Dew point temperature affects ascospore release of allergenic genus Leptosphaeria.

The genus Leptosphaeria contains numerous fungi that cause the symptoms of asthma and also parasitize wild and crop plants. In search of a robust and universal forecast model, the ascospore concentration in air was measured and weather data recorded from 1 March to 31 October between 2006 and 2012. The experiment was conducted in three European countries of the temperate climate, i.e., Ukraine, Poland, and the UK. Out of over 150 forecast models produced using artificial neural networks (ANNs) and multivariate regression trees (MRTs), we selected the best model for each site, as well as for joint two-site combinations. The performance of all computed models was tested against records from 1 year which had not been used for model construction. The statistical analysis of the fungal spore data was supported by a comprehensive study of both climate and land cover within a 30-km radius from the air sampler location. High-performance forecasting models were obtained for individual sites, showing that the local micro-climate plays a decisive role in biology of the fungi. Based on the previous epidemiological studies, we hypothesized that dew point temperature (DPT) would be a critical factor in the models. The impact of DPT was confirmed only by one of the final best neural models, but the MRT analyses, similarly to the Spearman's rank test, indicated the importance of DPT in all but one of the studied cases and in half of them ranked it as a fundamental factor. This work applies artificial neural modeling to predict the Leptosphaeria airborne spore concentration in urban areas for the first time.

Expression of the Arabidopsis redox-related LEA protein, SAG21 is regulated by ERF, NAC and WRKY transcription factors.

SAG21/LEA5 is an unusual late embryogenesis abundant protein in Arabidopsis thaliana, that is primarily mitochondrially located and may be important in regulating translation in both chloroplasts and mitochondria. SAG21 expression is regulated by a plethora of abiotic and biotic stresses and plant growth regulators indicating a complex regulatory network. To identify key transcription factors regulating SAG21 expression, yeast-1-hybrid screens were used to identify transcription factors that bind the 1685 bp upstream of the SAG21 translational start site. Thirty-three transcription factors from nine different families bound to the SAG21 promoter, including members of the ERF, WRKY and NAC families. Key binding sites for both NAC and WRKY transcription factors were tested through site directed mutagenesis indicating the presence of cryptic binding sites for both these transcription factor families. Co-expression in protoplasts confirmed the activation of SAG21 by WRKY63/ABO3, and SAG21 upregulation elicited by oligogalacturonide elicitors was partially dependent on WRKY63, indicating its role in SAG21 pathogen responses. SAG21 upregulation by ethylene was abolished in the erf1 mutant, while wound-induced SAG21 expression was abolished in anac71 mutants, indicating SAG21 expression can be regulated by several distinct transcription factors depending on the stress condition.

Plant WEE1 kinase is cell cycle regulated and removed at mitosis via the 26S proteasome machinery.

In yeasts and animals, premature entry into mitosis is prevented by the inhibitory phosphorylation of cyclin-dependent kinase (CDK) by WEE1 kinase, and, at mitosis, WEE1 protein is removed through the action of the 26S proteasome. Although in higher plants WEE1 function has been confirmed in the DNA replication checkpoint, Arabidopsis wee1 insertion mutants grow normally, and a role for the protein in the G2/M transition during an unperturbed plant cell cycle is yet to be confirmed. Here data are presented showing that the inhibitory effect of WEE1 on CDK activity in tobacco BY-2 cell cultures is cell cycle regulated independently of the DNA replication checkpoint: it is high during S-phase but drops as cells traverse G2 and enter mitosis. To investigate this mechanism further, a yeast two-hybrid screen was undertaken to identify proteins interacting with Arabidopsis WEE1. Three F-box proteins and a subunit of the proteasome complex were identified, and bimolecular fluorescence complementation confirmed an interaction between AtWEE1 and the F-box protein SKP1 interacting partner 1 (SKIP1). Furthermore, the AtWEE1-green fluorescent protein (GFP) signal in Arabidopsis primary roots treated with the proteasome inhibitor MG132 was significantly increased compared with mock-treated controls. Expression of AtWEE1-YFP(C) (C-terminal portion of yellow fluorescent protein) or AtWEE1 per se in tobacco BY-2 cells resulted in a premature increase in the mitotic index compared with controls, whereas co-expression of AtSKIP1-YFP(N) negated this effect. These data support a role for WEE1 in a normal plant cell cycle and its removal at mitosis via the 26S proteasome.

Misclassification of incident conditions using claims data: impact of varying the period used to exclude pre-existing disease.

BACKGROUND: Estimating the incidence of medical conditions using claims data often requires constructing a prevalence period that predates an event of interest, for instance the diagnosis of cancer, to exclude those with pre-existing conditions from the incidence risk set. Those conditions missed during the prevalence period may be misclassified as incident conditions (false positives) after the event of interest.Using Medicare claims, we examined the impact of selecting shorter versus longer prevalence periods on the incidence and misclassification of 12 relatively common conditions in older persons. METHODS: The source of data for this study was the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry linked to Medicare claims. Two cohorts of women were included: 33,731 diagnosed with breast cancer between 2000 and 2002, who had ≥ 36 months of Medicare eligibility prior to cancer, the event of interest; and 101,649 without cancer meeting the same Medicare eligibility criterion. Cancer patients were followed from 36 months before cancer diagnosis (prevalence period) up to 3 months after diagnosis (incidence period). Non-cancer patients were followed for up to 39 months after the beginning of Medicare eligibility. A sham date was inserted after 36 months to separate the prevalence and incidence periods. Using 36 months as the gold standard, the prevalence period was then shortened in 6-month increments to examine the impact on the number of conditions first detected during the incidence period. RESULTS: In the breast cancer cohort, shortening the prevalence period from 36 to 6 months increased the incidence rates (per 1,000 patients) of all conditions; for example: hypertension 196 to 243; diabetes 34 to 76; chronic obstructive pulmonary disease 29 to 46; osteoarthritis 27 to 36; congestive heart failure 20 to 36; osteoporosis 22 to 29; and cerebrovascular disease 13 to 21. Shortening the prevalence period has less impact on those without cancer. CONCLUSIONS: Selecting a short prevalence period to rule out pre-existing conditions can, through misclassification, substantially inflate estimates of incident conditions. In incidence studies based on Medicare claims, selecting a prevalence period of ≥24 months balances the need to exclude pre-existing conditions with retaining the largest possible cohort.

Perturbation of cytokinin and ethylene-signalling pathways explain the strong rooting phenotype exhibited by Arabidopsis expressing the Schizosaccharomyces pombe mitotic inducer, cdc25.

BACKGROUND: Entry into mitosis is regulated by cyclin dependent kinases that in turn are phosphoregulated. In most eukaryotes, phosphoregulation is through WEE1 kinase and CDC25 phosphatase. In higher plants a homologous CDC25 gene is unconfirmed and hence the mitotic inducer Schizosaccharomyces pombe (Sp) cdc25 has been used as a tool in transgenic plants to probe cell cycle function. Expression of Spcdc25 in tobacco BY-2 cells accelerates entry into mitosis and depletes cytokinins; in whole plants it stimulates lateral root production. Here we show, for the first time, that alterations to cytokinin and ethylene signaling explain the rooting phenotype elicited by Spcdc25 expression in Arabidopsis. RESULTS: Expressing Spcdc25 in Arabidopsis results in increased formation of lateral and adventitious roots, a reduction of primary root width and more isodiametric cells in the root apical meristem (RAM) compared with wild type. Furthermore it stimulates root morphogenesis from hypocotyls when cultured on two way grids of increasing auxin and cytokinin concentrations. Microarray analysis of seedling roots expressing Spcdc25 reveals that expression of 167 genes is changed by > 2-fold. As well as genes related to stress responses and defence, these include 19 genes related to transcriptional regulation and signaling. Amongst these was the up-regulation of genes associated with ethylene synthesis and signaling. Seedlings expressing Spcdc25 produced 2-fold more ethylene than WT and exhibited a significant reduction in hypocotyl length both in darkness or when exposed to 10 ppm ethylene. Furthermore in Spcdc25 expressing plants, the cytokinin receptor AHK3 was down-regulated, and endogenous levels of iPA were reduced whereas endogeous IAA concentrations in the roots increased. CONCLUSIONS: We suggest that the reduction in root width and change to a more isodiametric cell phenotype in the RAM in Spcdc25 expressing plants is a response to ethylene over-production. The increased rooting phenotype in Spcdc25 expressing plants is due to an increase in the ratio of endogenous auxin to cytokinin that is known to stimulate an increased rate of lateral root production. Overall, our data reveal important cross talk between cell division and plant growth regulators leading to developmental changes.

Gene dosage effect of WEE1 on growth and morphogenesis from arabidopsis hypocotyl explants.

BACKGROUND AND AIMS: How plant cell-cycle genes interface with development is unclear. Preliminary evidence from our laboratory suggested that over-expression of the cell cycle checkpoint gene, WEE1, repressed growth and development. Here the hypothesis is tested that the level of WEE1 has a dosage effect on growth and development in Arabidospis thaliana. To do this, a comparison was made of the development of gain- and loss-of-function WEE1 arabidopsis lines both in vivo and in vitro. METHODS: Hypocotyl explants from an over-expressing Arath;WEE1 line (WEE1(oe)), two T-DNA insertion lines (wee1-1 and wee1-4) and wild type (WT) were cultured on two-way combinations of kinetin and naphthyl acetic acid. Root growth and meristematic cell size were also examined. KEY RESULTS: Quantitative data indicated a repressive effect in WEE1(oe) and a significant increase in morphogenetic capacity in the two T-DNA insertion lines compared with WT. Compared with WT, WEE1(oe) seedlings exhibited a slower cell-doubling time in the root apical meristem and a shortened primary root, with fewer laterals, whereas there were no consistent differences in the insertion lines compared with WT. However, significantly fewer adventitious roots were recorded for WEE1(oe) and significantly more for the insertion mutant wee1-1. Compared with WT there was a significant increase in meristem cell size in WEE1(oe) for all three ground tissues but for wee1-1 only cortical cell size was reduced. CONCLUSIONS: There is a gene dosage effect of WEE1 on morphogenesis from hypocotyls both in vitro and in vivo.

Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab.

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival.

Arabidopsis T-DNA insertional lines for CDC25 are hypersensitive to hydroxyurea but not to zeocin or salt stress.

BACKGROUND AND AIMS: In yeasts and animals, cyclin-dependent kinases are key regulators of cell cycle progression and are negatively and positively regulated by WEE1 kinase and CDC25 phosphatase, respectively. In higher plants a full-length orthologue of CDC25 has not been isolated but a shorter gene with homology only to the C-terminal catalytic domain is present. The Arabidopis thaliana;CDC25 can act as a phosphatase in vitro. Since in arabidopsis, WEE1 plays an important role in the DNA damage/DNA replication checkpoints, the role of Arath;CDC25 in conditions that induce these checkpoints or induce abiotic stress was tested. Methods arath;cdc25 T-DNA insertion lines, Arath;CDC25 over-expressing lines and wild type were challenged with hydroxyurea (HU) and zeocin, substances that stall DNA replication and damage DNA, respectively, together with an abiotic stressor, NaCl. A molecular and phenotypic assessment was made of all genotypes Key RESULTS: There was a null phenotypic response to perturbation of Arath;CDC25 expression under control conditions. However, compared with wild type, the arath;cdc25 T-DNA insertion lines were hypersensitive to HU, whereas the Arath;CDC25 over-expressing lines were relatively insensitive. In particular, the over-expressing lines consistently outgrew the T-DNA insertion lines and wild type when challenged with HU. All genotypes were equally sensitive to zeocin and NaCl. CONCLUSIONS: Arath;CDC25 plays a role in overcoming stress imposed by HU, an agent know to induce the DNA replication checkpoint in arabidopsis. However, it could not enhance tolerance to either a zeocin treatment, known to induce DNA damage, or salinity stress.

Observed-to-expected ratio for adherence to treatment guidelines as a quality of care indicator for laryngeal cancer.

OBJECTIVES/HYPOTHESIS: To examine associations between survival and adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines using an observed-to-expected (O/E) ratio for greater adherence as a risk-adjusted hospital measure of quality care in elderly patients treated for larynx cancer. STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data. METHODS: Patients diagnosed with larynx cancer from 2004 to 2007 were evaluated using multivariate regression and survival analysis. A fit logistic regression model was used to calculate an O/E ratio for guideline adherence for each hospital using quality indicators derived from NCCN guidelines for recommended treatment and stratified by hospital volume. RESULTS: Of 1,721 patients treated at 395 hospitals, 43.0% of patients received NCCN guideline-adherent care. Low-volume hospitals (N = 295) treating six or fewer cases treated 765 patients (44.5%), with a mean O/E of 0.96 ± 0.45. Hospitals treating more then six cases with an O/E <1 (N = 32) treated 284 patients (16.5%), with a mean O/E of 0.77 ± 0.18. Hospitals treating more than six cases with an O/E ≥1 (N = 68) treated 672 patients (39.1%), with a mean O/E of 1.17 ± 0.11. Treatment at hospitals with an O/E ≥1 was associated with improved survival (hazard ratio [HR] = 0.83 [95% confidence interval [CI]: 0.70 to 0.98]) and lower mean incremental treatment-related costs (-$3,009 [-$5,226 to -$791]) compared with hospitals with an O/E <1 (HR = 1.00 [0.80 to 1.24]) and the reference group of low-volume hospitals. CONCLUSIONS: A hospital-specific O/E for NCCN treatment guideline adherence, combined with a minimum case volume criterion, is associated with survival and treatment-related costs in elderly patients with larynx cancer, and may be a feasible measure of larynx cancer quality of care. LEVEL OF EVIDENCE: NA Laryngoscope, 130:672-678, 2020.

Comparing care for breast cancer survivors to non-cancer controls: a five-year longitudinal study.

BACKGROUND: Deficiencies in care for cancer survivors may result from unclear roles for primary care providers (PCPs) and oncology specialists in follow-up. OBJECTIVES: To compare cancer survivors' care to non-cancer controls. DESIGN: Retrospective, longitudinal, controlled study starting 366 days post-diagnosis. SUBJECTS: Stage 1-3 breast cancer survivors age 65+ diagnosed in 1998 (n = 1961) and matched non-cancer controls (n = 1961). MEASUREMENTS: Using the SEER-Medicare database, we examined the number of visits to PCPs, oncology specialists, and other physicians; receipt of influenza vaccination, cholesterol screening, colorectal cancer screening, bone densitometry, and mammography; and whether care receipt was associated with physician mix visited. RESULTS: Survivors were consistently less likely to receive influenza vaccination, cholesterol screening, colorectal cancer screening, and bone densitometry but more likely to receive mammograms than controls (all p < 0.05). Over time, colorectal cancer screening and mammography decreased and influenza vaccination increased for both groups (all p < 0.0001). Trends over time in care receipt were similar for survivors and controls. In Year 1, survivors had more visits to PCPs but fewer visits to other physicians than controls (both p < 0.05). Over time, survivors' visits to PCPs and other physicians increased and to oncology specialists decreased (all p < 0.0001). Controls' visits to PCPs increased (p < 0.0001) faster than survivors' (p = 0.003). Controls' visits to other physicians increased (p < 0.0001) at a rate similar to survivors. Survivors who visited both a PCP and oncology specialist were most likely to receive each service. CONCLUSIONS: Better coordination between PCPs and oncology specialists may improve care for older breast cancer survivors.

Quality of care and short and long-term outcomes of oropharyngeal cancer care in the elderly.

OBJECTIVE: To examine associations between quality, short-term and long-term treatment-related outcomes, and costs in elderly patients treated for oropharyngeal squamous cell cancer (OPSCC). METHODS: We retrospectively evaluated Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 666 patients diagnosed with OPSCC from 2004 to 2007 using multivariate regression and survival analysis. Quality indicators were derived from guidelines for recommended care and performance measures. RESULTS: Higher quality care was associated with lower risk of death in patients with dysphagia (hazard ratio [HR] = 0.44 [0.32-0.60]), weight loss (HR = 0.42 [0.28-0.62]), gastrostomy (HR = 0.47 [0.33-0.68]), airway obstruction (HR = 0.41 [0.27-0.62]), tracheostomy (HR = 0.17 [0.05-0.67]), and pneumonia (HR = 0.53 [0.33-0.85]). There were no significant differences in mean incremental costs associated with airway and swallowing impairment for patients receiving higher quality care. CONCLUSIONS: Higher quality OPSCC care was associated with improved survival in elderly patients with airway and swallowing impairment. These data suggest that greater adherence to evidence-based guidelines has favorable implications for long-term outcomes.

Short-Term Post-Harvest Stress that Affects Profiles of Volatile Organic Compounds and Gene Expression in Rocket Salad During Early Post-Harvest Senescence.

Once harvested, leaves undergo a process of senescence which shares some features with developmental senescence. These include changes in gene expression, metabolites, and loss of photosynthetic capacity. Of particular interest in fresh produce are changes in nutrient content and the aroma, which is dependent on the profile of volatile organic compounds (VOCs). Leafy salads are subjected to multiple stresses during and shortly after harvest, including mechanical damage, storage or transport under different temperature regimes, and low light. These are thought to impact on later shelf life performance by altering the progress of post-harvest senescence. Short term stresses in the first 24 h after harvest were simulated in wild rocket (Diplotaxis tenuifolia). These included dark (ambient temperature), dark and wounding (ambient temperature), and storage at 4 °C in darkness. The effects of stresses were monitored immediately afterwards and after one week of storage at 10 °C. Expression changes in two NAC transcription factors (orthologues of ANAC059 and ANAC019), and a gene involved in isothiocyanate production (thiocyanate methyltransferase, TMT) were evident immediately after stress treatments with some expression changes persisting following storage. Vitamin C loss and microbial growth on leaves were also affected by stress treatments. VOC profiles were differentially affected by stress treatments and the storage period. Overall, short term post-harvest stresses affected multiple aspects of rocket leaf senescence during chilled storage even after a week. However, different stress combinations elicited different responses.

Expression of Arabidopsis WEE1 in tobacco induces unexpected morphological and developmental changes.

WEE1 regulates the cell cycle by inactivating cyclin dependent protein kinases (CDKs) via phosphorylation. In yeast and animal cells, CDC25 phosphatase dephosphorylates the CDK releasing cells into mitosis, but in plants, its role is less clear. Expression of fission yeast CDC25 (Spcdc25) in tobacco results in small cell size, premature flowering and increased shoot morphogenetic capacity in culture. When Arath;WEE1 is over-expressed in Arabidopsis, root apical meristem cell size increases, and morphogenetic capacity of cultured hypocotyls is reduced. However expression of Arath;WEE1 in tobacco plants resulted in precocious flowering and increased shoot morphogenesis of stem explants, and in BY2 cultures cell size was reduced. This phenotype is similar to expression of Spcdc25 and is consistent with a dominant negative effect on WEE1 action. Consistent with this putative mechanism, WEE1 protein levels fell and CDKB levels rose prematurely, coinciding with early mitosis. The phenotype is not due to sense-mediated silencing of WEE1, as overall levels of WEE1 transcript were not reduced in BY2 lines expressing Arath;WEE1. However the pattern of native WEE1 transcript accumulation through the cell cycle was altered by Arath;WEE1 expression, suggesting feedback inhibition of native WEE1 transcription.

Trends in follow-up and preventive care for colorectal cancer survivors.

BACKGROUND: As cancer patients transition from treatment to survivorship, the responsibility of primary care providers (PCPs) versus oncology specialists is unclear. OBJECTIVES: To explore (1) physician types (PCPs versus oncology specialists) survivors visit during survivorship year 1, (2) preventive care received, (3) how preventive care receipt relates to physician types visited, and (4) trends in physician types visited and preventive care received over time. DESIGN: Retrospective cross-sectional study of 5 cohorts of cancer survivors in survivorship year 1. SUBJECTS: Twenty thousand sixty-eight survivors diagnosed with stage 1-3 colorectal cancer between 1997 and 2001. MEASUREMENTS: Using the SEER-Medicare database, we assessed the mean number of visits to different physician types, the percentage of survivors receiving preventive services, how receipt of preventive services related to physician types visited, and trends over time in physician visits and preventive care. RESULTS: There was a trend over time of increased visits to all physician types, which was statistically significant for oncology specialists and other physicians (p < .001) but not PCPs. The percentage of survivors receiving preventive services remained relatively stable across the 5 cohorts, except for an increase in bone densitometry (p < .05). Survivors who visited both a PCP and oncology specialist were most likely to receive each preventive care service (p < .05). CONCLUSIONS: Oncology specialist follow-up in survivorship year 1 is intensifying over time. Survivors not being followed-up by both PCPs and oncology specialists were less likely to receive preventive care. Clarifying the roles of PCPs and oncology specialists during follow-up can improve the quality of care for survivors.

Multitrait analysis of fresh-cut cantaloupe melon enables discrimination between storage times and temperatures and identifies potential markers for quality assessments.

Fresh-cut cantaloupe melon is valued for its aroma but is highly perishable. Temperature of storage (typically 0-5°C) is critical for maintaining fresh-cut melon quality, but often reaches 10°C during transportation and in retail outlets. A comparison amongst 0, 5 and 10°C storage temperatures for fresh-cut melon over 14days reveals that storage at 0°C is optimal for avoiding increases in microbial load and loss of vitamin C especially at later time points. However, higher temperatures maintain better the balance of esters (acetate versus non-acetate) and phenolic content. The whole volatile organic compound (VOC) profile can be used to discriminate both time and temperature effects especially at earlier time points. Potential VOC markers for changes in vitamin C from day 0 to day 6 of storage (3-methyl butane nitrile) and temperature (limonene) are identified through a multi-trait analysis.

Speech-language pathology care and short- and long-term outcomes of oropharyngeal cancer treatment in the elderly.

OBJECTIVE: To examine associations between speech-language pathology (SLP) care and pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients treated for oropharyngeal squamous cell cancer (SCCA). STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. RESULTS: SLP care was documented in 25% of patients. High-volume hospital care (odds ratio (OR) = 3.2 [1.0-10.0]) and dysphagia during treatment (OR = 13.0 [3.6-47.1]) were the only significant predictors of SLP care during the initial treatment period. SLP care was significantly more likely during the first year (OR = 5.3 [3.1-9.1]) and second year (OR = 4.5 [2.4-8.2]) following initial treatment. Subsequent dysphagia (OR = 32.5 [16.9-62.4]), stricture (OR = 2.2 [1.2-4.0]), gastrostomy (OR = 1.7 [1.1-2.7]), and tracheostomy tube use (OR = 2.4 [1.2-4.8]) were significantly associated with long-term SLP care. After controlling for patient, tumor, and treatment-related variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (93%), stricture (35%), weight loss (8%), and airway obstruction (34%). Survival analysis, controlling for all other variables, demonstrated improved survival for patients under SLP care (hazard ratio = 0.73 [0.57-0.95]). CONCLUSION: SLP care is underutilized in elderly oropharyngeal SCCA patients and largely utilized after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care in this population during the initial treatment period and beyond. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1403-1411, 2018.

Quality indicators of oropharyngeal cancer care in the elderly.

OBJECTIVE: To examine associations between quality of care, survival, and costs in elderly patients treated for oropharyngeal squamous cell cancer (OPSCC). STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using multivariate regression and survival analysis. Using quality indicators derived from guidelines for recommended care, summary measures of quality were calculated for diagnosis, initial treatment, surveillance, treatment for recurrence, end-of-life care, performance, and an overall summary measure of quality. RESULTS: Higher-quality care was associated with significant differences in survival for initial treatment (hazard ratio [HR] = 0.55 [0.41 to 0.73]), surveillance (HR = 0.32 [0.22 to 0.48]), treatment of recurrence (HR = 2.37 [1.56 to 3.60]), performance measures (HR = 0.50 [0.36 to 0.69]), and the overall summary measure of quality (HR = 0.53 [0.39 to 0.71]). Higher-quality salvage surgery was associated with improved survival (HR = 0.16 [0.04 to 0.54]), whereas higher-quality chemotherapy given for recurrence was associated with worse survival (HR = 5.70 [1.92 to 16.94]). Overall, higher-quality care was not associated with differences in costs. Higher-quality care was associated with significantly lower mean incremental costs for treatment of recurrence and end-of-life care, and higher costs for diagnosis and surveillance. CONCLUSION: Higher-quality OPSCC care in elderly patients was associated with improved survival; however, higher-quality care was not associated with reduced costs, and higher-quality care for treatment of recurrence was associated with poorer survival, primarily due to poorer survival in patients treated with palliative chemotherapy. These data demonstrate a complex relationship between quality and costs in elderly OPSCC patients, which can be used to frame discussions of value and guide disease-specific quality-measure development. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:2312-2319, 2018.

Treatment, survival, and costs of oropharyngeal cancer care in the elderly.

OBJECTIVES/HYPOTHESIS: To examine associations between treatment, survival, and costs in elderly patients with oropharyngeal squamous cell cancer (OPSCC). STUDY DESIGN: Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using cross-tabulations, multivariate logistic and generalized linear regression modeling, and survival analysis. RESULTS: The majority of patients were nonsmokers (79%), had advanced-stage disease (59%), and received chemoradiation (38%) or radiation (28%). Surgery with postoperative radiation (hazard ratio [HR]: 0.33 [95% CI: 0.20-0.53]) and chemoradiation (HR: 0.45 [95% CI: 0.29-0.71]) were associated with improved survival, whereas stage IV disease was associated with poorer survival (HR: 1.95 [95% CI: 1.13-3.38]). Additional cancer-directed treatment after primary treatment was more likely following chemoradiation (odds ratio [OR]: 3.44 [95% CI: 1.78-6.63]). Salvage surgery was performed in 25% of patients undergoing subsequent additional cancer-directed treatment, and was associated with high-volume hospitals (OR: 2.81 [95% CI: 1.07-7.74]). Additional radiation (HR: 0.47 [95% CI: 0.31-0.72]) and salvage surgery (HR: 0.61 [95% CI: 0.38-0.99]) were associated with improved overall survival when performed >6 months following initial treatment, whereas salvage neck dissection alone was not significantly associated with survival after controlling for time to salvage (HR: 0.38 [95% CI: 0.05-2.78]). Treatment and 5-year overall costs were highest for chemoradiation, surgery with postoperative radiation, and additional cancer-directed treatment. CONCLUSIONS: Multimodality treatment in elderly OPSCC patients was associated with improved survival and increased costs. Chemoradiation was associated with an increased likelihood of additional cancer-directed treatment. Salvage surgery was centralized at high-volume hospitals, and was associated with improved survival when performed >6 months after last initial treatment date, but was performed in <20% of patients undergoing additional treatment. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1103-1112, 2018.

Short- and long-term outcomes of oropharyngeal cancer care in the elderly.

OBJECTIVE: To examine associations between pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients (age > 65 years) treated for oropharyngeal squamous cell cancer (SCCA). STUDY DESIGN: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data. METHODS: Longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 were evaluated using cross-tabulations, multivariate logistic regression, and survival analysis. RESULTS: Dysphagia (odds ratio [OR] = 1.3, 1.0-1.7), esophageal stricture (OR = 5.5, 2.6-11.9), and airway obstruction (OR = 1.6, 1.1-2.2) increased 1 year after treatment. The odds of airway obstruction, esophageal stricture, and pneumonia increased over subsequent years, with significantly increased risk at 5 years for airway obstruction (OR = 3.0, 1.4-6.4), pneumonia (OR = 4.5, 1.8-11.2), and stricture (OR = 5.5, 1.8-17.6). Pretreatment dysphagia was a significant predictor of long-term dysphagia, airway obstruction, and pneumonia. Chemoradiation, advanced stage disease, high-volume hospital care, male sex, and salvage surgery were significant predictors of long-term gastrostomy use. Long-term dysphagia, gastrostomy or tracheostomy dependence, weight loss, airway obstruction, and pneumonia were associated with poorer survival, with tracheostomy dependence (hazard ratio [HR] = 2.2, 1.7-2.9) and pneumonia (HR = 2.0, 1.7-2.4) associated with the greatest risk of late mortality. CONCLUSION: Airway and swallowing impairment is common after treatment of oropharyngeal SCCA in elderly patients, increases over time, and is associated with poorer survival. Patients with pretreatment dysphagia, advanced stage disease, initial treatment with chemoradiation, and salvage surgery represent a high-risk group with an increased risk of disability and death. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:2084-2093, 2018.

Readmission following primary surgery for larynx and oropharynx cancer in the elderly.

OBJECTIVE: To examine 30-day readmission rates and associations with risk factors, survival, length of hospitalization, and costs in elderly patients with laryngeal and oropharyngeal squamous cell cancer (SCC). STUDY DESIGN: Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated 1,518 patients diagnosed with laryngeal or oropharyngeal SCC from 2004 to 2007 who underwent primary surgery using cross-tabulations, multivariate regression modeling, and survival analysis. RESULTS: Thirty-day readmission occurred in 14.1% of hospitalizations. Readmission was more likely in patients with postoperative complications during initial hospitalization (24.8% vs. 4.5%, P < 0.001), and was associated with an increased 30-day mortality incidence rate (5.1% vs. 0.9%; P < 0.001). On multivariate analysis, 30-day readmission was significantly associated with advanced stage (odds ratio [OR] = 1.81 [1.13-2.90]), comorbidity (OR = 2.69 [1.65-4.39]), divorced/separated marital status (OR = 2.00 [1.19-3.38]), preoperative tracheostomy (OR = 3.39 [1.55-7.44]), major surgical procedures (OR = 2.58 [1.68-3.97]), greater length of initial hospitalization (OR = 1.72 [1.09-2.71]), pneumonia (OR = 2.86 [1.28-6.40]), postoperative dysphagia (OR = 5.97 [2.48-15.83]), and cardiovascular events (OR = 5.84 [1.89-17.96]). Thirty-day readmission was significantly associated with 30-day mortality (OR = 5.89 [2.21-15.70) and higher 1-year mortality (68.0% vs. 89.2%, P < 0.001). The mean incremental costs of surgical care were significantly greater for patients with unplanned readmission ($15,123 [$10,514-$19,732]), after controlling for all other variables. CONCLUSION: Unplanned readmissions are associated with increased short- and long-term mortality and costs. Elderly patients with advanced disease, advanced comorbidity, lack of spousal support, pretreatment organ dysfunction, more extensive surgery, postoperative pneumonia, postoperative dysphagia, and prolonged hospitalization are at increased risk of 30-day readmission. These findings suggest a need for targeted interventions before, during, and after hospitalization to reduce morbidity, mortality, and excess costs in this high-risk population. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:631-641, 2017.