Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Adults.

BACKGROUND: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level. METHODS AND RESULTS: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, and miR-193a-5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR-193b-3p, miR-194-5p, and miR-193a-5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all-cause mortality in the FHS. CONCLUSIONS: These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.

The when, why, and how of using glycopyrronium to diminish drooling in children with neurodevelopmental disabilities: Implications for clinical practice.

BACKGROUND: Despite the established efficacy of glycopyrronium bromide in reducing drooling among children with neurodevelopmental disabilities, evidence on its impact on the daily lives of children and parents and effectiveness in a real-world setting are scarce, especially among long-term users. This study explored timing and duration of glycopyrronium treatment, effect and impact on daily life, and occurrence of side effects to inform clinical practice. METHODS: This was a retrospective cohort study at a national referral centre for drooling, including 61 children with nonprogressive neurodevelopmental disabilities, treated with glycopyrronium for anterior and/or posterior drooling between 2011 and 2021. Data were obtained from medical records and supplemented by structured telephone interviews with parents. RESULTS: Anterior drooling severity decreased in 82% of the included children. Changes in the impact of drooling on burden of care, social interaction, and self-esteem were reported in 55%, 31%, and 36%, respectively. Side effects were noted for 71% of cases, yet only 36% of parents deemed these as outweighing the positive impact of treatment. A substantial majority (77%) of the included children were long-term users (≥6 months). Among these, 38% of parents reported decreasing effectiveness and 27% noticed more prominent side effects over time. CONCLUSIONS: Glycopyrronium demonstrated potential in mitigating the impact of drooling on daily life, although variations were observed in the specific aspects and extent of improvement. The real-world context of our study provides important insights for refining clinical practices, emphasizing the need for balanced consideration of treatment benefits and potential side effects to facilitate shared decision-making.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol.

INTRODUCTION: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. METHODS AND ANALYSIS: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. ETHICS AND DISSEMINATION: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings. TRIAL REGISTRATION NUMBER: NCT05972785.

The Rotterdam Study. Design update and major findings between 2020 and 2024.

The Rotterdam Study is a population-based cohort study, started in 1990 in the district of Ommoord in the city of Rotterdam, the Netherlands, with the aim to describe the prevalence and incidence, unravel the etiology, and identify targets for prediction, prevention or intervention of multifactorial diseases in mid-life and elderly. The study currently includes 17,931 participants (overall response rate 65%), aged 40 years and over, who are examined in-person every 3 to 5 years in a dedicated research facility, and who are followed-up continuously through automated linkage with health care providers, both regionally and nationally. Research within the Rotterdam Study is carried out along two axes. First, research lines are oriented around diseases and clinical conditions, which are reflective of medical specializations. Second, cross-cutting research lines transverse these clinical demarcations allowing for inter- and multidisciplinary research. These research lines generally reflect subdomains within epidemiology. This paper describes recent methodological updates and main findings from each of these research lines. Also, future perspective for coming years highlighted.

Comparing the evidence for botulinum neurotoxin injections in paediatric anterior drooling: a scoping review.

Paediatric anterior drooling has a major impact on the daily lives of children and caregivers. Intraglandular botulinum neurotoxin type-A (BoNT-A) injections are considered an effective treatment to diminish drooling. However, there is no international consensus on which major salivary glands should be injected to obtain optimal treatment effect while minimizing the risk of side effects. This scoping review aimed to explore the evidence for submandibular BoNT-A injections and concurrent submandibular and parotid (i.e. four-gland) injections, respectively, and assess whether outcomes could be compared across studies to improve decision making regarding the optimal initial BoNT-A treatment approach for paediatric anterior drooling. PubMed, Embase, and Web of Science were searched to identify relevant studies (until October 1, 2023) on submandibular or four-gland BoNT-A injections for the treatment of anterior drooling in children with neurodevelopmental disabilities. Similarities and differences in treatment, patient, outcome, and follow-up characteristics were assessed. Twenty-eight papers were identified; 7 reporting on submandibular injections and 21 on four-gland injections. No major differences in treatment procedures or timing of follow-up were found. However, patient characteristics were poorly reported, there was great variety in outcome measurement, and the assessment of side effects was not clearly described.   Conclusion: This review highlights heterogeneity in outcome measures and patient population descriptors among studies on paediatric BoNT-A injections, limiting the ability to compare treatment effectiveness between submandibular and four-gland injections. These findings emphasize the need for more extensive and uniform reporting of patient characteristics and the implementation of a core outcome measurement set to allow for comparison of results between studies and facilitate the optimization of clinical practice guidelines. What is Known: • There is no international consensus on which salivary glands to initially inject with BoNT-A to treat paediatric drooling. What is New: • Concluding on the optimal initial BoNT-A treatment based on literature is currently infeasible. There is considerable heterogeneity in outcome measures used to quantify anterior drooling.and clinical characteristics of children treated with intraglandular BoNT-A are generally insufficiently reported. • Consensus-based sets of outcome measures and patient characteristics should be developed and implemented.

Predicting non-response to intraglandular botulinum neurotoxin A injections for drooling in children with neurodevelopmental disabilities.

AIM: To develop robust multivariable prediction models for non-response to (1) submandibular botulinum neurotoxin A (BoNT-A) injections and (2) concurrent submandibular and parotid (four-gland) injections, to guide treatment decisions for drooling in children with neurodevelopmental disabilities, including cerebral palsy. METHOD: This was a retrospective cohort study including 262 children (155 males/107 females, median age 7 years 11 months [IQR 5 years 1 month], range 4 years 0 months - 17 years 11 months) receiving submandibular injections and 74 children (52 males/22 females, median age 7 years 7 months [IQR 4 years 3 months], range 4 years 9 months - 18 years 8 months) receiving four-gland injections. Multivariable logistic regression analyses were used to estimate associations between candidate predictors and non-response 8 weeks after injection. RESULTS: Ninety-six children (37%) were non-responders to submandibular injections, for which developmental age was the strongest predictor (adjusted odds ratio [aOR] 2.13; 95% confidence interval [CI] 1.02-4.45 for developmental age <4 years or 4-6 years with IQ <70). Other characteristics that showed a trend towards an increased risk of non-response were diagnosis, sex, and head position. Thirty-four children (46%) were non-responders to four-gland injections, for which tongue protrusion (aOR 3.10; 95% CI 1.14-8.43) seemed most predictive, whereas multiple preceding submandibular injections (aOR 0.34; 95% CI 0.10-1.16) showed a trend towards being protective. Predictors were, however, unstable across different definitions of non-response and both models (i.e. submandibular and four-gland) had insufficient discriminative ability. INTERPRETATION: Potential predictors of non-response to BoNT-A injections were identified. Nevertheless, the developed prediction models seemed inadequate for guidance of treatment decisions. WHAT THIS PAPER ADDS: Developmental age seemed most predictive of non-response to submandibular botulinum neurotoxin A injections. Non-response to concurrent submandibular and parotid injections was best predicted by tongue protrusion and number of previous injections. Multivariable prediction models including these clinical characteristics were unable to discriminate well. Predictors differed when non-response was defined using alternative outcome measures.

Multitechnique characterization of secondary minerals near HI-SEAS, Hawaii, as Martian subsurface analogues.

Secondary minerals in lava tubes on Earth provide valuable insight into subsurface processes and the preservation of biosignatures on Mars. Inside lava tubes near the Hawaii-Space Exploration and Analog Simulation (HI-SEAS) habitat on the northeast flank of Mauna Loa, Hawaii, a variety of secondary deposits with distinct morphologies were observed consisting of mainly sodium sulphate powders, gypsum crystalline crusts, and small coralloid speleothems that comprise opal and calcite layers. These secondary deposits formed as a result of hydrological processes shortly after the formation and cooling of the lava tubes and are preserved over long periods of time in relatively dry conditions. The coralloid speleothem layers are likely related to wet and dry periods in which opal and calcite precipitates in cycles. Potential biosignatures seem to have been preserved in the form of porous stromatolite-like layers within the coralloid speleothems. Similar secondary deposits and lava tubes have been observed abundantly on the Martian surface suggesting similar formation mechanisms compared to this study. The origin of secondary minerals from tholeiitic basalts together with potential evidence for microbial processes make the lava tubes near HI-SEAS a relevant analog for Martian surface and subsurface environments.

Virtues in Competency-Based Assessment Frameworks: A Text Analysis.

Introduction: Official documentation of specialty training provides comprehensive and elaborate criteria to assess residents. These criteria are commonly described in terms of competency roles and entrustable professional activities (EPA's), but they may also implicitly encompass virtues. Virtues are desirable personal qualities that enable a person, in this case, a medical specialist, to make and act on the right decisions. We articulate these virtues and explore the resulting implied ideal of a medical professional. Method: We applied a two-staged virtue ethical content analysis to analyze documents, specific to the Dutch training program of the Ear, Nose, and Throat (ENT) specialty. First, we identified explicit references to virtues. Next, we articulated implicit virtues through interpretation. The results were categorized into cardinal, intellectual, moral, and professional virtues. Results: Thirty virtues were identified in the ENT- training program. Amongst them, practical wisdom, temperance, and commitment. Furthermore, integrity, curiosity, flexibility, attentiveness, trustworthiness and calmness are often implicitly assumed. Notable findings are the emphasis on efficiency and effectiveness. Together, these virtues depict an ideal of a future medical specialist. Conclusion: Our findings suggest that competency-frameworks and EPA's implicitly appeal to virtues and articulate a specific ideal surgeon. Explicit attention for virtue development and discussion of the role and relevance of implied ideal professionals in terms of virtues could further improve specialty training.

Prioritizing parotid gland surgery: A call for the implementation of the MSRSGC classification.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is developed to aid diagnosis and management of salivary gland tumors. This study evaluates the time-to-treatment initiation (TTI) for parotid gland tumors in the Netherlands and relates these to the MSRSGC classification. Subsequently, the use of the MSRSGC in the Netherlands is evaluated. METHODS: Data regarding fine-needle aspiration cytology (FNAC) and histopathological resections of the parotid were gathered from the Dutch nationwide pathology data bank (PALGA). The TTI was calculated for each MSRSGC category and type of treating center. FNACs performed from 2018 to 2021 were gathered from PALGA to estimate how frequently the MSRSGC classification was applied. RESULTS: Median TTI in days were 86 for nondiagnostic (MSRSGC I), 75 for nonneoplastic (MSRSGC II), 65 for atypia of unknown significance (AUS) (MSRSGC III), 89 for benign (MSRSGC IVa), 52 for salivary gland neoplasm of unknown malignant potential (SUMP) (MSRSGC IVb), 31 for suspected malignant (MSRSGC V), and 30 for malignant (MSRSGC VI) categories. Significant variation in the TTI between the types of treating centers was found for the nondiagnostic, nonneoplastic, AUS, SUMP, and suspected malignant categories. In the first 3 years after the introduction of the MSRSGC, the pathologist stated the MSRSGC classification in 6.4% of all reports. CONCLUSIONS: The median TTI for most categories is long, and there is significant interhospital variation in TTI. Preoperative risk stratification and treatment prioritization in parotid gland surgery in the Netherlands should be improved. The MSRSGC could contribute to this. Until 2021, the MSRSGS classification was implemented on a limited scale in the Netherlands.

Predicting amyloid-beta pathology in the general population.

INTRODUCTION: Reliable models to predict amyloid beta (Aß) positivity in the general aging population are lacking but could become cost-efficient tools to identify individuals at risk of developing Alzheimer's disease. METHODS: We developed Aß prediction models in the clinical Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study (n = 4,119) including a broad range of easily ascertainable predictors (demographics, cognition and daily functioning, health and lifestyle factors). Importantly, we determined the generalizability of our models in the population-based Rotterdam Study (n = 500). RESULTS: The best performing model in the A4 Study (area under the curve [AUC] = 0.73 [0.69-0.76]), including age, apolipoprotein E (APOE) ε4 genotype, family history of dementia, and subjective and objective measures of cognition, walking duration and sleep behavior, was validated in the independent Rotterdam Study with higher accuracy (AUC = 0.85 [0.81-0.89]). Yet, the improvement relative to a model including only age and APOE ε4 was marginal. DISCUSSION: Aß prediction models including inexpensive and non-invasive measures were successfully applied to a general population-derived sample more representative of typical older non-demented adults.

Postoperative Airway Management after Submandibular Duct Relocation in 96 Drooling Children and Adolescents.

The aim of this study was to evaluate our institutions airway management and complications after submandibular duct relocation (SMDR). We analysed a historic cohort of children and adolescents who were examined at the Multidisciplinary Saliva Control Centre between March 2005 and April 2016. Ninety-six patients underwent SMDR for excessive drooling. We studied details of the surgical procedure, postoperative swelling and other complications. Ninety-six patients, 62 males and 34 females, were treated consecutively by SMDR. Mean age at time of surgery was 14 years and 11 months. The ASA physical status was 2 in most patients. The majority of children were diagnosed with cerebral palsy (67.7%). Postoperative swelling of the floor of the mouth or tongue was reported in 31 patients (32.3%). The swelling was mild and transient in 22 patients (22.9%) but profound swelling was seen in nine patients (9.4%). In 4.2% of the patients the airway was compromised. In general, SMDR is a well-tolerated procedure, but we should be aware of swelling of the tongue and floor of the mouth. This may lead to a prolonged period of endotracheal intubation or a need for reintubation which can be challenging. After extensive intra-oral surgery such as SMDR we strongly recommend a extended perioperative intubation and extubation after the airway is checked and secure.

Outpatient parotidectomy with or without the use of a post-operative drain: A retrospective bi-institutional study.

OBJECTIVE: Parotid surgery is historically performed as an inpatient procedure and suctions drains are predominantly used during surgery. Recent literature provides evidence that outpatient parotid surgery is safe and effective. Our study aims to describe the results of drainless outpatient parotidectomy and outpatient parotidectomy with drain placement and compare their outcomes. DESIGN: Retrospective cohort study. SETTING: Bi-institutional retrospective cohort study. PARTICIPANTS: Patients that underwent outpatient drain-less parotidectomy and patients that underwent outpatient parotidectomy with post-operative drain placement. MAIN OUTCOME MEASURES: Complication rates, unplanned post-operative visits, unplanned prolonged stay. RESULTS: Three hundred eighty patients underwent outpatient parotidectomy with drain placement and 31 patients underwent outpatient drainless parotidectomy in two different hospitals. The incidence of haematoma (drain: 3.1% vs. drainless: 0%, p = 1), infection (drain: 14.3% vs. drainless: 13.8%, p = 1) and salivary fistula (drain: 5.6% vs. drainless: 3.4, p = 1) were comparable between both groups. Seroma or sialocele was more frequently seen in the drain-less group (27.6% vs. 6.2%, p < .001), but were all managed conservatively. Within 10 days after surgery, unplanned visits seemed more frequent in the drain group, although the difference was not statistically significant (14.9% vs. 3.4%, p = .16). CONCLUSIONS: Outpatient parotid surgery with or without the use of a post-operative drain is safe, practical and feasible. Same-day discharge with and without drain placement yield comparable outcomes. However, the results need to be interpreted cautiously as this study was limited by a small cohort of parotidectomies without drain placement. Future studies should further compare both approaches.

Long-term effects of submandibular gland excision on drooling in children with neurodevelopmental disorders: A cross-sectional study.

AIM: Submandibular gland excision (SMGE) is suitable for the management of drooling in patients with non-progressive neurodisabilities. We aimed to investigate the long-term effects of SMGE. METHOD: Patients who had SMGE between 2007 and 2018 were included. Main outcomes were a Visual Analogue Scale (VAS), Drooling Severity (DS), and Drooling Frequency (DF) collected at baseline, 8 weeks, 32 weeks and with a median of 313 weeks after SMGE (long-term). Secondary outcomes were satisfaction with the procedure, Drooling Quotient (DQ) and adverse events (AEs). RESULTS: We included thirty-five patients in the long-term analysis with a mean age of 14.5 years. A baseline VAS score of 80.4 was found, which improved on the long-term (mean difference -21.8, t(26) = 4.636, p < 0.0005)). DS and DF decreased significantly at the long-term compared to baseline (Z = -4.361, p < 0.0001 for DS, Z = -3.065, p = 0.002 for DF). Twenty-three out of 35 (66%) patients would recommend the procedure to peers. INTERPRETATION: This study indicates a long-term stable effect on drooling after SMGE in patients with anterior drooling. Recurrence of drooling occurs due to unknown reasons, nevertheless most caregivers and/or patients are still satisfied and would recommend the procedure to others.

Validation of the Milan System for Reporting Salivary Gland Cytopathology and the diagnostic accuracy of FNA cytology for submandibular gland lesions.

BACKGROUND: The Milan System for Salivary Gland Cytopathology (MSRSGC) is a categorical system for salivary gland fine-needle aspiration cytopathology (FNAC) developed to aid clinicians in the management of salivary gland lesions. This classification is widely studied and validated, especially in cohorts that consist of mostly parotid gland lesions. However, only sparse literature describes the use of this classification for submandibular gland lesions in particular. METHODS: All patients in the Netherlands that underwent a submandibular gland resection between January 1, 2006, and January 1, 2017, with a FNAC before resection were identified with the use of the Dutch Pathology Registry database (PALGA). All FNAC results were retrospectively classified according to the MSRSGC. The risk of malignancy was calculated for all the MSRSGC categories. The sensitivity and specificity of the MSRSGC classification were calculated for submandibular gland FNAC. RESULTS: A total of 837 patients who underwent 975 FNAC aspirates from the submandibular glands were included in the analysis. Risks of malignancy for each of the MSRSGC categories were 14.4% in nondiagnostic, 4.4% in nonneoplastic, 37.0% in atypia of unknown significance, 3.9% in benign neoplasms, 40.7% in salivary gland neoplasms of unknown malignant potential, 76.2% in suspected malignant, and 91.3% in malignant cytology results. The sensitivity for diagnosing malignant submandibular gland tumors was 71.6% and specificity was 98.4%. CONCLUSIONS: The results of the present study validate the use of this classification for submandibular gland lesions. Risks of malignancy vary according to the anatomical subsites of the salivary gland lesions. LAY SUMMARY: The risks of malignancy of the various Milan System for Salivary Gland Cytopathology (MSRSGC) categories vary according to the anatomical subsite of the salivary gland lesion. The proposed management techniques of the MSRSGC are valid for use with submandibular gland lesions.

Flexible Endoscopic Biopsy: Identifying Factors to Increase Accuracy in Diagnosing Benign and Malignant Laryngopharyngeal Pathology.

OBJECTIVES: To assess the influence that several factors, such as the amount of obtained biopsies, difficult procedures, biopsy site and the experience of the attending physician, have on accuracy of flexible endoscopic biopsy (FEB). MATERIALS AND METHODS: 203 FEB procedures for benign or malignant laryngopharyngeal lesions were prospectively included. During the procedure, three representative biopsies (macroscopically containing vital tumor tissue and not only necrosis or healthy tissue) were obtained. The accuracy of each biopsy was separately analyzed. Difficulties during the procedures leading to failure of acquiring three representative biopsies were recorded and classified into tumor, patient and procedural factors. Histological results of FEB were defined correct when consistent with clinical context, additional biopsies or Positron emission tomography-computed tomography (PET-CT) revealed equivalent pathology, or the lesion was stable or resolved in >6 months follow-up. RESULTS: The first representative biopsy yielded a correct diagnosis in 65% of the cases. After the second representative biopsy, 78% was correctly diagnosed. The contribution of the third and fourth representative biopsies to accuracy was 3%. The overall accuracy of FEB was 85%. Difficult procedures were more likely to result in misdiagnosis, whereas biopsy site or experience of the attending physician did not influence results. CONCLUSIONS: FEB was accurate in diagnosing laryngopharyngeal lesions when at least two representative biopsies were obtained. Accuracy of FEB could be further improved by limiting possible constraints during the procedures, for example by selecting, informing, and anesthetizing patients carefully.

The medium to long-term effects of two-duct ligation for excessive drooling in neurodisabilities, a cross-sectional study.

OBJECTIVES: This study aims to evaluate the medium to long-term (1-12 years) effectiveness of two-duct ligation (2-DL) in patients with nonprogressive neurodisabilities. METHODS: Main outcomes included a Visual Analogue Scale (VAS), Drooling Severity (DS) and Drooling Frequency (DF), collected at baseline, 32 weeks postintervention and 1-12 years postintervention. Secondary outcomes were adverse events (AEs), and satisfaction. RESULTS: Forty-two patients were analyzed (mean age 17 years, mean baseline VAS 82). VAS decreased significantly from baseline to long-term (n = 30. Mean difference -36.5, CI -47.0 to -26.0, p ≤ 0.001; -26.1, CI -36.2 to -15.9, p ≤ 0.001). However, long-term VAS significantly increased compared to VAS at 32 weeks (+10.4, CI 1.0-19.8, p = 0.031). Out of 42 patients, 64% would recommend 2-DL to peers. CONCLUSION: There is a significant subjective 2-DL effect on drooling severity in the medium to long-term as reported by patients and caregivers, but there is also a certain degree of recurrence in this time span, and 33% of the patients required subsequent treatment. However, the majority of patients and/or caregivers would recommend 2-DL to peers.

Design, implementation and initial findings of COVID-19 research in the Rotterdam Study: leveraging existing infrastructure for population-based investigations on an emerging disease.

The Rotterdam Study is an ongoing prospective, population-based cohort study that started in 1989 in the city of Rotterdam, the Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. It focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. In response to the COVID-19 pandemic, a substudy was designed and embedded within the Rotterdam Study. On the 20th of April, 2020, all living non-institutionalized participants of the Rotterdam Study (n = 8732) were invited to participate in this sub-study by filling out a series of questionnaires administered over a period of 8 months. These questionnaires included questions on COVID-19 related symptoms and risk factors, characterization of lifestyle and mental health changes, and determination of health care seeking and health care avoiding behavior during the pandemic. As of May 2021, the questionnaire had been sent out repeatedly for a total of six times with an overall response rate of 76%. This article provides an overview of the rationale, design, and implementation of this sub-study nested within the Rotterdam Study. Finally, initial results on participant characteristics and prevalence of COVID-19 in this community-dwelling population are shown.

Surgery versus botulinum neurotoxin A to reduce drooling and improve daily life for children with neurodevelopmental disabilities: a randomized controlled trial.

AIM: To compare the effect of bilateral submandibular duct ligation and botulinum neurotoxin A (BoNT-A) on drooling severity and its impact on daily life and care in children and adolescents with moderate-to-severe drooling. METHOD: This was a randomized, interventional, controlled trial in which 53 children and adolescents (31 males, 22 females, mean age 11y, range 8-22y, SD 2y 10mo) with cerebral palsy (58.5%) or other non-progressive developmental disorders (41.5%) were randomized to BoNT-A (n=26) or bilateral submandibular duct ligation (n=27). A parent questionnaire on the severity of drooling in specific positions and daily activities and the impact of drooling on daily life and care was filled out at baseline and 8 and 32 weeks posttreatment. RESULTS: Both BoNT-A and bilateral submandibular duct ligation had a positive effect on daily care, damage to electronic equipment and/or furniture, social interactions, and self-esteem. However, bilateral submandibular duct ligation had a significant greater and longer-lasting short- (8wks) and medium-term (32wks) effect on daily care, reducing damage to electronic devices, and improving social interactions and satisfaction with life in general. INTERPRETATION: This randomized controlled trial confirms reduced drooling by both BoNT-A and bilateral submandibular duct ligation, but provides new evidence on improved well-being through a reduction in drooling. Even though there is a greater risk of complications and morbidity after bilateral submandibular duct ligation, compared to BoNT-A there was a significantly greater and longer-lasting positive effect on most outcomes. What this paper adds Bilateral botulinum neurotoxin A (BoNT-A) and submandibular duct ligation had a positive effect on the well-being of individuals with moderate-to-severe drooling. Bilateral submandibular duct ligation had a greater effect on the impact of drooling during daily care than BoNT-A. Bilateral submandibular duct ligation reduced damage to electronic devices and improved social interactions and satisfaction with life.

Accuracy of parotid gland FNA cytology and reliability of the Milan System for Reporting Salivary Gland Cytopathology in clinical practice.

BACKGROUND: Differentiating between malignant and benign salivary gland tumors with fine-needle aspiration cytology (FNAC) can be challenging. This study was aimed at testing the validity of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and at assessing possible differences in the sensitivity and specificity of parotid gland FNAC between dedicated head and neck (H&N) centers, subdivided into head and neck oncology centers (HNOCs) and head and neck oncology affiliated centers (HNOACs), and general hospitals (GHs). METHODS: The Dutch Pathology Registry (PALGA) database was searched for patients who had undergone a salivary gland resection between January 1, 2006, and January 1, 2017, and had a preoperative FNAC result. The FNAC reports were retrospectively assigned to MSRSGC categories. The risk of malignancy (ROM) was calculated for each category. The sensitivity and specificity for diagnosing malignancy were calculated and compared among HNOCs, HNOACs, and GHs. RESULTS: In all, 12,898 FNAC aspirates were evaluated. The ROMs for each category were as follows: 12.5% in MSRSGC I, 10.3% in MSRSGC II, 29% in MSRSGC III, 2.3% in MSRSGC IVa, 28.6% in MSRSGC IVb, 83% in MSRSGC V, and 99.3% in MSRSGC VI. The sensitivity of FNAC was highest in HNOCs (88.1%), HNOACs scored lower (79.7%), and GHs had a sensitivity of 75.0%. CONCLUSIONS: The MSRSGC is a valid tool for reporting parotid gland FNAC; therefore, these results strongly advocate its use. On the basis of the higher sensitivity of FNAC in dedicated H&N centers, the authors recommend that GHs use the presented management strategies to help to minimize the chances of a preoperative misdiagnosis.

Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps.

Introduction: Neutrophils contribute to host defense through different mechanisms, including the formation of neutrophil extracellular traps (NETs). The genetic background and underlying mechanisms contributing to NET formation remain unclear. Materials and Methods: We performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. GWAS was performed using haplotype reference consortium(HRC)-imputed genotypes of common variants in 3,514 individuals from the first and 2,076 individuals from the second cohort of the Rotterdam Study. We additionally performed exome-sequencing analysis in 960 individuals to investigate rare variants in candidate genes. Results: The GWAS yielded suggestive associations (p-value < 5.0 × 10-6) of SNPs annotated to four genes. In the exome-sequencing analysis, a variant in TMPRSS13 gene was significantly associated with MPO-DNA complex levels (p-value < 3.06×10-8). Moreover, gene-based analysis showed ten genes (OR10H1, RP11-461L13.5, RP11-24B19.4, RP11-461L13.3, KHDRBS1, ZNF200, RP11-395I6.1, RP11-696P8.2, RGPD1, AC007036.5) to be associated with MPO-DNA complex levels (p-value between 4.48 × 10-9 and 1.05 × 10-6). Pathway analysis of the identified genes showed their involvement in cellular development, molecular transport, RNA trafficking, cell-to-cell signaling and interaction, cellular growth and proliferation. Cancer was the top disease linked to the NET-associated genes. Conclusion: In this first GWAS and exome-sequencing analysis of NETs levels, we found several genes that were associated with NETs. The precise mechanism of how these genes may contribute to neutrophil function or the formation of NETs remains unclear and should be further investigated in experimental studies.