Ryan C. Branski

Measuring Quality of Life in Dysphonic Patients: A Systematic Review of Content Development in Patient-Reported Outcomes Measures

To review existing patient reported outcomes measures (PROMs) used in dysphonic populations to assess the procedures used in their development and the extent to which these meet current development standards for content generation and psychometric evaluation. The study is a systematic review. A systematic review of Medline, Cumulative Index to Nursing & Allied Health, and Health and Psychosocial Instruments databases was completed using voice, quality of life, and PROMs as keywords. We identified all patient or parent-reported questionnaires measuring quality of life associated with voice disorders from the review findings. Questionnaires were appraised for adherence to international guidelines for the development and evaluation of PROMs as outlined by the Scientific Advisory Committee of the Medical Outcome Trust. Nine PROMs fulfilled the inclusion criteria. The quality of these questionnaires was variable with regard to instrument development and none met all of the current, recommended criteria. Of the nine questionnaires, the Voice Symptom Scale underwent the most rigorous development process. Furthermore, many instruments have been augmented to allow for proxy administration, failing to address quality of life-related issues specific to the target population. Instrument development is often overlooked when attempting to quantify patient reported outcomes in dysphonic patients. Careful instrument development procedures are required to ensure that PROMs are valid, reliable, and responsive. Our review suggests that the deficits in psychometric properties of the current voice-related PROMs may be, at least in part, due to deficits in the development process. Furthermore, these data suggest the potential utility of a novel PROM adhering to rigorous international standards to better ensure that clinicians appreciate the variables most relevant to patients with voice disorders and address some of the psychometric shortcomings of the currently used questionnaires.

Acute Vocal Fold Wound Healing in a Rabbit Model

Several authors have eloquently described the characteristics of vocal fold scar, a long-term consequence of vocal fold injury. However, events in the acute stage of mucosal injury, which lead up to fibrosis, have been largely overlooked. The current study describes acute events with regard to mucosal re-formation in a rabbit model. Vocal fold injury was induced surgically. A fibrinous clot was present 1 day after injury. Massive cellular infiltration was noted on day 3, and complete epithelial coverage was achieved by day 5. Also, neo-matrix deposition was noted as early as 5 days after injury, and more mature collagen was seen by day 7. The general timetable described in the current study can contribute to the experimental foundation for the development of regenerative models of healing in the vocal folds. Most notably, the proliferation phase of wound healing appears to occur approximately 3 days after injury, indicating a critical time for intervention. Manipulation and/or alteration of naturally occurring neo-matrix deposition and organization may yield improved biophysical function of the injured vocal fold.

A systematic review of patient-reported outcome measures in head and neck cancer surgery.

Objective To identify, summarize, and evaluate patient-reported outcome questionnaires for use in head and neck cancer surgery with the view to making recommendations for future research. Data Sources A systematic review of the English-language literature, with the use of head-and-neck-surgery-specific keywords, was performed in the following databases: Medline, Embase, HAPI, CINAHL, Science/Social Sciences Citation Index, and PsycINFO from 1966 to March 2006. Data Extraction and Study Selection All English-language instruments identified as patient-reported outcome questionnaires that measure quality of life and/or satisfaction that had undergone development and validation in a head and neck cancer surgery population were included. Data Synthesis Twelve patient-reported outcome questionnaires fulfilled our inclusion criteria. Of these, four were developed from expert opinion alone or did not have a published development process and seven questionnaires lacked formal item reduction. Only three questionnaires (EORTC Head and Neck Module, University of Michigan Head and Neck Quality-of-life Questionnaire, and Head and Neck Cancer Inventory) fulfilled guidelines for instrument development and evaluation as outlined by the Medical Outcomes Trust. Conclusions Rigorous instrument development is important for creating valid, reliable, and responsive disease-specific questionnaires. As a direction for future instrument development, an increased focus on qualitative research to ensure patient input may help to better conceptualize and operationalize the variables most relevant to head and neck cancer surgery patients. In addition, the use of alternative methods of psychometric data analysis, such as Rasch, may improve the value of health measurement in clinical practice for individual patients.

Effects of exercise on swallowing and tongue strength in patients with oral and oropharyngeal cancer treated with primary radiotherapy with or without chemotherapy

Tongue strength is reduced in patients treated with chemoradiotherapy for oral/oropharyngeal cancer. Tongue strengthening protocols have resulted in improved lingual strength and swallowing in healthy individuals, as well as in patients following a neurological event. However, no studies have examined the efficacy of tongue strengthening exercises on tongue strength, swallowing, and quality of life (QOL; Head and Neck Cancer Inventory) in patients treated with chemoradiotherapy. A randomized clinical trial examined the effects of a tongue strengthening programme paired with traditional exercises vs. traditional exercises alone. Dependent variables included tongue strength, swallowing, and QOL in a group of patients with oral and oropharyngeal cancer treated with primary radiotherapy with or without chemotherapy. Differences with regard to tongue strength and oropharyngeal swallow efficiency (OPSE) were not observed within or between groups. QOL in the eating and speech domains improved following treatment in both groups. However, the experimental group demonstrated greater impairment in QOL in the social disruption domain following treatment, whereas the control group demonstrated a slight improvement in functioning. Tongue strengthening did not yield a statistically significant improvement in either tongue strength or swallowing measures in this patient cohort. Patient compliance and treatment timing may be factors underlying these outcomes.

Effects of Transforming Growth Factor-β1 on Human Vocal Fold Fibroblasts

Objectives: We studied the effect of transforming growth factor (TGF)–β on immortalized human vocal fold fibroblasts. Methods: Normal human vocal fold fibroblasts were subjected to sequential lentiviral transduction with genes for human telomerase (hTERT) and SV40 large T antigen in order to produce an “immortalized” cell line of normal phenotype. After confirmation of vocal fold fibroblast transfection, these cells, referred to as HVOX, were treated with various concentrations of exogenous TGF-β1 and assayed for collagen secretion, migration, and proliferation. In addition, components of the TGF-β signaling pathway were examined in this cell line. Results: TGF-β stimulated collagen secretion and migration without altering proliferation of HVOX. HVOX constitutively expressed type I and II TGF-β receptors, as well as messenger RNA for the Smad signaling proteins and for all TGF-β isoforms. Exogenous TGF-β1 induced temporally dependent alterations in Smad2 and Smad3 gene expression. TGF-β increased Smad7 expression at both 4 and 24 hours. Prolonged exposure to TGF-β decreased TGF-β1 gene expression. Conclusions: Insight into the underlying pathophysiology of vocal fold fibrosis is likely to yield improved therapeutic strategies to mitigate vocal fold scarring. Our data suggest that TGF-β signaling may be both paracrine and autocrine in this vocal fold fibroblast cell line, and we therefore propose that TGF-β may be a reasonable target for therapies to prevent and/or treat vocal fold fibrosis, given its putative role in both acute and chronic vocal fold injury, as well as its effects on vocal fold fibroblasts.

Diagnostic accuracy of history, laryngoscopy, and stroboscopy

Although clinical dogma suggests the value of laryngeal visualization (flexible laryngoscopy and stroboscopy) in dysphonic patients, recently published clinical guidelines suggest that, in many cases, history and/or physical examination are sufficient to guide clinical decision‐making regarding the timing of such examinations. We sought to prospectively quantify the diagnostic accuracy of history, laryngoscopy, and stroboscopy using direct laryngoscopy as the gold standard.

Shifts in biochemical markers associated with wound healing in laryngeal secretions following phonotrauma: a preliminary study.

The current study sought to determine whether shifts in key components of the inflammatory process could be detected from laryngeal secretions sampled before and after vocal loading. a healthy 44-year-old woman served as the subject. The vocal folds were swabbed to collect baseline secretions. Ten and 20 minutes after nearly constant loud phonation for 1 hour, the vocal folds were swabbed again. The findings indicated strong shifts in several key inflammatory mediators: interleukin-1β, tumor necrosis factor a, and matrix metalloproteinase 8. The concentrations of those mediators continued to increase from the 10- to 20-minute postloading time-points. Transforming growth factor β and prostaglandin E2 did not demonstrate clear shifts. In summary, mediators reflecting the acute inflammatory process could be detected from laryngeal secretions in an awake human. The upward slope of the curves at the 20-minute time interval indicates the need for longer follow-up sampling to determine the full biological response of the vocal folds to acute phonotrauma.

Morbidity and Patient Perception of Flexible Laryngoscopy

Objectives: The recently published Clinical Practice Guideline: Hoarseness (Dysphonia) revealed major deficits in the literature regarding relatively routine clinical decision-making. One of the more controversial points in the Guideline regarded the utility and timing of laryngeal visualization via flexible laryngoscopy, potentially because of sparse literature regarding the risks and potential morbidity. We sought to prospectively address this issue in order to optimize evaluation protocols. Methods: Two-hundred fifty consecutive patients with a variety of complaints completed a survey after undergoing flexible laryngoscopy. The survey queried 1) demographics; 2) discomfort of pretreatment anesthesia and scope placement in the nose and pharynx; 3) fear of future examinations; and 4) patient perception and past experience. Concurrently, the laryngoscopist reported the complications and anatomic variations encountered. Results: The discomfort and pain ratings from both the anesthetic spray and the scope placement were low. No statistically significant differences were observed with regard to sex; however, women reported greater fear associated with examinations (p = 0.0001). Anatomic abnormalities were observed in 14.4% of patients, and these patients reported greater discomfort, pain, and fear regarding the examination. No adverse events were observed. Conclusions: Flexible laryngoscopy was well tolerated, with little to no risk. The presence of nasal anatomic abnormalities predicted increased discomfort.

Hypertonic challenge to porcine vocal folds: effects on epithelial barrier function.

OBJECTIVE: Dehydration challenges can increase the chemical composition of surface fluid overlying vocal fold epithelia (hypertonic surface fluid). The vocal fold epithelium is posited to act as a barrier, shielding the lamina propria from perturbations in the airway lumen. However, the effects of hypertonic surface fluid on the barrier functions of vocal fold epithelia have not been quantified. We, therefore, sought to investigate whether hypertonic surface fluid compromises epithelial barrier function. We examined the effects of hypertonic surface fluid on vocal fold epithelial resistance, paracellular pathway morphology, and tight junction protein integrity. STUDY DESIGN: Ex vivo, between group design. SETTING: Laboratory. METHODS: Porcine vocal folds (n = 24) were exposed to hypertonic or isotonic challenge and examined by electrophysiology, transmission electron microscopy, and Western blot analyses. RESULTS: Hypertonic, but not isotonic, challenge significantly reduced transepithelial resistance. This decrease in resistance was observed immediately after the challenge and was consistent with the appearance of dilated paracellular pathway morphology. However, hypertonic challenge did not alter protein levels of occludin, zona occludens-1, E-cadherin, or β-catenin. CONCLUSION: Hypertonic surface fluid alters epithelial barrier function in the vocal folds. Specifically, exposure to hypertonic challenges increases epithelial permeability. Given the important role of the vocal fold epithelium in shielding the underlying mucosa from inhaled pathogens and pollutants, our data provide the impetus for future studies on pharmacological treatments aimed at restoring the hydration level and chemical composition of vocal fold surface fluid.

Cortical activation during swallowing rehabilitation maneuvers: a functional MRI study of healthy controls.

We hypothesize that the central response during swallowing rehabilitation is critical and may be exploited to maximize the therapeutic benefit. We seek to provide preliminary data regarding the neural networks associated with commonly employed rehabilitation strategies to increase our understanding of the neural bases underlying these maneuvers.