Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

BACKGROUND: Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. METHODS: A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. RESULTS: Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. CONCLUSION: Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in the treatment of acute pain following oral surgery. FUNDING: Laboratorios del Dr. Esteve, S.A.U.

Diagnóstico de mieloma múltiple a raíz de una lesión osteolítica mandibular / Diagnosis of multiple myeloma following an osteolytic mandibular lesion

Objetivo. El mieloma múltiple es una neoplasia de células plasmáticas con repercusión sistémica y lesiones osteolíticas. Su diagnóstico a raíz de una lesión mandibular es bastante infrecuente. Por ello presentamos un caso de mieloma múltiple diagnosticado a partir de sintomatología dolorosa e inflamatoria por una lesión osteolítica en la rama mandibular y revisamos la literatura para establecer el perfil clínico e imagen radiológica típica que nos faciliten sospechar el diagnóstico con más certeza. Material y métodos. Mujer de 46 años acude al servicio de Urgencias por inflamación y dolor preauricular. La ortopantomografía muestra una imagen radiolúcida multilobulada a lo largo de la rama y cóndilo mandibulares. El estudio anatomopatológico y de extensión desenmascaran un mieloma múltiple. Se hace además una revisión de la base de datos Pubmed para casos de diagnóstico de mieloma múltiple a partir de una lesión mandibular en los últimos 5 años. Resultados. Se encontraron 13 casos incluyendo el presente. La edad media era de 61 años con ligero predominio del sexo masculino; la clínica más frecuenta era inflamación indurada de la región mandibular afectada con o sin ulceración mucosa, y la imagen radiológica característica osteólisis uni o multilocular, en un caso con reacción perióstica. Conclusiones. La presentación inicial del mieloma múltiple mediante una lesión mandibular es poco frecuente. Sin embargo, el cirujano maxilofacial debe sospechar una neoplasia de células plasmáticas ante imágenes radiolúcidas mandibulares y no demorar un estudio más exhaustivo (AU)

Purpose. Multiple myeloma is a neoplasic proliferation of plasma cells with systemic repercussion and osteolytic lesions. The initial diagnosis by a mandibular lesion is extremely rare. Therefore we present a clinical case of multiple myeloma diagnosed following pain and swelling from an ostelytic mandibular lesion, and we review the literature in order establish a clinical profile and a typical radiological image that would allow us to suspect the diagnosis with more certainty. Material and methods. A 46 year-old woman comes to the Emergency Department complaining about preauricular pain and swelling. The orthopantomography shows a radiolucid multilolocular image along the mandibulary ramus and condyle. The histology and extension follow up concludes with a multiple myeloma diagnosis. A systematic review of Pubmed database was made searching for mandibular lesion at initial diagnosis of multiple myeloma within the last 5 years. Results. We found 13 cases including ours The mean age was 61 years with a slight male predominance; the most common clinical presentation was a firm to hard mandibular swelling with or without mucosal ulceration; and the most characteristic radiological image was a uni or multilocular osteolysis, with periostic reaction in one case. Conclusions. A mandibular lesion as a first sign of multiple myeloma is infrequent. Nevertheless, a maxilofacial surgeon should suspect a plasma cell neoplasia in cases of mandibular osteolytic images and start further studying without delay (AU)

Internal distraction osteogenesis with a unidirectional device for reconstruction of mandibular segmental defects.

PURPOSE: To present the authors' clinical experience with unidirectional internal distraction devices to reconstruct mandibular defects. PATIENTS AND METHODS: Five patients have been treated with mandibular distraction osteogenesis to reconstruct different acquired segmental defects. These mandibular defects (35 to 80 mm in length) were reconstructed by means of internal distraction devices with a transcutaneous activator. All the patients underwent complete resection of the affected bone and immediate placement of the distraction device on the remaining mandible. RESULTS: The results' analysis was based on clinical observation, postoperative radiographs, histopathologic findings and 3-dimensional computed tomographic scans. Successful distraction osteogenesis was achieved in 3 cases. In 1 case, extensive intraoral exposure of the device was observed, resulting in a failure of the procedure. One patient died of distant metastases 4 months after the resective surgery. CONCLUSION: Because of the limited number of cases, this study is preliminary. However, considering the good experimental and clinical results, this new technique offers an alternative for patients with segmental mandibular defects in which, because of local or general reasons, a more aggressive procedure should be avoided.