Fast Dissolving Sublingual Films of Ondansetron Hydrochloride: Effect of Additives on in vitro Drug Release and Mucosal Permeation

Ondansetron hydrochloride, a 5 HT3 antagonist is a powerful antiemetic drug which has oral bioavailability of 60% due to hepatic first pass metabolism and has a short half-life of 5 h. To overcome the above draw back, the present study was carried out to formulate and evaluate fast dissolving films of ondansetron hydrochloride for sublingual administration. The films were prepared from polymers such as polyvinylalcohol, polyvinyl pyrrolidone, Carbopol 934P in different ratios by solvent casting method. Propylene glycol or PEG 400 as plasticizers and mannitol or sodium saccharin as sweeteners were also included. The IR spectral studies showed no interaction between drug and polymer or with other additives. Satisfactory results were obtained when subjected to physico-chemical tests such as uniformity of weight, thickness, surface pH, folding endurance, uniformity of drug content, swelling index, bioadhesive strength, and tensile strength. Films were also subjected to in vitro drug release studies by using USP dissolution apparatus. Ex vivo drug permeation studies were carried out using porcine membrane model. In vitro release studies indicated 81–96% release within 7 min and 66–80% within 7 min during ex vivo studies. Drug permeation of 66–77% was observed through porcine mucosa within 40 min. Higher percentage of drug release was observed from films containing the sweeteners. The stability studies conducted for a period of 8 weeks showed no appreciable change in drug content, surface pH, and in vitro drug release

Prognostic importance of tissue velocity imaging during exercise echocardiography in patients with systolic heart failure

Resting echocardiography measurements are poor predictors of exercise capacity and symptoms in patients with heart failure (HF). Stress echocardiography may provide additional information and can be expressed using left ventricular ejection fraction (LVEF), or diastolic parameters (E/E′), but LVEF has some major limitations. Systolic annular velocity (S′) provides a measure of longitudinal systolic function, which is relatively easy to obtain and shows a good relationship with exercise capacity. The objective of this study was to investigate the relationship among S′, E/E′ and LVEF obtained during stress echocardiography and both mortality and hospitalisation. A secondary objective was to compare S′ measured using a simplified two-wall model. A total of 80 patients with stable HF underwent exercise stress echocardiography and simultaneous cardiopulmonary exercise testing. Volumetric and tissue velocity imaging (TVI) measurements were obtained, as was peak oxygen uptake (VO(2) peak). Of the total number of patients, 11 died and 22 required cardiac hospitalisation. S′ at peak exertion was a powerful predictor for death and hospitalisation. Cut-off points of 5.3 cm/s for death and 5.7 cm/s for hospitalisation provided optimum sensitivity and specificity. This study suggests that, in patients with systolic HF, S′ at peak exertion calculated from the averaged spectral TVI systolic velocity of six myocardial segments, or using a simplified measure of two myocardial segments, is a powerful predictor of future events and stronger than LVEF, diastolic velocities at rest or exercise and VO(2) peak. Results indicate that measuring S′ during exercise echocardiography might play an important role in understanding the likelihood of adverse clinical outcomes in patients with HF

Academic Affiliation and Surgical Volume Predict Survival in Head and Neck Cancer Patients Receiving Surgery

Objective: To determine whether the academic affiliation or surgical volume affects the overall survival (OS) of human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) patients receiving surgery. Methods: A retrospective study of 39 North Carolina Medical Centers was conducted. Treatment centers were classified as academic hospitals, community cancer centers, or community hospitals and were divided into thirds by volume. The primary outcome was 5-year OS. Hazard ratios (HR) were determined using Cox proportional hazard models, adjusting for demographics, tumor site, stage, insurance status, tobacco use, alcohol use, stage, chemotherapy, and radiation therapy. Patients were also stratified by stage (early stage and advanced stage). Results: Patients treated at community cancer centers had significantly better 5-year OS (HR 0.68, 95% confidence interval [CI] = 0.48–0.98), and patients treated at academic hospitals trended toward better 5-year OS (HR 0.72, 95% CI = 0.50–1.04) compared to patients treated at community hospitals. The effect for academic affiliation on survival was more pronounced for patients with advanced stage cancer at diagnosis (HR 0.60, 95% CI = 0.37–0.95). There were no significant survival differences among early stage patients by treatment center type. Top-third (HR = 0.64, 95% CI = 0.42–0.96) centers by surgical volume had significantly better 5-year OS, and middle-third (HR = 0.71, 95% CI = 0.51–1.03) centers by volume trended toward better 5-year OS when compared to the bottom-third centers by volume. Conclusion: Patients treated at academic hospitals, community cancer centers, and hospitals in the top third by case volume have favorable survival for HPV-negative HNSCC. The effect for academic hospitals is most pronounced among advanced stage patients. Level of Evidence: 4 Laryngoscope, 131:E479–E488, 2021

Sinonasal Squamous Cell Carcinoma Survival Outcomes Following Induction Chemotherapy vs Standard of Care Therapy

Objective To compare oncologic outcomes in sinonasal squamous cell carcinoma (SNSCC) treated with standard of care (SOC) definitive therapy, consisting of surgery or chemoradiotherapy, vs induction therapy followed by definitive therapy. Study Design Retrospective review.SettingAcademic tertiary care hospital. Methods The medical records of patients with biopsy-proven SNSCC treated between 2000 and 2020 were reviewed for demographics, tumor characteristics, staging, treatment details, and oncologic outcomes. Patients were matched 1-to-1 by age, sex, and cancer stage according to treatment received. Time-to-event analyses were conducted. Results The analysis included 26 patients with locally advanced SNSCC who received either induction therapy (n = 13) or SOC (n = 13). Baseline demographics, Charlson Comorbidity Index, and median follow-up time were well balanced. Weekly cetuximab, carboplatin, and paclitaxel were the most common induction regimen utilized. Tolerance and safety to induction were excellent. Objective responses were observed in 11 of 13 patients receiving induction. No difference in disease-free survival was found between the induction and SOC groups at 1 or 3 years. However, when compared with SOC, induction therapy resulted in significant improvement in overall survival at 2 years (100% vs 65.3%, P = .043) and 3 years (100% vs 48.4%, P = .016) following completion of definitive therapy. Two patients in the SOC group developed metastatic disease, as compared with none in the induction group. Conclusions Induction therapy was safe and effective. When compared with SOC, induction therapy improved 3-year overall survival

Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality

OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting inor being associated withshorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers

Socioeconomic Status Drives Racial Disparities in HPV-negative Head and Neck Cancer Outcomes

Objectives/Hypothesis: To determine drivers of the racial disparity in stage at diagnosis and overall survival (OS) between black and white patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). Study Design: Retrospective cohort study. Methods: Data were examined from of a population-based HNSCC study in North Carolina. Multivariable logistic regression and Cox proportional hazards models were used to assess racial disparities in stage at diagnosis and OS with sequential adjustment sets. Results: A total of 340 black patients and 864 white patients diagnosed with HPV-negative HNSCC were included. In the unadjusted model, black patients had increased odds of advanced T stage at diagnosis (OR 2.0; 95% CI [1.5–2.5]) and worse OS (HR 1.3, 95% CI 1.1–1.6) compared to white patients. After adjusting for age, sex, tumor site, tobacco use, and alcohol use, the racial disparity persisted for advanced T-stage at diagnosis (OR 1.7; 95% CI [1.3–2.3]) and showed a non-significant trend for worse OS (HR 1.1, 95% CI 0.9–1.3). After adding SES to the adjustment set, the association between race and stage at diagnosis was lost (OR: 1.0; 95% CI [0.8–1.5]). Further, black patients had slightly favorable OS compared to white patients (HR 0.8, 95% CI [0.6–1.0]; P =.024). Conclusions: SES has an important contribution to the racial disparity in stage at diagnosis and OS for HPV-negative HNSCC. Low SES can serve as a target for interventions aimed at mitigating the racial disparities in head and neck cancer. Level of Evidence: 4 Laryngoscope, 131:1301–1309, 2021

Prognostic impact of socioeconomic status compared to overall stage for HPV-negative head and neck squamous cell carcinoma

Objective: To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) Materials and methods: Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox proportional hazards models, survival gradients, Bayesian information criterion (BIC), and Harrell's C index were used to estimate the prognostic ability of SES compared to stage on overall survival (OS). Results: The sample consisted of 1229 patients with HPV-negative HNSCC. Patients with low SES had significantly increased risk of mortality at 5 years compared to patients with high SES (HR 3.11, 95% CI 2.07–4.67; p < 0.001), and the magnitude of effect was similar to overall stage (HR 3.01, 95% CI 2.35–3.86; p < 0.001 for stage IV versus I). Compared to overall stage, the SES classification system had a larger total survival gradient (35.8% vs. 29.1%), similar model fit (BIC statistic of 7412 and 7388, respectively), and similar model discriminatory ability (Harrell's C index of 0.61 and 0.64, respectively). The association between low SES and OS persisted after adjusting for age, sex, race, alcohol, smoking, overall stage, tumor site, and treatment in a multivariable model (HR 2.96, 95% CI 1.92–4.56; p < 0.001). Conclusion: SES may have a similar prognostic ability to overall stage for patients with HPV-negative HNSCC. Future research is warranted to validate these findings and identify evidence-based interventions for addressing barriers to care for patients with HNSCC

Pure adaptive search in monte carlo optimization

Pure adaptive search constructs a sequence of points uniformly distributed within a corresponding sequence of nested regions of the feasible space. At any stage, the next point in the sequence is chosen uniformly distributed over the region of feasible space containing all points that are equal or superior in value to the previous points in the sequence. We show that for convex programs the number of iterations required to achieve a given accuracy of solution increases at most linearly in the dimension of the problem. This compares to exponential growth in iterations required for pure random search.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47920/1/10107_2005_Article_BF01582296.pd

Field Measurements of Terrestrial and Martian Dust Devils

Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter