Frequency-specific efficacy of intratympanic steroid on idiopathic sudden sensorineural hearing loss.

Background: Hearing recovery would be different in each sound frequency in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).Aims/objectives: To analyze frequency-specific efficacy of intratympanic steroid on ISSNHL.Materials and methods: Of a total of 381 patients with ISSNHL (hearing threshold ≥40 dB; ≤30 days until treatment), 174 patients (174 ears) received systemic steroid plus hyperbaric oxygen therapy (HBO group), and 207 patients (208 ears) received systemic plus intratympanic steroid (IT group). Hearing thresholds at 125-8000 Hz were measured at every octave before and after treatment.Results: % of patients with hearing gains ≥10 dB in the IT group was significantly higher for 500 Hz and the average of 5 mid-frequencies, tended to be higher for 1000 Hz, but was significantly lower for 8000 Hz, compared to the HBO group. Multiple regression analysis showed that hearing recovery was negatively correlated with patients' age for 125/2000/4000/8000 Hz and with days from onset to treatment for all frequencies, and also revealed better hearing recovery at 500/1000 Hz in the IT group than in the HBO group.Conclusions: Intratympanic steroid is more effective than hyperbaric oxygen to yield better hearing outcomes at mid-frequencies and would be advantageous to restore sound/speech perception.Significance: Superiority of intratympanic steroid over hyperbaric oxygen for treating ISSNHL was verified.

Efficacy of Intratympanic Steroid on Idiopathic Sudden Sensorineural Hearing Loss: An Analysis of Cases With Negative Prognostic Factors.

Purpose We retrospectively studied the efficacy of intratympanic steroid administration in comparison with hyperbaric oxygen (HBO) therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) with negative prognostic factors. Method We enrolled 301 patients (302 ears) with ISSNHL (average hearing level at 250-4000 Hz ≥ 40 dB; time from onset to treatment ≤ 30 days). From August 2002 to March 2009, 174 patients (174 ears) received systemic steroid plus HBO therapy (HBO group), and from June 2015 to January 2018, 127 patients (128 ears) received systemic plus intratympanic steroid (IT group). Hearing outcomes were evaluated by 6 indices: cure rate, marked-recovery rate (percent of patients with hearing gain ≥ 30 dB), recovery rate (percent of patients with hearing gain ≥ 10 dB), hearing gain, hearing level after treatment, and percent hearing improvement compared to the unaffected contralateral ear. Results The recovery rate was significantly higher in the IT group than in the HBO group (80.5% vs. 68.4%, p = .019). The IT group showed a higher recovery rate than the HBO group in patients aged ≥ 60 years ( p = .010), patients with early (≤ 7 days from onset) treatment ( p = .005), patients with initial hearing levels ≥ 90 dB ( p = .037), and patients with vertigo/dizziness ( p = .040). The IT group also showed higher hearing gain and percent hearing improvement than the HBO group in patients with vertigo/dizziness ( p = .046 and p = .026, respectively). Conclusions Systemic plus intratympanic steroid is more effective for ISSNHL than systemic steroid plus HBO, particularly in patients with negative prognostic factors, such as old age, profound hearing loss, and/or presence of vertigo/dizziness.

Pharmacokinetics of initial full and subsequent reduced doses of S-1 in patients with locally advanced head and neck cancer-effect of renal insufficiency.

BACKGROUND: S-1 is a combination of tegafur [metabolized to 5-fluorouracil (5-FU)] with the modulators gimeracil (5-chloro-2,4-dihydroxypyridine) and oteracil potassium. 5-Chloro-2,4-dihydroxypyridine maintains plasma 5-FU concentrations by inhibiting dihydropyrimidine dehydrogenase, a pyrimidine catabolism enzyme that degrades 5-FU. As 50% of 5-chloro-2,4-dihydroxypyridine is excreted in urine, renal insufficiency may increase its blood level, increasing 5-FU concentrations. We investigated whether special dose modification is needed in the presence of renal insufficiency. OBJECTIVE: We compared steady state pharmacokinetics of 5-FU for the initial S-1 dose and reduced doses in patients with head and neck cancer requiring dose reduction due to renal and non-renal toxicities. METHODS: Chemoradiotherapy with S-1 and cisplatin was administered every 5 weeks for two courses with a radiation dose totaling 70 Gy over 33-35 fractions. Two additional courses of adjuvant chemotherapy were administered in the case of an objective response. The S-1 and/or cisplatin dose was reduced in response to renal, hematologic or other toxicities. The primary endpoint was the change in area under the plasma concentration-versus-time curve from time 0-10 hours (5-FU AUCss 0-10) between the initial and reduced S-1 doses. RESULTS: Although the mean 5-FU levels in patients with non-renal toxicities significantly decreased between the full and reduced dose, the full-dose and reduced-dose mean maximum 5-FU plasma concentrations at steady state (Css max) and AUCss 0-10 in patients with renal insufficiency were similar. CONCLUSIONS: Standard S-1 dose reduction for renal toxicity did not result in a significant decrease in 5-FU levels at steady state. A greater reduction to lower plasma 5-chloro-2,4-dihydroxypyridine may be necessary in patients with renal insufficiency.

Prediction model for hearing outcome in patients with idiopathic sudden sensorineural hearing loss.

The aim of this study is to develop a regression model for predicting hearing outcome in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 174 consecutive patients with ISSNHL (average of the hearing levels at 250, 500, 1,000, 2,000, and 4,000 Hz was ≥40 dB; time from onset to treatment was ≤30 days) were retrospectively analyzed. They received steroid administration (400 mg/day of hydrocortisone sodium succinate followed by tapered doses) in combination with hyperbaric oxygen therapy. The hearing improvement rate compared to the unaffected contralateral ear was calculated. Correlations between the hearing improvement rate and four prognostic factors (patient's age, days from onset to treatment, initial hearing level, and the presence of vertigo) were examined by simple and multiple regression analyses. In the simple regression analysis, significant correlations were observed between the hearing improvement rate and all four prognostic factors. In the multiple regression analysis, the correlation was significant for patient's age, days from onset to treatment, and the presence of vertigo with partial correlation coefficients of -0.221, -0.324, and -0.329, respectively, but was not significant for the initial hearing level. We subsequently formulated a multiple regression equation for predicting the hearing improvement rate. The multiple correlation coefficient was 0.495 with a p value of 1.42 × 10(-9). Using this regression model, the hearing improvement rate is still difficult to predict with 95% probability, but is predictable with 70% probability.