Longitudinal study of the role of salivary proteins on radiation-related caries onset in head and neck cancer patients using 5000 ppm fluoride dentifrice up to one-year post-intensity modulated radiotherapy.

OBJECTIVES: Longitudinal assessment of the role of specific proteins on radiotherapy caries (RC) onset in head and neck cancer patients(HNC) up to one-year post-IMRT using a 5000ppm fluoride paste daily. MATERIALS AND METHODS: Dental status/salivary protein data were obtained from 40 HNC patients pre-IMRT, six months (T1) and 12 months (T2) post-IMRT (ethical approval/consent). DMFT/salivary parameters were quantified, including flow rate, mucin 5B/7, Immunoglobulin A (IgA), cystatin S and α-amylase. RESULTS: 45% patients had at least one carious lesion at T2, a significant reduction in the number of remaining teeth (65% <21), salivary flow rate (< 50%) and, protein secretion (< 0.05) post-IMRT. T1 IgA concentration/secretion rate was associated with RC (p < 0.05). Finally, IgA and total protein concentration obtained at T1 could provide a predictive pattern (AUC 82.3%) for the patients more predisposed to developing RC at T2. CONCLUSIONS: This study demonstrated the significant association of RC with salivary proteins in HNC patients treated with IMRT, revealing the potential role of salivary proteins in the early diagnosis of RC. CLINICAL RELEVANCE: This research contributes to revealing salivary proteins association with RC, and its role in early diagnosis. Therefore, this could be the first step towards personalized medicine approaches to improve this group quality-of-life.

Analysis of the association between salivary proteins and oral mucositis in patients with head and neck cancer undergoing IMRT: a longitudinal study.

INTRODUCTION: This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT). METHODS: Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified. RESULTS: 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT. CONCLUSION: This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results. CLINICAL SIGNIFICANCE: The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL). RESEARCH QUESTION: What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients? AIM: To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy. NULL HYPOTHESIS: There is no association between salivary proteins and onset/severity of OM in HNC patients.

A Descriptive Study of the Caregiver's Experience of Managing Care for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder During the COVID-19 Pandemic: The UNCOVER Study.

Objective: To assess the perceived impact of the COVID-19 pandemic on treatment and quality of life for children and adolescents in the United States who have attention-deficit/hyperactivity disorder (ADHD).Methods: An online survey of members of PatientsLikeMe was conducted via the health-tracking platform between March 10 and April 2, 2021. Participants were adult caregivers of dependents aged 6-18 years with diagnosed ADHD and who were taking or not taking prescription medication for ADHD.Results: The study enrolled 37 adult caregivers of 37 children/adolescents; 36 caregivers responded to treatment questions for children/adolescents. Twenty were caregivers to dependents currently being treated for ADHD. Compared with before the pandemic, there was a decrease in the percentage of children/adolescents using prescription ADHD medication from 65% to 54% during the pandemic. At least 1 switch in ADHD medication and a dosage change were reported by 5 and 8 caregivers, respectively. Seven caregivers reported their dependents had had difficulty adhering to their medication regimen during the pandemic, which caregivers ascribed to a lack of a structured routine. Telehealth visits for their dependents were reported by 13 caregivers. None of the caregivers of dependents taking ADHD medication reported a major impact of the pandemic on ADHD-related medical care. Irrespective of treatment status, 17 caregivers reported that their dependents had ADHD management goals and agreed that the pandemic had a negative impact on progress toward those goals.Conclusions: Many caregivers of children/adolescents with ADHD found it challenging to manage their dependents' symptoms and treatment during the pandemic.Prim Care Companion CNS Disord 2024;26(1):23m03587. Author affiliations are listed at the end of this article.

The Experience of Adults With Attention-Deficit/Hyperactivity Disorder in 2021 During the COVID-19 Pandemic: The UNCOVER Study.

Background: This study surveyed adults with attention-deficit/hyperactivity disorder (ADHD) to understand the impact of the COVID-19 pandemic on aspects of their disorder, quality of life, and treatment experience.Methods: A cross-sectional survey of US-resident members of PatientsLikeMe (PLM) was conducted through the PLM health tracking platform between March 10 and April 2, 2021. Adult participants with self-reported ADHD currently taking prescription medication (treated) and those not taking medication (untreated) were enrolled.Results: The study included 93 adults, of whom 48 patients were taking medication for ADHD. Most of the 45 untreated patients were not taking medication for reasons unrelated to the pandemic. Of the 47 treated patients who also completed the survey, 22 patients had ≥ 1 switch in ADHD medication type, and nearly half had a dosage change during the pandemic. Further, 29 treated patients reported a negative impact of the pandemic on their daily ADHD medication routine, primarily due to a "lack of schedule" and "changes to structured routine," and 16 patients reported "increased difficulty" adhering to prescribed ADHD medication during the pandemic compared with before the pandemic. Of the total study population, 52 patients reported having a telehealth visit during the pandemic, and 38 patients had an ADHD management goal. All but 1 patient with an ADHD management goal reported a negative impact of the pandemic on progress toward their goal. More treated patients than untreated adults reported having control over bothersome ADHD symptoms.Conclusions: Adults with ADHD reported increased difficulty in managing their symptoms during the COVID-19 pandemic.Prim Care Companion CNS Disord 2023;25(4):22m03474. Author affiliations are listed at the end of this article.

Design of a real-world, prospective, longitudinal, observational study to compare vortioxetine with other standard of care antidepressant treatments in patients with major depressive disorder: a PatientsLikeMe survey.

BACKGROUND: Major depressive disorder (MDD) is a recurrent psychiatric condition that presents challenges in responding to treatment and achieving long-term remission. To improve outcomes, a shared decision-making treatment approach with patient and healthcare practitioner (HCP) engagement is vital. PatientsLikeMe (PLM), a peer community of patients, provides information on MDD, symptoms, and treatment through forums and resources, helping patients stay engaged in their treatment journey. Data on PLM can be harnessed to gain insights into patient perspectives on MDD symptom management, medication switches, and treatment goals and measures. METHODS: This ongoing, decentralized, longitudinal, observational, prospective study is being conducted using the PLM platform in two parts, enrolling up to 500 patients with MDD in the United States aged ≥ 18 years to compare vortioxetine with other monotherapy antidepressants. The first qualitative component consists of a webinar and discussion forum with PLM community members with MDD, followed by a pilot for functionality testing to improve the study flow and questions in the quantitative survey. The quantitative component follows on the PLM platform, utilizing patient-reported assessments, over a 24-week period. Three surveys will be conducted at baseline and weeks 12 and 24 to collect data on patient global impression of improvement, depression severity, cognitive function, quality of life (QoL) and well-being, medication satisfaction, emotional blunting, symptoms of anhedonia and resilience, as well as goal attainment. Quantitative results will be compared between groups. The qualitative component is complete; patient recruitment is underway for the quantitative component, with results expected in late 2023. DISCUSSION: These results will help HCPs understand patient perspectives on the effectiveness of vortioxetine versus other monotherapy antidepressants in alleviating symptoms of MDD and improvements in QoL. Data from the PLM platform will support a patient goal-based treatment approach, as results can be shared by patients with their HCPs, providing them with insights on patient-centric goals, treatment management and adherence, as well as allowing them to observe changes in patient-related outcomes scores. Findings from the study will also help to optimize the PLM platform to build scalable solutions and connectivity within the community to better serve patients with MDD.

The association between dental arch length and oral health-related quality of life in head and neck cancer patients post-radiotherapy.

AIMS: To assess the association between length of dental arch and oral health-related quality of life in head and neck cancer patients post-radiotherapy. METHODS: Thirty head and neck cancer participants reported their oral health-related quality of life using the oral health impact profile-14 instrument and their global self-rating of general and oral health. All patients had received chemotherapy and radiotherapy. The length of dental arch was assessed in three tooth relational categories: canine-to-canine, shortened (premolars to premolars), and long (molars to molars) dental arches. Inclusion of participants for any of the three categories required verification of opposing teeth relationship with Shim Stock paper. RESULTS: Out of 30 head and neck cancer patients, eight (27%) had a canine-to-canine dental arch, 14 (46%) had a shortened dental arch, and eight (27%) had a long dental arch. The median oral health impact profile-14 scores for participants respectively with the canine-to-canine dental arch was six (IQR = 9.25), seven (IQR = 8) for participants with shortened dental arch, and 11 (IQR = 12.5) for participants with long dental arch. There were no significant differences in oral health impact profile-14 scores between the three-tooth relational groups (Kruskal-Wallis H = 0.769, df = 2, P-value = .681). Similarly, there were no significant differences between three-tooth relational groups on the self rating of general (Chi-squared = 1.714, df = 2, P-value = .424) and oral health (Chi-squared = 1.393, df = 2, P-value = .498). CONCLUSION: Within the limitations of this study, no association was found between the length of dental arch and oral health-related quality of life in head and neck cancer patients post-radiotherapy. Other factors such as dry mouth, oral mucositis, loss of taste, and trismus should be considered as contributory factors to reduced oral health-related quality of life in head and neck cancer patients post-radiotherapy, particularly in relation to eating difficulties.

Structural basis for topological regulation of Tn3 resolvase.

Site-specific DNA recombinases play a variety of biological roles, often related to the dissemination of antibiotic resistance, and are also useful synthetic biology tools. The simplest site-specific recombination systems will recombine any two cognate sites regardless of context. Other systems have evolved elaborate mechanisms, often sensing DNA topology, to ensure that only one of multiple possible recombination products is produced. The closely related resolvases from the Tn3 and γδ transposons have historically served as paradigms for the regulation of recombinase activity by DNA topology. However, despite many proposals, models of the multi-subunit protein-DNA complex (termed the synaptosome) that enforces this regulation have been unsatisfying due to a lack of experimental constraints and incomplete concordance with experimental data. Here, we present new structural and biochemical data that lead to a new, detailed model of the Tn3 synaptosome, and discuss how it harnesses DNA topology to regulate the enzymatic activity of the recombinase.

Site-specific DNA recombinases alter the connectivity of DNA by recognizing specific DNA sequences, then cutting the DNA strands and pasting them together in a new configuration. Such enzymes play a variety of biological roles, often related to the dissemination of antibiotic resistance, and are also useful biotechnology tools. The simplest site-specific recombination systems will recombine any two cognate sites regardless of context. However, others have evolved elaborate mechanisms to ensure that only one of multiple possible recombination products is produced. Tn3 resolvase has long been known to be regulated by DNA topology­that is, it will cut and reconnect two target sequences only if they lie on the same DNA molecule, and if they are in the proper relative orientation. This study presents new structural and biochemical data that lead to a new, detailed model of the large protein­DNA complex formed by Tn3 resolvase and its cognate sites. This 3D model illustrates how DNA topology can be harnessed to regulate the activity of a recombinase and provides a basis for engineering Tn3 resolvase and related recombination systems as genome editing tools.

Dentists' perspectives on denture provision after radiotherapy for head and neck cancer: an exploratory study using the theoretical domains framework.

Introduction Patients are often keen to replace their missing teeth after radiotherapy for head and neck cancer (HNC), yet such replacement does not always take place.Aims This study aimed to investigate the influences on dentists' provision of dentures for patients treated with radiotherapy for HNC, including whether risk of osteoradionecrosis (ORN) is a factor influencing intention to provide dentures.Methods An online cross-sectional survey including a case scenario, self-reported behaviour and measures of factors (selected using the theoretical domains framework) that may affect dentists' decisions was completed by general dental practitioners (n = 150) and HNC multidisciplinary team dentists (n = 25) in England.Results Dentists' reluctance to provide dentures for HNC patients post-radiotherapy was often due to concerns about dry mouth and radiation caries rather than risk of ORN. Knowledge of guidelines and beliefs about consequences were independently associated with dentists' intention to replace missing teeth with dentures.Conclusion The likelihood of replacing missing teeth with dentures increased with awareness of clinical guidance on the use of dentures in HNC and that denture provision would have positive consequences that outweigh the costs.

Should the HPV positive oropharyngeal cancer patient be considered for a two-stage dental assessment for their radiation treatment?

Patients due to commence head and neck radiation treatment are expected to undergo a dental assessment and be deemed 'dentally fit'. Though this intervention is welcomed by the dental fraternity it is not without its challenges especially in human papilloma virus (HPV) related oropharyngeal cancer (OPC) which has seen a phenomenal rise over the past decade. This perspective piece presents these challenges and proposes a potential adaption of the dental assessment for HPV OPC patients though not necessarily exclusive to this tumour sub-site.

COVID-19's impact on primary care and related mitigation strategies: A scoping review.

BACKGROUND: The COVID-19 pandemic has had a substantial impact on primary care throughout Europe and globally. OBJECTIVES: This review aims to ascertain how the pandemic has impacted primary care service provision/patients and to examine strategies to mitigate these impacts. METHODS: The scoping review framework comprised a six-stage process developed by Arksey and O'Malley. The search process was guided by the Joanna Briggs Institute three-step search strategy and involved searching the PubMed, Embase, Scopus, CINAHL Plus, and Cochrane Library databases. The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A thematic analysis approach by Braun and Clarke was used to interpret the findings. RESULTS: Thirty-two studies from 18 countries and six continents were included, 13 reported original research, three were reviews, and 16 were case reports reporting healthcare systems' experiences of dealing with the pandemic. Emerging themes concerned the COVID-19 pandemic's impact on primary care service provision and patients, the impact of the rapid transition to telemedicine due to COVID-19 on primary care, and strategies to mitigate the impact of COVID-19 on primary care (i.e. infection prevention and control measures, alternatives/modifications to traditional service delivery or workflow, government policy responses, and education). CONCLUSION: The COVID-19 pandemic has considerably impacted on primary care at both service and patient levels, and various strategies to mitigate these impacts have been described. Future research examining the pandemic's ongoing impacts on primary care, as well as strategies to mitigate these impacts, is a priority.

A Place for the Professional Introduction in Practice.

This article describes a survey exploring the use of professional introductions by nurses.For this project, a survey inquiring about introduction practices was administered to nurses attending a regional research conference.

A meta-analysis of executive functions among survivors of subarachnoid haemorrhage.

Subarachnoid Haemorrhage (SAH) is a type of stroke which is suggested to result in Executive Functioning (EF) deficits. Within the SAH research, EF is typically assessed as a unitary cognitive construct. Therefore, the nature and extent to which the different components of EF are impacted post SAH remain unclear. In this meta-analysis, 10 studies met selection criteria including 248 SAH participants, treated by endovascular coiling. Participants were assessed by EF measures and compared with 230 controls. Searches were conducted in November 2018 including Medline, PsychINFO, Web of Science, Scopus and CINAHL databases. EF measures were assigned to categories including Cognitive Flexibility, Working Memory, Inhibitory Control and Planning/Problem Solving [Diamond, 2013. Executive functions. Annual Review of Psychology, 64(1), 135-168. https://doi.org/10.1146/annurev-psych-113011-143750]. A statistically significant effect was found for overall EF. Cognitive Flexibility (G = -0.76) and Inhibitory Control (G = -0.51) generated moderate effect sizes, while Working Memory and Planning/Problem Solving found a small effect size (G = -0.45 and G = -0.49, respectively). The I2 statistic suggested small to moderate heterogeneity between studies, hypothesized to relate to different cognitive tools. Underlying components of EF appear to be differentially impacted post SAH, with Cognitive flexibility demonstrating the largest degree of deficit. Recommendations for a standardized and uniform assessment of EF post SAH are outlined.

Use of dentures, receipt of information, quality of life, and oral function following radiotherapy for head and neck cancer.

BACKGROUND: Teeth with a poor prognosis are often extracted prior to radiotherapy for head and neck cancer (HNC) in order to help prevent the need for dental treatment after radiotherapy that might in turn lead to the development of osteoradionecrosis. However, the details and impact of replacing missing teeth after radiotherapy for HNC have received little attention, especially from the patients' perspective. AIMS: This study aimed to assess the use, satisfaction, and impact of denture use following radiotherapy for HNC. The study also sought to determine patients' satisfaction with information about replacing their missing teeth postradiotherapy. Finally, this study also aimed to assess interest in replacing missing teeth for those who had not done so. METHODS: A structured, validated, and reliable questionnaire was sent to HNC patients who had received radiotherapy and had missing teeth at the time of discharge. In addition to demographic details and self-reported oral hygiene, the questionnaire included questions on use of (or interest in) dentures, satisfaction with dentures, satisfaction with information about replacing missing teeth, QoL as measured by two questions from the short version of WHOQoL-BREF, and oral functioning as measured by BCSQ-H&N. Demographic details and clinical details were extracted from the hospital records. RESULTS: N = 80 (24%) returned a completed questionnaire. Participants had an average of 12 missing teeth (SD = 8.05). Most (n = 60, 75%) had not replaced their missing teeth. Of these, 35 (58%) were very or extremely interested in doing so. For HNC survivors who wore dentures, there was variable satisfaction and a number of side-effects of wearing dentures. Satisfaction with information about replacing missing teeth was low. There was no statistical difference in QoL or oral functioning between participants who wore dentures and participants who did not wear dentures. However, those with dentures reported fewer problems with carrying out daily routines as measured by the oral functioning tool. CONCLUSIONS: QoL and oral functioning were similar regardless of denture use, highlighting reduced oral function in both those with and without dentures. In those who had not replaced their missing teeth, there was substantial interest in doing so and thus may be an unmet need. The dental team could offer HNC survivors more support after radiotherapy and following denture provision to improve information about denture use and increase satisfaction with dentures.

Denture use and dental risk factors associated developing osteoradionecrosis after head and neck radiotherapy: A retrospective analysis of hospital records.

OBJECTIVES: This study aimed to assess the association between denture use and occurrence of osteoradionecrosis (ORN) following radiotherapy for head and neck cancer (HNC). MATERIALS AND METHODS: Medical records of 439 HNC patients treated with radiotherapy at Guy's & St Thomas' NHS Foundation Trust (London, UK) (2014-2019) who had missing teeth at the time of discharge were reviewed. Descriptive statistics were used to summarise the participant characteristics and outcome measures. Logistic regression analysis was used to identify factors associated with occurrence of ORN. RESULTS: Patients had an average of 14 missing teeth and 39 % wore dentures. Twenty-two (5 %) developed ORN. Out of 22 who developed ORN, 11 (50 %) wore dentures. Of these, 5 patients developed ORN in areas contacted by dentures. Denture use was not significantly associated with the occurrence of ORN (OR = 1.94; 95%CI = 0.79-4.81; p-value = 0.150). Longer duration of radiotherapy (OR =1.03; 95%CI = 1.00-1.06; p-value= 0.048) and more missing teeth in the lower anterior area (OR = 1.11; 95%CI = 1.01-1.22; p-value = 0.024) were significantly associated with the development of ORN. CONCLUSIONS: Within the limitations of this single-centre study in which few patients developed ORN, denture use may not be a risk factor for ORN following radiotherapy for HNC. This is likely to be the case if dentures are well-fitting and not causing sores or irritation. CLINICAL SIGNIFICANCE: Replacement of the missing teeth with dentures in HNC patients post-radiotherapy may be a suitable choice for many HNC survivors. However, a powered study in a large cohort that includes clinical evaluation of dentures and the quality of fit alongside denture wearing experience would be useful to further assess the impact of denture use on the development of ORN.

Identification of a brain fingerprint for overweight and obesity.

The brain plays a central role in the pathophysiology of overweight and obesity. Connectome-based Predictive Modeling (CPM) is a newly developed, data-driven approach that exploits whole-brain functional connectivity to predict a behavior or trait that varies across individuals. We used CPM to determine whether brain "fingerprints" evoked during milkshake consumption could be isolated for common measures of adiposity in 67 adults with overweight and obesity. We found that CPM captures more variance in waist circumference than either percent body fat or BMI, the most frequently used measures to assess brain correlates of obesity. In a post-hoc analysis, we were also able to derive a largely separable functional connectivity network predicting fasting blood insulin. These findings suggest that, in individuals with overweight and obesity, brain network patterns may be more tightly coupled to waist circumference than BMI or percent body fat and that adiposity and glucose tolerance are associated with distinct maps, pointing to dissociable central pathophysiological phenotypes for obesity and diabetes.

End-of-Life Nursing Knowledge Among Nursing Students.

BACKGROUND: The U.S. health care system is poorly designed to meet the needs of patients at the end of life (EOL) and their families. Nursing students often have reported feeling inadequate to provide EOL care. METHOD: Following an EOL simulation, reflective journals were collected from junior and senior nursing students and analyzed for themes using qualitative content analysis. The condensed meaning units were abstracted into codes based on Carper's fundamental patterns of knowing. RESULTS: Thirty-one junior and senior nursing students (mean age, 21.04 ± 0.52 years, 96.2% female) in a baccalaureate program participated in the study. The broad themes of student reflections included empirics (theoretical or natural historical) aesthetics (transformative nursing action), personal (interpersonal process of nurse-patient interaction), and ethics (emotion influences actions). CONCLUSION: Student perception and participation in all roles contributes to the gestalt of the experience of a highly emotional EOL simulation for both students and faculty. [J Nurs Educ. 2020;59(3):154-157.].