What's Love Got to do with it? Marital status and survival of head and neck cancer.

OBJECTIVE: To determine whether marital status independently predicts survival in a head and neck cancer (HNC) survivor population. METHODS: In this retrospective cohort study, we analysed data from 460 adult patients (59.31 ± 11.42) years diagnosed with HNC at an academic tertiary referral centre between 1997 and 2012. Cox proportional hazards model estimated the effect of marital status on survival. RESULTS: Our study had 73% men, and 82.2% were Whites. We found an association between marital status and HNC survival. Unmarried HNC patients had a 66% increase in hazard of death compared to married patients (aHR = 1.66, 95% CI = 1.23-2.23). This was after controlling for sociodemographic variables (age, race, sex and health insurance status), social habits (tobacco and alcohol), primary anatomical subsite (oral cavity, oropharyngeal, laryngeal and others), stage at presentation (early vs. late stage) and treatment modality (surgery, surgery with adjuvant therapies, other single modality therapy and palliative care). CONCLUSIONS: Being married confers survival advantage for HNC survivors. Our finding underscores the need to recognise this aspect of survivorship. Social support should be considered part of standard care for managing HNC. There may also be need to develop other support mechanisms, especially for unmarried HNC survivors.

Factors affecting adherence to intranasal treatment for allergic rhinitis: A qualitative study.

Objective: To determine the facilitators of and barriers to adherence to use of intranasal pharmacotherapy (daily intranasal corticosteroids and/or antihistamine, and nasal saline irrigation [NSI]), for allergic rhinitis (AR). Methods: Patients were recruited from an academic tertiary care rhinology and allergy clinic. Semi-structured interviews were conducted after the initial visit and/or 4-6 weeks following treatment. Transcribed interviews were analyzed using a grounded theory, inductive approach to elucidate themes regarding patient adherence to AR treatment. Results: A total of 32 patients (12 male, 20 female; age 22-78) participated (seven at initial visit, seven at follow-up visit, and 18 at both). Memory triggers, such as linking nasal routine to existing daily activities or medications, were identified by patients as the most helpful strategy for adherence at initial and follow-up visits. Logistical obstacles related to NSI (messy, takes time, etc.) was the most common concept discussed at follow-up. Patients modified the regimen based on side effects experienced or perceived efficacy. Conclusions: Memory triggers help patients adhere to nasal routines. Logistical obstacles related to NSI can deter from use. Health care providers should address both concepts during patient counseling. Nudge-based interventions that incorporate these concepts may help improve adherence to AR treatment. Level of Evidence: 2.

Radiation-Associated Sarcoma of the Head and Neck: Incidence, Latency, and Survival.

OBJECTIVES/HYPOTHESIS: Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN). STUDY DESIGN: Retrospective database analysis. METHODS: RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN. RESULTS: The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN. CONCLUSIONS: RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1034-1041, 2022.

Pediatric Post-Tonsillectomy Opioid Prescribing Practices.

OBJECTIVE: To evaluate the effect of discharge order sets on prescribing patterns of opioids after pediatric tonsillectomy. Secondary outcomes included encounters for postoperative pain, dehydration, and bleeding. METHODS: Retrospective chart review of pre- and post-intervention in pediatric post-tonsillectomy patients, 0-18 years old (n = 1486). Order sets were installed with age-specific analgesic medication defaults and recommendation of concurrent alternating scheduled ibuprofen and acetaminophen. Time-balanced pre- and post-intervention cohorts were established. Opioid outcomes calculated in morphine milligram equivalents per kilogram (MME/kg) per dosage and total prescribed. RESULTS: Discharge order set intervention resulted in 17% reduction of opioid dose prescribed (0.095 MME/kg [95% CI, 0.092-0.099] vs. 0.079 [95% CI, 0.076-0.083], P < .001). Total number of opioid doses prescribed was reduced after order set implementation (46.4 [95% CI, 43.6-49.1] to 20.3 [95% CI, 19.1-21.5], P < .001). Patients <7 years old prescribed opioids remained rare in pre- and post-intervention groups (1.6% and 1.8%, respectively, P = .86). Admissions and emergency department visits for postoperative dehydration and pain were significantly reduced. Post-intervention group showed an increase in readmissions for post-tonsillectomy hemorrhage (9.2% vs. 5.2%, P = .003) which was isolated to an increase in the older post-intervention group after stratification by age. CONCLUSION: Utilization of order sets with standardized analgesic medication regimen of acetaminophen, ibuprofen, and opioid helped effectively reduce opioid amount per dose, total opioid amount dispensed, and variability in the total opioid amount dispensed while maintaining pain control. An increase in post-tonsillectomy hemorrhage was recognized following this implementation which did not persist after the study period despite continuation of intervention. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1386-1391, 2021.

Survival outcomes for head and neck patients with Medicaid: A health insurance paradox.

PURPOSE: Privately insured patients with head and neck cancer (HNC) typically have better outcomes; however, differential outcome among Medicaid versus the uninsured is unclear. We aimed to describe outcome disparities among HNC patients uninsured versus on Medicaid. METHODS: A cohort of 18-64-year-old adults (n = 57 920) with index HNC from the Surveillance, Epidemiology, and End Results 18 database (2007-2015) was analyzed using Fine and Gray multivariable competing risks proportional hazards models for HNC-specific mortality. RESULTS: Medicaid (sdHR = 1.65, 95% CI 1.58, 1.72) and uninsured patients (sdHR = 1.55, 95% CI 1.46, 1.65) had significantly greater mortality hazard than non-Medicaid patients. Medicaid patients had increased HNC mortality hazard than those uninsured. CONCLUSION: Compared with those uninsured, HNC patients on Medicaid did not have superior survival, suggesting that there may be underlying mechanisms/factors inherent in this patient population that could undermine access to care benefits from being on Medicaid.

Prior intense exercise reduces arterial carbon dioxide pressure in extreme obesity.

PURPOSE: Unlike normal weight individuals, individuals with extreme obesity do not show a decrease in arterial carbon dioxide pressure (PaCO2) from rest to peak exercise. This indicates that breathing is compromised. The objective of this study was to determine if prior high intensity exercise lowers PaCO2 in comparison with a first bout, normalized for the same metabolic rate. METHODS: Oxygen consumption during incremental, ramped exercise was matched to constant workload exercise (75% of peak power). Both protocols were to volitional exhaustion 39 ± 8 min apart. Eleven obese subjects (BMI = 47 ± 8 kg/m², aerobic capacity = 2.3 ± 0.6 L/min) were evaluated. Forty paired samples were obtained at the same metabolic rate between the two protocols. RESULTS: The mean absolute difference and 95% CI were large for arterial oxygen pressure (PaO2) = 9 (6, 11) mmHg and alveolar to arterial oxygen pressure difference (AaDO2) = 7 (5, 8) mmHg. The mean absolute difference for arterial oxyhemoglobin saturation (%SaO2) = 0.5 (0.4, 0.7) %; PaCO2 = 4 (3, 4) mmHg; physiological dead space to tidal volume ratio (VD/VT) = 0.04 (0.03, 0.05); and alveolar ventilation (VA) = 3 (2, 4) L/min. The recovery period after the first bout of exercise reduced the PaCO2 by 3 mmHg when matched for similar metabolic rates. Constant workload exercise predicted VA, %SaO2, V(D)/V(T), and PaCO2, but not PaO2 or AaDO2 during incremental exercise at similar metabolic rates. CONCLUSION: Given a sufficient chemical stimulus, obese subjects will attempt to breathe more, although this does not mean more VA, which removes CO2.

The Current State of the Otolaryngology Workforce.

A shortage of otolaryngologists is predicted for the coming decades, primarily because of an aging population and aging workforce. However, many factors affect the agility of the workforce to expand or contract. This article discusses what is known about factors of the current otolaryngology workforce, including trends in residency and fellowship training, diversity of the specialty, its geographic distribution, and the challenges of caring for an aging population. Predicting the shortage and possible solutions through modeling is complex and prone to errors caused by incomplete data and assumptions about otolaryngology's similarity to other specialties of medicine at large.

Demographic predictors of head and neck cancer survival differ in the elderly.

OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) prognosis strongly correlates with demographic factors. This study aimed to determine whether demographic predictors of HNSCC survival differ between age cohorts, with an emphasis on the growing elderly demographic. STUDY DESIGN: Outcomes research. METHODS: Adults with squamous cell carcinoma of the upper aerodigestive tract were identified from the Surveillance, Epidemiology and End Results 18 database. Demographic and oncologic factors were compared between three age groups: 18 to 49, 50 to 74, and >75 years. Factors associated with cancer-specific survival were assessed in each cohort using subdistribution hazard ratio (sHR) and 95% confidence interval (CI) produced by multivariate competing risk models. RESULTS: A cohort of 69,098 patients included 10,588 (15.3%) 75 years or older and 9,882 (14.3%) less than 50 years old. Older patients were more often female (35.4% vs. 25.1% aged 18-49 years and 20.4% aged 50-74 years), white (78.7% vs. 69.4% and 75.9%), insured (63.5% vs. 46.5% and 56.8%), and married (56.6% vs. 53% and 51.1%), but received adequate treatment less often (72.0% vs. 86.3% and 82.7%). In the older cohort, male sex was associated with lower mortality (sHR: 0.92, 95% CI: 0.85-1.00), and unlike the younger cohorts, black race was no longer associated with mortality (sHR: 1.07, 95% CI: 0.94-1.22). Marriage was associated with lower mortality in all age groups but with diminishing effects (single sHR: young 1.52, middle 1.31, older 1.14). CONCLUSIONS: Elderly HNSCC patients have distinct effects from demographic prognostic factors and should be considered a separate subgroup with unique epidemiology, risks, and preferences. LEVEL OF EVIDENCE: 2c Laryngoscope, , 129:146-153, 2018.

Impact of gender on the association between marital status and head and neck cancer outcomes.

OBJECTIVES: To determine whether the impact of marital status on head and neck cancer (HNC) outcomes vary by gender. METHODS: The Surveillance, Epidemiology, and End Results 18 database from 2007 to 2014 was queried for eligible cases of HNC (n = 71,799). An interaction term (gender*marital status) was tested for each outcome of interest (cancer-specific survival, stage of presentation, adequate treatment), and when significant (p < 0.05), the model was stratified by gender. A competing risks proportional hazards (subdistribution [sd]) model estimated the interaction effect on cancer-specific survival. Logistic regression estimated effect on stage of presentation and treatment type. RESULTS: There was significant gender*marital status interaction for cancer-specific survival and stage of presentation. While married/partnered patients had the highest survival among both genders, males benefitted more: widowed (male sdHR = 1.41, 95% CI 1.31, 1.52; female sdHR = 1.15, 95% CI 1.06, 1.26), divorced/separated (males: sdHR = 1.39, 95% CI 1.32, 1.46; females: sdHR = 1.17, 95% CI 1.06, 1.28), or never married (males: sdHR = 1.42, 95% CI 1.36, 1.49; females: sdHR = 1.15, 95% CI 1.05, 1.26). When stratified by oropharyngeal cancer vs. non-oropharyngeal HNC, unmarried males had 50-60% increased hazard of death, while no difference was found for females. Unmarried males also had greater odds of presenting with late-stage disease compared with females. No gender*marital status interaction was observed for adequate treatment, although married/partnered survivors had greater odds of receiving adequate treatment. CONCLUSIONS: While there are survival benefits for married patients with HNC, married/partnered males, especially those with oropharyngeal cancer, may benefit more than females.

Oncologic and functional outcomes of pretreatment tracheotomy in advanced laryngeal squamous cell carcinoma: A multi-institutional analysis.

OBJECTIVES: Describe the influence of pretreatment tracheotomy and treatment modality (surgical versus non-surgical) on oncologic and functional outcomes. MATERIALS AND METHODS: Retrospective study of previously untreated advanced-stage laryngeal squamous cell carcinoma patients at two academic tertiary care institutions from 1995 to 2014. RESULTS: Primary outcomes evaluated were disease-free survival, disease-specific survival, and overall survival of pretreatment tracheotomy versus no pretreatment tracheotomy cohorts. Functional status, measured by tracheotomy decannulation and gastrostomy tube placement/removal, was assessed. Of the 226 patients, 31.4% underwent pretreatment tracheotomy. Five-year disease-specific survival was 72.9%, and overall survival was 48.8% for entire cohort. There was a statistically significant decrease in overall survival (p = .03) and disease-free survival (p = .02) for the pretreatment tracheotomy group compared to no pretreatment tracheotomy, which was largely explained by primary tumor stage. Pretreatment tracheotomy was associated with gastrostomy tube placement and was an independent predictor of worse odds of gastrostomy tube removal. Disease stage, distant metastasis, and age independently conferred worse odds of gastrostomy tube removal. CONCLUSION: Patients undergoing pretreatment tracheotomy for primary T4 laryngeal cancer had decreased overall survival compared to patients without pretreatment tracheotomy. There was no difference in local recurrence rates based on tracheotomy status. Organ preservation with chemotherapy and radiation did not result in better functional outcomes than surgery in the pretreatment tracheotomy group as nearly half of patients treated with organ preservation remained tracheotomy dependent. Based on this data, pretreatment tracheotomy may impact oncologic and functional outcomes in advanced disease, and it should be a consideration in an informed decision-making process.

Decreased cancer-independent life expectancy in the head and neck cancer population.

BACKGROUND: Aside from cancer mortality, patients with head and neck cancer have increased mortality risk. Identifying patients with the greatest loss of cancer-independent life expectancy can guide comprehensive survivorship programs. METHODS: Age-based survival data from the Surveillance, Epidemiology, and End Result (SEER) database for patients with head and neck cancer were censored for mortality from the index cancer. Life expectancy and years of life lost (YLL) referenced to the general population were calculated. Cox proportional regression models produced hazard ratios (HRs). RESULTS: Cancer-independent life expectancy for patients with head and neck cancer is 6.5 years shorter than expected. The greatest hazard and impact of other-cause mortality was associated with black race (HR 1.23; YLL 8.55), stage IV (HR 1.60; YLL 7.92), Medicaid (HR 1.55; YLL 12.9), and previous marriage (HR 1.49; YLL 11.4). CONCLUSION: Patients with head and neck cancer lives are foreshortened independent of their cancer diagnosis necessitating management of noncancer mortality to maximize overall survival.

Dynamic vs. fixed bag filling: impact on cardiac output rebreathing protocol.

The purpose of this study was to compare the repeatability (2.77 multiplied by the within-subject SD)between two different rebreathing protocols on cardiac output ( ˙Q ), pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), and pulmonary capillary blood volume (Vc). This study compared two bag volume protocols [Fixed Bag Volume (FBV) = bag volume fixed at 60% of forced vital capacity; Dynamic Bag Volume (DBV) = bag volume matched to tidal volume at each stage of exercise].Ten females (age = 27±8 yrs; ˙VO2, (peak)=2.5±0.6 L/min had measurements at rest (12%), 52%, 88%, and 100% of ˙VO2, (peak) on two study days. Neither the slope nor intercept of ˙Q vs. ˙VO2 were different between either bag volume protocols. The slope of DLCO vs. ˙Q was the same but the intercept was higher for the FBV protocol. The bag volume affected the slope and the intercept between DLNO vs. ˙Q (p < 0.05).The mean repeatability was similar between both protocols for ˙Q (2.0 vs. 2.3 L/min) and DLCO (3.8 vs.5.9 mL/min/mmHg), regardless of exercise intensity. Increasing exercise intensity made the measurement error worse for Vc and DLNO (p ≤ 0.06). Measurement error was lower for Vc when using the FBV protocol (p = 0.02). Also, the pattern of bag volume used during rebreathing maneuvers affected the relation between DLNO vs. ˙Q more than it affected DLCO vs. ˙Q , or Vc vs. ˙Q. Additionally, the FBV protocol provided less measurement error for Vc compared to the DBV protocol [corrected].

Bisphosphonate inhibition of a Plasmodium farnesyl diphosphate synthase and a general method for predicting cell-based activity from enzyme data.

We screened 26 bisphosphonates against a farnesyl diphosphate synthase from Plasmodium vivax, finding a poor correlation between enzyme and cell growth inhibition (R(2) = 0.06). To better predict cell activity data, we then used a combinatorial descriptor search in which pIC(50)(cell) = a pIC(50)(enzyme) + bB + cC + d, where B and C are descriptors (such as SlogP), and a-d are coefficients. R(2) increased from 0.01 to 0.74 (for a leave-two-out test set of 26 predictions). The method was then further validated using data for nine other systems, including bacterial, viral, and mammalian cell systems. On average, experimental/predicted cell pIC(50) correlations increased from R(2) = 0.28 (for an enzyme-only test set) to 0.70 (for enzyme plus two descriptor test set predictions), while predictions based on scrambled cell activity had no predictive value (R(2) = 0.13). These results are of interest since they represent a general way to predict cell from enzyme inhibition data, with in three cases, R(2) values increasing from approximately 0.02 to 0.72.