Courtney C. J. Voelker

A PRACTICAL GUIDE TO UNDERSTANDING KAPLAN-MEIER CURVES

In 1958, Edward L. Kaplan and Paul Meier collaborated to publish a seminal paper on how to deal with incomplete observations. Subsequently, the Kaplan-Meier curves and estimates of survival data have become a familiar way of dealing with differing survival times (times-to-event), especially when not all the subjects continue in the study. “Survival” times need not relate to actual survival with death being the event; the “event” may be any event of interest. Kaplan-Meier analyses are also used in nonmedical disciplines. The purpose of this article is to explain how Kaplan-Meier curves are generated and analyzed. Throughout this article, we will discuss Kaplan-Meier estimates in the context of “survival” before the event of interest. Two small groups of hypothetical data are used as examples in order for the reader to clearly see how the process works. These examples also illustrate the crucially important point that comparative analysis depends upon the whole curve and not upon isolated points.

The Transcriptome of Utricle Hair Cell Regeneration in the Avian Inner Ear

Sensory hair cell loss is the major cause of hearing and balance disorders. Mammals are incapable of sustained hair cell regeneration, but lower vertebrates can regenerate these mechano-electrical transducers. We present the first comprehensive transcriptome (by mRNA-Seq) of hair cell regeneration in the chick utricle. We provide pathway and pattern annotations and correlate these with the phenotypic events that occur during regeneration. These patterns are surprisingly synchronous and highly punctuated. We show how these patterns are a new resource for identifying components of the hair cell transcriptome and identify 494 new putative hair-cell-specific genes and validate three of these (of three tested) by immunohistochemical staining. We describe many surprising new components and dynamic expression patterns, particularly within NOTCH signaling. For example, we show that HES7 is specifically expressed during utricle hair cell regeneration and closely parallels the expression of HES5. Likewise, the expression of ATOH1 is closely correlated with HEYL and the HLH inhibitory transcription factors ID1, ID2, and ID4. We investigate the correlation between fibroblast growth factor signaling and supporting cell proliferation and show that FGF20 inhibits supporting cell proliferation. We also present an analysis of 212 differentially expressed transcription factor genes in the regenerative time course that fall into nine distinct gene expression patterns, many of which correlate with phenotypic events during regeneration and represent attractive candidates for future analysis and manipulation of the regenerative program in sensory epithelia and other vertebrate neuroepithelia.

A practical guide to understanding systematic reviews and meta-analyses

A systematic review is a transparent and unbiased review of available information. The published systematic review must report the details of the conduct of the review as one might report the details of a primary research project. A meta-analysis is a powerful and rigorous statistical approach to synthesize data from multiple studies, preferably obtained from a systematic review, in order to enlarge the sample size from smaller studies to test the original hypothesis and/or to generate new ones. The objective of this article is to serve as an easy to read practical guide to understand systematic reviews and meta-analyses for those reading them and for those who might plan to prepare them.

A Practical Guide to Surveys and Questionnaires

Surveys with questionnaires play a vital role in decision and policy making in society. Within medicine, including otolaryngology, surveys with questionnaires may be the only method for gathering data on rare or unusual events. In addition, questionnaires can be developed and validated to be used as outcome measures in clinical trials and other clinical research architecture. Consequently, it is fundamentally important that such tools be properly developed and validated. Just asking questions that have not gone through rigorous design and development may be misleading and unfair at best; at worst, they can result in under- or overtreatment and unnecessary expense. Furthermore, it is important that consumers of the data produced by these instruments understand the principles of questionnaire design to interpret results in an optimal and meaningful way. This article presents a practical guide for understanding the methodologies of survey and questionnaire design, including the concepts of validity and reliability, how surveys are administered and implemented, and, finally, biases and pitfalls of surveys.

An open label study to evaluate the safety and efficacy of intratympanic golimumab therapy in patients with autoimmune inner ear disease.

Objective To evaluate the safety and efficacy of intratympanically injected golimumab (GLM), a TNF-&agr; inhibitor, as a steroid-sparing agent for patients with steroid-dependent autoimmune inner ear disease (AIED). Study Design Open label. Setting Tertiary referral center. Patients Ten patients with steroid-dependent AIED were enrolled in Stage 2. The average patient age at enrollment was 59, with an average of 12.5 years from the start of bilateral hearing loss symptoms. The average dose of daily prednisone at the start of injections was 18 mg. Intervention Intratympanic injection of GLM. Main Outcome Measure Hearing loss progression (treatment failure) was defined as either an increase in pure-tone thresholds by frequency or a decrease in word recognition score. Results There were no serious adverse events. Five of seven per-protocol subjects experienced stable pure-tone thresholds in the injected ear, whereas 4 had stable word recognition scores. Two subjects experienced an improvement in word recognition scores. The results support the hypothesis that GLM may be a promising treatment. Conclusions The TNF-&agr; inhibitor GLM stabilized hearing in 3 of 7 per-protocol subjects with AIED and allowed a complete tapering off of prednisone in those 7 subjects. Studies with larger samples sizes are warranted.

A practical guide for understanding confidence intervals and P values

The 95 percent confidence interval about the mean demarcates the range of values in which the mean would fall if many samples from the universal parent population were taken. In other words, if the same observation, experiment, or trial were done over and over with a different sample of subjects, but with the same characteristics as the original sample, 95 percent of the means from those repeated measures would fall within this range. This gives a measure of how confident we are in the original mean. It tells us not only whether the results are statistically significant because the CI falls totally on one side or the other of the no difference marker (0 if continuous variables; 1 if proportions), but also the actual values so that we might determine if the data seem clinically important. In contrast, the P value tells us only whether the results are statistically significant, without translating that information into values relative to the variable that was measured. Consequently, the CI is a better choice to describe the results of observations, experiments, or trials.

Clinical Practice Guideline: Benign Paroxysmal Positional Vertigo (Update) Executive Summary:

The American Academy of Otolaryngology—Head and Neck Surgery Foundation has published a supplement to this issue of Otolaryngology–Head and Neck Surgery featuring the “Clinical Practice Guideline: Benign Paroxysmal Positional Vertigo (Update).” To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 recommendations developed emphasize diagnostic accuracy and efficiency, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary testing, and increasing the appropriate therapeutic repositioning maneuvers. An updated guideline is needed due to new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.

Practical Guide to Choosing an Appropriate Data Display

The primary objective of graphing research data is to communicate key information visually in a rapid, accurate, and concise way. Graphs might be considered visual take-home lessons of the major point(s) of the manuscript. In choosing a graph, it is tempting to concentrate only on ways of illustrating summary statements characterizing the group(s). However, individual patients are unique, and their characteristics or outcomes may not be predicted by a group summary. Consequently, if possible, graphs should demonstrate individual responses as well as group summaries. “Graphical literacy,” “graphical excellence,” and “graphical acumen” are achievable with work and collaboration. To produce a well-designed graph, a combination of by-subject detail and overall results should be the goal within the same illustration. The practice gap addressed in this article is that little attention from authors, reviewers, editors, and publishers seems to be paid to graphical literacy. The purpose of this article is to present some practical guidelines for choosing or evaluating more appropriate data displays.

Comparison of the gaze stabilization test and the dynamic visual acuity test in unilateral vestibular loss patients and controls.

Objective Compare the dynamic visual acuity test (DVAT) and gaze stabilization test (GST) in patients with unilateral vestibular loss (UVL) and healthy control subjects using a novel computerized testing system prototype. Study Design Cross-sectional study. Setting Tertiary academic referral laboratory. Patients Seventeen UVL patients (median age 62 yr) with bithermal caloric asymmetry (≥49%) or ablative surgery and 17 control subjects (median age 57 yr). Intervention(s) Diagnostic. Main Outcome Measure(s) Comparison of DVAT and GST results during self-generated sinusoidal head movements using transient unpredictable target presentations less than 95 milliseconds in duration. Results UVL patients had significantly higher DVAT scores toward the lesioned side compared with controls (p = 0.001) and the non-lesioned side (p = 0.003), but the non-lesioned side was not significantly different from controls (p = 0.157). When comparing GST scores, UVL patients required a slower head velocity to maintain visual acuity with movement toward the lesioned side compared with controls (p < 0.001) and the non-lesioned side (p = 0.004). In addition, UVL patients had significantly lower scores toward the non-lesioned side (p = 0.002) compared to controls. ROC curve analysis identified optimal thresholds for abnormal test results to discriminate the lesioned side from controls. A DVAT score greater than or equal to 0.3 &Dgr;logMAR provided 65% sensitivity and 88% specificity while a GST score less than or equal to 95 degrees/s provided 71% sensitivity and 100% specificity. When GST results were normal, adding DVAT increased overall sensitivity to 88% with 88% specificity. Conclusions Both GST and DVAT demonstrated reduced gaze stabilization toward the lesioned side in the patient group compared with normal controls. Performing GST first and utilizing DVAT when GST was normal provides optimal identification of patients with vestibular dysfunction.

Translabyrinthine resection of neurofibromatosis type 2 associated vestibular and facial schwannomas, repair of facial nerve, and placement of auditory brainstem implant

We present video of gross-total resection of a large cerebellopontine angle tumor consisting of both vestibular and facial schwannoma components via the translabyrinthine route in a patient with neurofibromatosis type 2. The facial nerve is reconstructed using a greater auricular nerve graft, and an auditory brainstem implant is placed. Prior to surgery the patient had no facial nerve function on the operative side and had lost useful hearing. He also had usable vision only on the ipsilateral side and had contralateral vocal cord paralysis. The video can be found here: http://youtu.be/IOkEND-0vhI .