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.

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.

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.

Spontaneous Pneumothorax; a Collapse in Management?

Revised guidelines for the management of spontaneous pneumothoraces were published by the British Thoracic Society in 2010, however compliance remains poor. A retrospective review was performed on patients diagnosed with a pneumothorax over a 26 month period (January 2012 to March 2014). Of the 57 patients identified, 43 (75%) were diagnosed with spontaneous pneumothorax. 12 patients (21%) had pre-existing lung disease, and 16 patients (28%) admitted to having had a previously documented pneumothorax. 19 patients (33%) were reported as smokers. The main symptoms reported were chest pain (93%) and shortness of breath (54%). Observation was appropriate in 18 cases (31%), while aspiration alone was performed in 9 (16%) with chest drains required in 25 cases (44%). Five patients (9%) were admitted directly under a medical team. Our study demonstrated good compliance with BTS guidelines. The decision to observe, aspirate, insert a chest drain or directly refer to the medical team was appropriate in the majority of cases studied.

Distinct magnetic phase transition at the surface of an antiferromagnet.

In the majority of magnetic systems the surface is required to order at the same temperature as the bulk. In the present Letter, we report a distinct and unexpected surface magnetic phase transition at a lower temperature than the Néel temperature. Employing grazing incidence x-ray resonant magnetic scattering, we have observed the near-surface behavior of uranium dioxide. UO2 is a noncollinear, triple-q, antiferromagnet with the U ions on a face-centered cubic lattice. Theoretical investigations establish that at the surface the energy increase-due to the lost bonds-is reduced when the spins near the surface rotate, gradually losing their component normal to the surface. At the surface the lowest-energy spin configuration has a double-q (planar) structure. With increasing temperature, thermal fluctuations saturate the in-plane crystal field anisotropy at the surface, leading to soft excitations that have ferromagnetic XY character and are decoupled from the bulk. The structure factor of a finite two-dimensional XY model fits the experimental data well for several orders of magnitude of the scattered intensity. Our results support a distinct magnetic transition at the surface in the Kosterlitz-Thouless universality class.

Evaluation of mild cognitive impairment subtypes in Parkinson's disease.

Mild cognitive impairment in Parkinson's disease (PD-MCI) is common and increases the risk for dementia. Establishing distinct PD-MCI cognitive subtypes could be valuable for eventually predicting those most likely to convert to dementia. However, the study of PD-MCI subtypes has not yielded consistent results among cohorts. To determine whether there are distinct cognitive subtypes among participants diagnosed with PD-MCI in the Pacific Northwest Udall Center Clinical Consortium, we cognitively subtyped 95 patients with PD-MCI, using the Movement Disorders Society Task Force diagnostic guidelines. Psychometric test scores were then subjected to principle components factor analysis to determine whether similar cognitive subgroups could be identified using statistical methodology. Multiple-domain PD-MCI was diagnosed in 95% of the sample, and a range of cognitive impairments were noted. Factor analysis yielded seven factors and demonstrated overlap of phonemic verbal fluency on two factors, as well as the loading of verbal fluency on the same factor as a visuospatial measure; however, these factors did not partition the sample into distinct cognitive subtypes. Separation of cognitive subtypes based on the current PD-MCI criteria, or via statistical methods, may not provide sufficient information to describe distinct PD groups. Future efforts to validate the PD-MCI criteria and identify combinations of genetic or other risk factors for cognitive impairment are warranted.

People with Parkinson's disease and normal MMSE score have a broad range of cognitive performance.

Cognitive impairment, including dementia, is common in Parkinson's disease (PD). The Mini-Mental State Examination (MMSE) has been recommended as a screening tool for Parkinson's disease dementia (PDD), with values below 26 indicative of possible dementia. Using a detailed neuropsychological battery, we examined the range of cognitive impairment in PD patients with an MMSE score of 26 or higher. In this multicenter, cross-sectional, observational study, we performed neuropsychological testing in a sample of 788 PD patients with MMSE scores of 26 or higher. Evaluation included tests of global cognition, executive function, language, memory, and visuospatial skills. A consensus panel reviewed results for 342 subjects and assigned a diagnosis of no cognitive impairment, mild cognitive impairment, or dementia. Sixty-seven percent of the 788 subjects performed 1.5 standard deviations below the normative mean on at least one test. On eight of the 15 tests, more than 20% of subjects scored 1.5 standard deviations or more below the normative mean. Greatest impairments were found on Hopkins Verbal Learning and Digit Symbol Coding tests. The sensitivity of the MMSE to detect dementia was 45% in a subset of participants who underwent clinical diagnostic procedures. A remarkably wide range of cognitive impairment can be found in PD patients with a relatively high score on the MMSE, including a level of cognitive impairment consistent with dementia. Given these findings, clinicians must be aware of the limitations of the MMSE in detecting cognitive impairment, including dementia, in PD.

Prediction and model evaluation for space-time data.

Evaluation metrics for prediction error, model selection and model averaging on space-time data are understudied and poorly understood. The absence of independent replication makes prediction ambiguous as a concept and renders evaluation procedures developed for independent data inappropriate for most space-time prediction problems. Motivated by air pollution data collected during California wildfires in 2008, this manuscript attempts a formalization of the true prediction error associated with spatial interpolation. We investigate a variety of cross-validation (CV) procedures employing both simulations and case studies to provide insight into the nature of the estimand targeted by alternative data partition strategies. Consistent with recent best practice, we find that location-based cross-validation is appropriate for estimating spatial interpolation error as in our analysis of the California wildfire data. Interestingly, commonly held notions of bias-variance trade-off of CV fold size do not trivially apply to dependent data, and we recommend leave-one-location-out (LOLO) CV as the preferred prediction error metric for spatial interpolation.

A puzzle over several decades: eye anomalies with FRAS1 and STRA6 mutations in the same family.

Fraser syndrome (FS) and microphthalmia syndromic 9 (MCOPS9) are autosomal recessive conditions with distinct, and some overlapping features affecting the ocular, respiratory and cardiac systems. Mutations in FRAS1 and FREM2 occur in FS, and mutations in STRA6 occur in MCOPS9. We report two sibships, in the same family, where four deceased offspring had ocular, respiratory and cardiac abnormalities. Two sibs with microphthalmia had syndactyly and laryngeal stenosis, suggesting a clinical diagnosis of FS. Our results indicate that they were compound heterozygotes for novel FRAS1 mutations, p.Cys729Phe and p.Leu3813Pro. The other two sibs, first cousins to the first sib pair, had anophthalmia, lung hypoplasia and cardiac anomalies, suggesting a retrospective diagnosis of MCOPS9. Our results indicate compound heterozygous STRA6 mutations, a novel frameshift leading to p.Tyr18* and a p.Thr644Met mutation. The one surviving individual from these sibships is heterozygous for the p.Tyr18*STRA6 mutation and has bilateral ocular colobomata and microphthalmia. This work emphasises the need for careful phenotypic characterisation to determine genes for assessment in ocular syndromic conditions. It also indicates that heterozygous STRA6 mutations may rarely contribute to microphthalmia and coloboma.

Two weeks of reduced-volume sprint interval or traditional exercise training does not improve metabolic functioning in sedentary obese men.

AIMS: To investigate the effects of short-term, reduced-volume sprint interval training (SIT) compared to traditional exercise recommendations (TER) in sedentary obese men. METHODS: Sixteen subjects [37.8 ± 5.8 years; body mass index (BMI) 32.8 ± 4.7 kg/m(2)] were randomly allocated to 2 weeks of either SIT (6 sessions of 8-12 × 10 s sprints) or TER [10 sessions of 30 min at 65% peak oxygen consumption (VO(2peak))] cycle exercise. Fasting plasma glucose, insulin, non-esterified fatty acids (NEFA), homeostasis model assessment of insulin sensitivity (HOMA-IR), body composition and VO(2peak) were assessed at baseline and approximately 72 h after the final training bout. Skeletal muscle biopsy samples were also obtained before and 72 h after training and analysed for AS160 phosphorylation and COX II, COX IV, GLUT-4, Nur77 and SIRT1 protein expression. RESULTS: No changes in BMI, body composition, VO(2peak), glucose, insulin, NEFA and HOMA-IR were observed after training, either within or between groups. Skeletal muscle markers of glucose metabolism and mitochondrial function also remained unaltered after 2 weeks of exercise training. CONCLUSIONS: Our findings show that 2 weeks of reduced-volume SIT or TER did not elicit any measurable metabolic adaptations in sedentary obese men. Further work is needed to determine the minimal amount of exercise required for short-term adaptations in this population.

Muscle oxygenation and blood volume reliability during continuous and intermittent running.

The reliability of near infrared spectroscopy derived tissue oxygenation index (TOI) and total haemoglobin concentration (tHb) were examined during continuous (CR) and interval (INT) running. In a repeated measures design, 10 subjects twice performed 30 min of CR at 70% of their peak treadmill velocity, followed by 10 bouts of INT at 100%. Between trial reliability of mean and amplitude changes in TOI and tHb during CR were determined. Muscle de-oxygenation and re-oxygenation rates during INT were calculated using 3 analytical methods; i) linear modelling, ii) minimum and maximum values during work/rest intervals, and iii) mean values during work/rest intervals. Reliability was assessed using coefficient of variation (CV; %). During CR, mean TOI was more reliable (3.5%) compared with TOI amplitude change (34.7%), while mean tHb (12%) was similar to both absolute (9.2%) and relative (10.2%) amplitude changes. During INT, de-oxygenation rates analysed via linear modelling produced the lowest CV (7.2%), while analysis using min-max values produced the lowest CV (9.3%) for re-oxygenation rates. In conclusion, while the variables demonstrated CVs lower than reported changes in training-induced adaptations and/or differences between athletes and controls (23- 450%), practitioners are encouraged to consider the advantages/disadvantages of each method when performing their analysis.

First Report of Transmission of Little cherry virus 2 to Sweet Cherry by Pseudococcus maritimus (Ehrhorn) (Hemiptera: Pseudococcidae).

Little cherry virus 2 (LChV2; genus Ampelovirus, family Closteroviridae) is associated with Little Cherry Disease (LCD), one of the most economically destructive diseases of sweet cherry (Prunus avium (L.)) in North America (1). Since 2010, incidence of LCD associated with LChV2 confirmed by reverse transcription (RT)-PCR assays has increased in orchards of Washington State. LChV2 was known to be transmitted by the apple mealybug (Phenacoccus aceris (Signoret)) (3). However, the introduction of Allotropus utilis, a parasitoid platygastrid wasp (2) for biological control, contributed to keeping insect populations below the economic threshhold. In recent years, the population of grape mealybug (Pseudococcus maritimus (Ehrhorn)) increased in cherry orchards of Washington State (Beers, personal observation). Since grape mealybug is reported to transmit Grapevine leafroll associated virus 3 (Ampelovirus) in grapevine (4), this study investigated whether this insect would also transmit LChV2. A colony of grape mealybugs on Myrobalan plum (Prunus cerasifera Ehrh.) trees was identified visually and morphologically from slide mounts. In a growth chamber, first and second instar crawlers were fed on fresh cut shoots of sweet cherry infected with a North American strain (LC5) of LChV2. After an acquisition period of 7 days, 50 crawlers were transferred to each young potted sweet cherry trees, cv. Bing, confirmed free from LChV2 by RT-PCR. This process was repeated in two trials to yield a total of 21 potted trees exposed to grape mealybug. One additional tree was left uninfested as a negative control. After 1 week, the trees were treated with pesticide to eliminate the mealybugs. Two to four months after the inoculation period, leaves were collected from each of the recipient trees and tested by RT-PCR for the presence of LChV2. To reduce the possibility of virus contamination from residual mealybug debris on leaf surfaces, the trees were allowed to defoliate naturally. After a 3-month dormant period, the new foliage that emerged was then tested. Two sets of primers: LC26L (GCAGTACGTTCGATAAGAG) and LC26R (AACCACTTGATAGTGTCCT) (1); and LC2.13007F (GTTCGAAAGTGTTTCTTGA) and LC2.14545R (CATTATYTTACTAATGGTATGAC) (this study) were used to amplify a partial segment of the replicase gene (409 bp) and the complete (1,080 bp) coat protein gene of LChV2, respectively. Of 21 trees tested, 18 yielded positive results for LChV2. The reaction products from six randomly selected trees were cloned and the virus identity was verified by sequencing. The sequences of RT-PCR amplicons from both primer pairs showed ≥99% identity to LChV2, strain LC5 (GenBank Accession No. AF416335). The result confirmed that P. maritimus transmits LChV2, a significant finding for this cherry production region. Grape mealybug is of increasing concern in the tree fruit industry because it is difficult to control in established orchards. The presence of infested orchards that serve as reservoirs of both LCD and this insect vector present a challenge for management. To the best of our knowledge this is the first report to show transmission of LChV2 by grape mealybug. References: (1) K. C. Eastwell and M. G. Bernardy. Phytopathology 91:268, 2001. (2) C. F. W. Muesbeck. Can Entomol. 71:158, 1939. (3) J. R. D. Raine et al. Can. J. Plant Pathol. 8:6, 1986. (4) R. Sforza et al. Eur. J. Plant Pathol. 109:975, 2003.

Neuropsychologic assessment in collaborative Parkinson's disease research: a proposal from the National Institute of Neurological Disorders and Stroke Morris K. Udall Centers of Excellence for Parkinson's Disease Research at the University of Pennsylvania and the University of Washington.

Cognitive impairment (CI) and behavioral disturbances can be the earliest symptoms of Parkinson's disease (PD), ultimately afflict the vast majority of PD patients, and increase caregiver burden. Our two Morris K. Udall Centers of Excellence for Parkinson's Disease Research were supported by the National Institute of Neurological Disorders and Stroke (NINDS) in an effort to recommend a comprehensive yet practical approach to cognitive and behavioral assessment to further collaborative research. We recommend a stepwise approach with two levels of standardized evaluation to establish a common battery, as well as an alternative testing recommendation for severely impaired subjects, and review supplemental tests that may be useful in specific research settings. Our flexible approach may be applied to studies with varying emphasis on cognition and behavior, does not place undue burden on participants or resources, and has a high degree of compatibility with existing test batteries to promote collaboration.

Help-seeking from clergy and spiritual counselors among veterans with depression and PTSD in primary care.

Little is known about the prevalence or predictors of seeking help for depression and PTSD from spiritual counselors and clergy. We describe openness to and actual help-seeking from spiritual counselors among primary care patients with depression. We screened consecutive VA primary care patients for depression; 761 Veterans with probable major depression participated in telephone surveys (at baseline, 7 months, and 18 months). Participants were asked about (1) openness to seeking help for emotional problems from spiritual counselors/clergy and (2) actual contact with spiritual counselors/clergy in the past 6 months. At baseline, almost half of the participants, 359 (47.2%), endorsed being "very" or "somewhat likely" to seek help for emotional problems from spiritual counselors; 498 (65.4%) were open to a primary care provider, 486 (63.9%) to a psychiatrist, and 409 (66.5%) to another type of mental health provider. Ninety-one participants (12%) reported actual spiritual counselor/clergy consultation. Ninety-five (10.3%) participants reported that their VA providers had recently asked them about spiritual support; the majority of these found this discussion helpful. Participants with current PTSD symptoms, and those with a mental health visit in the past 6 months, were more likely to report openness to and actual help-seeking from clergy. Veterans with depression and PTSD are amenable to receiving help from spiritual counselors/clergy and other providers. Integration of spiritual counselors/clergy into care teams may be helpful to Veterans with PTSD. Training of such providers to address PTSD specifically may also be desirable.

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.

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.

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.

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.