Voice outcome after vocal fold injection augmentation with carboxymethyl cellulose versus calcium hydroxyapatite.

BACKGROUND: Vocal fold injection augmentation is a recognised treatment modality for glottic insufficiency. Causes of glottal closure insufficiency include vocal fold paralysis, paresis, atrophy, sulcus vocalis, scarring and vocal fold deficiency after laryngeal surgery. A variety of materials exist for injection augmentation. This study aimed to compare voice improvement after injection augmentation between two injectable materials: carboxymethyl cellulose and calcium hydroxyapatite. METHOD: This retrospective study included 66 consecutive patients with glottic insufficiency who underwent injection augmentation. RESULTS: Among the patients who received their first injection augmentation with carboxymethyl cellulose and their second injection augmentation with calcium hydroxyapatite (n = 28), voice quality improved significantly after both injection augmentations. No significant differences were observed in any of the objective and subjective voice quality measurements examined following carboxymethyl cellulose and calcium hydroxyapatite injections. CONCLUSION: Voice improvement after injection augmentation depends mainly on the improvement of glottic closure, rather than the injection material.

Cold Atmospheric Plasma, Created at the Tip of an Elongated Flexible Capillary Using Low Electric Current, Can Slow the Progression of Melanoma.

INTRODUCTION: Cold Atmospheric Plasma Jet (CAPJ), with ion temperature close to room temperature, has tremendous potential in biomedical engineering, and can potentially offer a therapeutic option that allows cancer cell elimination without damaging healthy tissue. We developed a hand-held flexible device for the delivery of CAPJ to the treatment site, with a modified high-frequency pulse generator operating at a RMS voltage of <1.2 kV and gas flow in the range 0.3-3 l/min. The aims of our study were to characterize the CAPJ emitted from the device, and to evaluate its efficacy in elimination of cancer cells in-vitro and in-vivo. METHODS AND RESULTS: The power delivered by CAPJ was measured on a floating or grounded copper target. The power did not drastically change over distances of 0-14 mm, and was not dependent on the targets resistance. Temperature of CAPJ-treated target was 23°-36° C, and was dependent on the voltage applied. Spectroscopy indicated that excited OH- radicals were abundant both on dry and wet targets, placed at different distances from the plasma gun. An in-vitro cell proliferation assay demonstrated that CAPJ treatment of 60 seconds resulted in significant reduction in proliferation of all cancer cell lines tested, and that CAPJ activated medium was toxic to cancer cells. In-vivo, we treated cutaneous melanoma tumors in nude mice. Tumor volume was significantly decreased in CAPJ-treated tumors relatively to controls, and high dose per fraction was more effective than low dose per fraction treatment. Importantly, pathologic examination revealed that normal skin was not harmed by CAPJ treatment. CONCLUSION: This preliminary study demonstrates the efficacy of flexible CAPJ delivery system against melanoma progression both in-vitro and in-vivo. It is envisioned that adaptation of CAPJ technology for different kinds of neoplasms use may provide a new modality for the treatment of solid tumors.

Abdominal aortic aneurysm screening: how many life years lost from underuse of the medicare screening benefit?

BACKGROUND: Since 2007, Medicare has provided one-time abdominal aortic aneurysm (AAA) screening for men with smoking history, and men and women with a family history of AAA as part of its Welcome to Medicare visit. OBJECTIVE: We examined utilization of the new AAA screening benefit and estimated how increased utilization could influence population health as measured by life years gained. Additionally, we explored the impact of expanding screening to women with smoking history. DESIGN: Analysis of Medicare claims and a simulation model to estimate the effects of screening, using published data for parameter estimates. SETTING: AAA screening in the primary care setting. PATIENTS: Newly-enrolled Medicare beneficiaries aged 65 years, with smoking history or family history of AAA. MAIN MEASURES: Life expectancy, 10-year survival rates. KEY RESULTS: Medicare data revealed low utilization of AAA screening, under 1% among those eligible. We estimate that screening could increase life expectancy per individual invited to screening for men with smoking history (0.11 years), with family history of AAA (0.17 years), and women with family history (0.08 years), and smoking history (0.09 years). Average gains of 131 life years per 1,000 persons screened for AAA compare favorably with the grade B United States Preventive Services Task Force (USPSTF) recommendation for breast cancer screening, which yields 95-128 life years per 1,000 women screened. These findings were robust over a range of scenarios. LIMITATIONS: The simulation results reflect assumptions regarding AAA prevalence, treatment, and outcomes in specific populations based on published research and US survey data. Published data on women were limited. CONCLUSIONS: The Welcome to Medicare and AAA screening benefits have been underutilized. Increasing utilization of AAA screening would yield substantial gains in life expectancy. Expanding screening to women with smoking history also has the potential for substantial health benefits.

Association between the functional independence measure following spinal cord injury and long-term outcomes.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: To estimate the association between the Functional Independence Measure (FIM) for spinal cord injury (SCI) patients at time of discharge from rehabilitation and long-term resource utilization, residential status and employment. The intention was to assess the value of FIM for projecting economic burden in SCI. SETTING: Federally designated spinal cord injury model system facilities throughout the USA. METHODS: We analyzed data from the National Spinal Cord Injury Statistical Center database (n = 14 620) (1988-2010), excluding subjects with: age < 6 years, normal motor function, death before discharge or etiology from gunshot or penetrating wound (n = 11685 retained). We investigated the association between motor FIM at rehabilitation discharge and residential status, survival and outcomes at 1, 5, 10, 15 and 20 years follow-up, including FIM, residential status, hospitalizations, days hospitalized in previous year, daily paid and total care and paid hours worked. Regression controlled for injury completeness, neurological level, demographic characteristics and temporal effects. RESULTS: All outcomes were statistically associated with higher FIM scores at discharge. Each one-point increment in FIM was associated with improvements in: probability of institution care at discharge (-0.34%) and at follow-up (-0.13%), FIM score at follow-up (0.76 points), hospitalizations and days hospitalized/year (-0.0044 and -0.071, respectively), probability of needing paid assistance (-0.72%) or any assistance (-0.85%) and probability of paid work (0.41%). CONCLUSION: The FIM at discharge has predictive value for long-term outcomes. Improvement in FIM suggests reduced economic burden in SCI patients. SPONSORSHIP: Novartis Pharmaceuticals Corporation.

Transplantation risks and the real world: what does 'high risk' really mean?

Candidates for, and recipients of, transplants face numerous risks that receive varying degrees of attention from the media and transplant professionals. Characterizations such as 'high risk donor' are not necessarily accurate or informative unless they are discussed in context with the other risks patients face before and after transplantation. Moreover, such labels do not provide accurate information for informed consent discussions or decision making. Recent cases of donor-transmitted diseases from donors labeled as being at 'high risk' have engendered concern, new policy proposals and attempts to employ additional testing of donors. The publicity and policy reactions to these cases do not necessarily better inform transplant candidates and recipients about these risks. Using comparative risk analysis, we compare the various risks associated with waiting on the list, accepting donors with various risk characteristics, posttransplant survival and everyday risks we all face in modern life to provide some quantitative perspective on what 'high risk' really means for transplant patients. In our analysis, donor-transmitted disease risks are orders of magnitude less than other transplantation risks and similar to many everyday occupational and recreational risks people readily and willingly accept. These comparisons can be helpful for informing patients and guiding future policy development.

[Fiberoptic endoscopic evaluation of swallowing--the Tel Aviv Voice and Swallowing Disorders Clinic].

Fiberoptic endoscopic evaluation of swallowing (FEES) involves passing a fiberoptic laryngoscope transnasally to visualize the hypopharynx, larynx, and proximal trachea in order to assess swallowing disorders. FEES has been compared with the modified barium swallow (MBS) (the presumed "gold standard"). To date, reports have demonstrated that FEES is as sensitive as, or even more sensitive, for use as a tool in swallowing assessment compared with the MBS. FEES provides the clinician with a safe, portable, effective, and valid means of evaluating individuals with swallowing disturbances. FEES allows the examiner to identify swallowing physiology, determine the safest and least restrictive level of oral intake, implement appropriate compensatory techniques, and identify a dysphagia rehabilitation plan. In this article we present the Tel-Aviv Voice and Swallowing Disorders Center experience. Out of 100 patients that were referred to our center for swallowing evaluation 97 patients underwent 102 FEES examinations. Three patients couldn't tolerate the examination. In 63% of the patients swallowing pathology was found. FEES were performed by teamwork involving a speech-language pathologist and otolaryngologist collaborating together thus optimally managing the individual with dysphagia safely and efficiently.

[The reflux symptom index--a clinical tool for the diagnosis of laryngopharyngeal reflux].

BACKGROUND: Laryngopharyngeal reflux (LPR) refers to the backflow of stomach contents into the throat. Patients with LPR suffer from hoarseness, throat discomfort, dysphonia, chronic cough, chronic throat clearing and dysphagia. In 2001 Koufman et al. published the self-administered nine-item reflux symptom index (RSI) to assist clinicians in detecting and documenting the presence of LPR. This instrument appears to be valid and highly reproducible. OBJECTIVE: To develop the Hebrew version of the Reflux Symptom Index (RSI). METHODS: Validation of the Hebrew questionnaire included translation of the original instrument from English to Hebrew by three independent translators and retranslation back from Hebrew to English by three other translators. In the United States, patients completed the original and back-translated questionnaires. Scores correlation of the two instruments was performed using correlation coefficient analysis. Validation of the questionnaire was performed by measuring the association between the mean RSI score and the reflux findings upon flexible endoscopy. A control group of 9 patients with no clinical signs of reflux was chosen for our outpatient clinic. RESULTS: A total of '14 patients in the United States completed the original and the back-translated questionnaires. The correlation coefficient (r) was 0.92 (p < 0.001). In the second part of the study. 21 consistent Israeli patients that were referred to our voice center because of voice problems were requested to complete the questionnaire. History and endoscopic examinations did not reveal tumors, paralysis, functional voice problems or smoking. The mean age was 53 years (range 37-69 years). There were 14 women in the study group. Twenty patients had RSI higher then 10 (considered positive to the presence of reflux disease). Examination of the larynx demonstrated presence of reflux (e.g. edema of the vocal cords, posterior commissure hypertrophy, arythenoids edema, subglottic edema) in 19 cases (90.5% of patients). All the patients in the control group had a RSI lower then 10. CONCLUSIONS: The Hebrew RSI is an easy self-administered and reliable instrument that can help the clinician detect patients suffering from LPR and monitor their treatment.

The subcranial approach for the treatment of cerebrospinal fluid rhinorrhea: a report of 10 cases.

PURPOSE: Because of the likelihood of meningitis and other intracranial complications, optimal treatment for a cerebrospinal fluid (CSF) fistula is to close the leak. The neurosurgical approach to the management of CSF rhinorrhea has been by intracranial access. Extracranial approaches are now gaining acceptance as the preferred method for initial treatment of CSF leakage, because the success rates are reasonable, and the morbidity is lower. This report describes the results of using such an approach. PATIENTS AND METHODS: The extended subcranial approach was used in 10 patients with CSF rhinorrhea. Selection criteria included defects of the anterior skull base greater than 15 mm in diameter, defects not accessible by endoscopes, fistula sites that could not be localized preoperatively, and multiple and transverse fractures of the cribriform region. Follow-up ranged from 8 to 23 months, with a mean of 17 months. RESULTS: Resolution of rhinorrhea was achieved in 9 (90%) of the patients. Anosmia was the only postoperative complication, occurring in 8 patients. CONCLUSION: The authors conclude that the extended subcranial approach to the anterior skull base is a safe, versatile, and effective procedure for the surgical treatment of CSF rhinorrhea involving the anterior skull base.

The development of a stochastic physiologically-based pharmacokinetic model for lead.

This presentation describes the development of a prototype Monte Carlo module for the physiologically-based pharmacokinetic (PBPK) model for lead, created by Dr Ellen O'Flaherty. The module uses distributions for the following: exposure parameters (soil and dust concentrations, daily soil and ingestion rate, water lead concentration, water ingestion rate, air lead concentration, inhalation rate and dietary lead intake); absoption parameters; and key pharmacokinetic parameters (red blood binding capacity and half saturation concentration). Distributions can be specified as time-invariant or can change with age. Monte Carlo model predicted blood levels were calibrated to empirically measured blood lead levels for children living in Midvale, Utah (a milling/smelting community). The calibrated model was then evaluated using blood lead data from Palmerton, Pennsylvania (a town with a former smelter) and Sandy, Utah, (a town with a former smelter and slag piles). Our initial evaluation using distributions for exposure parameters showed that the model accurately predicted geometric (GM) blood lead levels of Palmerton and Sandy and slightly over predicted the GSD. Consideration of uncertainty in red blood cell parameters substantially inflated the GM. Future model development needs to address the correlation among parameters and the use of parameters for long-term exposure derived from short-term studies.

Recent trends in childhood blood lead levels.

Blood lead levels in children in the United States have declined through 1994, the date of the most recent National Health and Nutrition Examination Survey. In this investigation, the authors analyzed whether blood lead levels have changed since 1994 and quantified the magnitude of any change. The authors evaluated blood lead levels from 12 longitudinal data sets from 11 states and 1 city. Geometric mean blood lead levels declined between 4%/year and 14%/year in 8 of the data sets. No differences in decline rates were observed between data sets from states that had universal screening as a goal or that included repeat measures for an individual child and those data sets that did not. The authors' best estimate for these populations was a decline rate of 4-7%/year, which was comparable to the decline rate prior to 1994.

Blood lead slope factor models for adults: comparisons of observations and predictions.

Here we explore the appropriateness of various parameter values for the Bowers et al. model [Risk Anal 14:183-189, 1994] in the context of predicting the influence of site-related exposure to lead in soil on the blood lead (PbB) levels of women of childbearing age. We outline the parameters prescribed by Bowers et al. as well as those prescribed by the U.S. Environmental Protection Agency (U.S. EPA). Comparison of the PbB levels predicted by the Bowers et al. model to those predicted by the validated O'Flaherty pharmacokinetic model indicates that the Bowers et al. model performs favorably when parameter values prescribed here are used. Use of the U.S. EPA-prescribed parameters yields predicted PbB levels that substantially exceed the validated O'Flaherty model predictions. Finally, both the U.S. EPA-prescribed parameter values and the parameter values recommended herein are used to predict PbB levels among adults living in four Superfund communities. Comparison of predicted PbB levels for these communities indicates that the U.S. EPA parameters overstate the incremental influence of lead in soil on PbB levels. Differences between the parameter values prescribed here and the U.S. EPA-prescribed parameters yield substantially different cleanup criteria for lead in soil, although conservative parameter values may still be appropriate for screening purposes.

Life years lost at hazardous waste sites: remediation worker fatalities vs. cancer deaths to nearby residents.

We present a hypothetical case study using the Years of Potential Life Lost (YPLL) metric to compare cancer risks incurred by residents living near a Superfund site to occupational fatality risks incurred by workers employed in that site's remediation. Since cancer occurs late in life, and because we assume its mortality rate is 60%, each case results in 8.8 YPLL. Each occupational fatality, which typically occurs earlier in life, results in 38.1 YPLL. In our case study, the residential population of 5000 incurred 1.3 YPLL, compared to 5.7 YPLL incurred by the 500 workers. Several uncertain assumptions may influence our calculations; moreover, occupational risks may be viewed as more "voluntary" than risks incurred by residents. However, because the magnitude of the YPLL incurred by workers and residents may be comparable, risk managers should consider occupational risks when evaluating remedial alternatives.

The use of Monte Carlo simulation techniques to predict population blood lead levels.

Effective management of the risks posed by lead depends on an understanding of the relationship between exposure (the presence and accessibility of lead in the environment) and dose (blood lead levels). Our paper begins by outlining the type of information most valuable to a decision maker addressing the lead problem. A useful exposure-dose characterisation must address multiple contamination sources simultaneously, provide estimates of the number of people with blood lead levels exceeding critical thresholds, and assess the influence of "modifying factors" (e.g. the soil and dust ingestion rate) on population blood lead variability. We describe a pilot effort to develop an "urban setting" lead exposure-dose model, and use this model to compare three approaches for generating model input quantities: (1) worst-case estimates, (2) central estimates and (3) Monte Carlo simulation. Using the criteria outlined above, we find that the Monte Carlo technique provides the most useful model output. We describe the population blood lead level distribution generated by the model, as well as the relative influence of environmental and behavioural factors on the variability of the population distribution. Finally, we assess the impact of parameter uncertainty on the model output, and contend this type of information can help identify areas in which further empirical study would be most valuable.

The challenge of risk characterization: current practice and future directions.

Risk characterization is perhaps the most important part of risk assessment. As currently practiced, risk characterizations do not convey the degree of uncertainty in a risk estimate to risk managers, Congress, the press, and the public. Here, we use a framework put forth by an ad hoc study group of industry and government scientists and academics to critique the risk characterizations contained in two risks assessments of gasoline vapor. After discussing the strengths and weaknesses of each assessment's risk characterization, we detail an alternative approach that conveys estimates in the form of a probability distribution. The distributional approach can make use of all relevant scientific data and knowledge, including alternative data sets and all plausible mechanistic theories of carcinogenesis. As a result, this approach facilitates better public health decisions than current risk characterization procedures. We discuss methodological issues, as well as strengths and weaknesses of the distributional approach.