La viscosuplementación del líquido sinovial mediante la inyección intraarticular (IA) de ácido hialurónico (AH) es un tratamiento sintomático ampliamente utilizado en la artrosis de rodilla (AR). ...Además de los productos diseñados para realizar inyecciones múltiples (normalmente de 3 a 5 inyecciones, en intervalos de 1 semana), se presta especial atención a los productos de una única inyección, ya que ofrecen ventajas específicas, como son un menor número de visitas al médico y de intervenciones invasivas con sus riesgos asociados. Sin embargo, aún existen dudas sobre la eficacia de estas inyecciones únicas, en comparación con los regímenes de inyecciones múltiples.
Se realizó un estudio multicéntrico, abierto, prospectivo, post-mercado (ART-ONE 75) con el producto de inyección única ARTHRUM 2,5% (3 ml, 75 mg AH), en 214 pacientes que sufrían de AR. Los pacientes fueron seguidos en D30, D60, D120 y D180 (días). El perfil promedio de los pacientes en el momento de la inclusión fue de 62,9 años, 56% mujeres, grados I-III de Kellgren-Lawrence (46% KL III), IMC de 27,2 kg/m2 y 4 años desde el diagnóstico de AR. Se realizó una comparación post-hoc con una inyección IA única de placebo (326 pacientes, agrupados de 3 estudios ECA), que proporcionaron un perfil de paciente similar.
el criterio principal fue la variación desde el inicio de la puntuación de la escala WOMAC A (dolor, escala 0-100) en D60, que se redujo en 28,9 (17,4) para la población por intención de tratar (ITT, por sus siglas en inglés) (199 pacientes), 28,0 (17,8) para la población por protocolo (PP) en la inclusión (175 pacientes), y en 27,7 (16,8) para la población PP al finalizar (143 pacientes).
Los criterios secundarios y accesorios incluyeron WOMAC A en otras ocasiones, WOMAC B (rigidez), WOMAC C (función), calidad de vida y discapacidad en cada momento de seguimiento. Todos los índices mejoraron significativamente y continuaron mejorando al final del estudio. La evaluación terapéutica en D180 mostró que más del 75% de los pacientes se encontraban satisfechos con la reducción del dolor, la mejora de la movilidad, y la reducción de analgésicos y AINE. El porcentaje de pacientes definidos como respondedores de OMERACT-OARSI fue superior al 86%, a partir de D60 y en adelante. La tolerancia general fue buena, sin que ocurriera ningún evento adverso grave. El resultado de la comparación post-hoc para la escala WOMAC A mostró un tamaño del efecto IC 95% desde TE = 0,33 0,15; 0,51 en D60 a TE = 0,65 0,45; 0,85 en D180 (p <0,001), frente a la inyección de placebo (solución salina), lo cual es un resultado clínicamente relevante a favor de ARTHRUM 2,5%.
El presente estudio confirma la eficacia clínica de una única inyección IA de 3 ml de solución de AH conteniendo 75 mg de AH nativo de alto PM (> 2 MDa).
La viscosupplémentation du liquide synovial par injection intra-articulaire d'acide hyaluronique est un traitement symptomatique de l'arthrose, largement utilisé dans la gonarthrose (arthrose du ...genou). À côté des produits conçus pour être administrés par injections multiples (typiquement 3 à 5 injections à intervalles de 1 semaine), un intérêt particulier se porte sur produits en injection unique (mono-injection) qui offrent des avantages spécifiques tels que la réduction du nombre de visites au médecin et du nombre d'interventions invasives avec leurs risques associés. Il subsiste toutefois une question concernant l'efficacité de ces mono-injections, par rapport aux protocoles à injections multiples.
Une étude post-commercialisation, prospective, multicentrique, ouverte (ART-ONE 75), a été réalisée avec le produit pour injection unique Arthrum 2,5 % (3 mL, 75 mg d'acide hyaluronique) (LCA Pharmaceutical, Chartres, France), sur 214 patients atteints de gonarthrose. Les patients ont été suivis à 30, 60, 120 et 180 jours. Le profil moyen des patients à l'inclusion était un âge de 62,9 ans, 56 % de femmes, un stade radiologique Kellgren-Lawrence de I à III (46 % KL III), un indice de masse corporelle de 27,2 kg/m2 et une antériorité de 4 ans pour la gonarthrose. Une comparaison post hoc a été réalisée par rapport à une injection intra-articulaire unique de placebo (326 patients regroupés à partir de 3 essais randomisés contrôlés), et présentant un profil similaire de patients.
Le critère principal était la variation par rapport à la baseline, de l'indice Western Ontario and McMaster Universities, sous-échelle de la douleur (WOMAC A) dont le score (base 0–100), était réduit à 60 jours, de 28,9 (17,4) pour la population en intention de traiter (199 patients), de 28,0 (17,8) pour la population per protocole à l'inclusion (175 patients), et de 27,7 (16.8) pour la population per protocole ayant terminé l'étude (143 patients). Les critères secondaires et accessoires comprenaient le score WOMAC A aux autres dates, le score WOMAC B (raideur), le score WOMAC C (fonction), la qualité de vie et le handicap à chaque date de suivi. Tous les indices étaient significativement améliorés et continuaient à s'améliorer à la fin de l’étude. L’évaluation thérapeutique à 180 jours a montré que plus de 75 % des patients étaient satisfaits de la réduction de la douleur, de l'amélioration de la mobilité et de la réduction de la consommation d'analgésiques et d'anti-inflammatoires non stéroïdiens. Le pourcentage de patients définis comme répondeurs selon les critères de l'OMERACT–OARSI Initiative était > 86 %, à partir de 60 jours. La tolérance globale était bonne, sans aucun évènement indésirable grave. Les résultats de la comparaison post hoc pour le score WOMAC A ont montré une taille d'effet variant de 0,33 (IC 95 % 0,15–0,51), à 60 jours à 0,65 (IC 95 % 0,45–0,85) à 180 jours (p < 0.001), versus placebo injecté (solution saline), qui est cliniquement significative en faveur d'Arthrum 2,5 %.
La présente étude suggère l'efficacité clinique d'une mono-injection IA de 3 mL de solution viscoélastique contenant 75 mg d'AH natif de haut poids moléculaire (> 2 MDa).
Purpose:
The purpose of this study was to obtain information on safety and short-term efficiency of a single intra-articular injection of mannitol-modified cross-linked hyaluronic acid (HANOX-M-XL) ...in patients with painful first metatarsophalangeal joint osteoarthritis (1stMTPJ-OA).
Methods:
The study involved an observational, single-arm, prospective multicentre trial, with a 3-month follow-up. Inclusion criteria were patients with symptomatic 1st MTPJ-OA not relieved by analgesics and / or non-steroidal-anti-inflammatory drugs and / or foot orthotic. All patients received a single, imaging-guided intra-articular (IA) injection of 1 mL of HANOX-M-XL in the 1st MTPJ. The primary outcome was the change in pain between the date of injection and month 3. The secondary outcomes were the patient assessment of effectiveness, the decrease in painkiller use and the influence of the radiographic score on the clinical efficacy.
Results:
Sixty-five participants (72.3% women, mean age = 60) were included in the trial. Coughlin-Shurnas radiological grade was 1 in 28 patients, 2 in 29, and 3 in 6. At baseline and month 3, the average pain (0-10) was 6.5 ± 1.8 and 2.8 ± 2.3, respectively. The change in pain score was highly significant (−3.1 ± 2.9; P < .0001). At baseline there was no statistically difference in pain between the radiological stages (P = .69). At endpoint, the average pain score was 2.0 ± 1.9 in x-ray stage 1, 3.1 ± 2.3 in stage 2 and 3.3 ± 2.4 in stage 3 (P = .001). Mild to moderate adverse reactions were reported by 15 patients. All were a transient increase of the hallux pain that occurred immediately and up to 6 hours after injection and resolved in 1 to 7 days.
Conclusion:
This pilot study suggests that a single IA injection of HANOX-M-XL is safe and mainly benefits patients with mild moderate 1st MTPJ-OA. Further randomized controlled trials are necessary to confirm these preliminary encouraging results.
Viscosupplementation of the synovial liquid, by intra-articular injection of hyaluronic acid, is a widely used symptomatic treatment in knee osteoarthritis. Besides products designed for ...multi-injections (typically 3–5 injections at 1-week intervals), special interest is being given to single-injection products that offer specific advantages such as the reduction of the number of visits to the doctor and the number of invasive interventions with their associated risks. However, a question remains about the efficacy of these monoinjections, compared with the multi-injections regimens.
A postmarket, prospective, multicenter, open study (ART-ONE 75), was performed with the single-injection product Arthrum 2.5% (3 mL, 75 mg hyaluronic acid) (LCA Pharmaceutical, Chartres, France), on 214 patients with knee osteoarthritis. Patients were followed at 30, 60, 120, and 180 days. The average patient profile at inclusion was age 62.9 years, 56% were women, Kellgren-Lawrence (KL) grade I through III (46% Kellgren-Lawrence status III), body mass index 27.2, and 4 years osteoarthritis anteriority. A post hoc comparison was performed using a single intra-articular injection placebo (326 patients, pooled from 3 randomized controlled trials) providing a similar patient profile.
The main criterion was the variation from baseline of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, pain subscale (A) score (range 0-100), at 60 days, which was reduced by 28.9 (17.4) for the intent-to-treat population (199 patients), 28.0 (17.8) for the per protocol at inclusion population (175 patients), and by 27.7 (16.8) for the per protocol completed population (143 patients). The secondary and accessory criteria included WOMAC A score at the other times, WOMAC B (stiffness) score, WOMAC C (function) score, quality of life, and handicap at each follow-up time. All indexes were significantly improved and continued to improve at the end of the study. The therapeutic assessment at 180 days showed more than 75% of patients were satisfied with pain reduction, mobility improvement, and reduction in taking analgesics and nonsteroidal anti-inflammatory drugs. The percentage of patients defined as Outcome Measures in Rheumatology Clinical Trials–Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) responders was >86%, from 60 days onward. The overall tolerance was good, without any serious adverse event. The result of the post hoc comparison for the WOMAC A score showed an effect size from 0.33 (95% CI 0.15–0.51) at 60 days to 0.65 (95% CI 0.45–0.85) at 180 days (P < 0.001), versus injected placebo (saline solution), which is clinically relevant in favor of Arthrum 2.5%.
The present study suggests the clinical efficacy of a single intra-articular injection of 3 mL intra-articular hyaluronic acid solution containing 75 mg high molecular weight (>2 MDa) native hyaluronic acid.
Purpose:
To assess safety and search predictive factors of efficacy of a single intra-articular injection of a mannitol-modified hyaluronic acid (HA) viscosupplement, in patients having ...trapeziometacarpal (TMC) osteoarthritis (OA).
Methods:
Patients with symptomatic TMC OA, not adequately relieved by analgesic therapy and/or by the use of a thumb splint, were included in a 3-month prospective multicentre open-label trial. All underwent plain radiographs with the Kapandji incidences allowing the Dell radiological grade assessment (1-4). Primary end point was the variation between injection (D0) and day 90 (D90) of the thumb pain (11-point Likert scale). Treatment consisted in a single injection of 0.6 to 1 mL of a viscosupplement made of a cross-linked HA combined with mannitol. All injections were performed under imaging guidance. Predictive factors of pain decrease were studied in univariate and multivariate analysis.
Results:
A total of 122 patients (76% women, mean age 60, mean disease duration 36 months) were included and 120 (98%) were assessed at 3 months. The TMC OA was of Dell’s grade 1, 2, 3, and 4 in 23%, 36.8%, 36.8%, and 3.5% of cases, respectively. At D0, the average (SD) pain level was 6.5 ± 1.6 without significant difference between Dell groups (P = .21). At day 90, pain decreased from 6.5 ± 1.6 to 3.9 ± 2.5 (difference −2.7 ± 2.5; −42%; P < .0001) without significant difference between Dell grade (P = .055), despite a seemingly smaller number of responders in stage 2 patients. The average analgesic consumption decreased in more than 1 out of 2 patients. In multivariate analysis, no predictor of response was identified. There was no safety issue. All adverse events (11%) were transient increase in pain during or following HA administration and resolved without sequel within 1 to 7 days.
Conclusions:
This study suggests that a single course of HANOX-M-XL injection is effective in relieving pain in patients with TMC OA, without safety concern. Patients with advanced stage of OA benefit the treatment as much as those with mild or moderate OA.
We investigated prognostic factors associated with refractory left ventricle (LV) failure leading to LV assist device (LVAD), heart transplant or death in patients on an axial flow pump support for ...cardiogenic shock (CS). Sixty-two CS patients with an Impella
CP or 5.0 implant were retrospectively enrolled, and clinical, biological, echocardiographic, coronarographic and management data were collected. They were compared according to the 30-day outcome. Patients were mainly male (
= 55, 89%), 58 ± 11 years old and most had no history of heart failure or coronary artery disease (70%). The main etiology of CS was acute coronary syndrome (
= 57, 92%). They presented with severe LV failure (LV ejection fraction (LVEF) 22 ± 9%), organ malperfusion (lactate 3.1 ± 2.1 mmol/L), and frequent use of inotropes, vasopressors, and mechanical ventilation (59, 66 and 30%, respectively). At 24 h, non-recovery was associated with higher total bilirubin (odds ratios (OR) 1.07 (1.00-1.14);
= 0.039), lower LVEF (OR 0.89 (0.81-0.96);
= 0.006) and the number of administrated amines (OR 4.31 (1.30-14.30);
= 0.016). Early evaluation in patients with CS with an axial flow pump implant may enable the identification of factors associated with an unlikely recovery and would call for early screening for LVAD or heart transplant.
Aims
Left ventricular assist devices (LVADs) have reduced the mortality of patients with advanced heart failure both as bridge‐to‐transplant and as destination therapy. However, LVADs are associated ...with various complications, including bleedings, which affect the prognosis. The aim of the study was to explore the prevalence, management, and outcomes of haemorrhagic adverse events in LVAD recipients.
Methods and results
We conducted a retrospective, single‐centre, cohort study including all patients who received an LVAD from January 2008 to December 2019 in our tertiary centre (Rangueil University Hospital, Toulouse, France). Bleeding events, death, and heart transplantation were collected from electronic medical files. Eighty‐eight patients were included, and 43 (49%) presented at least one bleeding event. Gastrointestinal (GI) bleeding was the most frequent (n = 21, 24%), followed by epistaxis (n = 12, 14%) and intracranial haemorrhage (n = 9, 10%). Bleeding events were associated with increased mortality hazard ratio (HR) 3.8, 95% confidence interval (CI) 1.5–9.3, P < 0.01, particularly in case of intracranial haemorrhage (HR 14.6, 95% CI 4.2–51.1, P < 0.0001). GI bleedings were associated with a trend towards increased mortality (HR 3.0, 95% CI 0.9–9.3, P = 0.05). Each bleeding episode multiplied the risk of death by 1.8 (95% CI 1.2–2.7, P < 0.01). Finally, only early bleedings (<9 months post‐implantation) had an impact on mortality (HR 4.2, 95% CI 1.6–11.1, P < 0.01). Therapeutic management was mainly based on temporary interruption of anticoagulation and permanent interruption of antiplatelet therapy. Invasive management was rarely performed.
Conclusions
Haemorrhagic events in LVAD recipients are frequent and associated with increased mortality. GI bleedings are the most frequent, and intracranial haemorrhages the most associated with mortality. Management remains empirical requiring more research.
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