Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Vocal fold nodules: A disorder of phonation organs or auditory feedback?

OBJECTIVE: Increasing evidence supports that auditory feedback of one's own voice closely relates to real-time adjustments of vocal control. Previous studies highlighted that the low-frequency modulations of below 3 Hz (LFM) embedded in vocal fundamental frequency (F0) showed a reflex-like response to altered auditory inputs. However, the auditory feedback control of different vocal disorders remains unclear. DESIGN: A cross-sectional, case-controlled study. SETTING: A tertiary medical centre. PARTICIPANTS: Sustained vocalisations of vowel/a/ from adult healthy controls and patients with vocal fold nodules, vocal fold polyps and vocal fold cysts, respectively. The vocalisations were made at a comfortable pitch and at the intensity of 70 ~ 80 dBC under the following four auditory conditions: natural hearing, 90-dBC speech noise, 10-dBC enhanced feedback of self-produced voice and both the noise and voice feedback. MAIN OUTCOME MEASURES: Power spectral analysis of F0 contour of sustained vowel. RESULTS: Patients with vocal fold nodules presented with different audio-vocal feedback behaviour and audio-vocal response to speech noise from the other two vocal pathologies of vocal fold polyp and vocal fold cyst as well as the healthy controls (P < .001, one-way ANOVA). CONCLUSION: The vocal fold nodules may be not only a vocal fold disease but also a disease caused by abnormal audio-vocal feedback. Moreover, the distinct audio-vocal feedback of vocal fold nodules could be revealed by power spectral analysis of vocal fundamental frequencies. Although further investigations are necessary, adjustments of audio-vocal feedback behaviour may provide a new insight and benefit to the treatment of vocal fold nodules in the future.

Effect of mouth-opening levels on sound field gain in the ear canal.

The human external auditory canal can become deformed when the mandible moves, and this changes the sound field in the external auditory canal. This study measured the sound field gain in the external auditory canal while varying mouth-opening in three levels. The mandible was fixed at the 1/3, the 2/3, and the maximal mouth-opening levels. Seven 65-dB tones of 200, 500, 1000, 2000, 4000, 6000, and 8000 Hz, which are the sound pressure level and frequency range when people are talking at a normal level, were adopted as the sound stimulus to measure sound field gains at 5, 10, 15, and 20 mm to the interior of the external auditory canal. The results show that, with the exception of the 1.25 dB decrease from 12.96 to 11.71 dB at a depth of 5 mm with a stimulus at 8000 Hz, the differences in the sound field gain at the other depths and stimulus frequencies were within 1 dB and were not statistically significant. These results suggest that mouth-opening level has no effect on the measurement of the sound field in the external auditory canal.

Responses of Middle-Frequency Modulations in Vocal Fundamental Frequency to Different Vocal Intensities and Auditory Feedback.

OBJECTIVES AND BACKGROUND: Auditory feedback can make reflexive responses on sustained vocalizations. Among them, the middle-frequency power of F0 (MFP) may provide a sensitive index to access the subtle changes in different auditory feedback conditions. MATERIALS AND METHODS: Phonatory airflow temperature was obtained from 20 healthy adults at two vocal intensity ranges under four auditory feedback conditions: (1) natural auditory feedback (NO); (2) binaural speech noise masking (SN); (3) bone-conducted feedback of self-generated voice (BAF); and (4) SN and BAF simultaneously. The modulations of F0 in low-frequency (0.2 Hz-3 Hz), middle-frequency (3 Hz-8 Hz), and high-frequency (8 Hz-25 Hz) bands were acquired using power spectral analysis of F0. Acoustic and aerodynamic analyses were used to acquire vocal intensity, maximum phonation time (MPT), phonatory airflow, and MFP-based vocal efficiency (MBVE). RESULTS: SN and high vocal intensity decreased MFP and raised MBVE and MPT significantly. BAF showed no effect on MFP but significantly lowered MBVE. Moreover, BAF significantly increased the perception of voice feedback and the sensation of vocal effort. CONCLUSIONS: Altered auditory feedback significantly changed the middle-frequency modulations of F0. MFP and MBVE could well detect these subtle responses of audio-vocal feedback.

Snoring Sounds Predict Obstruction Sites and Surgical Response in Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Snoring sounds generated by different vibrators of the upper airway may be useful indicators of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study aimed to investigate associations between snoring sounds, obstruction sites, and surgical responses (≥50% reduction in the apnea-hypopnea index [AHI] and <10 events/hour) in patients with OSAHS. This prospective cohort study recruited 36 OSAHS patients for 6-hour snoring sound recordings during in-lab full-night polysomnography, drug-induced sleep endoscopy (DISE), and relocation pharyngoplasty. All patients received follow-up polysomnography after 6 months. Fifteen (42%) patients with at least two complete obstruction sites defined by DISE were significantly, positively associated with maximal snoring sound intensity (40-300 Hz; odds ratio [OR], 1.25, 95% confidence interval [CI] 1.05-1.49) and body mass index (OR, 1.48, 95% CI 1.02-2.15) after logistic regression analysis. Tonsil obstruction was significantly, inversely correlated with mean snoring sound intensity (301-850 Hz; OR, 0.84, 95% CI 0.74-0.96). Moreover, baseline tonsil obstruction detected by either DISE or mean snoring sound intensity (301-850 Hz), and AHI could significantly predict the surgical response. Our findings suggest that snoring sound detection may be helpful in determining obstruction sites and predict surgical responses.

Human amygdala activation by the sound produced during dental treatment: A fMRI study.

During dental treatments, patients may experience negative emotions associated with the procedure. This study was conducted with the aim of using functional magnetic resonance imaging (fMRI) to visualize cerebral cortical stimulation among dental patients in response to auditory stimuli produced by ultrasonic scaling and power suction equipment. Subjects (n = 7) aged 23-35 years were recruited for this study. All were right-handed and underwent clinical pure-tone audiometry testing to reveal a normal hearing threshold below 20 dB hearing level (HL). As part of the study, subjects initially underwent a dental calculus removal treatment. During the treatment, subjects were exposed to ultrasonic auditory stimuli originating from the scaling handpiece and salivary suction instruments. After dental treatment, subjects were imaged with fMRI while being exposed to recordings of the noise from the same dental instrument so that cerebral cortical stimulation in response to aversive auditory stimulation could be observed. The independent sample confirmatory t-test was used. Subjects also showed stimulation in the amygdala and prefrontal cortex, indicating that the ultrasonic auditory stimuli elicited an unpleasant response in the subjects. Patients experienced unpleasant sensations caused by contact stimuli in the treatment procedure. In addition, this study has demonstrated that aversive auditory stimuli such as sounds from the ultrasonic scaling handpiece also cause aversive emotions. This study was indicated by observed stimulation of the auditory cortex as well as the amygdala, indicating that noise from the ultrasonic scaling handpiece was perceived as an aversive auditory stimulus by the subjects. Subjects can experience unpleasant sensations caused by the sounds from the ultrasonic scaling handpiece based on their auditory stimuli.

Relationships Between Formant Frequencies of Sustained Vowels and Tongue Contours Measured by Ultrasonography.

PURPOSE: The purpose of this study was to explore the formant-articulation relationships in corner vowels by acoustic analysis of speech signals and measuring tongue contour using ultrasonography. METHOD: Eighteen healthy adults (8 men, 10 women), aged between 20 and 40 years, were enrolled. Speech signals of sustained vowels /ɑ/, /i/, and /u/ were recorded to obtain the first 2 formant frequencies. Tongue height, tongue advancement, and lengths of posterior tongue surface (LPTS) and anterior oral cavity (LAOC) were obtained using ultrasound image processing technique in order to examine the resonance mechanism of the oral vocal tract. RESULTS: LPTS and LAOC, as well as mean frequencies of the first and second formants, showed significant differences between sexes and among vowels. The first formant significantly and better correlated with LPTS than with tongue height (r = -.78, p < .001, Pearson's correlation). The correlation of the second formant with LAOC (r = -.85, p < .001) was also significant and better than the correlation with tongue advancement. Sex, however, did not show significant correlation with the formant frequencies. CONCLUSIONS: Ultrasonographic measurements of tongue contour correlated well to the formant frequencies. The results stressed the importance of tongue shaping in articulation. Although more studies are necessary in clinical implications, disorders associated with abnormal tongue shaping may be the target applications in the future.

Anthropometry of external auditory canal by non-contactable measurement.

Human ear canals cannot be measured directly with existing general measurement tools. Furthermore, general non-contact optical methods can only conduct simple peripheral measurements of the auricle and cannot obtain the internal ear canal shape-related measurement data. Therefore, this study uses the computed tomography (CT) technology to measure the geometric shape of the ear canal and the shape of the ear canal using a non-invasive method, and to complete the anthropometry of external auditory canal. The results of the study show that the average height and width of ear canal openings, and the average depth of the first bend for men are generally longer, wider and deeper than those for women. In addition, the difference between the height and width of the ear canal opening is about 40% (p < 0.05). Hence, the circular cross-section shape of the earplugs should be replaced with an elliptical cross-section shape during manufacturing for better fitting.

Comparative effects of snoring sound between two minimally invasive surgeries in the treatment of snoring: a randomized controlled trial.

BACKGROUND: Minimally invasive surgeries of the soft palate have emerged as a less-invasive treatment for habitual snoring. To date, there is only limited information available comparing the effects of snoring sound between different minimally invasive surgeries in the treatment of habitual snoring. OBJECTIVE: To compare the efficacy of palatal implant and radiofrequency surgery, in the reduction of snoring through subjective evaluation of snoring and objective snoring sound analysis. PATIENTS AND METHOD: Thirty patients with habitual snoring due to palatal obstruction (apnea-hypopnea index ≤15, body max index ≤30) were prospectively enrolled and randomized to undergo a single session of palatal implant or temperature-controlled radiofrequency surgery of the soft palate under local anesthesia. Snoring was primarily evaluated by the patient with a 10 cm visual analogue scale (VAS) at baseline and at a 3-month follow-up visit and the change in VAS was the primary outcome. Moreover, life qualities, measured by snore outcomes survey, and full-night snoring sounds, analyzed by a sound analytic program (Snore Map), were also investigated at the same time. RESULTS: Twenty-eight patients completed the study; 14 received palatal implant surgery and 14 underwent radiofrequency surgery. The VAS and snore outcomes survey scores were significantly improved in both groups. However, the good response (postoperative VAS ≤3 or postoperative VAS ≤5 plus snore outcomes survey score ≥60) rate of the palatal implant group was significantly higher than that of the radiofrequency group (79% vs. 29%, P = 0.021). The maximal loudness of low-frequency (40-300 Hz) snores was reduced significantly in the palatal implant group. In addition, the snoring index was significantly reduced in the radiofrequency group. CONCLUSIONS: Both palatal implants and a single-stage radiofrequency surgery improve subjective snoring outcomes, but palatal implants have a greater effect on most measures of subjective and objective snoring. Multi-stage radiofrequency surgery was not tested. TRIAL REGISTRATION: ClinicalTrials.gov NCT01955083.

A phantom and in vivo study of mice following an ischemic stroke using sodium MRI.

Sodium is one of the essential indicators of cell viability in vivo. Regarding extant literature, sodium MRI is widely employed for various studies, including research on tumors, strokes, and neurocognition, because it can non-invasively provide data of physiological metabolism in vivo. Currently, strokes are among the 3 leading causes of death worldwide, and can be categorized as hemorrhagic or ischemic. Approximately 70% to 80% of stroke patients experience an ischemic stroke. Although numerous relevant studies have focused on larger animal models, such as rats, cats, and nonhuman primates, literature that employs mice experimental models is scarce. In this study, we conducted sodium MRI on the brains of mice after an ischemic stroke to observe sodium signal variations in the brain following this type of stroke. The findings indicated that the sodium signals in the brain regions affected by stroke were 2.3 times stronger than those in the lateral ventricles.

Energy types of snoring sounds in patients with obstructive sleep apnea syndrome: a preliminary observation.

BACKGROUND: Annoying snore is the principle symptom and problem in obstructive sleep apnea syndrome (OSAS). However, investigation has been hampered by the complex snoring sound analyses. OBJECTIVE: This study was aimed to investigate the energy types of the full-night snoring sounds in patients with OSAS. PATIENTS AND METHOD: Twenty male OSAS patients underwent snoring sound recording throughout 6 hours of in-lab overnight polysomnogragphy. Snoring sounds were processed and analyzed by a new sound analytic program, named as Snore Map®. We transformed the 6-hour snoring sound power spectra into the energy spectrum and classified it as snore map type 1 (monosyllabic low-frequency snore), type 2 (duplex low-&mid-frequency snore), type 3 (duplex low- & high-frequency snore), and type 4 (triplex low-, mid-, & high-frequency snore). The interrator and test-retest reliabilities of snore map typing were assessed. The snore map types and their associations among demographic data, subjective snoring questionnaires, and polysomnographic parameters were explored. RESULTS: The interrator reliability of snore map typing were almost perfect (κ = 0.87) and the test-retest reliability was high (r = 0.71). The snore map type was proportional to the body mass index (r = 0.63, P = 0.003) and neck circumference (r = 0.52, P = 0.018). Snore map types were unrelated to subjective snoring questionnaire scores (All P>0.05). After adjustment for body mass index and neck circumference, snore map type 3-4 was significantly associated with severity of OSAS (r = 0.52, P = 0.026). CONCLUSIONS: Snore map typing of a full-night energy spectrum is feasible and reliable. The presence of a higher snore map type is a warning sign of severe OSAS and indicated priority OSAS management. Future studies are warranted to evaluate whether snore map type can be used to discriminate OSAS from primary snoring and whether it is affected by OSAS management.

The natural vibration characteristics of human ossicles.

BACKGROUND: Recently, a model of the ossicular chain for finite element analysis has been developed. However, the natural vibration characteristics of human ossicles have never been studied. Herein, we investigated the dynamic characteristics of the coupling of in-vivo ossicles using finite element analysis. METHODS: The geometry of the ossicular chain was obtained by high-resolution computed tomography of the temporal bone, and a 3D model of the ossicular chain was reconstructed by the medical imaging software, Amira®. The file was then imported into the finite element analysis software, ANSYS®. The natural vibration characteristics of human ossicles were measured by finite element analysis. RESULTS: The characteristic dimensions of the model were measured and compared with previously published data. The malleus resonated to sound stimuli at 3 kHz and 4 kHz; the incus and stapes did not resonate to sound stimuli at any frequency. A coupling of the incus and malleus easily resonated to sound stimuli at 5 kHz. A coupling of the incus and stapes easily resonated to sound stimuli at 3 kHz. The coupling of the ossicular chain easily resonated to sound stimuli at 5 kHz, 6 kHz and 8 kHz. CONCLUSION: The dynamic characteristics of the ossicular chain were analyzed by finite element analysis method. The characteristics of a free vibration model of the ossicles could be determined, which would be helpful in evaluation and consultation for ossicular prosthesis development.

Magnetic resonance imaging of the in-vivo human tympanic membrane.

BACKGROUND: To obtain magnetic resonance images of the in-vivo human tympanic membrane to avoid radiation exposure. METHODS: Images of the in-vivo human tympanic membrane were obtained by magnetic resonance imaging (MRI). The differences in resolution of the images obtained by multi slice single echo (MSSE) and 3-dimentional (3D) SNAP sequences were then compared. RESULTS: The resolution of the 2D MR images acquired by MSSE sequences was higher than that obtained by 3D SNAP. The voxel size of the MR images was smaller than that with 3D SNAP because of the narrower slice thickness. Therefore, the spatial resolution of the 3D SNAP sequenced images was better than that of MSSE images. The scanning time for MSSE and 3D SNAP were 12 minutes and 40 seconds and 1 minute and 42 seconds respectively. The signal-to-noise ratio (SNR) of MR images with 3D SNAP was 0.32 decibels higher than that with MSSE. CONCLUSION: In this study, MR images of the in-vivo human tympanic membrane could be obtained with a 9-cm surface coil with MSSE and 3D SNAP sequences. The spatial resolution of MR images acquired with 3D SNAP was better than that with MSSE. The scanning time with 3D SNAP was shorter than that with MSSE based on similar SNRs. The structure and geometry of the tympanic membrane can be observed clearly, which would be helpful for diagnosis in clinics and can avoid radiation exposure.

Gain affected by the interior shape of the ear canal.

OBJECTIVE: This study investigated the correlation of gain distribution and the interior shape of the human external ear canal. STUDY DESIGN: Cross-sectional study of gain measurement at the first bend and second bend. SETTING: Chang Gung Memorial Hospital and Chang Gung University. SUBJECTS AND METHODS: There were 15 ears in patients aged between 20 and 30 years (8 men/7 women) with normal hearing and middle ears. Stimulus frequencies of 500, 1000, 2000, 3000, and 4000 Hz were based on the standard clinical hearing test. Measurements closer to the tympanic membrane and the positions at the first and second bends were confirmed by using otoscope. Real ear measurement to analyze the canal resonance in human external ears was adopted. RESULTS: This study found that gain at stimulus frequencies of 4000 Hz was affected by the interior shape of the ear canal (P < .005), particularly at the first and second bends, whereas gain was only affected by the length of the ear canal for stimulus frequencies of 2000 Hz (P < .005). CONCLUSION: This study found that gain was affected not only by the length of the external auditory canal (EAC) but also by the interior shape of the EAC significantly. The findings of this study may have potential clinical applications in canalplasty and congenital aural atresia surgery and may be used to guide surgeries that attempt to reshape the ear canal to achieve more desirable hearing outcomes.

A novel opto-electromagnetic actuator coupled to the tympanic membrane.

A new type of electromagnetic vibration transducer designed to be placed onto the tympanic membrane was developed. The actuator consisted of two photodiodes, two permanent magnets, an aluminum ring, two opposing wound coils, a latex membrane and a Provil Novo membrane. An optic probe was designed to allow sound and light signals to enter the ear canal, thereby preventing the acoustic occlusion effect of traditional ear molds. Two light-emitting diodes were used for carrying the input signals. The corresponding photodiodes were used for receiving the light signals and generating currents in the actuator. The opto-electromagnetic vibration actuator was fabricated and tested using a Laser Doppler vibrometer. The actuator showed displacements of vibration between 30 and 1 nm from 300 to 6500Hz and reduced in amplitude at higher frequencies. The average gain of the actuator with 140microA on the umbo displacement was about 20 dB relative to 87 dBA at the distance of 6cm from the tympanic membrane and 0microA in actuator.