Background: The hollow-fiber infection model (HFIM) is a valuable tool for evaluating pharmacokinetics/pharmacodynamics relationships and determining the optimal antibiotic dose in monotherapy or combination therapy, but the application for personalized precision medicine in tuberculosis treatment remains limited. This study aimed to evaluate the efficacy of adjusted antibiotic doses for a tuberculosis patient using HFIM. Methods: Model-based Bayesian forecasting was utilized to assess the proposed reduction of the isoniazid dose from 300 mg daily to 150 mg daily in a patient with an ultra-slowacetylation phenotype. The efficacy of the adjusted 150-mg dose was evaluated in a timeto-kill assay performed using the bacterial isolate Mycobacterium tuberculosis (Mtb) H37Ra in a HFIM that mimicked the individual pharmacokinetic profile of the patient. Results: The isoniazid concentration observed in the HFIM adequately reflected the target drug exposures simulated by the model. After 7 days of repeated dose administration, isoniazid killed 4 log 10 Mtb CFU/mL in the treatment arm, while the control arm without isoniazid increased 1.6 log 10 CFU/mL. Conclusion Our results provide an example of the utility of the HFIM for predicting the efficacy of specific recommended doses of anti-tuberculosis drugs in real clinical setting.

Pediatric patients with coronavirus disease 2019 (COVID-19) are increasing, and severe cases such as multisystem inflammatory syndrome are being reported. Nafamostat, a repurposing drug, is currently being explored for the treatment of COVID-19 in adults. However, the data supporting its exposure in pediatrics remains scarce. Physiologically-based pharmacokinetic (PBPK) modeling enables the prediction of drug exposure in pediatrics based on ontogeny of metabolic enzymes and age dependent anatomical and physiological changes. The study aimed to establish a PBPK model of nafamostat in adults, then scale the adult PBPK model to children for predicting pediatric exposures of nafamostat and an optimal weight-based nafamostat dose in pediatric population. The developed model adequately described adult exposure data in healthy volunteers following i.v. administration with three doses (10, 20, and 40 mg). Scaling adult PBPK models to five pediatric groups predicted that as age advances from neonate to adult, the exposure of nafamostat slightly increased from neonate to infant, steadily decreased from infant to child, and then increased from child to adult after the administration of 0.2 mg/kg/h for 14 days, a dosing regimen being conducted in a clinical trial for COVID-19. Based on the fold change of predicted area under the curve for the respective pediatric group over those of adults, weight-based dosages for each pediatric group may be suggested. The novel PBPK model described in this study may be useful to investigate nafamostat pharmacokinetics in a pediatric subgroup further.

It is challenging to achieve sufficient hearing gain in patients with mixed hearing loss. In chronic middle ear diseases, conventional passive reconstructive surgeries often result in suboptimal hearing gain and additional hearing aids may have limitations due to insufficient sound amplification, occlusion effect, acoustic feedback, and skin irritation. Middle ear implantation (MEI) using Vibrant Soundbridge (VSB) is another option for auditory rehabilitation in mixed hearing loss as well as sensorineural hearing loss. The floating mass transducer of VSB can be placed on various middle ear structures either directly or using different types of couplers in order to deliver vibratory mechanical energy to the cochlea. We report a patient who presented with bilateral mixed hearing loss due to chronic otitis media and had limitations using conventional hearing aids in the worse hearing ear. The patient was successfully treated with MEI using the Bell coupler together with middle ear surgery in a single step.
Acoustics ; Cochlea ; Ear ; Ear, Middle* ; Hearing ; Hearing Aids ; Hearing Loss, Mixed Conductive-Sensorineural* ; Hearing Loss, Sensorineural ; Humans ; Ossicular Prosthesis* ; Otitis Media ; Rehabilitation ; Skin ; Transducers

BACKGROUND AND OBJECTIVES: The early assessment of treatment is not done for benign paroxysmal positional vertigo (BPPV) since the well-known phenomenon of fatigability after a repeated positional test can mimic successful treatment. The aim of this study is to evaluate the clinical implication of ‘fatigability’ after Epley maneuver and to identify the therapeutic efficacy of Epley maneuver in posterior canal BPPV (PC-BPPV). SUBJECTS AND METHOD: This study was prospectively conducted by two dizziness clinics on 51 consecutive patients diagnosed with PC-BPPV. All patients included in the study received Epley maneuver treatment. The therapeutic results were reassessed immediately after a single trial of Epley maneuver. After 30 minutes, results were reassessed repeatedly to confirm the fatigability of diagnostic procedure immediately after treatment. If the treatment was not successful after 30 minutes, Epley maneuver was repeatedly performed until complete resolution. RESULTS: Immediately after the first maneuver, 45 of 51 (88.2%) patients had neither vertigo nor nystagmus during the positional test. All patients demonstrated complete resolution after receiving one to three Epley maneuvers on the day of diagnosis. ‘Fatigability (false negative result)’ was confirmed for only one case (1 of 6 patients, 16.7%), in which nystagmus was observed after 30 minutes but not identified immediately after the first Epley maneuver. CONCLUSION: The therapeutic efficacy of Epley maneuver is very high in PC-BPPV. Considering the possibility of fatigability when reassessment is performed immediately after therapeutic maneuver, clinicians should avoid assessing the outcome immediately after treatment in patients with PC-BPPV.
Benign Paroxysmal Positional Vertigo* ; Diagnosis ; Dizziness ; Fatigue ; Humans ; Methods ; Prospective Studies ; Vertigo

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness of computerized dynamic posturography (CDP) in patients with acute vestibular neuritis (AVN) by identifying the recovery period of Sensory Organization Test (SOT) and comparing the result of SOT with those of the vestibulo-ocular reflex (VOR) tests and subjective symptoms. SUBJECTS AND METHOD: A prospective study was conducted on 41 patients who were diagnosed with AVN. The SOT was measured daily until the equilibrium composite score recovered the normal value. A survey, composing of questionnaires on Visual Analogue Scale (VAS), Dizziness Handicap Inventory (DHI), motion sensitive quotient (MSQ) and Activities-Specific Balance Confidence Scale (ABC), was conducted on the patient's initial visit and on the day the normal value of SOT was recovered. Videonystagmography and the caloric test were also performed, and the results were compared with those of the SOT. RESULTS: The mean duration from the onset of vertigo to the recovery of SOT scores was 3.7±2.9 days (median 3.0 days) and that from the onset of vertigo to the disappearance of spontaneous nystagmus was 17.1±27.2 days (median 6.0 days). The scores of 4 questionnaires (VAS, DHI, MSQ, and ABC) were significantly different between the initial day and the day of recovery to the normal value of SOT (p<0.001). However, the velocity of spontaneous nystagmus on the initial visit and the degree of canal paresis from the caloric test showed no significant correlations to recovery duration from the onset of vertigo to the normalization of SOT score. CONCLUSION: The recovery duration of vestibulospinal reflex (VSR) is much shorter than that of VOR in patients with AVN. The recovery of subjective symptoms showed close correlation with the recovery of VSR, but the results of VSR was not correlated with that of VOR. Therefore, CDP could be a very useful test for monitoring the resolution of subjective symptoms in patients with AVN.
Caloric Tests ; Compensation and Redress* ; Cytidine Diphosphate ; Dizziness ; Humans ; Methods ; Paresis ; Prospective Studies ; Reference Values ; Reflex ; Reflex, Vestibulo-Ocular ; Vertigo ; Vestibular Neuronitis*

It is known that about 30% of patients with sudden hearing loss present with vertigo or dizziness. In clinical practice, this is called sudden hearing loss with vertigo (SHLV) although definite diagnostic criteria have not been established. Dizziness in SHLV is known to be caused by the dysfunction of the vestibular end-organs as well as the superior vestibular nerve or both vestibular nerve divisions. Lesions of the inferior vestibular nerve or a single semicircular canal have also been reported in these patients. Herein we report a 71-year-old male patient with SHLV who demonstrated vestibular dysfunction involving only the posterior semicircular canal. The patient showed normal results in the bithermal caloric test and the cervical vestibular evoked myogenic potentials test as well as positional test. Video head impulse test showed decreased gain only in the posterior semicircular canal. This case is significant in showing that dizziness in SHLV patients can occur by an abnormality involving only a single semicircular canal.
Aged ; Caloric Tests ; Dizziness ; Head Impulse Test ; Hearing Loss, Sudden ; Humans ; Male ; Semicircular Canals ; Vertigo ; Vestibular Evoked Myogenic Potentials ; Vestibular Nerve

OBJECTIVES: The purpose of this study was to examine the clinical manifestations and significance of pseudo-spontaneous nystagmus (PSN) and head-shaking nystagmus (HSN) in horizontal canal benign paroxysmal positional vertigo (HC-BPPV). METHODS: Two hundred fifty-two patients diagnosed as HC-BPPV were reviewed retrospectively. After excluding 55 patients with ipsilateral vestibular diseases, multiple canal BPPV, or those who were lost to follow-up, we analyzed the direction of PSN and HSN in patients with HC-BPPV. We also compared the clinical characteristics and treatment outcome between PSN-positive and PSN-negative groups. RESULTS: Our study included 197 patients composed of 80 patients with geotropic HC-BPPV and 117 patients with apogeotropic HC-BPPV. PSN was observed in 13.7% patients and HSN was observed in 45.2%. The incidence of HSN was higher in apogeotropic HC-BPPV, while the proportion of PSN was not statistically significant between the two subtypes. There was no directional preponderance in geotropic HC-BPPV, while ipsilesional PSN and contralesional HSN showed higher incidence in apogeotropic HC-BPPV. The dizziness handicap inventory score in the PSN-positive group was higher than that in the PSN-negative group (p<0.001), and the duration of symptom onset in the PSN-positive group was shorter than that in the PSN-negative group (p=0.047). However, there was no significant difference in the treatment outcome between the two groups. CONCLUSIONS: The incidence of HSN was higher than that of PSN in patients with apogeotropic HC-BPPV. Patients with HC-BPPV showing PSN demonstrated more severe initial symptoms and visited the hospital in a shorter period of time after the onset of symptoms.
Benign Paroxysmal Positional Vertigo ; Dizziness ; Humans ; Incidence ; Lost to Follow-Up ; Retrospective Studies ; Treatment Outcome ; Vestibular Diseases

BACKGROUND: For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients’ characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections. MATERIALS AND METHODS: At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) ≤50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P <0.05 for selection and P <0.01 for elimination. RESULTS: Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CL(cr)/47 for piperacillin and CL = 1.76 + 4.81 × CL(cr)/47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam. CONCLUSION: The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance.
Anti-Bacterial Agents ; Body Weight ; Continental Population Groups ; Creatinine ; Humans ; Methods ; Piperacillin

OBJECTIVE: The purpose of this study was to identify the diverse patterns of nystagmus and analyze their clinical significance in benign paroxysmal positional vertigo (BPPV) of the anterior semicircular canal. METHODS: Fifty-three patients diagnosed with anterior canal BPPV (AC-BPPV) were analyzed retrospectively. Patients were classified according to the presence or absence of the torsional component of the nystagmus and the direction of Dix-Hallpike test which induced the nystagmus. We compared the clinical characteristics and treatment outcomes among the different patient groups. RESULTS: There were 11 patients with unilateral down beat (DB) nystagmus, 11 patients with bilateral DB nystagmus, 14 patients with ipsilateral torsional down beat (TDB) nystagmus, 7 patients with contralateral TDB nystagmus, and 7 patients with bilateral TDB nystagmus. There were no differences between the unilateral and the bilateral DB groups in terms of the duration of nystagmus or vertigo and the number of treatment sessions. In addition, the ipsilateral TDB group showed no significant clinical difference compared to the contralateral or bilateral TDB group. CONCLUSION: Various nystagmus patterns can be seen in AC-BPPV. There was no statistically significant difference in the clinical characteristics according to the different nystagmus patterns. This information may be helpful for clinicians in counseling and managing the patients with AC-BPPV.
Benign Paroxysmal Positional Vertigo ; Counseling ; Humans ; Retrospective Studies ; Semicircular Canals ; Vertigo