[Postoperative risk of bleeding after removal of third molars in healthy patients - a prospective observational clinical study]. / Nabloedingsrisico na verwijdering derde molaar bij gezonde patiënten; een prospectief observationeel klinisch onderzoek.

Removal of third molars in healthy patients is considered a procedure with a low risk of bleeding. However, exactly how low the incidence of postoperative bleeding is remains unclear due to the heterogeneity of available studies. To determine the exact postoperative risk of bleeding after the removal of third molars in healthy patients, a prospective observational multicentre study was conducted. A total of 1,035 patients with complete follow-up was included. Of these, 329 patients reported subsequent bleeding, but did not consult their attending physician. A total of 15 patients visited the hospital, 8 of whom required minimally invasive (re)treatment. No hospitalizations were necessary. There was a large difference between the incidence of postoperative bleeding reported by patients and postoperative bleeding requiring clinical examination and/or treatment. To reduce this difference in future, patients should be given detailed information about what degree of postoperative bleeding is considered normal after removal of a third molar.

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. RESULTS: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. CONCLUSIONS: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. TRIAL REGISTRATION: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

[Dental aspects of Marfan syndrome]. / Tandheelkundige aspecten van het syndroom van Marfan.

Marfan syndrome is characterized by several (severe) medical disorders, the most important of which is aortic dilatation. Treatment of these disorders has consequences for oral care, in particular with regard to endocarditis prophylaxis and the use of anticoagulation. Furthermore, several orofacial anomalies of Marfan syndrome relevant to dental care are described in the literature. These anomalies may affect different areas within the spectrum of dental care, ranging from orthodontics to periodontology. Within these areas, Marfan syndrome is associated with a characteristic countenance and the prevalence of temporomandibular dysfunction, caries, endodontic anomalies and periodontitis. Medical-dental interaction with patients with Marfan syndrome should also be taken into consideration.

[The use of analgesics in Dutch oral care from 2016 through 2020]. / Het gebruik van pijnstillers in de mondzorg in de periode 2016 tot en met 2020.

Oral care providers frequently prescribe analgesics for the management of dental pain. To get an overview of the analgesics prescribed in the Netherlands from 2016 through 2020, we collected data from the Stichting Farmaceutische Kengetallen (foundation [for] pharmaceutical indicators). Annually, more than 300,000 analgesics are prescribed by dentists in general practice and dental specialists. The largest group concerns NSAIDs (88%), followed by weak opioids (9%), acetaminophen (2%) and strong opioids (1%). Of the NSAIDs, ibuprofen is the most prescribed by all groups of oral care providers (84-91%). Of the weak opioids, dentists and oral and maxillofacial surgeons mainly prescribe codeine and codeine/ acetaminophen (64% and 78%, respectively), while orthodontists mainly prescribe tramadol (53%). Of the strong opioids, oxycodone is the most frequently prescribed by all groups of oral care providers (77-87%). Analgesics are a large part of the prescription medications in Dutch oral care and mainly concern NSAIDs (ibuprofen) and weak opioids (codeine/ acetaminophen). There are no major differences in prescription behaviour among different oral care providers.

[Use of analgesics in oral care]. / Toepassing van pijnstillers in de mondzorg.

To alleviate acute dental pain, dentists and dental specialists frequently prescribe analgesics to patients, either on prescription or not. In order to effectively manage dental pain, it is advisable to follow a step-by-step plan based on the WHO analgesic ladder: step 1, start with acetaminophen step 2, add an NSAID (e.g. ibuprofen, diclofenac, naproxen); step 3, add a weak opioid (e.g. tramadol) in combination with acetaminophen or an NSAID; step 4, replace a weak opioid with a strong opioid (e.g. morphine or oxycodone). A dentist in general practice or a dental specialist needs to know, the mechanism of action and the most important interactions, contraindications and adverse effects of each of these groups of medications. Attention is needed when prescribing analgesics to risk groups such as frail elderly, pregnant and lactating women, and children.

[Medicaments and oral healthcare. Medicaments potentially inducing angioedema and/or urticaria]. / Serie: Medicamenten en mondzorg. Medicamenten die angio-oedeem en/of urticaria kunnen induceren.

Angioedema stems from increased vasodilation and vascular permeability, resulting in extravasation of fluid. Hereditary and acquired types of angioedema can be distinguished, with 3 and 4 subtypes, respectively. Groups of medicaments potentially inducing angioedema are, among others: ACE inhibitors, angiotensin II receptor blockers, dipeptidyl peptidase-4 inhibitors, thrombocyte aggregation inhibitors and immunosuppressive agents. Urticaria is characterised by red, slightly raised swellings, usually associated with a strong itching sensation and can be subdivided in an acute and a chronic type. Mast cells in the uppermost layer of the skin or the mucous membranes release a lot of histamine, increasing the dilation and permeability of blood capillaries, resulting in extravasation of fluid. Medicaments potentially inducing urticaria are, among others, the following groups: analgesics, anaesthetics, antibiotics, antidepressants, antihistamines, antihypertensives, antifungals, corticosteroids, H2 blockers, cancer medicaments, muscle relaxants, thrombocyte aggregation inhibitors and vaccines. Medical history and being alert when administering and prescribing anaesthetics, analgesics and antibiotics are very important in the prevention or treatment of angioedema and/or urticaria.

Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

[Antithrombotics: backgrounds with haemostasis and antithrombotic therapy]. / Antitrombotica: achtergronden bij stolling en antistolling.

The clinical guidelines on antithrombotics, published by the Dutch Institute of Expertise for Oral Healthcare, give advice on policy to be followed in cases of dental procedures involving bleeding. The guidelines allow room for professional assessment of bleeding risks, for which background knowledge about haemostasis, thrombosis and antithrombotic processes is necessary. Normal haemostasis can be divided in several steps: vasoconstriction, primary haemostasis by aggregation of thrombocytes, and secondary haemostasis by the formation of fibrin out of coagulation factors. In the case of thrombosis, a blood clot forms inside a blood vessel, causing obstruction of blood flow to the underlying tissue. Various antithrombotics are prescribed for the prevention and treatment of thrombosis. Thrombocyte aggregation inhibitors only have an effect on primary haemostasis. Vitamin K antagonists influence secondary haemostasis by lowering the production of several coagulation factors. The direct oral anticoagulants have an immediate effect on an activated coagulation factor, and are currently prescribed in large quantities [in the Netherlands]. Low-molecular-weight heparin also inhibits activated coagulation factors, but is not used for long-term antithrombotic therapy since it is administrated subcutaneously.

[Using the new clinical guidelines on antithrombotics in the dental practice]. / Toepassen van nieuwe richtlijn 'Antitrombotica' in de mondzorgpraktijk.

A 64-year-old man has deep caries in tooth 37 without acute pain; extraction is indicated, however. According to his list of medications, he takes the antithrombotics apixaban and clopidogrel. Or: a 78-year-old woman has upper and lower dentures that don't function well, and she experiences retention problems. Implant-bearing upper and lower dentures on 4 and 2 implants, respectively, are indicated. The patient takes acenocoumarol and reports that the clotting time value of her blood (INR) sometimes fluctuates. The clinical guidelines 'Dental procedures in patients using antithrombotic medication', which recently appeared, offer oral healthcare providers recommendations for reducing the risk of bleeding while observing the risk of thrombosis. These guidelines by the Dutch Institute of Expertise for Oral Healthcare replace the previous guidelines from 2012. The recommendations are up to date with current practice in the Netherlands and take into account all antithrombotics patients may currently use in an outpatient setting. Furthermore, the responsibilities of the oral healthcare providers and the agreements with thrombosis services are formalised in these guidelines.

[Osteoporosis: risk factor for implants?] / Osteoporose: risicofactor voor implantaten?

Many, mostly older patients suffer from osteoporosis: a chronic skeletal disease causing bone to become more porous and less strong. 2 recent systematic reviews and one long-term prospective multicentre case-control study showed that placing implants in osteoporosis patients is not contraindicated. From these studies it can be concluded that results comparable to those with patients who do not suffer from osteoporosis can be reached. Osseointegration, implant survival rate, marginal bone loss and mucosal parameters do not behave differently than they do in the healthy group of patients.

[Medicaments and oral healthcare. Adverse effects of medications on the oral mucosa]. / Serie: Medicamenten en mondzorg. Bijwerkingen van medicatie op de orale mucosa.

Many medications prescribed in the Netherlands have adverse effects on the oral mucosa. Adverse events often described are stomatitis, white lesions, abnormal pigmentation and sensibility disorders. Stomatitis is frequently observed in patients using medications for the treatment of malignancies or auto-immune diseases. Important causative classes of medicines are alkylating agents, anthracyclines, monoclonal antibodies, protein kinase inhibitors, purine derivatives, pyrimidine antagonists, taxanes and vinca alkaloids. White oral lesions often concern candidiasis and are frequently seen in patients using certain immunosuppressants and antibiotics. Abnormal pigmentation is frequently seen in patients using hydroxycarbamide, an antineoplastic agent. Sensibility disorders of the oral mucosa are described in several classes of medications, including protein kinase inhibitors. It is very important oral healthcare professionals can recognise possible adverse effects of medications on the oral mucosa. When it is probable an anomaly of the oral mucosa is caused by medication, the oral healthcare professional should contact the prescribing physician to discuss the possibility of adjusting or discontinuing the medication.

[Medicaments and oral healthcare. Hyperpigmentation of oral soft tissues due to afamelanotide]. / Serie: Medicamenten en mondzorg. Hyperpigmentatie van de orale slijmvliezen door afamelanotide.

The medicament afamelanotide is an analogue of endogenous ?-melanocyte-stimulating hormone. It promotes cutaneous pigmentation, providing protection from sunlight. In dermatology, afamelanotide seems to establish therapeutic results for polymorphic light eruption, solar urticaria, erythropoietic protoporphyria, Hailey-Hailey disease, vitiligo and acne vulgaris. Afamelanotide is available for non-medical use to realise quick and easy skin tanning. Adverse effects of afamelanotide mentioned in the scientific literature are development and aggravation of melanocytic naevi, degeneration of melanocytic naevi to melanomas, melanonychia, systemic toxicity, rhabdomyolysis, posterior reversible encephalopathy syndrome, priapism and hyperpigmentation of oral soft tissues. Furthermore, numerous adverse effects of afamelanotide have been reported to the Netherlands pharmacovigilance centre LAREB as well as numerous adverse effects due to overdosage of afamelanotide to the National Poisons Information Centre. Dentists should be alert to hyperpigmentation of oral soft tissues due to afamelanotide.

[Can dental students and dental care providers in the Netherlands effectively and safely prescribe drugs?] / Serie: Onderwijs en de tandarts anno 2025. Kunnen tandheelkunde­studenten en mondzorgverleners in Nederland effectief en veilig geneesmiddelen voorschrijven?

Dentists and dental specialists are qualified to prescribe drugs. In this study, we assessed and compared the pharmacotherapeutic knowledge and skills of final year dental students, dentists and dental specialists in the Netherlands. In 2017, a random sample of these three groups was invited to complete an assessment. The knowledge assessment comprised 40 multiple choice questions covering often prescribed drugs. The skills assessment comprised three patient cases for which participants had to write a treatment plan. For the knowledge assessment, the response rates were 26 (20%) dental students, 28 (8%) dentists and 19 (19%) dental specialists, and for the skills assessment the response rates were 14 (11%) dental students, eight (2%) dentists, and eight (8%) dental specialists. On average, all three groups had inadequate knowledge scores (smaller 80%) and only a small proportion (smaller 30%) of their treatment plans was assessed as correct. These results suggest that dental students, dentists and dental specialists lack prescribing competence, which could be caused by poor pharmacotherapy education during under- and postgraduate dental training.

[Oral graft-versus-host-disease: implications for dental professionals]. / Orale graft-versus-hostziekte: implicaties voor mondzorgverleners.

Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transpl antation, which frequently affects the mouth. GVHD is the result of an immunological attack of donor-derived cells against the tissue of patients. Chronic oral GVHD can affect the mucosa and/or damage salivary glands and can cause sclerotic changes to the head and neck area. Patients can experience painful oral and gingival mucosa, dry mouth, taste changes and limited mouth opening. Due to painful mucosa and salivary glands, and limited mouth opening, performing oral hygiene and dental interventions can be difficult. Immunosuppression in combination with altered salivary production increases the risk of secondary infectious complications, such as dental caries and candida infections. Dental professionals can play an important role in the prevention of oral complications.

[Antibiotic prophylaxis in patients with joint prostheses]. / AB-profylaxe bij patiënten met een gewrichtsprothese.

A systematic literature review was carried out in order to formulate a new Dutch guideline regarding policies for patients with a joint prosthesis who are to undergo a dental procedure. The research question was: Is antibiotic prophylaxis indicated in patients with a joint prosthesis who undergo dental procedures? The literature comprised studies in which patients with joint prostheses underwent a dental procedure resulting in hematogenous periprosthetic joint infection or in which a correlation between prophylactic antibiotics and hematogenous periprosthetic joint infection were described. The GRADE/AGREE II method was used to determine the strength of the evidence. A supplementary review of literature to gain further insight into pathophysiology, risk factors and risk intervention was carried out. The included studies did not provide any conclusive evidence that the use of antibiotic prophylaxis reduces the incidence of dental hematogenous periprosthetic joint infection. The results of the supplementary review of literature also supported the conclusion that antibiotic prophylaxis should be discouraged in dental procedures.

[The medical-dental interactions scanner: an Electronic Health Record-integrated quality and safety module for medical-dental interactions]. / De MTI-scanner: een EPD-geïntegreerde kwaliteits- en veiligheidsmodule voor medisch tandheelkundige interacties.

Dental professionals will be confronted more frequently with medically compromised patients due to an increasing life expectancy in Western countries. The patients' systemic diseases and medication usage can both have consequences for oral health and dental treatment. It is often impossible to have all medical-dental interactions handy in the dental practice. To support the dental professional in providing safe healthcare, a tool has been developed. The medical-dental interactions scanner supports both patients and dental professionals in taking a patient's medical history and linking that information to the available literature. By that means, it is possible for the caregiver to provide patient-specific recommendations concerning possible adverse effects of medicaments,intra-oral manifestations of systemic diseases and measures to prevent medical emergencies.

[Maxillary osteonecrosis after denosumab treatment]. / Verlies van de bovenkaak door denosumab.

A 58-year-old patient with a history of intravenous use of denosumab was referred to the department of oral and maxillofacial surgery with inadequate recovery after a series of extractions. During physical and radiological examination, several sites of exposed necrotic bone with purulent discharge were seen, and the maxilla appeared fractured at the level of Le Fort 1. Treatment consisted of intravenous administration of antibiotics with consecutive sequestrectomy of the maxilla under general anaesthesia. While Medication Related Osteonecrosis of the Jaw (MRONJ) is most commonly seen in patients treated with bisphosphonates, in the past decade, it has become apparent that other types of medication, most notably denosumab, can cause comparable disorders. Treatment of MRONJ strongly depends on the stage the disease is in. In patients with a history of denosumab or bisphosphonate use (administered either intravenously or orally in combination with corticosteroids), abnormal radiological findings, or developing osteonecrosis, referral to a department of oral and maxillofacial surgery is recommended.

Antibiotic prophylaxis is not indicated prior to dental procedures for prevention of periprosthetic joint infections

Background and purpose: To minimize the risk of hematogenous periprosthetic joint infection (HPJI), international and Dutch guidelines recommended antibiotic prophylaxis prior to dental procedures. Unclear definitions and contradictory recommendations in these guidelines have led to unnecessary antibiotic prescriptions. To formulate new guidelines, a joint committee of the Dutch Orthopaedic and Dental Societies conducted a systematic literature review to answer the following question: can antibiotic prophylaxis be recommended for patients (with joint prostheses) undergoing dental procedures in order to prevent dental HPJI? Methods - The Medline, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs), reviews, and observational studies up to July 2015. Studies were included if they involved patients with joint implants undergoing dental procedures, and either considered HPJI as an outcome measure or described a correlation between HPJI and prophylactic antibiotics. A guideline was formulated using the GRADE method and AGREE II guidelines. Results - 9 studies were included in this systematic review. All were rated "very low quality of evidence". Additional literature was therefore consulted to address clinical questions that provide further insight into pathophysiology and risk factors. The 9 studies did not provide evidence that use of antibiotic prophylaxis reduces the incidence of dental HPJI, and the additional literature supported the conclusion that antibiotic prophylaxis should be discouraged in dental procedures. Interpretation - Prophylactic antibiotics in order to prevent dental HPJI should not be prescribed to patients with a normal or an impaired immune system function. Patients are recommended to maintain good oral hygiene and visit the dentist regularly

Oral complications in hematopoietic stem cell recipients: the role of inflammation.

Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis.

Cytotoxicity of poly(96L/4D-lactide): the influence of degradation and sterilization.

The cytotoxicity of poly(96L/4D-lactide) (PLA96), and of its accumulated degradation products, was investigated following different sterilization methods and pre-determined heat-accelerated degradation intervals. PLA96 samples sterilized by either steam, ethylene oxide, or gamma irradiation were left untreated (S0 samples), or were degraded for 30 h or 60 h (S30 and S60 samples) at 90 degrees C in water. Extracts of the samples and of the remaining degradation fluids (F30 and F60) were prepared. The toxicity of both unfiltered and filtered extracts was analyzed in a cell growth inhibition (CGI) assay and a lactate dehydrogenase (LDH) leakage assay. Physical analysis of the extracted samples and of the degradation fluids also was performed. The S0 extracts demonstrated no significant CGI. The CGI of the S30 extracts ranged from 37 to 78%, whereas the CGI of the S60 extracts ranged from 6 to 33%. The CGI of the F30 extracts ranged from 19 to 38% and the CGI of the F60 extracts was 98 to 123%. The LDH leakage assay only showed a high response to the unfiltered F60 extracts. Neither sterilization nor filtration appeared to influence the cytotoxicity of the extracts. Particle accumulation, however, might affect cell membrane permeability resulting in LDH leakage. The results of this study suggest that the cytotoxicity of PLA96 is related to the pH and possibly the osmolarity of the tested extracts. The pH and osmolarity, in turn, may depend on variations in the amounts of solubilized lactic acid and oligomers. These variations appear to result from degradation stage-dependent differences in crystallinity, molecular weight and molecular weight distribution of the PLA96 samples.