either EBM or sucrose two minutes before venepuncture, together with nonnutritive sucking and swaddling, then the opposite procedure at a later point. Pain was measured with the premature infant pain profile (PIPP) and crying was also measured. RESULTS There were no statistically significant differences between the groups. The PIPP scores were seven (4-9) with breast milk and six (4-8.25) with sucrose (p = 0.28). The 11 infants born at under 28 weeks of age showed higher median scores of nine (9-14) for breast milk and four (4-7) for sucrose (p = 0.009). CONCLUSION EBM and 24% sucrose had the same analgesic effect during venipuncture in most of the preterm neonates, but sucrose worked better in extremely preterm infants.
-
3.
Efficacy and safety of a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for pain relief in patients with osteoarticular diseases and dyspeptic symptoms.
Scheinberg, M, Pott Júnior, H, Macêdo, EA, Bocchi de Oliveira, MF, Ecclissato, C, Amazonas, RB
Drug design, development and therapy. 2018;:2775-2783
Abstract
PURPOSE This study investigated the safety and efficacy of fixed-dose combination tablets of naproxen/esomeprazole magnesium and nimesulide/pantoprazole to determine if both regimens are equally suited to relieve pain in patients with osteoarticular diseases and dyspeptic symptoms. METHODS Patients were randomly assigned to receive either nimesulide/pantoprazole (100 mg/20 mg) twice daily or naproxen/esomeprazole magnesium (500 mg/20 mg) twice daily for 14 days. The primary endpoint was defined as the mean change in modified Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Secondary endpoints were mean visual analog scale score of dyspeptic symptoms (nausea, abdominal discomfort/pain, epigastric burning, postprandial fullness), mean visual analog scale score of individual dyspeptic symptoms, and individual score of dyspeptic symptoms according to patient diary. This study is registered at ClinicalTrials.gov: NCT01670552. RESULTS A total of 490 patients were enrolled and randomized, and 399 completed treatment (naproxen/esomeprazole, n=201; nimesulide/pantoprazole, n=198). The difference in mean change in the modified Western Ontario and McMaster Universities Osteoarthritis Index pain score after 7 days of treatment between the two treatment groups was 2.33 mm (95% CI, -1.22 to 5.89 mm). After 14 days of therapy, the difference was 0.45 mm (95% CI, -3.29 to 4.19 mm). The most common adverse events in the pooled group were abdominal discomfort, abdominal distention, dyspepsia, and nausea, but none of these was deemed to be clinically meaningful. CONCLUSION The present study demonstrated noninferiority of a 14-day regimen with a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for the treatment of osteoarticular pain.
-
4.
Evolution of pain at 3 months by oral resveratrol in knee osteoarthritis (ARTHROL): protocol for a multicentre randomised double-blind placebo-controlled trial.
Nguyen, C, Boutron, I, Baron, G, Coudeyre, E, Berenbaum, F, Poiraudeau, S, Rannou, F
BMJ open. 2017;(9):e017652
Abstract
INTRODUCTION Osteoarthritis (OA) pathophysiology is driven in part by joint inflammation. Resveratrol has in vitro anti-inflammatory properties. We aim to assess the efficacy of oral resveratrol for knee pain at 3 months in people with knee OA. METHODS AND ANALYSIS We will conduct a randomised double-blind placebo-controlled trial. Overall, 164 individuals with knee OA fulfilling 1986 American College of Rheumatology criteria will be recruited in three tertiary care centres in France and randomised to receive oral resveratrol, 40 mg (two caplets) two times per day for 1 week, then 20 mg (one caplet) two times per day or a matching placebo for a total of 6 months. Randomisation will be centralised and stratified by centre. The allocation ratio of assignments will be 1:1. The primary outcome will be the mean change from baseline in knee pain on a self-administered 11-point pain Numeric Rating Scale at 3 months. Secondary outcomes will be the mean change in knee pain at 6 months, the function subscore of the Western Ontario and McMaster Universities Arthritis Index score, patient global assessment, proportion of responders according to the Osteoarthritis Research Society International-Outcome Measures in Rheumatology criteria at 3 and 6 months, and self-reported number of intra-articular injections of corticosteroids or hyaluronic acid and consumption of analgesics and non-steroidal anti-inflammatory drugs since the last contact. Other interventions will be allowed and self-reported. Adherence will be monitored by capsule counts and a booklet and adverse events recorded at 3 and 6 months. Statisticians, treating physicians and participants will be blinded to the allocated treatment. ETHICS AND DISSEMINATION The oral resveratrol in knee osteoarthritis (ARTHROL) trial has been authorised by the AgenceNationale de Sécurité du Médicament et des Produits de Santé and ethics were approved by the Comité deProtection des Personnes Île-de-France III. The findings of the study will be published in a peer-reviewed journal and disseminated at conferences. The design of ARTHROL will warrant the translation of its findings into clinical practice. TRIAL REGISTRATION NUMBER ClinicalTrials.gov identifier: NCT02905799. Pre-results. First received: 14 September 2016. Last updated: 16 September 2016. Status: not yet recruiting.
-
5.
Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.
Basch, E, Pugh, SL, Dueck, AC, Mitchell, SA, Berk, L, Fogh, S, Rogak, LJ, Gatewood, M, Reeve, BB, Mendoza, TR, et al
International journal of radiation oncology, biology, physics. 2017;(2):409-418
-
-
Free full text
-
Abstract
PURPOSE To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS AND MATERIALS Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. RESULTS Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." CONCLUSIONS Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.
-
6.
Intra-articular hylastan versus steroid for knee osteoarthritis.
Housman, L, Arden, N, Schnitzer, TJ, Birbara, C, Conrozier, T, Skrepnik, N, Wei, N, Bockow, B, Waddell, D, Tahir, H, et al
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2014;(7):1684-92
Abstract
PURPOSE To assess the efficacy and safety of one and two intra-articular (IA) injections of the new viscosupplement, hylastan, compared with a single IA corticosteroid injection for pain due to knee osteoarthritis (OA). Hylastan is a high-molecular-weight hyaluronan derivative prepared from bacterial fermented sodium hyaluronate that was developed to remain in the joint for longer than most other viscosupplements. METHODS This 6-month, double-blind, randomized, parallel group, multicenter trial enrolled patients aged ≥40 years who met American College of Rheumatology criteria for knee OA and had continued pain despite conservative treatment. Patients were randomized 1:1:1 to one of three arms: 2 × 4 mL hylastan (n = 129; arthrocentesis then IA hylastan Day 0, same treatment Week 2); 1 × 4 mL hylastan (n = 130; arthrocentesis then IA hylastan Day 0, arthrocentesis only Week 2); steroid (n = 132; arthrocentesis then IA methylprednisolone acetate 40 mg Day 0, arthrocentesis only Week 2). Participants and evaluators were blinded to treatment. The primary clinical outcome measure was change from baseline in WOMAC A pain score over all postbaseline visits to Week 26. RESULTS Statistically significant pain reduction was observed in all three arms, with similar mean (95 % CI) changes in WOMAC A 2 × 4 mL hylastan -0.9 (-1.0, -0.7); 1 × 4 mL hylastan -0.8 (-0.9, -0.7); steroid -0.9 (-1.0, -0.8); all P < 0.0001 versus baseline. Changes in secondary outcomes (OMERACT-OARSI and WOMAC A responder rates, patient/clinical observer global assessments, and WOMAC A1 walking pain) were similar in all three arms. Target knee adverse events were comparable for all treatments. CONCLUSIONS Both IA hylastan injection regimens were effective in relieving pain with an acceptable safety profile. IA hylastan did not show a difference versus IA corticosteroid; therefore, the hypothesis of superior pain relief was not met. Further research is needed to compare the efficacy and safety of hylastan with other viscosupplements.
-
7.
Comparison of two doses of ketoprofen to treat pain: a double-blind, randomized, noninferiority trial.
Riou, B, Plaisance, P, Lecomte, F, Soulat, L, Orcel, P, Mazoit, JX
Fundamental & clinical pharmacology. 2014;(1):20-8
Abstract
The aim of our study was to compare the efficacy and safety of two doses of ketoprofen (200 mg vs. 300 mg/day) in ambulatory emergency patients with pain related to traumatic and nontraumatic bone and joint diseases. We tested the hypothesis that the efficacy of the lower dose was not lower than that of the higher dose in a double-blind, randomized, noninferiority trial. Patients included in the study were aged 18-65 years with closed benign trauma of the motor system or acute noninfectious rheumatologic conditions, with a resting pain intensity ≥3/10 on a numeric pain scale (NPS), requiring ketoprofen for 5 days. The main end-point was based on two efficacy co-criteria: (i) mean change from baseline of resting pain intensity at the end of the day over 5 days and (ii) total intake of concomitant analgesics. We included 409 patients: 200 in the 200-mg group and 209 in the 300-mg group. The mean change in pain intensity at rest (difference between groups: 0.0, 95% CI -0.4 to 0.4; P = 1.00) and in analgesic consumption (difference between groups: -0.6, 95% CI -1.9 to 0.6; P = 0.33) was not significantly different between the two groups, and the differences were lower than the predefined inferiority margins (0.5 and 1.5, respectively), thus demonstrating noninferiority. No significant difference was noted in the incidence of adverse events (21% vs. 20%, P = 0.71). The efficacy of the 200-mg daily dose of ketoprofen in relieving pain in emergency cases was not inferior to that of the 300-mg dose.
-
8.
Lasting effects of workplace strength training for neck/shoulder/arm pain among laboratory technicians: natural experiment with 3-year follow-up.
Mortensen, P, Larsen, AI, Zebis, MK, Pedersen, MT, Sjøgaard, G, Andersen, LL
BioMed research international. 2014;:845851
Abstract
OBJECTIVES This study investigated long-term effects and implementation processes of workplace strength training for musculoskeletal disorders. METHODS 333 and 140 laboratory technicians from private and public sector companies, respectively, replied to a 3-year follow-up questionnaire subsequent to a 1-year randomized controlled trial (RCT) with high-intensity strength training for prevention and treatment of neck, shoulder, and arm pain. Being a natural experiment, the two participating companies implemented and modified the initial training program in different ways during the subsequent 2 years after the RCT. RESULTS At 3-year follow-up the pain reduction in neck, shoulder, elbow, and wrist achieved during the first year was largely maintained at both companies. However, the private sector company was rated significantly better than the public sector company in (1) training adherence, (2) training culture, that is, relatively more employees trained at the workplace and with colleagues, (3) self-reported health changes, and (4) prevention of neck and wrist pain development among initially pain-free employees. CONCLUSIONS This natural experiment shows that strength training can be implemented successfully at different companies during working hours on a long-term basis with lasting effects on pain in neck, shoulder, and arm.
-
9.
Women's use of nipple shields-Their influence on breastfeeding duration after a process-oriented education for health professionals.
Ekström, A, Abrahamsson, H, Eriksson, RM, Mårtensson, BL
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2014;(9):458-66
Abstract
AIM: This study investigated if a process-oriented training for health professionals will influence women's use and reasons for using a nipple shield, the baby's weight, and the duration of breastfeeding. MATERIALS AND METHODS An intervention was performed for health professionals that included a process-oriented training program on breastfeeding support. Primiparas living in either the intervention municipality or in a control municipality were asked to participate in a longitudinal study to evaluate the care given. Data collection for control group A (CGA) (n=162) started before the intervention was initiated. Data for control group B (CGB) (n=172) were collected simultaneously with those for the intervention group (IG) (n=206). The mothers responded to questionnaires at 3 days, at 3 months, and at 9 months postpartum. RESULTS The mothers' use of nipple shields related to the finding that if the women had a higher body mass index in the beginning of the pregnancy, the babies had difficulty in grasping over the nipple, and the mothers had pain or wound on the nipple. For the mothers in the IG group, there was no significant difference if they had used nipple shields or not in relation to breastfeeding duration. In contrast, the mothers in the control groups had a significant shorter breastfeeding duration if they had used nipple shields. In the IG, there were no significant difference between the use of nipple shields and the babies' weights at 3 or 9 months. The babies of women in the CGB who used nipple shields had a significantly lower weight at 3 months than the babies of those who did not use nipple shields (p=0.02). CONCLUSIONS A process-oriented training in breastfeeding counseling prolongs the duration of breastfeeding for women with breastfeeding problems, where the problems are remedied by the use of nipple shields.
-
10.
A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis.
Conaghan, PG, Dickson, J, Bolten, W, Cevc, G, Rother, M
Rheumatology (Oxford, England). 2013;(7):1303-12
Abstract
OBJECTIVE To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS; A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12. RESULTS A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg). CONCLUSION IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain. TRIAL REGISTRATION ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.