Optimal size threshold for PIRADSv2 category 5 upgrade and its positive predictive value: is it predictive of "very high" likelihood of clinically-significant cancer?

AIM: To identify the optimal size metric and threshold for Prostate Imaging Reporting and Data System (PIRADS) 5 upgrade, calculate its positive predictive value (PPV) for clinically-significant prostate cancer (csPCA), and determine if it is indicative of a "very high" likelihood of csPCA. MATERIALS AND METHODS: One hundred and forty-three PIRADS 4 or 5 lesions were evaluated. Lesion diameters were used to calculate lesion volume (LV). Pearson correlation between maximum lesion diameter (MLD) and LV was calculated. Area under the curve (AUC) for discriminating csPCA (Gleason grade ≥ 3 + 4) was calculated using MLD and LV. Optimal size thresholds (using Youden index) and highly predictive size thresholds were identified for the whole prostate (WP), peripheral zone (PZ), and transitional zone (TZ). RESULTS: There was high correlation between MLD and LV (r=0.77-0.81), with comparable AUCs for MLD and LV in the identification of csPCA in the WP (0.73, 0.72), PZ (0.73, 0.73), and TZ (0.79, 0.75). Optimal MLD thresholds were 1.4, 1.4, and 1.6 cm in the WP, PZ, and TZ respectively, with PPVs of 76%, 81%, and 69%, respectively. An MLD threshold of 2.7 cm would be needed in the WP to achieve a PPV approaching 90%, with sensitivity decreasing to 10%. CONCLUSIONS: There is high correlation between MLD and LV with comparable discrimination of csPCA using each. PIRADSv2's 1.5 cm MLD threshold is near the optimal threshold for PIRADS 5 upgrade but has moderate PPV. A much higher threshold would be needed to increase its PPV, with significant sacrifice in sensitivity.

The Perceptions of Patients, their Parents and Healthcare Providers on the Transition of Young Adults with Type 1 Diabetes to Adult Services in the West of Ireland.

Aim This study aims to describe the perceptions of young adults', parents of young adults' and health care professionals' (HCPs) of the transition process for young adults with Type 1 Diabetes in the West of Ireland. Methods Thematic analysis of semi-structured interviews conducted with the three stakeholder groups was performed. Results Young adults hardly noticed the transition, with many of them seeing it as a physical move, whereas parents were more anxious and felt their involvement was still needed but not accommodated. Both groups perceived the young adults' ability to manage their diabetes as a facilitator, as well as the continuity of care provided by the diabetes nurse. Resource limitations and an inability of a young adult to self-manage were identified as barriers to smooth transition by parents, whilst HCPs were experiencing problems with non-attendance and a lack of a psychology service. Conclusion This study highlights the importance of encouraging adolescents' autonomy in the years leading to transition. A key healthcare professional link between both services appears to facilitate smooth transition. Being flexible and supportive of both parents and adolescents including the provision of mental health services are other important considerations.

Endogenous retroviral LTRs as promoters for human genes: a critical assessment.

Gene regulatory changes are thought to be major factors driving species evolution, with creation of new regulatory regions likely being instrumental in contributing to diversity among vertebrates. There is growing appreciation for the role of transposable elements (TEs) in gene regulation and, indeed, laboratory investigations have confirmed many specific examples of mammalian genes regulated by promoters donated by endogenous retroviruses (ERVs) or other TEs. Bioinformatics studies have revealed hundreds of additional instances where this is likely to be the case. Since the long terminal repeats (LTRs) of retroviruses naturally contain abundant transcriptional regulatory signals, roles for ERV LTRs in regulating mammalian genes are eminently plausible. Moreover, it seems reasonable that exaptation of an LTR regulatory module provides opportunities for evolution of new gene regulatory patterns. In this Review we summarize known examples of LTRs that function as human gene alternative promoters, as well as the evidence that LTR exaptation has resulted in a pattern of novel gene expression significantly different from the pattern before LTR insertion or from that of gene orthologs lacking the LTR. Available data suggest that, while new expression patterns can arise as a result of LTR usage, this situation is relatively rare and is largely restricted to the placenta. In many cases, the LTR appears to be a minor, alternative promoter with an expression pattern similar to that of the native promoter(s) and hence likely exerts a subtle overall effect on gene expression. We discuss these findings and offer evolutionary models to explain these trends.

Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution.

Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific rearrangements and expansions of this locus have yielded different copy numbers among primates and rodents, with human retaining a single functional copy and mouse possessing several copies, depending on the strain. Roles for this gene in disease have been documented, but little is known about transcriptional regulation of NAIP. We show here that NAIP has multiple promoters sharing no similarity between human and rodents. Moreover, we demonstrate that multiple, domesticated long terminal repeats (LTRs) of endogenous retroviral elements provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves as a tissue-specific promoter, active primarily in testis. However, in rodents, our evidence indicates that an ancestral LTR common to all rodent genes is the major, constitutive promoter for these genes, and that a second LTR found in two of the mouse genes is a minor promoter. Thus, independently acquired LTRs have assumed regulatory roles for orthologous genes, a remarkable evolutionary scenario. We also demonstrate that 5' flanking regions of IAP family genes as a group, in both human and mouse are enriched for LTR insertions compared to average genes. We propose several potential explanations for these findings, including a hypothesis that recruitment of LTRs near NAIP or other IAP genes may represent a host-cell adaptation to modulate apoptotic responses.

Objective tinnitus in children.

OBJECTIVE: To discuss the various symptoms and causes of objective tinnitus in children. STUDY DESIGN: Retrospective case review. PATIENTS: Five children who had audible signals emanating from their ears caused by audible spontaneous otoacoustic emissions, palatal myoclonus, arteriovenous malformation, and acoustic trauma. MAIN OUTCOME MEASURE: The tinnitus reported by the patients was linked to acoustic signals that could be measured objectively or heard by the examiner. RESULTS: Four of the five children had essentially normal hearing. The one child who demonstrated a hearing loss audiometrically was thought to have normal hearing sensitivity, but his intense roaring objective tinnitus appeared to mask his low-frequency thresholds. All five patients had measurable acoustic signals in the ear canal that matched the patients' descriptions of their tinnitus. CONCLUSION: The cases illustrate how the objective tinnitus was diagnosed and measured, how a treatment algorithm was applied, and the expected results of treatment. In addition, the cases provide support for the use of psychologic counseling throughout the examination and treatment of objective tinnitus in children.

Isolated cervical recurrence of squamous cell carcinoma in the previously treated neck.

PURPOSE: Our study goal was to identify clinical factors associated with, and that might predict, treatment outcome for patients with an isolated cervical recurrence of squamous cell carcinoma in the previously treated neck (ICR-PTN). MATERIALS AND METHODS: We reviewed all patients with noncutaneous head and neck squamous cell carcinoma treated at our tertiary care center between 1987 and 1997, and identified 17 patients (2%) who later developed an isolated recurrence in a previously treated neck. These patients made up our study group, and their charts were thoroughly reviewed. Outcome of salvage therapy (surgery, radiation, or combined therapy) for these patients was compared with pooled clinicopathologic data using the Fisher exact test (one tail). RESULTS: Fifteen such ICR-PTN patients consented to salvage therapy. Six patients were without disease at last follow-up, and 3 were successfully palliated. A statistically significant association between the side of ICR-PTN relative to the primary tumor and outcome of salvage therapy (P =.026) was noted, with ipsilateral neck recurrence being a favorable prognostic factor. Trends that did not meet the standard for statistical significance were observed between a better outcome of salvage therapy and the following parameters: age of less than 60, nonsurgical initial treatment of the neck, and lack of a history of a recurrence before they developed the ICR-PTN. CONCLUSIONS: The current study showed that only the side of the ICR-PTN relative to the primary site is associated with outcome of salvage therapy. Based on our findings and a review of the literature, we have developed a summary of factors that might predict which patients with an ICR-PTN are most likely to benefit from aggressive salvage therapy.

Providing services to Asian Americans with developmental disabilities and their families: mainstream service providers' perspective.

This survey investigated the opinions and perceptions of 44 mainstream social service providers regarding barriers to Asian Americans with developmental disabilities and their families receiving appropriate supportive services. Six main barriers were identified: (1) Language and communication difficulties; (2) Lack of knowledge concerning mainstream service delivery system; (3) Perceived cultural differences; (4) Being a "minority within a minority" in the service delivery system; (5) Individual differences within families and differences among Asian ethnic groups; and (6) Lack of resources to meet needs within the family. Implications of the interrelationships among the identified barriers were discussed.

External and middle ear trauma resulting from ear impressions.

When taking an impression of the external ear canal and ear, the audiologist is engaged in an invasive procedure whereby a foreign body is first placed into the ear canal and then removed. There is always an element of risk for significant medical problems when a clinician is performing an invasive procedure. Although some minor patient discomfort and, at times, some slight trauma to the ear canal occur when taking ear impressions, the incidence of significant trauma to the external or middle ear appears to be low. The purpose of this report is to provide some illustrative cases of significant external and middle ear trauma as a result of taking impressions of the external ear. Audiologists are advised to develop and implement an appropriate risk management program for taking ear impressions to reduce the potential risks associated with this procedure to their patients and to their practices.

Measurements of loudness growth in 1/2-octave bands for children and adults with normal hearing.

The loudness growth in 1/2-octave bands (LGOB) procedure has been shown previously to provide valid estimates of loudness growth for adults with normal hearing and those with hearing loss (Allen, Hall, & Jeng, 1990), and it has been widely incorporated into fitting strategies for adult hearing aid users by a hearing aid manufacturer. Here, we applied a simple modification of LGOB to children and adults with normal hearing and then compared the loudness growth functions (as obtained from end-point data) between the two age groups. In addition, reliability data obtained within a single session and between test sessions were compared between the two groups. Large differences were observed in the means between the two groups for the lower boundary values, the upper boundary values, and the range between boundaries both within and across all frequencies. The data obtained from children also had greater variance than the adult data. In addition, there was more variability in the data across test sessions for children. Many test-retest differences for children exceeded 10 dB. Adult test-retest differences were generally less than 10 dB. Although the LGOB with the modifications used in this study may be used to measure loudness growth in children, its poor reliability with this age group may limit its clinical use for children with hearing loss. Additional work is needed to explore whether loudness growth measures can be adapted successfully to children and whether these measures contribute worthwhile information for fitting hearing aids to children.

Zenker's diverticulum: analysis of surgical complications from diverticulectomy and cricopharyngeal myotomy.

OBJECTIVE: To identify risk factors for postoperative complications in patients undergoing diverticulectomy and cricopharyngeal (CP) myotomy for Zenker's diverticulum. STUDY DESIGN: Retrospective. MATERIALS AND METHODS: A chart review was conducted of all patients with a Zenker's diverticulum who were treated with diverticulectomy and cricopharyngeal myotomy at three tertiary care centers in central Indiana between 1988 and 1998. RESULTS: Of the 24 patients identified, 9 developed postoperative complications (2 medical and 7 surgical). Statistical analysis of multiple potential risk factors revealed that only diverticulum size greater than 10 cm2 at surgery placed the patient at increased risk for postoperative surgical complications. To our knowledge, this is the first report that has specifically addressed diverticulum size as an independent risk factor for postoperative surgical complications following diverticulectomy and CP myotomy. CONCLUSIONS: Given our findings, we recommend considering diverticulopexy rather than diverticulectomy in a patient with a Zenker's diverticulum greater than 10 cm2 in size if a cervical approach is the selected treatment.

Field trial evaluations of a switched directional/omnidirectional in-the-ear hearing instrument.

The use of directional microphones is one of the few methods available for hearing aids to increase the signal-to-noise ratio. The smaller microphones available with today's technology have increased the viability of their application for in-the-ear (ITE) hearing aids. This study evaluated an ITE hearing aid containing two nondirectional microphones that provides wearer-selectable omnidirectional/directional operating modes. Ten sensorineural hearing-impaired patients were fitted binaurally. During the first trial period, the low-frequency gain decrease produced by the directional mode was not compensated for. The frequency responses were matched during the second trial period. For both trial periods, Hearing in Noise Test results using two uncorrelated noise sources indicated significant speech recognition improvements for the directional mode relative to the omnidirectional mode. Responses on Abbreviated Profile of Hearing Aid Benefit questionnaires, paired-comparison judgments, and interview data revealed that most subjects preferred the directional mode in noisier environments, but many also preferred the omnidirectional mode in quiet listening.

Wound complications associated with brachytherapy for primary or salvage treatment of head and neck cancer.

Brachytherapy can be employed in the primary or salvage treatment of head and neck cancer. The advantage of brachytherapy is the stereotactic limitation of radiation exposure to noninvolved tissues. Wound complications associated with brachytherapy have been discussed only sporadically in the literature. This retrospective study examines 28 patients, 20 for initial treatment and eight for salvage, with varying site and stage head and neck cancer treated with brachytherapy in addition to external beam radiation therapy and/or surgery. The overall complication rate was 50% (14/28), with infection and minor flap breakdown being the most common problems. Tumor site in the primary treatment group was the only significant factor in wound complications. In the salvage group complications were minor and primarily related to flap coverage of brachytherapy catheters.

Differences in performance between Oticon MultiFocus Compact and ReSound BT2-E hearing aids.

Differences in performance were evaluated between binaural fittings of the Oticon MultiFocus (MF) and ReSound BT2-E on 25 hearing-impaired subjects across two sites. Subjects were initially fit using each manufacturer's algorithm and adjustments were made at 1 week based on subjects' responses to diary questions. Performance was assessed after a 4- to 6-week trial period with each hearing aid set using the Speech Perception in Noise (SPIN) test administered at 50, 65, and 80 dB SPL, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, loudness judgments of female connected discourse at 65 and 80 dB SPL, and an overall preference selection. The MF yielded significantly better SPIN scores at 50 and 65 dB SPL, while the BT2-E yielded a significantly better score at 80 dB SPL. No statistically significant differences were found in the APHAB benefit scores between the hearing aid sets, but both sets were significantly better than the subjects' own hearing aids on three of the four subscales. The MF produced slightly higher mean loudness judgments at both input levels than the BT2-E. Finally, 12 subjects preferred the BT2-E, 10 subjects preferred the MF, and three subjects stated no preference. The results are discussed in terms of audiogram effects on preference and effects of differences in signal processing approaches between the devices.

Prediction of 8-hour noise dose from brief duration samples.

The purpose of this study was to determine whether brief duration samples of noise dose measurements could predict the noise exposure levels of employees as measured by 8-hour dosimetry. Sampled noise dose measurements were obtained for 1, 5, 10, 15, and 20 minutes and 8 hours for four workers at each of four industrial sites. Statistical analyses indicated no significant differences or interactions among trials and sample durations. A simple linear prediction model provided the best fit for the four shortest of the five abbreviated sample durations, whereas an exponential regression model provided the best predictions using the 20-minute sample duration. The high variance and low correlations across all measures permitted only poor predictions from these abbreviated sample data. Based on these results, sampled noise measurements of short duration (1 to 20 minutes) do not appear to be a valid means for predicting the amount of noise exposure during an 8-hour shift.