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Aim: In Europe, approximately 150.000 patients are diagnosed with head and neck cancer annually. Dentists play an important role in prevention and detection at an early stage when survival rates are best. This study aims to evaluate content of head and neck cancer education curricula of European dental schools. Materials and Methods: A questionnaire, comprising 20 questions about content of curricula and teaching methods, was distributed to the deans of all 234 members of the Association for Dental Education in Europe. Results: The response rate was 24%. All dental schools included head and neck cancer screening practices in their curricula, two-thirds had their students perform this screening on all patients routinely and education was mostly divided over various courses (65%). A variation in content of education in screening practices and counselling patients about various risk factors was reported. Alcohol and tobacco use were included in most curricula as risk factors for head and neck cancer (98%), gastro-oesophageal reflux was less frequently included (41%). The human papillomavirus (HPV) as a risk factor for oropharyngeal cancer was included in 94% of curricula and 87% also contained education about strategies to discuss prevention of HPV-related cancer. No association was found between curricula containing strategies about discussing HPV-related cancer and inclusion of the HPV vaccine in national immunisation programmes. Conclusion: Head and neck cancer teaching programmes show a considerable variation across European dental schools. Development of a unified teaching programme suitable for all European dental schools seems warranted.

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.Mondzorgverleners schrijven frequent pijnstillers voor om dentogene pijn te bestrijden. Om inzicht te krijgen in de pijnstillers die van 2016 tot en met 2020 werden voorgeschreven, werden gegevens van de Stichting Farmaceutische Kengetallen opgevraagd. Jaarlijks worden er ruim 300.000 pijnstillers verstrekt door tandartsen-algemeen practici en tandarts-specialisten. De grootste groep betreft NSAID’s (88%), gevolgd door zwakwerkende opioïden (9%), paracetamol (2%) en sterkwerkende opioïden (1%). Van de NSAID’s wordt ibuprofen door alle mondzorgverleners het meest voorgeschreven (84-91%). Van de zwakwerkende opioïden schrijven tandartsen en mka-chirurgen vooral codeïne en codeïne/paracetamol voor (respectievelijk 64% en 78%), terwijl orthodontisten vooral tramadol voorschrijven (53%). Van de sterkwerkende opioïden wordt oxycodon door alle mondzorgverleners het meest voorgeschreven (77-87%). Pijnstillers maken een groot deel uit van de voorgeschreven geneesmiddelen in de mondzorg. Het betreffen vooral NSAID’s (ibuprofen) en zwakwerkende opioïden (codeïne/paracetamol). Er zijn geen grote verschillen in het voorschrijfgedrag tussen verschillendemondzorgverleners.

Objectives Although bowel symptoms are often predominant, inflammatory bowel disease (IBD) patients can have several oral manifestations. The aim of this study was to investigate the prevalence of dental caries and periodontal disease in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to an age and gender-matched control group of patients without IBD. Material and methods The DMFT (Decayed, Missing, Filled Teeth) scores and the DPSI (Dutch Periodontal Screening Index) of 229 IBD patients were retrieved from the electronic health record patient database axiUm at the Academic Centre for Dentistry Amsterdam (ACTA) and were compared to the DMFT scores and DPSI from age and gender-matched non-IBD patients from the same database. Results The total DMFT index was significantly higher in the IBD group compared to the control group. When CD and UC were analyzed separately, a statistically significant increased DMFT index was observed in CD patients but not in UC patients. The DPSI did not differ significantly between the IBD and non-IBD groups for each of the sextants. However, in every sextant, IBD patients were more frequently edentulous compared to the control patients. Conclusion CD patients have significantly more dental health problems compared to a control group. Periodontal disease did not differ significantly between IBD and non-IBD groups as determined by the DPSI. Clinical relevance It is important that IBD patients and physicians are instructed about the correlation between their disease and oral health problems. Strict oral hygiene and preventive dental care such as more frequent checkups should be emphasized by dental clinicians.

Objective Sjögren’s syndrome patients use different dry-mouth interventions for the relieve of their oral dryness. Recently, it was shown that patients with dry-mouth complaints have regional differences in perceived intra-oral dryness. Therefore, the aim of the present study was to investigate whether the use of dry-mouth interventions is related to the perceived regional oral dryness. Materials and methods A cross-sectional study was performed among Sjögren’s patients. Volunteers could anonymously administer various questionnaires, including the Regional Oral Dryness Inventory (RODI), Xerostomia Inventory (XI), Bother Index (BI) and a list of dry-mouth interventions. Results Sjögren’s syndrome patients use a wide variety for the relieve of oral dryness. “Drinking water’’ and “moistening the lips’’ were used most frequently. Dry-mouth interventions, “drinking water’’, “rinsing of the mouth”, and “drinking small volumes” had significant associations with the RODI-scores of the posterior palate, and anterior and posterior tongue, respectively. On the other hand, “using mouth gel’’ had a significant association with the RODI-scores of the inside cheeks. Conclusion Sjögren’s syndrome patients are more likely to use mouth gels when their inside cheeks were experienced as most dry, while they drank water, rinsed their mouth or drank small volumes if the posterior palate, and anterior and posterior tongue were considered as dry. It can be concluded that intra-oral dryness affects dry-mouth perception and thereby also the use of the various dry-mouth interventions. Clinical relevance The therapeutic choice of dry-mouth interventions by Sjögren’s syndrome patients seems to some extent to be related to dryness at specific intra-oral regions.

Diet and nutrition play a fundamental role in general health and oral health in children and adults. Dietary guidelines have been developed to provide evidence-based recommendations for populations promoting a diet that meets the best nutritional requirements and prevents diet-related diseases such as overweight, obesity, diabetes and dental caries. Lifestyle and dietary habits are strongly influenced by the (social) media and the products on offer in the supermarkets. Knowledge of the field of the development of foodstuffs and lifestyle trends contributes to effective, appropriate and individualised advice for a healthy mouth in children. Sugar-free flavoured waters with aroma are a good alternative to fizzy drinks, they are tooth friendly and promote a healthy weight.Het eetpatroon en de voeding spelen een fundamentele rol bij de algehele en de mondgezondheid van kinderen en volwassenen. Voedingsrichtlijnen zijn ontwikkeld om te voorzien in evidence based aanbevelingen voor populaties gericht op de promotie van een voedings-patroon dat het meest voldoet aan de voedingsbehoefte en het voorkomen van voedingsgerelateerde ziekten zoals overgewicht, obesitas, diabetes en cariës. Leefstijl en voedingsgewoonten zijn sterk onderhevig aan de invloed van de (sociale) media en het aanbod in de supermarkten. Om een goed passend individueel advies voor een gezonde mond zo vroeg mogelijk aan kinderen te kunnen geven, draagt kennis op het gebied van de ontwikkelingen van voedingsmiddelen en leefstijltrends bij. Suikervrije smaakwaters met aroma zijn een goed alternatief voor frisdrank, zijn gebitsvriendelijk en dragen bij aan een gezond gewicht.

Objectives Recently, it was shown that the Regional Oral Dryness Inventory (RODI) could determine differences in dry-mouth perception at different intra-oral locations. The main aim of this study was to determine whether the RODI might help to discriminate between various causes of oral dryness in dry-mouth patients. The second aim was to ascertain whether the RODI could become an additional diagnostic tool in dry-mouth patients. Materials and methods Data were collected retrospectively from patients who visited a specialized saliva clinic. Salivary flow rates, Xerostomia Inventory scores, and RODI scores were extracted from the medical records. Patients were stratified into subgroups according to their health status. Results Five hundred twenty-eight patients participated in this study (mean age of 59.6 ± 16.0 years; 68.4% female). Specific patient groups differed with regard to the region of the mouth they experienced as the most and least dry. The posterior palate was the area perceived as most dry by controls and Sjögren patients. In patients using limited or multiple medications, it was the anterior tongue. RODI scores also differed significantly among dry-mouth patient groups: whereas controls and patients using limited medication had the lowest RODI scores and experienced less intra-oral dryness, Sjögren patients had the highest RODI scores. Conclusion Our use of the RODI questionnaire showed that perceived intra-oral dryness differed between the various dry-mouth patients. Clinical relevance The RODI can be a valuable clinical diagnostic tool in dry-mouth diagnostics, in which it can be used to discriminate between the various causes of oral dryness in patients.

Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Funding Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

© 2020, European Academy of Paediatric Dentistry.Purpose: To investigate associations between levels of blood parameters used to monitor liver-transplanted children with their salivary levels, and compare the salivary parameters of transplant recipients with those of healthy controls. Methods: Saliva and blood samples from 30 liver transplanted recipients, mean age 11.7 years and saliva from age and sex matched 27 healthy patients were analyzed using a standard complete blood count test. Results: Uric acid and alkaline phosphatase levels correlated significantly between saliva and blood samples in the transplanted subjects. Median salivary sodium level was significantly lower and the median salivary potassium level significantly higher in transplant recipients compared with healthy subjects. No differences were found between the groups in salivary glucose, urea, chloride, total protein, albumin, calcium, phosphorus, uric acid, total bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), triglycerides, cholesterol, iron, transferrin, glutamic pyruvic transaminase (GPT) and gamma-glutamyltranspeptidase (GGT). Conclusion: Specific correlations of serum and salivary chemistry were found in liver transplant patients. Such information may lead to the development of noninvasive monitoring tools for this population.

Purpose Symptoms of oral chronic graft-versus-host-disease (cGVHD) may significantly affect the oral health–related quality of life (OHRQoL). This study aimed to assess the OHRQoL in patients with oral cGVHD and to examine whether oral cGVHD symptoms, mucosal cGVHD, and salivary gland function correlated with OHRQoL. Methods Patients referred to the oral cGVHD outpatient clinic were included. Severity of oral mucosal cGVHD, oral cGVHD symptoms, and OHRQoL was assessed by the NIH OMS, NIH OSS, and OHIP-14, respectively. Unstimulated and stimulated whole salivary flow rates were determined and categorized into “hyposalivation,” “normal salivary flow,” and “hypersalivation.” Results Of 56 included patients, 80% had mild, moderate, or severe oral mucosal cGVHD. Mean total score of OHRQoL was 16.5 (±11.7), negatively affected by functional problems. Patients reported highest scores regarding oral sensitivity and xerostomia. Significant correlations were found between severity of oral pain and OHRQoL and between oral sensitivity and OHRQoL. No correlation was found between oral mucosal cGVHD and OHRQoL. Patients with hyposalivation, normal salivary flow, and hypersalivation reported equal levels of OHRQoL. Conclusion Results demonstrate that the OHRQoL was mostly negatively affected by complaints of oral pain and oral sensitivity and less by the severity of oral mucosal cGVHD assessed by the NIH OMS score. Special attention of (oral) health care professionals for patients with oral cGVHD is mandatory to alleviate their symptoms and improve OHRQoL.

Purpose A defunctioning stoma reduces the risk of symptomatic anastomotic leakage after low anterior resection for rectal cancer and mitigates the consequences when a leakage occurs, but the impact on mortality and oncological outcomes is unclear. The aim was to investigate the associations of a defunctioning stoma with short- and long-term outcomes in patients undergoing low anterior resection for rectal cancer. Methods Data from all patients who underwent curative low anterior resection for rectal cancer between 1995 and 2010 were obtained from the Swedish Colorectal Cancer Register. A total of 4130 patients, including 2563 with and 1567 without a defunctioning stoma, were studied. Flexible parametric models were used to estimate hazard ratios for all-cause mortality, 5-year local recurrence, and distant metastatic disease in relation to the use of defunctioning stoma, adjusting for confounding factors and accounting for potential time-dependent effects. Results During a median follow-up of 8.3 years, a total of 2169 patients died. In multivariable analysis, a relative reduction in mortality was observed up to 6 months after surgery (hazard ratio = 0.82: 95% CI 0.67–0.99), but not thereafter. After 5 years of follow-up, 4.2% (173/4130) of the patients had a local recurrence registered and 17.9% (741/4130) had developed distant metastatic disease, without difference between patients with and without defunctioning stoma. Conclusion A defunctioning stoma is associated with a short-term reduction in all-cause mortality in patients undergoing low anterior resection for rectal cancer without any difference in long-term mortality and oncological outcomes, and should be considered as standard of care.

Objective To assess the effect of sialendoscopy of the major salivary glands on salivary flow and xerostomia in patients with Sjögren’s syndrome (SS). Methods Forty-five patients with SS were randomly assigned to a control group (no irrigation, control, n = 15), to irrigation of the major salivary glands with saline (saline, n = 15) or to irrigation with saline followed by corticosteroid application (triamcinolone acetonide in saline, saline/TA, n = 15). Unstimulated whole saliva flow (UWSF), chewing-stimulated whole saliva flow (SWSF), citric acid-stimulated parotid flow, Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) and EULAR SS Patient Reported Index (ESSPRI) scores were obtained 1 week before (T0), and 1, 8, 16, 24, 36, 48 and 60 weeks after sialendoscopy. Data were analysed using linear mixed models. Results Irrespective of the irrigation protocol used, sialendoscopy resulted in an increased salivary flow during follow-up up to 60 weeks. Significant between-group differences in the longitudinal course of outcomes were found for UWSF, SWSF, XI and ESSPRI scores (P = 0.028, P = 0.001, P = 0.03, P = 0.021, respectively). UWSF at 60 weeks was higher compared with T0 in the saline group (median: 0.14 vs median: 0.10, P = 0.02) and in the saline/TA group (median: 0.20, vs 0.13, P = 0.035). In the saline/TA group SWSF at 48 weeks was higher compared with T0 (median: 0.74 vs 0.38, P = 0.004). Increase in unstimulated salivary flow was also reflected in improved CODS, XI and ESSPRI scores compared with baseline. Conclusion Irrigation of the major salivary glands in patients with SS increases salivary flow and reduces xerostomia.

The relationship between xerostomia and reduced saliva secretion is known to occur in patients suffering from dry mouth. These are mainly (frail) older people experiencing reduced saliva secretion as a result of the use of medication. In the current research, we investigated whether the severity of xerostomia could be used as predictor for saliva secretion in young adults. 369 dentistry students participated in this study, of whom 33.4% were male and 66.6% were female, with an average age of 20.2 ± 2.4 years. It was found that the severity of xerostomia in the young adult students had a weak correlation with the unstimulated saliva secretion rate. This indicates that dry mouth complaints in this age group are not a good predictor for saliva secretion. In addition, it is concluded that hyposalivation is not restricted to older people or to specific patient groups, but that even among a trial population of young adults, individuals can suffer from dry mouth and/or reduced saliva secretion.De relatie tussen xerostomie en verminderde speekselsecretie is bekend bij patiënten die drogemondklachten hebben. Dit zijn veelal (kwetsbare) ouderen die ten gevolge van medicijngebruik een verminderde speekselsecretie ervaren. In het huidige onderzoek is juist bij een groep jongvolwassenen onderzocht of de mate van xerostomie ook een voorspellende factor kan zijn voor de speekselsecretie. Aan het onderzoek namen 369 tandheelkundestudenten deel, van wie 33,4% man en 66,6% vrouw was, met een gemiddelde leeftijd van 20,2 ± 2,4 jaar. De mate van xerostomie vertoonde bij hen slechts een zwakke correlatie met de secretiesnelheid van ongestimuleerd speeksel. Dat betekent dat voor deze leeftijdsgroep het drogemondgevoel geen goede voorspeller is voor de speekselsecretie. Daarnaast is gebleken dat hyposialie niet voorbehouden is aan ouderen en specifieke patiëntengroepen, maar dat ook in een jonge onderzoekspopulatie individuen kunnen lijden aan drogemondklachten en/of verminderde speekselsecretie.

BACKGROUND: Although ulcerative colitis primarily involves the colon, extra-intestinal manifestations are common and oral and dental complaints are no exception.OBJECTIVE: This study aims at evaluating oral and dental health problems and salivary function and composition in ulcerative colitis patients and its correlation with disease activity.METHODS: Xerostomia Inventory score, (unstimulated/stimulated) salivary flow rates, salivary amylase and mucin/ Mucin 5B levels, self-reported oral and dental complaints, the oral health related quality of life, Simple Clinical Colitis Activity Index and inflammatory bowel disease-specific health related quality of life were determined.RESULTS: The cohort consisted of 51 ulcerative colitis patients. Hyposalivation was experienced by 16% of patients under resting conditions and 24% under chewing-stimulated conditions. Xerostomia was not correlated with salivary flow rates. Disease activity did not influence salivary amylase and Mucin 5B concentrations. The Xerostomia Inventory score was correlated with the Simple Clinical Colitis Activity Index (p = 0.042) and inflammatory bowel disease-specific health related quality of life (p = 0.001). Most reported oral health problems were halitosis (29%) and aphthae (28%). Frequently reported dental problems were cavities (35%) and gum problems (31%). Patients with active disease experienced significantly more oral and dental complaints. The number of oral problems was positively correlated with the Simple Clinical Colitis Activity Index (p = 0.045) and negatively correlated with the inflammatory bowel disease-specific health related quality of life (p = 0.005).CONCLUSION: The subjective feeling of a dry mouth (xerostomia) is related to disease activity and disease activity-associated quality of life in ulcerative colitis patients, whereas the objective saliva secretion rate is not. Oral and dental health problems are frequently observed in patients with ulcerative colitis, especially during active disease.

Purpose Determination of intra-oral surface areas might contribute to our understanding of the physiology of the oral cavity and oral diseases. In previous studies, the intra-oral surface area was determined using a laborious and technically challenging method. Our aim was to develop an easy and non-invasive method to determine the intra-oral surface areas. Methods In this study, we used cone-beam computed tomography (CBCT) and digital analysis in 20 human cadavers to determine various intra-oral surface areas, based on digital segmentation. Next, we explored whether there was a relationship between various intra-oral surface areas and anthropometric measurements of the head using Pearson correlation coefficient. Results Using CBCT and digital analysis, it was possible to determine various intra-oral surface areas. On average, the total intra-oral surface area was 173 ± 19 cm2. Moderate, statistical significant correlations were observed between (1) the length of the head and the palatal surface area, as well as (2) the depth of the head and the surface area of the tongue. These correlations suggest the feasibility of estimating intra-oral surface areas without relying on CBCT imaging. Conclusions This study presents a technique for measuring the intra-oral surface areas by CBCT imaging in combination with digital analysis. The results of this study suggest that anthropometric measurements of the head might be used to estimate the surface areas of the palate and tongue.

Background Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is conflicting evidence with regards to their potential as a clinically relevant imaging biomarker in multiple sclerosis (MS). Methods To perform a systematic review and meta-analysis of EPVS as visualized by MRI in MS. Nine out of 299 original studies addressing EPVS in humans using MRI were eligible for the systematic review and meta-analysis including a total of 457 MS patients and 352 control subjects. Results In MS, EPVS have been associated with cognitive decline, contrast-enhancing MRI lesions, and brain atrophy. Yet, these associations were not consistent between studies. The meta-analysis revealed that MS patients have greater EPVS prevalence (odds ratio = 4.61, 95% CI = [1.84; 11.60], p = 0.001) as well as higher EPVS counts (standardized mean difference [SMD] = 0.46, 95% CI = [0.26; 0.67], p p = 0.01) compared to controls. Conclusions Available literature suggests a higher EPVS burden in MS patients compared to controls. The association of EPVS to neuroinflammatory or -degenerative pathology in MS remains inconsistent. Thus, there is currently insufficient evidence supporting EPVS as diagnostic and/or prognostic marker in MS. In order to benefit future comparisons of studies, we propose recommendations on EPVS assessment standardization in MS. PROSPERO No: CRD42019133946.

Background: Evidence for the association between body mass index (BMI) and multiple sclerosis (MS) among men remains mixed. Objective and methods: Swedish military conscription and other registers identified MS after age of 20 years and BMI at ages 16–20 years ( N = 744,548). Results: Each unit (kg/m2) BMI increase was associated with greater MS risk (hazard ratio and 95% confidence interval = 1.034, 1.016–1.053), independent of physical fitness (1.021, 1.001–1.042). Categorised, overweight and obesity were associated with statistically significant raised MS risk compared to normal weight, but not after adjustment for physical fitness. Conclusion: MS risk rises with increasing BMI, across the entire BMI range.

Purpose: The purpose of this study was to observe the impact of oral oncological treatment, including the recovery of several tongue functions (force, mobility, and sensory functions), and to determine the influence of these functions on masticatory performance. Materials and methods: Masticatory performance and tongue force, mobility, and sensory functions were determined in 123 patients with oral cavity cancer. The assessments were performed 4 weeks before treatment and 4 to 6 weeks, 6 months, 1 year, and 5 years after treatment. Generalized estimation equations and mixed model analyses were performed, correcting for previously identified factors in the same population. Results: A significant deterioration in tongue mobility and sensory function was observed in patients with mandible and tongue and/or floor-of-mouth tumors. Better tongue force and sensory function (thermal and tactile) positively influenced masticatory performance, and this effect was stronger where fewer occlusal units were present. The effect of both the tongue force and maximum bite force was weaker in dentate patients in comparison with patients with full dentures. A web-based application was developed to enable readers to explore our results and provide insight into the coherence between the found factors in the mixed model. Conclusions: Tongue function deteriorates after oral oncological treatment, without statistically significant recovery. Adequate bite and tongue forces are especially important for patients with a poor prosthetic state. Patients with sensory tongue function deficits especially benefit from the presence of more occluding pairs.

Background Heart transplants have become a successful treatment for some cardiovascular diseases. To prevent rejection of the transplanted heart, patients have to take immunosuppressive medication. Aims The aims of this study were to identify and review oral health complications after heart transplantation. Methods The electronic database PubMed was searched for relevant articles. The search yielded 332 papers, of which 24 matched the criteria for this review. Results Gingival hyperplasia was observed in 8.3-67% of the patients. Heart transplant patients who received professional periodontal treatment starting six months after transplantation showed significantly better scores on the Gingival Index (GI) and gingival hyperplasia. In comparison to a control group, heart transplant patients did not differ significantly in the DMF(T) index. The incidence of fungal infection in patients receiving a heart transplant varied between 10% and 25%. Heart transplant patients had a 4.3 times higher chance of developing oral cancer. Conclusion Patients who underwent a heart transplant and subsequently used immunosuppressive medicines appear to have a higher risk of gingival hyperplasia, periodontal conditions, the presence of Candida species and oral malignancies, in comparison to healthy individuals. The association between heart transplants and dental caries was unclear. It is recommended that heart transplant patients receive frequent oral examination and professional dental cleaning.

A 52-year-old man with a history of krokodil (desomorphine) use was admitted to the department of oral and maxillofacial surgery with drug intoxication and severe pain in his jaw. During clinical and radiological examination, several sites of exposed necrotic bone with purulent discharge were seen. In krokodil-using patients osteonecrosis of the jaw is a frequently occurring manifestation. Other oral aspects associated with the use of krokodil include mucosal changes, a high risk of caries and periodontitis. Systemic effects can interfere with dental and oral and maxillofacial treatment. Treatment consists of sequestrectomy of the necrotic bone under general anaesthesia. The clinical picture of osteonecrosis in krokodil users is similar to cases of 'phossy jaw' and Medication Related Osteonecrosis of the Jaw (MRONJ).Een 52-jarige met een voorgeschiedenis met het gebruik van de drug krokodil (desomorfine) presenteerde zich op een afdeling Mond-, Kaak-, en Aangezichtschirurgie met een drugsintoxicatie en ernstige pijnklachten in de kaak. Na klinisch en röntgenologisch onderzoek werd op meerdere plaatsen in de mond necrotisch bot met een purulente afvloed gezien. Osteonecrose van de kaak is een frequent voorkomende manifestatie bij krokodilgebruikers. Andere orale aspecten geassocieerd met krokodilgebruik betreffen veranderingen van de orale mucosa, een hoog cariësrisico en parodontitis. Systemische effecten kunnen interfereren met tandheelkundige en mka-chirurgische behandeling. De behandeling bestaat uit een sekwestrectomie van het necrotische bot onder algehele anesthesie. Het klinisch beeld van osteonecrose van de kaak bij krokodilgebruikers is vergelijkbaar met casussen van de phossy jaw en medicatiegerelateerde osteonecrose van de kaak (MRONJ).

Summary Background BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. Methods The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. Findings 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0–54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population. Interpretation Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Funding Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.

Worldwide and also in the Netherlands there is an increasing human papillomavirus (HPV)-attributable oropharyngeal cancer incidence. This type of cancer is more common at a younger age than the classical oropharyngeal cancer, which is usually caused by smoking and excessive drinking. Most often, the tumor occurs in the tonsils and at the base of the tongue. This study explored the level of knowledge of dentists about oropharyngeal cancer, its association with the human papillomavirus and their willingness to play a role in prevention. 7.364 digital questionnaires were sent to oral health-care providers and data from 607 dentists was analyzed. 48% of knowledge questions were answered correctly by more than half of the respondents. Significantly more female caregivers were aware of the relationship between HPV and oropharyngeal cancer and the availability of an HPV vaccine. Respondents considered it important that the relationship between HPV and oropharyngeal cancer is discussed with patients and that a protocol is developed that is useful in screening for mouth and throat cancer.Wereldwijd en ook in Nederland is er een toename van de incidentie van humaan papillomavirus geassocieerde orofarynxkanker. Deze kanker komt op jongere leeftijd vaker voor dan de klassieke orofarynxkanker die meestal wordt veroorzaakt door roken en overmatig alcoholgebruik. De tumor komt vooral voor in de tonsillen en de tongbasis. In dit onderzoek is gekeken naar de kennis van tandartsen over orofarynxkanker, de associatie ervan met het humaan papillomavirus en de bereidheid om te adviseren over preventieve maatregelen. Er werden 7.364 digitale vragenlijsten naar mondzorgverleners verstuurd en data van 607 tandartsen werden geanalyseerd. Van de kennisvragen werd 48% door meer dan de helft van de respondenten correct beantwoord. Significant meer vrouwen waren op de hoogte van de associatie tussen het virus en orofarynxkanker en de beschikbaarheid van een vaccin. Respondenten vonden het belangrijk dat de relatie tussen humaan papillomavirus en orofarynxkanker met patiënten wordt besproken en wensten een protocol dat bruikbaar is bij de screening op mondholte- en keelkanker.

Tartar is formed by the precipitation of calcium phosphate on dental plaque, particularly in an alkaline environment. Fruit is acidic and contains a lot of carbohydrates besides, leading to acidification in dental plaque. In a large-scale population study, fruit consumption was therefore associated with a reduced risk of tartar build-up. Protein degradation does create an alkaline environment. However, consumption of dairy products, which are rich in protein and calcium ions, does not lead to increased formation of tartar. Oral care products containing the amino acid arginine or urea, both generating an alkaline environment, do not lead to increased tartar formation either. These studies suggest that the effect of diet on the metabolism in dental plaque is insufficient to cause an increase in tartar formation.Tandsteen ontstaat door het neerslaan van calcium- fosfaten op tandplaque, vooral in een basisch milieu. Fruit is zuur en bevat daarnaast veel koolhydraten, wat leidt tot zuurvorming in tandplaque. In bevolkingsonderzoek bleek fruitconsumptie dan ook geassocieerd met een verlaagd risico op de vorming van tandsteen. Bij eiwitafbraak kan wel een basisch milieu ontstaan. Consumptie van zuivelproducten, die eiwitrijk zijn en ook veel calciumionen bevatten, leidt echter niet tot meer tandsteenvorming. Ook mondverzorgings­producten met het aminozuur arginine of met ureum, die beide een basisch milieu genereren, leiden niet tot meer tandsteenvorming. Op basis van deze onderzoeken kan geconcludeerd worden dat voeding het metabolisme in tandplaque onvoldoende beïnvloedt om te leiden tot meer tandsteenvorming.

Objectives: The aim of this study was to identify the prevalence of and independent risk factors for long-term effects of childhood cancer treatment on the dentition and oral health in childhood cancer survivors (CCSs). Methods: This cross-sectional study is part of the Dutch Childhood Cancer Survivor Study (DCCSS) LATER 2. CCSs were diagnosed with cancer between 1963 and 2001. This study focuses on survey data of 154 CCSs on whom information about their oral health was received from their dentists (71.3%). Descriptive statistics and univariable and multivariable Poisson regression analyses were performed to determine the association between treatment characteristics and oral health data. Results: Of the study group, 36.3% had at least one DDD. The most prevalent DDDs were short-root anomaly (14.6%), agenesis (14.3%), and microdontia (13.6%). Risk factors for at least one DDD were younger age at diagnosis (&lt, 3 years) and dose-dependent alkylating agent therapy. Conclusions: This study provides more insight into risk factors for oral health problems in Dutch CCSs. This information is essential in order to improve early detection, prevention, dental care, and quality of life. Further studies are needed in order to better define dose-related radiotherapy exposure of the developing teeth in correlation with oral health problems.

Car microenvironments significantly contribute to the daily pollution exposure of commuters, yet health and socioeconomic studies focused on in-car exposure are rare. This study aims to assess the relationship between air pollution levels and socioeconomic indicators (fuel prices, city-specific GDP, road density, the value of statistical life (VSL), health burden and economic losses resulting from exposure to fine particulate matter ≤2.5 µm; PM2.5) during car journeys in ten cities: Dhaka (Bangladesh); Chennai (India); Guangzhou (China); Medellin (Colombia); Sao Paulo (Brazil); Cairo (Egypt); Sulaymaniyah (Iraq); Addis Ababa (Ethiopia); Blantyre (Malawi); and Dar-es-Salaam (Tanzania). Data collected by portable laser particle counters were used to develop a proxy of car-user exposure profiles. Hotspots on all city routes displayed higher PM2.5 concentrations and disproportionately high inhaled doses. For instance, the time spent at the hotspots in Guangzhou and Addis Ababa was 26% and 28% of total trip time, but corresponded to 54% and 56%, respectively, of the total PM2.5 inhaled dose. With the exception of Guangzhou, all the cities showed a decrease in per cent length of hotspots with an increase in GDP and VSL. Exposure levels were independent of fuel prices in most cities. The largest health burden related to in-car PM2.5 exposure was estimated for Dar-es-Salam (81.6 ± 39.3 μg m−3), Blantyre (82.9 ± 44.0) and Dhaka (62.3 ± 32.0) with deaths per 100,000 of the car commuting population per year of 2.46 (2.28–2.63), 1.11 (0.97–1.26) and 1.10 (1.05–1.15), respectively. However, the modest health burden of 0.07 (0.06–0.08), 0.10 (0.09–0.12) and 0.02 (0.02–0.03) deaths per 100,000 of the car commuting population per year were estimated for Medellin (23 ± 13.7 μg m−3), Sao Paulo (25.6 ± 11.7) and Sulaymaniyah (22.4 ± 15.0), respectively. Lower GDP was found to be associated with higher economic losses due to health burdens caused by air pollution in most cities, indicating a socioeconomic discrepancy. This assessment of health and socioeconomic parameters associated with in-car PM2.5 exposure highlights the importance of implementing plausible solutions to make a positive impact on peoples’ lives in these cities.

BACKGROUNDThere is a rising concern about treatment-associated cardiotoxicities in breast cancer patients.OBJECTIVESThis study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure and ischemic heart disease in women diagnosed with breast cancer.METHODSA register-based matched cohort study was conducted including 8338 breast cancer patients diagnosed from 2001-2008 in the Stockholm-Gotland region and followed-up until 2017. Overall and time dependent risks of arrhythmia, ischemic heart disease and heart failure in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.RESULTSDuring a median follow-up of 10.8 years, the hazard ratios for arrhythmia, heart failure and ischemic heart disease, were 1.27 (95% CI = 1.18-1.37), 1.38 (95% CI = 1.23-1.55), and 0.93 (95% CI = 0.84-1.03), respectively. Time-dependent analyses revealed long-term increased risks of arrhythmia, and heart failure in breast cancer patients compared to matched controls. The risk of ischemic heart disease was only elevated in the first year after cancer diagnosis. Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following loco-regional radiotherapy.CONCLUSIONSAdministration of systemic adjuvant therapies appear to be associated with increased risks of heart disease. The risk estimates observed in this study may serve as reference to aid adjuvant therapy decision-making and patient counseling in oncology practices.

Aim: To explore the feasibility of screening for periodontitis by measuring biomarkers, namely total proteolytic activity (TPA), matrix metalloproteinase (MMP)-8, chitinase, lysozyme or their combination, in saliva, oral rinse and gingival crevicular fluid (GCF). Material and methods: Subjects were recruited among healthy/gingivitis individuals and untreated periodontitis patients in Academic Centre for Dentistry Amsterdam (ACTA). All participants donated samples of unstimulated whole saliva, oral rinse and GCF. The protein concentrations and MMP-8 levels were determined by ELISA. Enzymatic activities were measured using appropriate fluorogenic substrates. Results: In oral rinse samples, periodontitis patients (n = 19) exhibited significantly higher concentrations of MMP-8 and TPA than controls (n = 20). MMP-8 in combination with chitinase explained 88% of the variance and assigned a subject to control or periodontitis group, with best accuracy (87.2%) in oral rinse. Conclusions: The combination of MMP-8 and chitinase in the current oral rinse procedure has the potential to discriminate periodontitis from periodontal health/gingivitis.

The coronavirus pandemic is caused by the SARS-CoV-2. Vaccination appears to offer the way out of this pandemic. Vaccines against this virus make use of the SARS-CoV-2's spike protein, an essential protein on the surface of the virus that it uses to attach itself to the host cells. In viral vector vaccines (AstraZeneca, Sputnik, JohnsonJohnson) the gene for the spike protein is introduced into an adenovirus. Following vaccination, the modified adenovirus will infect cells of the host, which will subsequently start to produce the spike protein, causing an immune response. RNA vaccines (Pfizer, Moderna) only introduce messenger RNA for the spike protein into host cells, which the messenger RNA uses to produce spike protein. Viral vector vaccines and RNA vaccines are not only faster to develop and safer to produce than traditional vaccines, they are also easier to modify to new viruses and virus variants. The latter may be of great importance for future pandemics.De COVID-19-pandemie wordt veroorzaakt door het SARS-CoV-2. Vaccinatie lijkt een uitweg uit deze pandemie te bieden. Vaccins tegen dit virus maken gebruik van het spike-eiwit van het SARS-CoV-2, een essentieel eiwit op het oppervlak van het virus waarmee het aan gastheercellen bindt. In virale vectorvaccins (AstraZeneca, Sputnik, Janssen) wordt het gen voor het spike-eiwit in een adenovirus gebracht. Na vaccinatie infecteert het adenovirus gastheercellen, die vervolgens het spike-eiwit gaan produceren waartegen een afweerreactie ontstaat. RNA-vaccins (Pfizer, Moderna) brengen alleen messenger-RNA voor het spike-eiwit in gastheercellen, die het messenger-RNA gebruiken om spike-eiwit te produceren. Virale vectorvaccins en RNA-vaccins zijn niet alleen sneller te ontwikkelen en veiliger te produceren dan traditionele vaccins, maar ook makkelijker aan te passen aan nieuwe virussen en virusvarianten. Dit laatste kan van groot belang zijn voor toekomstige pandemieën.

Introduction The narcotic drug krokodil is a semi-synthetic drug used as a cheap alternative to heroin. With its active ingredient desomorphine it is a highly addictive and destructive drug mainly used in Russia and Eastern Europe. Relatively little is known about the physical effects of krokodil. With this review we present more insight into oral health problems associated with krokodil use and how the use of this drug could influence dental and oral- and maxillofacial treatment. Methods The online electronic databases Pubmed, Web of Science, Cochrane Library and Google scholar were searched for articles concerning desomorphine or krokodil and oral side effects or pathology. Reference lists of included articles were manually screened for additional publications. Results Thirteen articles were included in this review. In total 684 patients were described in the included publications, mainly retrospective clinical case series and case reports. Eleven studies reported on osteonecrosis of the jaw and two studies reported on other physical and oral side effects associated with desomorphine abuse. Conclusion Osteonecrosis of the maxillofacial bones is a serious and mutilating oral side effect associated with krokodil use. Other oral aspects associated with its use include mucosal changes, high risk of caries and periodontitis. In addition, physical effects of the drug, which indirectly can affect oral health, have also been described. The use of the drug krokodil can interfere with dental and oral- and maxillofacial treatment.

Cardiovascular diseases are among the most common disorders in the Netherlands. Dental hygienists will often be confronted with patients who suffer from these diseases. The aim of this research was to explore the current knowledge of dental hygienists in the Netherlands about cardiovascular diseases. 979 dental hygienists in the Netherlands received a written questionnaire by post. The results were tested with the Mann-Whitney tests, the chi-square tests and the Kruskal-Wallis-H tests. A total of 150 dental hygienists participated in the study. Of the 12 case-oriented statements, the dental hygienists answered just over half of the questions correctly (on average 6.59 of 12). Dental hygienists who rated their knowledge about cardiovascular diseases high gave significantly more correct answers (average 7.04 of 12) than dental hygienists who rated themselves lower (average 6.16 of 12). This suggests that dental hygienists' knowledge of cardiovascular diseases, particularly concerning blood clotting, could be improved.Hart- en vaatziekten behoren tot de meest voorkomende aandoeningen in Nederland. Mondhygiënisten zullen hierdoor vaak worden geconfronteerd met patiënten die hieraan lijden. Het doel van dit onderzoek was om meer inzicht te verkrijgen in de actuele kennis van mondhygiënisten in Nederland over hart- en vaatziekten. Per post ontvingen 979 mondhygiënisten in Nederland een schriftelijke vragenlijst. De resultaten zijn getoetst met de Mann-Whitney-toetsen, de chi-kwadraattoetsen en de Kruskal-Wallis-H-toetsen. In totaal namen 150 mondhygiënisten deel aan het onderzoek. Van de 12 casus-georiënteerde stellingen hadden de mondhygiënisten gemiddeld iets meer dan de helft van de vragen correct beantwoord (gemiddeld 6,59/12). Mondhygiënisten die zichzelf een hoge score gaven voor hun kennis over hart- en vaatziekten, hadden significant meer antwoorden correct (gemiddeld 7,04/12) dan mondhygiënisten die zichzelf een lagere score gaven (gemiddeld 6,16/12). De kennis van mondhygiënisten over hart- en vaatziekten, vooral over bloedstolling, lijkt voor verbetering vatbaar.

Objectives Several questionnaires, such as the internationally validated and frequently used Xerostomia Inventory (XI), have been developed to quantify the subjective feeling of a dry mouth. These questionnaires quantify the overall perception of dry mouth but lack the possibility to differentiate between various intra-oral regions. In this light, a novel questionnaire, the Regional Oral Dryness Inventory (RODI), which quantifies the severity of dryness at various locations in the mouth, was evaluated. Materials and methods A retrospective case report study was designed. Data were collected from patients who visited the saliva clinic for Special Care Dentistry in Amsterdam. Data, including the saliva secretion rates, RODI scores, the Xerostomia Inventory (XI) score, and Clinical Oral Dryness Score (CODS), were extracted from the electronic health record system Oase Dental. Results A total of 337 patients participated in this study with an average age of 54 ± 17 years. The majority of the patients were female (68.5%). The perceived dryness as determined by the RODI was the highest for the posterior palate and the lowest for the floor of the mouth. The highest correlations were found between the corresponding regions in the RODI and regionally related individual items of the XI and CODS. Conclusion There is a significant difference in dry-mouth feeling at different intra-oral locations. Clinical relevance Regional evaluation of xerostomia with RODI might improve diagnosis of xerostomia by helping to discriminate between different potential causes of oral dryness in patients and for evaluating the efficacy of mouth-moistening products. RODI is highly accessible and easy to perform in dental practices during routine clinical assessment.

A sensation of dry mouth can be determined with a general questionnaire, the Xerostomia Inventory (XI). This questionnaire, however, does not distinguish among regional differences of oral dryness. In this study, therefore, a new questionnaire was evaluated, the Regional Oral Dryness Inventory (RODI), quantifying the severity of dryness in various intraoral locations. 337 patients participated in this study with an average age of 54 ± 17 years. It appeared there is a significant difference in the sensation of dry mouth between different intraoral locations; the perceived dryness scored highest for the posterior palate and lowest for the floor of the mouth. Introduction of the RODI might help to discriminate among different potential causes of oral dryness in patients. The RODI is highly accessible and easy to carry out in dental practices during routine clinical assessment.Een drogemondgevoel kan worden vastgesteld met een algemene vragenlijst, de Xerostomia Inventory. Deze vragenlijst maakt echter geen onderscheid in regionale verschillen van monddroogte. In dit onderzoek is daarom een nieuwe vragenlijst geëvalueerd, de Regional Oral Dryness Inventory (RODI), die de ernst van de droogte op verschillende intraorale regio’s kwantificeert. Aan het onderzoek 337 hebben patiënten deelgenomen, de gemiddelde leeftijd was 54 ± 17 jaar. Er bleek een significant verschil in monddroogte tussen verschillende intraorale regio’s, waarbij het achterste deel van het verhemelte het droogst en de mondbodem het minst droog werd ervaren. Introductie van de RODI kan helpen om onderscheid te maken tussen verschillende oorzaken van monddroogte bij patiënten. De RODI is eenvoudig af te nemen in mondzorgpraktijken tijdens routinematig klinisch onderzoek.

IntroductionWe established a promising sialendoscopic treatment for in vivo enhancement of salivation in salivary glands affected by Sjögren’s syndrome (SS). In this technique, the ducts of the salivary glands are irrigated with saline and steroids. This allows for dilatation of ductal strictures and removal of debris. Unfortunately, it is not possible to assess the delivery and penetration of saline or medications in the ductal system and parenchyma. To address this problem, we will conduct contrast-enhanced ultrasound sialendoscopy (CEUSS) using sulphur hexafluoride microbubbles. To the best of our knowledge, microbubbles have never been used for the treatment of salivary glands in SS. It is, therefore, imperative to test this application for its safety and feasibility.Methods and analysisA single-arm phase I study will be performed in 10 SS patients. Under local anaesthesia, ultrasound (US) guided infusion of the parotid and submandibular glands with microbubbles will be performed. Continuous US imaging will be used to visualise the glands, including the location of strictures and occlusions. Main outcomes will be the evaluation of safety and technical feasibility of the experimental treatment. Secondary outcomes will consist of determinations of unstimulated whole mouth saliva flow, stimulated whole mouth saliva flow, stimulated parotid saliva flow, clinical oral dryness, reported pain, xerostomia, disease activity, salivary cytokine profiles and clinical SS symptoms. Finally, salivary gland topographical alterations will be evaluated by US.Ethics and disseminationEthical approval for this study was obtained from the Medical Ethics Committee of the Amsterdam University Medical Centre, Amsterdam, The Netherlands (NL68283.029.19). data will be presented at national and international conferences and published in a peer-reviewed journal. The study will be implemented and reported in line with the Standard Protocol Items: Recommendations for Interventional Trials’ statement.Trial registration numbersThe Netherlands Trial Register: NL7731, MREC Trial Register: NL68283.029.19; Pre-results.

OBJECTIVES: Patients with inflammatory bowel disease have an increased risk of developing oral health problems. The aim of this study was to investigate whether oral diseases in these patients are related to inflammation of the intestine and if there is a correlation between inflammatory bowel disease-specific health-related quality of life (IBD-HR-QOL) and oral health problems.STUDY DESIGN: The study was a cross-sectional survey and analysis of self-reported oral health of individuals with a stoma for Crohn's disease (CD), ulcerative colitis (UC), and treated colon cancer (CC). Validated international questionnaires were sent to members of the Stoma Federation of The Netherlands. Because there was an unequal distribution of male and female patients with CD and CC, data of 169 age-matched female patients with CD, UC, and CC with a stoma were analyzed.RESULTS: Patients with CD had significantly more oral health problems compared with those with UC or CC. Patients with CD and UC both had significantly more gingival-related problems compared with patients with CC. There was a significant negative correlation between IBD-HR-QOL and oral health problems.CONCLUSIONS: In the 3 distinguishable groups of patients with a stoma, patients with CD had an increased risk for oral health problems, independently from surgical removal of (a part of) the inflamed intestine, suggesting a general increased susceptibility of patients with CD for oral health problems.

Cars are a commuting lifeline worldwide, despite contributing significantly to air pollution. This is the first global assessment on air pollution exposure in cars across ten cities: Dhaka (Bangladesh); Chennai (India); Guangzhou (China); Medellín (Colombia); São Paulo (Brazil); Cairo (Egypt); Sulaymaniyah (Iraq); Addis Ababa (Ethiopia); Blantyre (Malawi); and Dar-es-Salaam (Tanzania). Portable laser particle counters were used to develop a proxy of car-user exposure profiles and analyse the factors affecting particulate matter ≤2.5 μm (PM2.5; fine fraction) and ≤10 μm (PM2.5–10; coarse fraction). Measurements were carried out during morning, off- and evening-peak hours under windows-open and windows-closed (fan-on and recirculation) conditions on predefined routes. For all cities, PM2.5 and PM10 concentrations were highest during windows-open, followed by fan-on and recirculation. Compared with recirculation, PM2.5 and PM10 were higher by up to 589% (Blantyre) and 1020% (São Paulo), during windows-open and higher by up to 385% (São Paulo) and 390% (São Paulo) during fan-on, respectively. Coarse particles dominated the PM fraction during windows-open while fine particles dominated during fan-on and recirculation, indicating filter effectiveness in removing coarse particles and a need for filters that limit the ingress of fine particles. Spatial variation analysis during windows-open showed that pollution hotspots make up to a third of the total route-length. PM2.5 exposure for windows-open during off-peak hours was 91% and 40% less than morning and evening peak hours, respectively. Across cities, determinants of relatively high personal exposure doses included lower car speeds, temporally longer journeys, and higher in-car concentrations. It was also concluded that car-users in the least affluent cities experienced disproportionately higher in-car PM2.5 exposures. Cities were classified into three groups according to low, intermediate and high levels of PM exposure to car commuters, allowing to draw similarities and highlight best practices.

BACKGROUND Onychomycosis is a fungal disease that affects the fingernails and toenails and is predominantly caused by dermatophytes. VT-1161 is a novel inhibitor of fungal CYP51 through the inhibition of lanosterol demethylase, and has demonstrated potent activity against Trichophyton rubrum and Trichophyton mentagrophytes. OBJECTIVES To evaluate the safety and efficacy of four dosing regimens of orally administered VT-1161 compared with placebo in patients with moderate-to-severe distal and lateral subungual onychomycosis of the toenail. METHODS This was a phase II, randomized, double-blind, placebo-controlled, multicentre study (ClinicalTrials.gov identifier NCT02267356). Patients aged 18-70 years (n = 259) who had 25-75% mycotic involvement were randomized to five treatment groups. They received 300 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks, or 600 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks. All treatments were followed by a nontreatment period of 36 weeks. A matching placebo arm was included. RESULTS In the intent-to-treat population, at week 48 the complete cure rates were 0% in the placebo group and ranged from 32% to 42% in the VT-1161 treatment groups (P < 0·001 vs. placebo). VT-1161 was well tolerated, with no evidence of an adverse effect on liver function or QT intervals. CONCLUSIONS VT-1161 treatment led to high nail clearance rates and a favourable safety profile. VT-1161 exhibits characteristics that appear promising for the treatment of this chronic and difficult-to-treat condition and warrants further evaluation in larger studies.

Objectives This systematic review aimed to investigate the oral health of post-liver transplant recipients (postLTx), in terms of dental and periodontal clinical results. Data sources Pubmed/MEDLINE and Cochrane Library databases were searched electronically. Data selection Prospective, cross-sectional and case-control studies comparing periodontal and dental health of postLTx patients with healthy and/or pre-liver transplant patients. Data extraction This was performed independently by two authors. Quality assessment was done by using tools from the National Heart, Lung, and Blood Institute. Data synthesis Nine studies were eligible for inclusion in the systematic review. A meta-analysis was performed on gingival inflammation, expressed by scores, on four studies including healthy controls. The gingival index scores were significantly higher in postLTx patients compared with healthy controls (p 2 = 99.5%). Increased tendency of gingival enlargement was noticed in postLTx patients, especially after immunosuppression with Cyclosporine A. Controversial results were reported for the prevalence of caries in postLTx recipients, but there seems to be an increase. Conclusion The results suggest that patients with liver transplants, due to systemic condition and immunosuppressive therapy, exhibit a higher degree of gingival inflammation compared with unexposed patients. Prospero registration number: CRD42019121893.

Objective To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. Design National register based birth cohort study with a sibling comparison design. Setting Sweden. Participants 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014. Main outcome measure Fractures by attained age up to 32 years. Results During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ≥10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. Conclusion Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.

Background: Inflammation is associated with cardiac remodeling and heart failure, but how it is initiated in response to nonischemic interventions in the absence of cell death is not known. We tested the hypothesis that activation of Ca 2+ /calmodulin-dependent protein kinase II δ (CaMKIIδ) in cardiomyocytes (CMs) in response to pressure overload elicits inflammatory responses leading to adverse remodeling. Methods: Mice in which CaMKIIδ was selectively deleted from CMs (cardiac-specific knockout [CKO]) and floxed control mice were subjected to transverse aortic constriction (TAC). The effects of CM-specific CaMKIIδ deletion on inflammatory gene expression, inflammasome activation, macrophage accumulation, and fibrosis were assessed by quantitative polymerase chain reaction, histochemistry, and ventricular remodeling by echocardiography. Results: TAC induced increases in cardiac mRNA levels for proinflammatory chemokines and cytokines in ≤3 days, and these responses were significantly blunted when CM CaMKIIδ was deleted. Apoptotic and necrotic cell death were absent at this time. CMs isolated from TAC hearts mirrored these robust increases in gene expression, which were markedly attenuated in CKO. Priming and activation of the NOD-like receptor pyrin domain-containing protein 3 inflammasome, assessed by measuring interleukin-1β and NOD-like receptor pyrin domain-containing protein 3 mRNA levels, caspase-1 activity, and interleukin-18 cleavage, were increased at day 3 after TAC in control hearts and in CMs isolated from these hearts. These responses were dependent on CaMKIIδ and associated with activation of Nuclear Factor-kappa B and reactive oxygen species. Accumulation of macrophages observed at days 7 to 14 after TAC was diminished in CKO and, by blocking Monocyte Chemotactic Protein-1 signaling, deletion of CM Monocyte Chemotactic Protein-1 or inhibition of inflammasome activation. Fibrosis was also attenuated by these interventions and in the CKO heart. Ventricular dilation and contractile dysfunction observed at day 42 after TAC were diminished in the CKO. Inhibition of CaMKII, Nuclear Factor-kappa B, inflammasome, or Monocyte Chemotactic Protein-1 signaling in the first 1 or 2 weeks after TAC decreased remodeling, but inhibition of CaMKII after 2 weeks did not. Conclusions: Activation of CaMKIIδ in response to pressure overload triggers inflammatory gene expression and activation of the NOD-like receptor pyrin domain-containing protein 3 inflammasome in CMs. These responses provide signals for macrophage recruitment, fibrosis, and myocardial dysfunction in the heart. Our work suggests the importance of targeting early inflammatory responses induced by CM CaMKIIδ signaling to prevent progression to heart failure.