Binaural summation of amplitude modulation involves weak interaural suppression.

The brain combines sounds from the two ears, but what is the algorithm used to achieve this summation of signals? Here we combine psychophysical amplitude modulation discrimination and steady-state electroencephalography (EEG) data to investigate the architecture of binaural combination for amplitude-modulated tones. Discrimination thresholds followed a 'dipper' shaped function of pedestal modulation depth, and were consistently lower for binaural than monaural presentation of modulated tones. The EEG responses were greater for binaural than monaural presentation of modulated tones, and when a masker was presented to one ear, it produced only weak suppression of the response to a signal presented to the other ear. Both data sets were well-fit by a computational model originally derived for visual signal combination, but with suppression between the two channels (ears) being much weaker than in binocular vision. We suggest that the distinct ecological constraints on vision and hearing can explain this difference, if it is assumed that the brain avoids over-representing sensory signals originating from a single object. These findings position our understanding of binaural summation in a broader context of work on sensory signal combination in the brain, and delineate the similarities and differences between vision and hearing.

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.

BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. METHODS: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. RESULTS: Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). CONCLUSIONS: The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

The role of inflammation in the association between gestational diabetes and obstructive sleep apnea: A pilot study.

BACKGROUND: Obstructive sleep apnea is associated with pregnancy complications including gestational diabetes. Mechanisms underlying the association between obstructive sleep apnea and gestational diabetes remain to be elucidated. METHODS: Twenty-three participants with gestational diabetes underwent home sleep apnea testing. Obstructive sleep apnea was defined as an apnea hypopnea index > 5. Fasting morning blood samples were measured using multianalyte profiling (xMAP) multiplexed bead array immunoassay for Interleukin 6, tumor necrosis factor-alpha, and Interleukin 8. RESULTS: Age, body mass index, and gestational age at enrollment were 31 + 4.4 years, 35.7 + 7.4 kg/m2, and 28 ± 4 weeks, respectively. Participants were 52% Caucasian and 16% had obstructive sleep apnea. We observed positive correlations between apnea hypopnea index and Interleukin 6 (r = 0.62, p = 0.005), Interleukin 8 (r = 0.56, p = .56), and tumor necrosis factor-alpha (r = .58, p = .009). Women with obstructive sleep apnea had higher levels of Interleukin 6 (F = 5.01, p = .037) and Interleukin 8 (F = 6.33, p = .021) vs. women without obstructive sleep apnea. CONCLUSION: These preliminary results indicate that in women with gestational diabetes, apnea hypopnea index is associated with an elevated inflammatory profile.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

Measurement reliability for acupoint activity determined with the prognos ohmmeter.

The concepts of meridians and acupoints are critical to traditional Chinese medicine but are met with skepticism in Western medicine. Empirical validation of these concepts is in its beginning stages and still hampered by problems with measurement. A promising avenue and foundation for validity testing is the demonstration that acupoint activity can be reliably measured via determination of electrical resistance at well-defined body surface points. In this article, efforts are described to maximize measurement reliability; we tested a variety of protocols to determine which method of data aggregation is associated with maximal reliability. Twenty-one healthy individuals were subjected to 5 repeated measurement cycles to test the predicted increase in reliability with increasing number of aggregated measurements. Reliability, defined as internal consistency, was indeed highest for 5 measurements (mean alpha = .88). Even the aggregate of only three measures was quite reliable (alpha = .84). Reliability for measuring acupoints on the left side of the body was roughly .05 higher than on the right side. Consistent with previous literature, we conclude that with repeated measures the reliability of electrical resistance measurements at acupoints is high and that a strong foundation for validation research is now laid.

Second-order modulation detection thresholds for pure-tone and narrow-band noise carriers.

Modulation perception has typically been characterized by measuring detection thresholds for sinusoidally amplitude-modulated (SAM) signals. This study uses multicomponent modulations. "Second-order" temporal modulation transfer functions (TMTFs) measure detection thresholds for a sinusoidal modulation of the modulation waveform of a SAM signal [Lorenzi et al., J. Acoust. Soc. Am. 110, 1030-2038 (2001)]. The SAM signal therefore acts as a "carrier" stimulus of frequency fm, and sinusoidal modulation of the SAM signal's modulation depth (at rate f'm) generates two additional components in the modulation spectrum at fm - f'm and fm + f'm. There is no spectral energy at the envelope beat frequency f'm in the modulation spectrum of the "physical" stimulus. In the present study, second-order TMTFs were measured for three listeners when fm was 16, 64, and 256 Hz. The carrier was either a 5-kHz pure tone or a narrow-band noise with center frequency and bandwidth of 5 kHz and 2 Hz, respectively. The narrow-band noise carrier was used to prevent listeners from detecting spectral energy at the beat frequency f'm in the "internal" stimuli's modulation spectrum. The results show that, for the 5-kHz pure-tone carrier, second-order TMTFs are nearly low pass in shape; the overall sensitivity and cutoff frequency measured on these second-order TMTFs increase when fm increases from 16 to 256 Hz. For the 2-Hz-wide narrow-band noise carrier, second-order TMTFs are nearly flat in shape for fm = 16 and 64 Hz, and they show a high-pass segment for fm = 256 Hz. These results suggest that detection of spectral energy at the envelope beat frequency contributes in part to the detection of second-order modulation. This is consistent with the idea that nonlinear mechanisms in the auditory pathway produce an audible distortion component at the envelope beat frequency in the internal modulation spectrum of the sounds.

Simple predictors of uvulopalatopharyngoplasty outcome in the treatment of obstructive sleep apnea.

STUDY OBJECTIVE: Our objective was to determine whether baseline polysomnography, cephalometry, and anthropometry data could predict uvulopalatopharyngoplasty (UPPP) success or failure. DESIGN: We retrospectively reviewed polysomnography, cephalometry, and anthropometry data from patients who underwent UPPP for obstructive sleep apnea (OSA). SETTING: A university medical center. PATIENTS: OSA was diagnosed by polysomnography in 46 patients who underwent UPPP surgery for their sleep disorder. INTERVENTIONS: UPPP surgery with/or without tonsillectomy. MEASUREMENTS AND RESULTS: The mean patient age was 43 years, and the mean body mass index was 32.5 kg/m(2). The mean presurgical apnea-hypopnea index (AHI) was 45, and the mean baseline nadir oxygen saturation was 81%. Successful surgery was defined as a reduction in AHI to < 10 or to < 20 with a 50% reduction from the patient's baseline AHI. Of the 46 patients, 16 were successfully treated and 30 did not respond to surgical treatment. A mandibular-hyoid distance (MP-H) > 20 mm was found to be significantly (p = 0.05) predictive of failure of UPPP. When stepwise regression analysis was performed utilizing postsurgical AHI as the dependent variable and presurgical AHI, age, body mass index, baseline nadir O(2) saturation, and five cephalometric measurements as independent variables, MP-H distance significantly (r = 0.524; p = 0.01) correlated positively with postsurgical AHI. The distance between the superior point of a line-constructed plane of the sphenoidale (parallel to Frankfort horizontal) and a point at the intersection of the palatal plane perpendicular to the hyoid correlated negatively with postsurgical AHI (r = 0.586; p = 0.05). By creating a logistic model of this data, an MP-H distance < 21 mm, an angle created by point A to the nasion to point B < 3 degrees, and the presence of a baseline AHI < 38 enhanced the predictability of UPPP success. CONCLUSIONS: The presence of a baseline AHI < 38 and an MP-H < or = 20 mm, and the absence of retrognathia are predictors of improvement after UPPP. Based on these findings, we would advocate the continued evaluation of cephalometric measurements and careful consideration of surgical treatment options for OSA.

The use of nicotine replacement therapy during hospitalization.

Recent findings suggest that smokers who are hospitalized experience significant craving for cigarettes. Thus, nicotine replacement therapy (NRT) may be a particularly important tool for use during hospitalization. The goal of this study is to evaluate the utilization of the transdermal nicotine patch and/or nicotine gum by hospitalized smokers. The data represented in this article are from 580 smokers who participated in a study of a motivational intervention for smoking cessation that was delivered during hospitalization. The primary outcome for this analysis was use of NRT during hospitalization. The results revealed that, among the entire sample, only 7.1% of the overall sample used NRT during hospitalization; 6% of the hospitalized smokers used the transdermal nicotine patch, and 1.1% used nicotine gum. Use of NRT was significantly greater among patients who reported that they were doing anything to help themselves quit smoking at the time of admission (OR = 4.1), those who were seriously planning to quit smoking within the next 30 days (OR = 2.36), those who were nicotine dependent (OR = 2.81), and those for whom a physician had ever offered to prescribe NRT (OR = 1.9). The finding that there is a very low rate of NRT use during hospitalization provides important information to hospital-based care providers and smoking cessation intervention planners. Barriers to NRT use among hospitalized patients should be identified, and strategies designed to maximize use when appropriate. The AHCPR Guideline on Smoking Cessation recommends routine use of NRT in health care settings. Further research is needed to determine why NRT use was so low. In addition, these data suggest that efforts to increase NRT use during hospitalization are needed.

The role of the primary care physician in recognizing obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder among middle-aged adults. However, OSA is a recently described disorder for which most primary care physicians do not have formal training. The primary objectives of this article are to evaluate what percentage of patients referred by primary care physicians for sleep studies had OSA; to characterize the clinical features of these patients and compare them with our known OSA population; and to determine whether primary care physicians asked key questions contained in a work sheet to make the diagnosis of OSA. METHODS: A retrospective chart review at a hospital-based sleep center that is accredited to evaluate all sleep disorders, not just OSA. The health maintenance organization is a staff model one. PATIENTS: Sixty-nine patients who were referred for a sleep study by a health maintenance organization internist or family practitioner between June 1, 1994, and May 30, 1995. RESULTS: Ninety-six percent of the 68 patients referred for polysomnography had OSA. Most were very symptomatic and obese. These 68 patients represent 0.13% of the primary care patient panel. In addition, most of the patients were referred by a few physicians; 6 (11%) of the 55 physicians ordered 33% of the 68 studies. CONCLUSIONS: Primary care physicians did recognize obese patients with prominent symptoms of sleep apnea. However, only a small percentage of their patient panel was referred, suggesting that this condition is still underdiagnosed. This seems particularly true as most of the sleep studies were ordered by a small group of physicians. Future work incorporating educational interventions is necessary to improve detection and treatment of OSA.

Psychiatric comorbidity in methadone maintained patients.

Diagnosing comorbid psychiatric disorders in methadone maintained patients may help to identify subgroups with different outcomes and needs for treatment. In this study, 75 methadone maintenance clinic patients in treatment longer than 30 days were assessed with the Addiction Severity Index, Global Assessment Scale and Mini-Mental Status Exam, and were interviewed for DSM-III-R psychiatric diagnosis using the computerized Diagnostic Interview Schedule. Psychiatric diagnoses were prevalent in the sample with depression, phobic disorders, antisocial personality and generalized anxiety the most common. Both number of DSM-III-R diagnoses and severity of psychopathology were correlated with outcome measures such as concurrent drug abuse, family-social problems and employment status.

Identification and modification of environmental noise in an ICU setting.

STUDY OBJECTIVES: Noise levels in the hospital setting are exceedingly high, especially in the ICU environment. We set out to determine what caused the noises producing sound peaks > or = 80 A-weighted decibels (dBA) in our ICU settings, and attempted to reduce the number of sound peaks > or = 80 dBA through a behavior modification program. DESIGN: The study was divided into two separate phases: noise identification and a trial of behavior modification. During the noise identification phase we simultaneously recorded sound peaks and the loudest noise heard subjectively by one observer in the medical ICU (MICU) and the respiratory ICU (RICU). During the behavior modification phase of the study we implemented a behavior modification program, geared toward noise reduction, in all of the MICU staff. Sound levels were monitored before and at the end of the behavior modification trial. SETTING: The MICU and RICU of a 720-bed teaching hospital in Providence, RI. PARTICIPANTS: All ICU staff during the study period. INTERVENTIONS: Once the noises that were determined to be amenable to behavior modification were identified, a behavior modification program was conducted during a 3-week period in our MICU. Baseline and post-behavior modification noise recordings were compared in 6-h intervals after sites were matched by number of patients in a room and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. MEASUREMENTS AND RESULTS: We identified several causes of sound peaks > or = 80 dBA amenable to behavior modification; television and talking accounted for 49%. We also significantly reduced the 24-h mean peak noise level (p=0.0001), as well as the mean peak noise level (p=0.0001) and the number of sound peaks > or = 80 dBA (p=0.0001) in all 6-h blocks except for the 12 AM to 6 AM period. CONCLUSIONS: We conclude that many of the noises causing sound peaks > or =80 dBA are amenable to behavior modification and that it is possible to reduce the noise levels in an ICU setting significantly through a program of behavior modification.

Enuresis and obstructive sleep apnea in adults.

Adult enuresis is an unusual symptom of obstructive sleep apnea (OSA). Although it is described as a classic symptom of childhood OSA, enuresis is encountered infrequently in adult sleep medicine. Five adults with enuresis associated with sleep apnea presented to our Sleep Disorders Center. In all five cases, the onset of enuresis was associated with the progression of sleep apnea symptoms. In each case, the enuresis resolved with treatment with nasal continuous positive airway pressure. Current medical literature on the postulated mechanisms of nocturia and enuresis in sleep apnea is reviewed. Based on the experience of the authors and review of the medical literature, one may conclude that severe OSA may lead to new-onset enuresis in adults and that effective treatment of OSA is associated with resolution of enuresis.

The Taskforce 2000 survey on medical education in sleep and sleep disorders.

Previous research has shown evidence of a widening gap between scientific research and clinical teaching in sleep and sleep disorders. To address the deficiencies in current medical education in sleep, the Taskforce 2000 was established by the American Sleep Disorders Association. The present study was undertaken to assess the teaching activities, needs and interests of the membership of the two largest professional sleep societies (American Sleep Disorders Association and Sleep Research Society). Survey instruments included a brief, 5-item postcard survey, which was mailed to all members, followed by an in-depth, 34-item questionnaire, which was completed by 158 respondents from the intitial postcard survey (N = 808). Results indicated that the majority of respondents (65.2%) are currently involved in teaching sleep to medical students or postgraduate trainees, although the average amount of teaching time was only 2.1 hours for undergraduate and 4.8 hours for graduate education in sleep. Teaching of sleep laboratory procedures and clinical evaluation of sleep-disordered patients is limited at either an undergraduate or postgraduate level. The major deficiencies noted were the lack of time in the medical curriculum and the need for better resources and teaching facilities. A large majority of respondents indicated their willingness to be involved in sleep education for physicians, and rated this a high priority for the professional organization.

Oral appliances in the treatment of snoring and sleep apnea.

Oral appliances have been developed that are effective in snoring patients and in patients with mild to moderate sleep apnea. This article reviews the types of appliances that are available, their possible modes of action, and their efficacy. In addition, the clinician is provided with guidelines on how to choose the appropriate patient for this therapy.