Needle-free anesthesia: clinical efficacy of a mucoadhesive patch for atraumatic anesthesia in dental procedures.

This study showcases the clinical efficacy of mucoadhesive patches designed for the buccal delivery of lidocaine and prilocaine hydrochlorides (1:1, 30 mg/patch). Such patches were developed for needle-free pre-operative local anesthesia in dentistry, aiming at mitigating the use of infiltrative anesthesia for medium-complexity clinical procedures. The patches were manufactured encompassing drug-release, mucoadhesive and backing layers, all prepared through film casting using biocompatible materials. Fifty-eight (n = 58) adult patients (65% women and 35% men) were randomly selected and included in a one-arm open clinical prospective cohort study. The average age of the subjects was of 50 years. The majority (59%) of the subjects, mostly women (82%), reported needle-phobia or anxiety due to dental procedures, which was assessed through a questionnaire approved by the ethical council for human use in research. The patches were positioned in the gingival region of the teeth involved in the procedure (86% on the maxillary and 14% on the mandibular bone). Two anesthetic patches were applied on each patient: one in the vestibular region and another in the palate/lingual portion, and these patches remained attached to the placement sites throughout the procedures. Concerning the dental procedures performed, 40% were cavity preparations and dental restorations of medium cavities; 29% staple facilities; 10% gingival retractions; 9% subgingival scrapings; 3% gingivalplasties; 3% supragingival preparations; 3% occlusal adjustments; and 2% subgingival preparations. In 90% of the cases, it was not necessary to complement with conventional infiltrative local anesthesia during the procedures. Patients did not report any discomfort or side effect during or after the administration of the patches. Among the cases in which there was the need for complementation, 50% were cavity preparations and dental restorations; 33% supragingival preparations; and 17% gingivoplasties. The complementary anesthesia volume was of 0.63 ± 0.23 mL and women corresponded to 83% of the participants who needed such intervention. Furthermore, in most cases, the patch was capable of initiating the anesthesia within a short time frame (5 minutes) and reaching the maximum anesthetic effect within 15 and 25 min, lasting at least 50 min. Undesirable side effects were not reported either 2 h after the administration or within the 6-month follow-up. Therefore, the anesthetic patches developed provide needle-free, painless, safe, and patient/dentist-friendly advances in performing routine medium-complexity dental procedures.

Surrogate endpoints: when to use and when not to use? A critical appraisal of current evidences.

Clinical research needs to formulate a question, which must be answered by obeying ethical precepts with well-defined inclusion/exclusion criteria and approval of the study on platforms of ethical appreciation and clinical trial records. In comparing the results or clinically relevant outcomes should be prioritized in the study of techniques, products, inputs, drugs and therapies. However, it is not always possible to use long study drawings, with many participants, and with many costs, then look for study designs with surrogate outcomes, usually a shorter path, with less sample size and considerably lower costs to the research, with shorter intervention time. Considering these outcomes as major challenges in clinical research, the premise of this work was to examine in relevant research platforms, studies on the feasibility of using surrogate endpoints for clinically relevant parameters in dentistry, with a critical evaluation of the advantages, disadvantages, and need for validation of substitute parameters for clinical studies. After a critical analysis of the results, it could be concluded that surrogate endpoints may have an important role in the initial process of developing new drugs, faster, with less sampling, and lower risk of side effects for the patient. Careful use of the surrogate endpoints is advised because, even if validated, they can provide ambiguous evidence and not be extrapolated to other populations, and may lead to bias due to the individual interpretation of each researcher. The use of unplanned surrogate outcomes that arise during the study requires a lot of caution.

Surrogate endpoints: when to use and when not to use? A critical appraisal of current evidences

Abstract Clinical research needs to formulate a question, which must be answered by obeying ethical precepts with well-defined inclusion/exclusion criteria and approval of the study on platforms of ethical appreciation and clinical trial records. In comparing the results or clinically relevant outcomes should be prioritized in the study of techniques, products, inputs, drugs and therapies. However, it is not always possible to use long study drawings, with many participants, and with many costs, then look for study designs with surrogate outcomes, usually a shorter path, with less sample size and considerably lower costs to the research, with shorter intervention time. Considering these outcomes as major challenges in clinical research, the premise of this work was to examine in relevant research platforms, studies on the feasibility of using surrogate endpoints for clinically relevant parameters in dentistry, with a critical evaluation of the advantages, disadvantages, and need for validation of substitute parameters for clinical studies. After a critical analysis of the results, it could be concluded that surrogate endpoints may have an important role in the initial process of developing new drugs, faster, with less sampling, and lower risk of side effects for the patient. Careful use of the surrogate endpoints is advised because, even if validated, they can provide ambiguous evidence and not be extrapolated to other populations, and may lead to bias due to the individual interpretation of each researcher. The use of unplanned surrogate outcomes that arise during the study requires a lot of caution.

A new heterologous fibrin sealant as scaffold to recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins for the repair of tibial bone defects.

Tissue engineering has special interest in bone tissue aiming at future medical applications Studies have focused on recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins due to the osteogenic properties of rhBMP-2 and the angiogenic characteristic of fraction 1 protein (P-1) extracted from the rubber tree Hevea brasiliensis. Furthermore, heterologous fibrin sealant (FS) has been shown as a promising alternative in regenerative therapies. The aim of this study was to evaluate these substances for the repair of bone defects in rats. A bone defect measuring 3mm in diameter was created in the proximal metaphysis of the left tibia of 60 rats and was implanted with rhBMP-2 or P-1 in combination with a new heterologous FS derived from snake venom. The animals were divided into six groups: control (unfilled bone defect), rhBMP-2 (defect filled with 5µg rhBMP-2), P-1 (defect filled with 5µg P-1), FS (defect filled with 8µg FS), FS/rhBMP-2 (defect filled with 8µg FS and 5µg rhBMP-2), FS/P-1 (defect filled with 8µg FS and 5µg P-1). The animals were sacrificed 2 and 6 weeks after surgery. The newly formed bone projected from the margins of the original bone and exhibited trabecular morphology and a disorganized arrangement of osteocyte lacunae. Immunohistochemical analysis showed intense expression of osteocalcin in all groups. Histometric analysis revealed a significant difference in all groups after 2 weeks (p<0.05), except for the rhBMP-2 and FS/rhBMP-2 groups (p>0.05). A statistically significant difference (p<0.05) was observed in all groups after 6 weeks in relation to the volume of newly formed bone in the surgical area. In conclusion, the new heterologous fibrin sealant was found to be biocompatible and the combination with rhBMP-2 showed the highest osteogenic and osteoconductive capacity for bone healing. These findings suggest a promising application of this combination in the regeneration surgery.