Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non-hypertensive Alzheimer’s patients

Introduction: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD. Methods: A nested case-control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients ≥65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow-up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60-day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events. Results: We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]). Discussion: This is the first study assessing the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP

Postoperative administration of the acetylcholinesterase inhibitor, donepezil, interferes with bone healing and implant osseointegration in a rat model

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer’s disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing

Differences in platelet-rich plasma composition influence bone healing

Aim: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. Materials and Methods: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. Results: Double-spin L-PRP contained higher concentrations of platelets than singlespin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3 ) compared to single-spin L-PRP (1.42 ± 0.27 mm3 ) or filtered L-PRP (1.38 ± 0.28 mm3 ). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. Conclusion: The preparation method of L-PRP affects their composition and potential to regenerate bone

Clinical effects of platelet-rich fibrin (PRF) following surgical extraction of lower third molar

Objective: The purpose of this study was to assess the effect of platelet-rich fibrin (PRF) on postoperative pain, analgesic consumption, soft tissue healing and socket complications following the extraction of mandibular third molars. Methods: A total number of 50 impacted third molars were surgically removed from 47 patients (13 males and 34 females; with a mean age of 25.24 ± 7.04 years). PRF clots were placed in the extraction sockets of patients included in the study group, while the sockets remained empty in the control group. The variables assessed were pain, analgesic consumption, soft tissue healing and socket complications encountered during the first postoperative week. Results: In the study group, a significantly less pain was recorded in the fifth, sixth and seventh postoperative days (P = 0.041, 0.031 and 0.005 respectively). Patients included in the study group also significantly consumed less analgesics for the second, third, sixth and seventh postoperative days (P = 0.019, 0.039, 0.045 and 0.020 respectively). PRF significantly reduced the incidence of alveolar osteitis (P = 0.037) but not the infected or inflamed sockets (P = 1.00 and 0.312 respectively). No significant difference was observed between PRF and control groups regarding soft tissue healing (P = 0.187). Conclusion: PRF could reduce alveolar osteitis, pain, and analgesic consumption following removal of impacted mandibular third molars

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP. 2023 Sadighparvar, Al Hamed, Sharif-Naeini and Meloto.Scopu

Regenerative Effect of Platelet Concentrates in Oral and Craniofacial Regeneration

International audiencePlatelet concentrates (PCs) are biological autologous products derived from the patient's whole blood and consist mainly of supraphysiologic concentration of platelets and growth factors (GFs). These GFs have anti-inflammatory and healing enhancing properties. Overall, PCs seem to enhance bone and soft tissue healing in alveolar ridge augmentation, periodontal surgery, socket preservation, implant surgery, endodontic regeneration, sinus augmentation, bisphosphonate related osteonecrosis of the jaw (BRONJ), osteoradionecrosis, closure of oroantral communication (OAC), and oral ulcers. On the other hand, no effect was reported for gingival recession and guided tissue regeneration (GTR) procedures. Also, PCs could reduce pain and inflammatory complications in temporomandibular disorders (TMDs), oral ulcers, and extraction sockets. However, these effects have been clinically inconsistent across the literature. Differences in study designs and types of PCs used with variable concentration of platelets, GFs, and leucocytes, as well as different application forms and techniques could explain these contradictory results. This study aims to review the clinical applications of PCs in oral and craniofacial tissue regeneration and the role of their molecular components in tissue healing

Regenerative potential of platelet concentrates in chronic oral mucosal lesions

Chronic oral mucosal diseases (COMDs) represent a significant challenge for clinicians and patients. They are commonly associated with chronic pain and negative effects on healing and patient's quality of life. Regenerative medicine including the use of biological autologous blood-derived substances (e.g., platelet concentrates [PCs]), has been reported to improve healing and reduce pain in orthopedic and maxillofacial surgeries as well as chronic oral mucosal diseases. In this review, we aim to describe the different types of PCs and their applications in the management of COMDs such as lichen planus, mucositis, pemphigus vulgaris, mucous membrane pemphigoid, and plasma cell mucositis, in terms of healing potential, pain control, and quality of life. Overall, PC applications seem to enhance healing and reduce pain in patients with COMDs. However, due to the small sample size and the lack of standardized clinical trials, further research is required to support these findings

High toughness resorbable brushite-gypsum fiber-reinforced cements

[EN] The ideal bone substitute material should be mechanically strong, biocompatible with a resorption rate matching the rate of new bone formation. Brushite (dicalcium phosphate dihydrate) cement is a promising bone substitute material but with limited resorbability and mechanical properties. To improve the resorbability and mechanical performance of brushite cements, we incorporated gypsum (calcium sulfate dihydrate) and diazonium-treated polyglactin fibers which are well-known for their biocompatibility and bioresorbability. Here we show that by combining brushite and gypsum, we were able to fabricate biocompatible composite cements with high fracture toughness (0.47 MPa center dot m1/2) and a resorption rate that matched the rate of new bone formation. Adding functionalized polyglactin fibers to this composite cement further improved the fracture toughness up to 1.00 MPa center dot m1/2. XPS and SEM revealed that the improvement in fracture toughness is due to the strong interfacial bonding between the functionalized fibers and the cement matrix. This study shows that adding gypsum and functionalized polyglactin fibers to brushite cements results in composite biomaterials that combine high fracture toughness, resorbability, and biocompatibility, and have great potential for bone regeneration.We thank Dr. David Liu, for assistance with the mineral characterization and McGill University's Facility for Electron Microscopy Research (FEMR) for assisting in many ways with this work. This study was supported by the Libyan Ministry of Education and Scientific Research (H. M.) , the Canadian Foundation for Innovation (CFI, F.T.) , NSERC Discovery Grants RGPIN-2019-04340 (F.T.) , "Le Reseau de recherche en sante buccodentaire et osseuse" (RSBO) , and the Canada Research Chair program (F.T. and M.C.) . MS-S acknowledges support from the UK Engineering and Physical Sciences Research Council (EPSRCEP/P001114/1) .Moussa, H.; El Hadad, A.; Sarrigiannidis, S.; Saad, A.; Wang, M.; Taqi, D.; Al-Hamed, FS.... (2021). High toughness resorbable brushite-gypsum fiber-reinforced cements. Materials Science and Engineering C: Biomimetic materials, sensors and systems (Online). 127:1-11. https://doi.org/10.1016/j.msec.2021.11220511112

Socket Shield Technique to Improve the Outcomes of Immediate Implant: A Systematic Review and Meta-Analysis

Background: The socket shield technique (SST) could address the challenges in immediate implant placement by minimizing post-extraction bone resorption while maintaining soft tissue levels. This study aimed to summarize the available evidence and systematically assess the effectiveness of SST immediate implant placement regarding all outcomes (bone loss, esthetics, implant stability, probing depth, complications, and survival rate). Methods: We searched seven electronic databases through April 2023 to identify randomized clinical trials that assessed the effect of immediate implant placed with SST (test group) versus other implant placement protocols without SST. The risk of bias was assessed using Cochrane’s randomized trial quality assessment Tool (RoB 2.0). Random-effects meta-analysis was conducted, with mean difference and 95% confidence intervals (MD, 95% CI) as effect estimates. We used the GRADE approach to assess the certainty of evidence. Results: Twelve RCTs, involving 414 immediate implants, placed in 398 patients, were included. Meta-analyses revealed that the immediate implants placed with SST had a statistically significant decrease in horizontal (MD = −0.28, 95% CI [−0.37, −0.19], p p p = 0.002) bone loss, as well as probing depth (MD = −0.64, 95% CI [−0.99, −0.29], p = 0.0003). Additionally, SST had a significant increase in implant stability (MD = 3.46, 95 % CI [1.22, 5.69], p = 0.002) and pink esthetic score (MD = 1.60, 95% CI [0.90, 2.30], p < 0.0001). Only two studies reported shield exposure incidences in the SST group; however, all studies revealed no implant failure and a 100% survival rate. The evidence certainty was assessed as very low. Conclusions: Based on limited evidence, SST was more effective in minimizing bone resorption and improving implant stability and esthetic outcomes than conventional immediate implant placement. Still, SST could not be recommended as a routine clinical protocol due to the lack of a standardized surgical approach; thus, further high-quality RCTs are required to support this conclusion