A Prospective Longitudinal Study of Early Childhood Caries Onset in Initially Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex oral disease that is prevalent in US children. OBJECTIVES: The purpose of this 2-y prospective cohort study was to examine baseline and time-dependent risk factors for ECC onset in initially caries-free preschool children. METHODS: A cohort of 189 initially caries-free children aged 1 to 3 y was recruited. At each 6-mo study visit, children were examined using the ICDAS index; salivary samples were collected to assess mutans streptococci (MS), lactobacilli, Candida species, salivary cortisol (prior and after a stressor), and salivary IgA. Diet and oral health behavior were assessed from parent report. Child and family stress exposure was assessed from measures of psychological symptoms, stressful life event exposure, family organization and violence exposure, and social support. Sociodemographic factors were also considered. A Kaplan-Meier estimator of survival function of time to ECC and a Cox proportional hazards model were used to identify predictors of ECC onset. RESULTS: Onset of ECC was associated with high salivary MS levels at baseline (log-rank test, P < 0.0001). Cox proportional hazards regression showed that the risk of dental caries significantly increased with salivary MS in log scale over the 6-mo period (hazard ratio, 1.08; P = 0.01). Other risk factors in the model did not reach statistical significance. CONCLUSION: Our results provide prospective evidence that an increase in salivary MS predicts ECC onset in young, initially caries-free children, confirming that a high salivary MS count likely plays a causal role in ECC onset, independent of covariates. KNOWLEDGE TRANSFER STATEMENT: These results suggest that we must focus on reducing salivary MS counts in young children and preventing or delaying MS colonization in infants and young children determined to be at risk for ECC.

Effect modification of the association between fine particulate air pollution during a wildfire event and respiratory health by area-level measures of socio-economic status, race/ethnicity, and smoking prevalence.

Fine particulate air pollution (PM2.5) is decreasing in most areas of the United States, except for areas most affected by wildfires, where increasing trends in PM2.5 can be attributed to wildfire smoke. The frequency and duration of large wildfires and the length of the wildfire season have all increased in recent decades, partially due to climate change, and wildfire risk is projected to increase further in many regions including the western United States. Increasingly, empirical evidence suggests differential health effects from air pollution by class and race; however, few studies have investigated such differential health impacts from air pollution during a wildfire event. We investigated differential risk of respiratory health impacts during the 2008 northern California wildfires by a comprehensive list of socio-economic status (SES), race/ethnicity, and smoking prevalence variables. Regardless of SES level across nine measures of SES, we found significant associations between PM2.5 and asthma hospitalizations and emergency department (ED) visits during these wildfires. Differential respiratory health risk was found by SES for ED visits for chronic obstructive pulmonary disease where the highest risks were in ZIP codes with the lowest SES levels. Findings for differential effects by race/ethnicity were less consistent across health outcomes. We found that ZIP codes with higher prevalence of smokers had greater risk of ED visits for asthma and pneumonia. Our study suggests that public health efforts to decrease exposures to high levels of air pollution during wildfires should focus on lower SES communities.

Increased Emergency Department Utilization and Costs for Medicare Cancer Patients with Malnutrition Diagnoses.

BACKGROUND: Malnutrition or its risk affects up to 70% of cancer patients. Compared to adequately nourished oncology patients, those with malnutrition experience more complications and have poorer prognoses, thus higher needs for healthcare. We compared utilization of emergency department (ED) services and costs for Medicare-covered cancer patients with or without a malnutrition diagnosis. METHODS: We used the Centers for Medicare and Medicaid Services (CMS) Standard Analytic File to identify fee-for-service beneficiaries who had a cancer diagnosis, and had one or more outpatient claims in 2018. We totaled individual claims and costs for ED visits per beneficiary, then calculated mean per-person claims and costs for malnourished vs non-malnourished patients. RESULTS: Using data from over 2.8 million claims of patients with cancer diagnoses, the prevalence of diagnosed malnutrition was 2.5%. The most common cancer types were genitourinary, hematologic/blood, and breast. Cancer patients with a malnutrition diagnosis, compared to those without, had a significantly higher annual total number of outpatient claims (21.4 vs. 11.5, P<.0001), including a 2.5-fold higher rate of ED visits (1.43 vs. 0.56, p<.0001). As result, such patients incurred more than 2-fold higher mean ED claim costs than did their adequately nourished counterparts ($10,724 vs. $4,935, P<.0001). CONCLUSIONS: Our results suggest that malnutrition in cancer patients imposes a high outpatient burden on resource utilization and costs of care in terms of ED use. We propose that nutritional interventions can be used to improve health outcomes for people with cancer and to improve economic outcomes for patients and providers.

Social, Psychological, and Behavioral Predictors of Salivary Bacteria, Yeast in Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex, multifactorial oral disease that is a major public health concern because it is prevalent, profoundly alters a child's quality of life, is difficult to treat effectively, and has a distressing tendency to recur following treatment. OBJECTIVES: The purpose of the study was to examine social, psychological, and behavioral predictors of salivary bacteria and yeast in young children at risk for ECC. METHODS: A sample of 189 initially caries-free preschool children was assessed for child stress physiology from salivary cortisol, child and family stress exposure, diet, oral health behaviors, and sociodemographic risks. Multiple logistic regression analysis was implemented to examine the associations between these risk factors and cariogenic microorganisms: mutans streptococci (MS), lactobacilli (LB), and Candida species. RESULTS: Higher baseline salivary cortisol (odds ratio [OR] = 6.26; 95% confidence level [CL], 1.69-23.16) and a blunted response to an acute laboratory stressor (OR = .56; 95% CL, .37-.83) were associated with an increased likelihood of elevated salivary MS (≥105 colony-forming units/mL) in caries-free children. Sociodemographic risk for cariogenic microorganisms was also found. Specifically, lower education attainment of the parent/primary caregiver was associated with children being more likely to carry salivary Candida species and elevated salivary MS; in addition, children from households with an unemployed parent/primary caregiver were more likely (OR = 3.13; 95% CL, 1.2-8.05) to carry salivary Candida species and more likely (OR = 3.03; 95% CL, 1.25-7.33) to carry elevated levels of MS and/or salivary Candida and/or LB. CONCLUSIONS: The impact of sociodemographic risk and stress physiology on cariogenic disease processes are evident prior to ECC onset. The findings provide novel data on the early onset of cariogenic processes in children and the importance of considering sociodemographic, psychosocial, and behavioral factors when judging ECC risk. KNOWLEDGE TRANSFER STATEMENT: The findings provide valuable and novel findings that, pre-ECC onset, the caries disease process is explicable from a detailed assessment of behavioral, sociodemographic, and psychosocial stress variables.

Emerging themes in necrotising otitis externa: a scoping review of the literature from 2011 to 2020 and recommendations for future research.

OBJECTIVE: Necrotising otitis externa is an invasive, infective condition, with minimal evidence underpinning its diagnosis and management. This work aimed to analyse literature from the past decade, to identify emerging themes and important topics for future research. METHODS: A robust literature search and review were conducted by two researchers. Sixty studies were filtered into the final review. A grounded theory approach was used to identify core themes. Data within these themes formed the basis of the review. RESULTS: There is no consensus regarding a clinical definition or outcome measures of necrotising otitis externa, and there exists no level 1, 2 or 3 evidence to diagnose, investigate, monitor or treat necrotising otitis externa. Emerging themes in the literature direct researchers to important topics for future clinical trials, including risk factors, microbiological culture, management strategies and radiology. CONCLUSION: In order to optimise understanding and management of necrotising otitis externa, future research requires robust clinical trials and consistently reported outcome measures.

Necrotising otitis externa: the increasing financial burden on the National Health Service.

OBJECTIVE: Necrotising otitis externa is increasingly being seen and treated within the UK. The aim of this study was to explore the potential cost of a cohort of patients with necrotising otitis externa presenting to a single tertiary NHS trust. METHOD: This was a retrospective study with data from 14 patients with confirmed necrotising otitis externa who were treated, monitored, discharged or who died between October 2016 and November 2018. Direct costs using the tariffs from the 2018 to 2019 financial year included in-patient stay, imaging, peripheral inserted central catheter line cost, ENT and out-patient parenteral antibiotic therapy visits and antimicrobial duration. RESULTS: The mean cost of treatment per patient was £17 615 (range, £9407 to £38 230) with an extreme outlier costing more than £122 000. CONCLUSION: Awareness and education at a primary care level and research into robust imaging to aid termination of treatment may lower costs in the future by catching pathology early and reducing treatment duration.

Prescribing Exercise for Cancer Survivors:Time for Physicians to Become More Proactive.

Survivorship has become an integral component of the cancer care continuum. Advances in diagnosis and treatment have resulted in decreasing cancer mortality and a subsequent increase in the cancer survivorship population. International guidelines recommend counselling these patients with regards to healthy lifestyle changes. Increased physical activity has been shown to have profound impacts on quality of life and has also been shown to reduce recurrence rates in patients with breast, colon and prostate cancer. However physicians remain reluctant to prescribe exercise for these patients. Contributing factors include inadequate understanding of the benefits of these programmes, as well as uncertainty with regards to their patients' ability to tolerate such an intervention. It is thus imperative to raise awareness of the benefits of exercise, to guide physicians' selection of patients for exercise and to outline the available options to promote and increase physical activity as part of a healthy lifestyle.

Airway obstruction during general anaesthesia in a patient with a vagal nerve stimulator.

For patients with epilepsy refractory to medical management, vagal nerve stimulator implantation may reduce the number of seizures and/or reduce their severity. A 34-year-old woman with epilepsy underwent a change in vagal nerve stimulator battery under general anaesthesia with a supraglottic airway device and total intravenous anaesthesia. During the procedure, she developed clinically significant airway obstruction, which resolved only when the device was disabled. We recommend that anaesthetists and others providing peri-operative care for patients with a vagal nerve stimulator remain vigilant to the possibility of device-related airway obstruction, which may occur even in asymptomatic patients. All patients with a vagal nerve stimulator are provided with a magnet that will disable the device, should complications arise. There is a need to establish a standard approach to the peri-operative care of these patients, including the identification and management of device-related airway obstruction.

Leptomeningeal Relapse of Embryonal Rhabdomyosarcoma after 15 years.

Aim Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour of childhood. We present the case of a late relapse of RMS to the leptomeninges after 15 years. Methods A 20 year old male presented with a 3 week history of headaches and nausea. He previously had RMS of his right ear diagnosed at age 5 years which was treated with concurrent chemoradiotherapy. An MRI Brain and Spine confirmed extensive leptomeningeal disease and CSF analysis confirmed the presence of recurrent embryonal RMS. Results He completed two cycles of cyclophosphamide and topotecan followed by 45Gy/25Fr of craniospinal radiotherapy. Conclusion Late relapses beyond five years can be seen in up to 9% of patients, however very late recurrences (>10 years) are exceedingly rare. Molecular based methods such as gene expression profiling can aid risk stratification and survivorship clinics may become increasingly useful in following patients with high risk features.

Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets. OBJECTIVES: To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. METHODS: Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. RESULTS: Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low-risk group (n = 239) vs. 85·4% in the AMLo high-risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69-9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93-9·56; P = 0·068) in stage IB patients. CONCLUSIONS: Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early-stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow-up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.

Associations between maternal inflammation during pregnancy and infant birth outcomes in the Seychelles Child Development Study.

PROBLEM: Markers of maternal inflammation may determine infant birth outcomes. METHOD OF STUDY: Maternal serum samples were collected at 28 weeks gestation (n = 1418) in the Seychelles Child Development Study Nutrition Cohort 2 and analyzed for immune markers by MSD multiplex assay, including cytokines from the Th1 (IFN-γ, IL-1ß, IL-2 and TNF-α) and Th2 (IL-4, IL-5, IL-10) subsets, with IL-6, MCP-1, TARC, sFlt-1 and VEGF-D. Associations of log-transformed immune markers with birthweight, length, head circumference and gestational age were assessed by multiple linear regression models, which were adjusted for maternal age, BMI, parity, child sex, gestational age and socioeconomic status. RESULTS: Neither total Th1, Th2 nor Th1:Th2 were significantly associated with any birth outcome. However, the angiogenesis marker VEGF-D was predictive of a lower birthweight, (ß = -0.058, P = 0.017) and birth length (ß = -0.088, P = 0.001) after adjusting for covariates. Higher concentrations of CRP were predictive of a lower birthweight (ß = -0.057, P = 0.023) and IL-2 (ß = 0.073, P = 0.009) and the chemokine MCP-1 (ß = 0.067, P = 0.016) were predictive of a longer gestational age. CONCLUSIONS: In our cohort of healthy pregnant women, we found no evidence for associations between the Th1 or Th2 inflammatory markers with birth outcomes. However, VEGF-D and CRP appear to predict lower birthweight and IL-2 and MCP-1 a longer gestation. Greater understanding is required of the variation in these immune markers at different gestational stages, as well as the factors which may regulate their balance in healthy pregnancy. n = 233.

Malignant otitis externa, an increasing burden in the twenty-first century: review of cases in a UK teaching hospital, with a proposed algorithm for diagnosis and management.

BACKGROUND: Malignant otitis externa is a potentially fatal infection of the skull base. With an ageing population and increasing prevalence of diabetes, the incidence of malignant otitis externa in the British population is rising. To date, there remain no accepted diagnostic criteria, few prognostic indicators and no consensus treatment pathways. METHOD: A prospective case series was conducted at a tertiary referral teaching hospital. RESULTS: A cohort of susceptible individuals predominates (elderly, male, with immunosuppression and diabetes), with 25 per cent reporting a preceding incident. Otorrhoea, otalgia and canal granulation were the commonest presenting features, alongside positive pseudomonas cultures. No clear markers for predicating disease severity were isolated; however, a high initial haemoglobin A1c level demonstrated a significant moderately positive correlation with length of treatment. CONCLUSION: A treatment pathway designed to provide a standardised approach to investigation and treatment is proposed, which aims to increase earlier diagnosis, streamline care and facilitate the development of best practice.

Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii.

Toxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl hydrazone (KG8) as the most promising compound; KG8 displayed potent in vitro activity against T. gondii but only marginal in vivo efficacy in a T. gondii animal model. To define the potential of this new lead compound, we now describe a baseline structure-activity relationship for this chemotype. Several derivatives displayed IC50's comparable to that of the control treatment pyrimethamine with little to no cytotoxicity. The best of these, KGW44 and KGW59, had higher metabolic stability than KG8. In an in vivo T. gondii murine model, KGW59 significantly increased survivorship. This work provides new insights for optimization of this novel chemotype.

Oculostapedial synkinesis following idiopathic facial palsy: something to listen out for.

OBJECTIVE: This paper presents a rare case of oculostapedial synkinesis.Case reportAfter partial resolution of an idiopathic facial palsy, a male patient presented with persistent distortion of hearing when blinking and closing his eye. Audiometry findings were unremarkable, and cross-sectional imaging of the facial nerve revealed no abnormalities apart from an incidental contralateral meningioma. Initial conservative management, with referral to a specialist physiotherapist, failed to resolve the symptoms. The patient subsequently opted for surgical intervention, and underwent a transmeatal tympanotomy and transection of the stapedial tendon. Following this, he had complete resolution of symptoms. CONCLUSION: Oculostapedial synkinesis is a rare complication of facial palsy, but is recognised in the literature. Given its unusual presentation, it can be overlooked, especially by more junior team members. This case highlights the need to pay careful attention to patients' symptoms and listen out for the description of hearing distortion on facial movement.

Reporting in stapes surgery: are we following the guidelines?

OBJECTIVE: This paper highlights the importance of reporting air-bone gap closure in stapes surgery according to the American Academy of Otolaryngology - Head and Neck Surgery guidelines and reviews compliance in recent years. METHODS: A retrospective case series was conducted and the outcomes were reviewed. Closure of the air-bone gap was calculated in 204 adult patients using the aforementioned guidelines. Results were recalculated ignoring the Carhart phenomenon to determine any significant difference. Adherence to guidelines was also reported as a secondary outcome. RESULTS: Ignoring the Carhart phenomenon resulted in 75 per cent over-reporting of successful air-bone gap closure (p < 0.001). Over-reporting occurred in 5.9 per cent of papers, and in 11.8 per cent it was difficult to determine how the results were reached. CONCLUSION: Despite the existence of clear guidelines, stapes surgery outcomes are still being over-reported as successful. This can lead to incorrect information being provided to patients during the consent process and makes comparative studies difficult.

Behaviour of under sleeper pads at switches and crossings - Field measurements.

Major growth in rail traffic in many parts of the world in recent years has brought railway networks close to capacity and restricted the time available for track access to carry out maintenance work without costly temporary route closures. There are, therefore, significant benefits in designing or modifying ballasted track systems to reduce maintenance and associated access requirements. Under sleeper pads (USPs) offer the potential to extend ballasted track system life and to extend the intervals between routine maintenance. This paper presents and evaluates field measurements, made using geophones and high speed filming with digital image correlation (DIC), of the performance of a renewed section of track incorporating two switches and crossings (S&C) over a period of two years. One S&C was fitted with two types of USP (categorised as medium and soft), while the other had no USPs and acted as a control. Measurements demonstrate that the bearers with USPs fitted showed less variability in movement than bearers without USPs fitted. The provision of soft USPs caused large increases (>40%) in vertical bearer movements relative to bearers without USPs, although the medium USPs showed little difference. Increased movements of elongated bearers supporting both tracks fitted with soft USPs led to increased bearer rotations towards the loaded track. This effect was aided by the rigid steel collar fixing in the middle of the bearer used in this design of S&C, and raises questions concerning the desirability of this feature. DIC measurements showed that the at rest position of the elongated bearers rotated towards the track on which a train had most recently passed.

Assessing the impacts of bait collection on inter-tidal sediment and the associated macrofaunal and bird communities: The importance of appropriate spatial scales.

Bait collection is a multibillion dollar worldwide activity that is often managed ineffectively. For managers to understand the impacts on protected inter-tidal mudflats and waders at appropriate spatial scales macrofaunal surveys combined with video recordings of birds and bait collectors were undertaken at two UK sites. Dug sediment constituted approximately 8% of the surveyed area at both sites and is less muddy (lower organic content) than undug sediment. This may have significant implications for turbidity. Differences in the macrofaunal community between dug and undug areas if the same shore height is compared as well as changes in the dispersion of the community occurred at one site. Collection also induces a 'temporary loss of habitat' for some birds as bait collector numbers negatively correlate with wader and gull abundance. Bait collection changes the coherence and ecological structure of inter-tidal mudflats as well as directly affecting wading birds. However, as ß diversity increased we suggest that management at appropriate hectare/site scales could maximise biodiversity/function whilst still supporting collection.

Synchronous diffuse large B cell lymphomas of the endometrium and breast: a staging dilemma.

BACKGROUND: A 66 years old presented with abnormal postmenopausal vaginal bleeding and was diagnosed with an endometrial lymphoma (diffuse large B cell type, DLBCL). A left breast lesion was found on PET CT which was subsequently biopsy-proven as a separate stage IE DLBCL, but she had no lymph node, bone marrow or spleen involvement. AIMS: This study aimed to review the available literature and discuss the management and staging of synchronous extra-nodal DLBCL's. RESULTS: Our patient was staged as having synchronous stage IE DLBCL's of the endometrium and breast. Subsequent molecular analysis (IgH gene rearrangement analysis) on both lesions, confirmed the two lesions to be clonally unrelated. CONCLUSIONS: Staging of synchronous extra-nodal lymphomas, particularly when they arise in rare sites such as the endometrium and breast, is difficult and previously unreported. We present our rationale for defining our patient's disease as synchronous stage IE DLBCL's.

Correction: The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency.

Correction for 'The nanotipped hairs of gecko skin and biotemplated replicas impair and/or kill pathogenic bacteria with high efficiency' by X. Li, et al., Nanoscale, 2016, 8, 18860-18869.