Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy.

BACKGROUND: Patients treated with epidermal growth factor receptor inhibitors (EGFRIs) frequently experience dermatologic toxic effects. Whereas the impact of these effects on quality of life and EGFRI dosing has been described, their impact on physical health has not been ascertained. We examined the prevalence of infections that complicate dermatologic toxic effects of EGFRIs. METHODS: We used retrospective chart review methods to analyze 221 patients who were treated in the Skin and Eye Reactions to Inhibitors of EGFR and Kinases clinic, a referral clinic for dermatologic toxic effects of cancer therapies. We reviewed results of bacterial cultures, histopathologic assessment of biopsy samples, and immunohistochemical staining of skin specimens for viral pathogens that were recorded in the patients' medical records. Associations between patient demographic and treatment characteristics and the development of infections were examined using the Fisher exact test. All statistical tests were two-sided. RESULTS: Eighty-four (38%) of the 221 patients showed evidence of infection at sites of dermatologic toxic effect. Fifty (22.6%) of the 221 patients had cultures positive for Staphylococcus aureus, and 12 (5.4%) of the 221 patients cultured positive for methicillin-resistant S aureus. Less frequent infections included herpes simplex (3.2%), herpes zoster (1.8%), and dermatophytes (10.4%). The seborrheic region was the most prevalent site of infection, and patients with leukopenia had higher risk for infection than patients who did not have leukopenia (P = .005). Demographic factors and associated treatments were not associated with the occurrence of a dermatologic infection (P > or = .05). CONCLUSIONS: Patients with dermatologic toxic effects following treatment with EGFRIs have a high prevalence of cutaneous infections. Most notably, bacterial infections developed at sites previously affected by dermatologic toxic effects, with leukopenic patients being at greater risk.

Precursors to speech in infancy: the prediction of speech and language disorders.

During the canonical stage of infant babbling, infants produce well-formed syllables, often in reduplicated sequences such as "bababa." Although nearly all infants with normal hearing begin the canonical stage by 10 months of age, a few are delayed, and these infants may be of special interest. Recent studies indicate that late onset of canonical babbling may be a predictor of disorders. A simple screening procedure that focuses on canonical babbling was used to evaluate over 3400 infants at risk who were about 10 months of age. Among infants who showed late onset of canonical babbling, fewer than half had been previously diagnosed as having a significant medical problem that might have accounted for the delay. A follow-up study indicated that infants with delayed canonical babbling had smaller production vocabularies at 18, 24, and 30 months than did infants in the control group. The results suggest that late onset of canonical babbling, a factor that can be monitored effectively through an interview with a parent, can predict delay in the onset of speech production.

An event-based analysis of the coordination of early infant vocalizations and facial actions.

This study used an event-based approach to provide empirical evidence regarding the nature of coordination in 3- and 6-month-old infants. Vocalizations and facial actions of 12 normally developing infants interacting with their caregivers were coded. Coded vocalizations and facial actions were considered coordinated when they temporally overlapped. Results indicate that infants coordinated their vocalizations and facial actions more than expected by chance. Coordinated events were governed by 2 sequence patterns. When 2 communicative events were temporally associated across modalities, 1 event tended to be completely embedded within the other, and vocalizations tended to end before facial actions. This study provides new information about how infant communication is structured, confirms results from other coordination studies, and describes a new method for analysis of event-based data.

Late onset canonical babbling: a possible early marker of abnormal development.

By their 10th month of life, typically developing infants produce canonical babbling, which includes the well-formed syllables required for meaningful speech. Research suggests that emerging speech or language-related disorders might be associated with late onset of canonical babbling. Onset of canonical babbling was investigated for 1,536 high-risk infants, at about 10-months corrected age. Parental report by open-ended questionnaire was found to be an efficient method for ascertaining babbling status. Although delays were infrequent, they were often associated with genetic, neurological, anatomical, and/or physiological abnormalities. Over half the cases of late canonical babbling were not, at the time they were discovered associated with prior significant medical diagnoses. Late canonical-babbling onset may be a predictor of later developmental disabilities, including problems in speech, language, and reading.

Development of precursors to speech in infants exposed to two languages.

The study of bilingualism has often focused on two contradictory possibilities: that the learning of two languages may produce deficits of performance in each language by comparison with performance of monolingual individuals, or on the contrary, that the learning of two languages may produce linguistic or cognitive advantages with regard to the monolingual learning experience. The work reported here addressed the possibility that the very early bilingual experience of infancy may affect the unfolding of vocal precursors to speech. The results of longitudinal research with 73 infants aged 0;4 to 1;6 in monolingual and bilingual environments provided no support for either a bilingual deficit hypothesis nor for its opposite, a bilingual advantage hypothesis. Infants reared in bilingual and monolingual environments manifested similar ages of onset for canonical babbling (production of well-formed syllables), an event known to be fundamentally related to speech development. Further, quantitative measures of vocal performance (proportion of usage of well-formed syllables and vowel-like sounds) showed additional similarities between monolingual and bilingual infants. The similarities applied to infants of middle and low socio-economic status and to infants that were born at term or prematurely. The results suggest that vocal development in the first year of life is robust with respect to conditions of rearing. The biological foundations of speech appear to be such as to resist modifications in the natural schedule of vocal development.

Longitudinal speech perception performance of young children with cochlear implants and tactile aids plus hearing aids.

Nineteen profoundly deaf children who utilize either cochlear implants (CIs) or multichannel tactile aids plus hearing aids (T + HAs) and who were enrolled in a full-day educational program that specializes in the use of sensory aids were evaluated using a battery of speech perception tests either developed in house or chosen because they were part of a standard battery of tests developed for children with sensory aids. The tests were organized into four perceptual levels ranging from pattern perception at level one to open set word identification at level four. For each level, data were analyzed for changes over time and for differences between performance of CI children and those using T + HAs. The results indicate that overall, across levels, both groups improved significantly over time but no differences were found between users of T + HAs and CIs at any level.

Practical evaluation procedure to assess and remediate speech perception skills.

The University of Miami/Dade County Public Schools Model Program for the Deaf and Hard of Hearing is a research and training effort dedicated to the utilization of sensory aids including hearing aids, tactual vocoders, and cochlear implants. The program's teachers and clinicians follow the Miami Cochlear Implant, Auditory, and Tactile Skills (CHATS) Curriculum for the development of individualized speech perception and production goals. A series of peech perception tests has been used for the past five years to evaluate the children's progress. The test battery, administered at six month intervals, is extensive and impractical for school clinicians and teachers to administer to their students. To assist teachers and clinicians in the process of selecting appropriate goals and objectives for sensory aid training, a speech perception test has been developed to accompany the curriculum. This paper includes a discussion of the test design as it correlates with the curriculum.

A longitudinal evaluation of the speech perception capabilities of children using multichannel tactile vocoders.

Thirty children (mean age 6:11, range 4:3 to 11:0, SD = 2:3) with profound hearing impairments were followed longitudinally over a 3-year period and evaluated every 6 months with a battery of speech perception tests. The battery spanned several levels of perception, from pattern perception to open-set word recognition. The children were all enrolled in a single full-day educational program that used multichannel tactile aids in addition to hearing aids. Testing was conducted in Auditory alone (A), Tactile plus Auditory (TA), Tactile alone (T), and in one instance, Tactile plus Auditory plus Vision (TAV) conditions because the primary interest of the work was the relationship between auditory and tactile training on perception. Results indicated that children's performance improved with age, with the oldest children achieving open-set speech recognition in the TA condition. Performance in the TA condition generally exceeded that in both A and T conditions. Outcomes were compared to those from two studies in the literature for children of similar age with cochlear implants and tactile aids on the same tests. Results suggest that performance of children who had cochlear implants for an average of 21 months was similar to TA and TAV performance of children in the present study who had tactile experience over a similar period.

Early vocal development in tactually aided children with severe-profound hearing loss.

The vocalizations of six children with severe-profound hearing loss were audio-recorded in two conditions during individual speech-language intervention sessions: (a) auditory amplification alone, and (b) auditory amplification plus the Tactaid II, a two-channel vibrotactile device (Franklin, 1986). Utterances were categorized according to the infraphonological framework described by Oller (1980, 1986) and Oller and Lynch (1992). Vocalizations were categorized in a developmental framework relative to mature speech. Those utterances containing well-formed consonant-vowel syllables were transcribed with broad phonetic transcription and analyzed at both the syllabic and segmental levels. Statistically significant differences were found between the two conditions for vocal volubility (i.e., quantity of vocalizations produced); subjects vocalized more when using both auditory amplification and the Tactaid II together than with auditory amplification alone. Trends in the early vocal development of these children with severe-profound hearing loss are described at the infraphonologic, segmental, and syllabic levels.

Automated electrophysiologic hearing testing using a threshold-seeking algorithm.

The efficacy of utilizing an automated algorithm to identify auditory brainstem responses (ABR) was studied. A microcomputer-based threshold-seeking algorithm utilizing click-evoked ABR was developed to determine evoked-response thresholds for automated hearing screening. The software consists of an evoked-response recognizer unit, which determines the presence or absence of a response, and a threshold-tracking unit, which controls the click intensity in order to track the threshold. The response recognizer is based upon correlation methods. Threshold tracking is accomplished using a Parameter Estimation by Sequential Testing (PEST) procedure, which is commonly used to study psychophysical properties of the auditory system. Sound level is automatically adjusted, based on the results of the recognizer and the threshold tracker. Test results were generally obtained in less than 15 minutes per ear. The results of the automated procedure correlate very highly with expert judgments of ABR threshold and show good test-retest reliability, suggesting that automated procedures are viable alternatives to traditional testing methods.

Speech-like vocalizations in infancy: an evaluation of potential risk factors.

This work reports longitudinal evaluation of the speech-like vocal development of infants born at risk due to prematurity or low socio-economic status (SES) and infants not subject to such risk. Twenty infants were preterm (10 of low SES) and 33 were full term (16 of low SES), and all were studied from 0;4 through 1;6. The study provides the indication that at-risk infants are not generally delayed in the ability to produce well-formed speech-like sounds as indicated in tape-recorded vocal samples. At the same time, premature infants show a tendency to produce well-formed syllables less consistently than full terms after the point at which parents and laboratory personnel note the onset of the canonical babbling stage (the point after which well-formed syllables are well established in the infant vocal repertoires). Further, even though low SES infants produce well-formed speech-like structures on schedule, they show a reliably lower tendency to vocalize in general, as reflected by fewer utterances per minute in recorded samples.

Infant vocalizations and the early diagnosis of severe hearing impairment.

To determine whether late onset of canonical babbling could be used as a criterion to determine risk of hearing impairment, we obtained vocalization samples longitudinally from 94 infants with normal hearing and 37 infants with severe to profound hearing impairment. Parents were instructed to report the onset of canonical babbling (the production of well-formed syllables such as "da," "na," "bee," "yaya"). Verification that the infants were producing canonical syllables was collected in laboratory audio recordings. Infants with normal hearing produced canonical vocalizations before 11 months of age (range, 3 to 10 months; mode, 7 months); infants who were deaf failed to produce canonical syllables until 11 months of age or older, often well into the third year of life (range, 11 to 49 months; mode, 24 months). The correlation between age at onset of the canonical stage and age at auditory amplification was 0.68, indicating that early identification and fitting of hearing aids is of significant benefit to infants learning language. The fact that there is no overlap in the distribution of the onset of canonical babbling between infants with normal hearing and infants with hearing impairment means that the failure of otherwise healthy infants to produce canonical syllables before 11 months of age should be considered a serious risk factor for hearing impairment and, when observed, should result in immediate referral for audiologic evaluation.

Classification of audiograms by sequential testing: reliability and validity of an automated behavioral hearing screening algorithm.

In 1990, CAST (classification of audiograms by sequential testing) was proposed and developed as an automated, innovative approach to screening infant hearing using a modified Bayesian method. The method generated a four-frequency audiogram in a minimal number of test trials using VRA (visual reinforcement audiometry) techniques. Computer simulations were used to explore the properties (efficiency and accuracy) of the paradigm. The current work is designed to further test the utility of the paradigm with human infants and young children. Accordingly, infants and children between 6 months and 2 years of age were screened for hearing loss. The algorithm's efficacy was studied with respect to validity and reliability. Validity was evaluated by comparing CAST results with tympanometric data and outcomes of staircase-based testing. Test-retest reliability was also assessed. Results indicate that CAST is a valid, efficient, reliable, and potentially cost-effective screening method.

Perception of the stop/glide contrast in infancy.

Much of the published research in infant speech perception has emphasized how well infants have done with a number of speech contrasts, and have noted similarities in pattern of discrimination of adults and infants. Often it has been suggested that infants begin life with the ability to perceive any speech contrast, and that the process of acquiring a language involves inhibition of the ability to perceive contrasts not present in the target language. Indeed some studies have shown infants able to discriminate contrasts on which adults fail if the contrasts are not drawn from the native language of the adults. Other studies, however, have suggested that infants may not always be so perceptually capable. The present work focusses on the stop-glide contrast. The results are inconsistent with the prevalent view and with previously reported studies on the perception of the stop-glide contrast by infants. The results indicate that in a vigilance paradigm adapted for both infant and adult testing, infants perform poorly on the contrasts when compared with adults. Furthermore the pattern of relative perception observed in the adults on stimuli with long or short vowels is quite unlike that of the infants. It is concluded that much work remains in order to evaluate the relative performance of infants and adults in speech perception, since it appears that changes in experimental paradigm or particular stimulus parameters may affect outcomes in fundamental ways.

A study of perceptual development for musical tuning.

Musical tuning perception in infancy and adulthood was explored in three experiments. In Experiment 1, Western adults were tested in detection of randomly located mistunings in a melody based on musical interval patterns from native and nonnative musical scales. Subjects performed better in a Western major scale context than in either a Western augmented or a Javanese pelog scale context. Because the major scale is used frequently in Western music and, therefore, is more perceptually familiar than either the augmented scale or the pelog scale are, the adults' pattern of performance is suggestive of musical acculturation. Experiments 2 and 3 were designed to explore the onset of culturally specific perceptual reorganization for music in the age period that has been found to be important in linguistically specific perceptual reorganization for speech. In Experiment 2, 1-year-olds had a pattern of performance similar to that of the adults, but 6-month-olds could not detect mistunings reliably better than chance. In Experiment 3, another group of 6-month-olds was tested, and a larger degree of mistuning was used so that floor effects might be avoided. These 6-month-olds performed better in the major and augmented scale contexts than in the pelog context, without a reliable performance difference between the major and augmented contexts. Comparison of the results obtained with 6-month-olds and 1-year-olds suggests that culturally specific perceptual reorganization for musical tuning begins to affect perception between these ages, but the 6-month-olds' pattern of results considered alone is not as clear. The 6-month-olds' better performance on the major and augmented interval patterns than on the pelog interval pattern is potentially attributable to either the 6-month-olds' lesser perceptual acculturation than that of the 1-year-olds or perhaps to an innate predisposition for processing of music based on a single fundamental interval, in this case the semitone.

Open-set word identification by an adult with profound hearing impairment: integration of touch, aided hearing, and speechreading.

The ability of an adult with profound hearing impairment to integrate speech information from touch, aided hearing, and speechreading in identification of open-set words was investigated. A list was obtained of 735 words that the subject failed to identify using any single modality: touch, with either the Tacticon 1600, a multichannel electrocutaneous vocoder (TV), or the Tactaid II, a 2-channel vibrotactile aid (TA); aided hearing (H); or speechreading (S). To test integration, observed word identification performance in combined-modality conditions was compared with predicted performance calculated from single-modality scores. Words were randomly assigned to seven conditions: (a) S+H, (b) H+TV, (c) H+TA, (d) S+TV, (e) S+TV+H, and (f) S+TA+H. Results indicated that the subject integrated speech information across modalities, with highest performance in the S+TV+H and S+TA+H conditions. Integration also occurred when both speechreading and touch were used and when both speechreading and aided hearing were used.

FFT-based digital tactile vocoder system for real-time use.

A microprocessor-based real-time digital vibrotactile vocoder system has been developed to train the deaf and for artificial hearing research. The system is composed of a microcomputer module with a digital signal processor, interface units and an attenuator/driver circuit. Live or digitised (stored or synthetic) speech is presented to the skin spectrally through a belt housing eight or 16 vibrators. Speech is processed in real time using a fast Fourier transform. The system is also capable of presenting any arbitrary spatiotemporal pattern on the skin for artificial hearing experiments. A preliminary experiment with a deaf subject indicates that the system is potentially an effective device for artificial hearing.

Speech perception in adult subjects with familial dyslexia.

Speech perception was investigated in a carefully selected group of adult subjects with familial dyslexia. Perception of three synthetic speech continua was studied: /a/-/e/, in which steady-state spectral cues distinguished the vowel stimuli; /ba/-/da/, in which rapidly changing spectral cues were varied; and /sta/-/sa/, in which a temporal cue, silence duration, was systematically varied. These three continua, which differed with respect to the nature of the acoustic cues discriminating between pairs, were used to assess subjects' abilities to use steady state, dynamic, and temporal cues. Dyslexic and normal readers participated in one identification and two discrimination tasks for each continuum. Results suggest that dyslexic readers required greater silence duration than normal readers to shift their perception from /sa/ to /sta/. In addition, although the dyslexic subjects were able to label and discriminate the synthetic speech continua, they did not necessarily use the acoustic cues in the same manner as normal readers, and their overall performance was generally less accurate.

Influences of acculturation and musical sophistication on perception of musical interval patterns.

Influences of acculturation and musical sophistication on music perception were examined. Judgments for mistuning were obtained for Ss differing in musical sophistication who listened to a melody that was based on interval patterns from Western and Javanese musical scales. Less musically sophisticated Ss' judgments were better for Western than Javanese patterns. Musicians' thresholds did not differ across Western and Javanese patterns. Differences in judgments across scales are accountable to acculturation through listening exposure and musical sophistication gained through formal experience.