Medical errors during training: how do residents cope?: a descriptive study.

BACKGROUND: Physicians' self-perceived medical errors lead to substantial emotional distress, which has been termed the "second victim phenomenon." Medical errors during residency are associated with increased burnout and depression. It is important to know how residents cope with self-perceived medical errors and how they gain personal and emotional support in order to develop effective interventions. OBJECTIVE: To assess the impact of self-perceived medical errors on residents' well-being, the range of coping strategies during training, and the extent of personal and institutional support. METHODS: An online cross-sectional survey was administered via email in October 2018 to 286 residents across all specialties in a 548-bed single urban academic medical center. The survey covered three domains focusing on residents' most serious self-perceived medical error: (1) emotional response, (2) coping strategies using the BRIEF COPE Inventory, and (3) personal and institutional support. RESULTS: 109/286 residents from various specialties responded. Internal Medicine, Pediatrics and Emergency Medicine constituting 80 % of respondents. Self-perceived medical errors during residency were widespread (95 %). One in five medical errors was classified as moderate to severe. Most residents acknowledged a sense of guilt, remorse and/or inadequacy. Use of maladaptive coping strategies was high. Open-ended responses pointed to fear of retaliation, judgement, shame and retribution. Most residents disclosed their error to a senior resident but did not discuss it with the patient's family. Only 32 % of residents participated in a debriefing session. CONCLUSIONS: Most residents were directly involved in medical errors, which affected their emotional well-being. The use of maladaptive coping strategies was high. Residents' fear of consequences prevented disclosure and discussion of self-perceived medical errors. This information is relevant to implement targeted interventions.

Azithromycin treatment in children hospitalized with asthma: a retrospective cohort study.

Objective: Azithromycin has anti-inflammatory properties in the lungs and decreases the duration of asthma-like episodes in children. We sought to evaluate length of stay (LOS) and readmission rates of children receiving azithromycin therapy during hospitalization for acute asthma exacerbations.Methods: This was a retrospective cohort study at an urban, quaternary-care children's hospital including patients under 18 years old hospitalized for asthma, without concurrent infection, from 2002 to 2011. The primary predictor was azithromycin therapy administered within 48 hours of admission. The primary outcome was LOS and the secondary outcomes were 7, 30, and 90-day hospital readmission rates for asthma.Results: Azithromycin therapy was administered to 174 (3%) of 5335 unique patients admitted for asthma, without concurrent infection, over the 10-year period. The overall median LOS was 2.3 days [Interquartile range, 1.8-3.1] and 9% (480) were readmitted for asthma within 90 days of discharge. Azithromycin therapy was associated with a 20% (11 hour) longer LOS (adjusted beta coefficient for log-transformed LOS, 0.18; 95% Confidence Interval (CI): 0.11-0.26), less than the 29% (16 hour) difference determined a priori as clinically relevant. Azithromycin therapy was not associated with 90-day readmission for asthma (adjusted odds ratio, 0.89; 95% CI: 0.46-1.72]. The limited number of 7 and 30-day readmissions in the azithromycin treated group precluded adjusted analysis.Conclusions: Azithromycin therapy was not associated with a clinically relevant difference in hospital LOS or with readmission rates for children hospitalized with asthma. Prospective trials are needed to determine the clinical effects of azithromycin therapy in children with asthma.

Safety of High-Flow Nasal Cannula Outside the ICU for Previously Healthy Children With Bronchiolitis.

BACKGROUND: High-flow nasal cannula (HFNC), a form of noninvasive respiratory support, is effective for the treatment of respiratory distress in ICUs. Although HFNC has been used outside of the ICU, there is little research that examines its safety in this less-monitored setting. METHODS: Children ≤ 24 months old admitted with bronchiolitis to a pediatric floor at a tertiary care center from April 1 2013, to March 31 2015, were identified by using standard diagnostic codes. Exclusion criteria were concomitant pneumonia or complex comorbidities. Demographic and clinical characteristics were abstracted. Outcomes included transfer to the ICU, higher levels of respiratory support, intubation, pneumothorax, or aspiration events. RESULTS: Eighty children admitted with bronchiolitis who were treated with HFNC while on the pediatric floor were examined. The median age was 4.6 months, 45% were girls, and the majority were either Hispanic (41%) or black (36%). Flow ranged from 3 to 10 L/min. Thirty-three subjects (41% of the sample) required subsequent transfer to the ICU. No children were intubated or developed a pneumothorax. Eighty-three percent were fed while on HFNC. No children had an aspiration event. CONCLUSIONS: HFNC may be a safe modality of respiratory support outside of the ICU for children ages ≤ 24 months with bronchiolitis and without comorbidities up to a maximum flow of 10 L/min. There were no adverse events among the subjects who were fed while on HFNC.

Radiation Exposure of Premature Infants Beyond the Perinatal Period.

OBJECTIVES: To determine the odds of premature compared with term infants exceeding the recommended radiation exposure threshold in the first year after discharge from birth hospitalization. METHODS: In this observational retrospective cohort study, we compared the radiation exposure of premature and term infants between 2008 and 2015 in an urban hospital system. The primary outcome was crossing the radiation exposure threshold of 1 millisievert. We assessed prematurity's effect on this outcome with multivariable logistic regression. RESULTS: In our study, 20 049 term and 2047 preterm infants met inclusion criteria. The population was approximately one-half female, predominantly multiracial or people of color (40% African American and 44% multiracial), and of low socioeconomic status. Premature infants had 2.25 times greater odds of crossing the threshold compared with term infants after adjustment for demographics (95% confidence interval [CI]: 1.66-3.05). Adjustment for complex chronic conditions, which are validated metrics of pediatric chronic illness, attenuated this association; however, premature infants still had 1.58 times greater odds of crossing the threshold (95% CI: 1.16-2.15). When the final model was analyzed by degree of prematurity, very preterm and extremely preterm infants were significantly more likely to cross the threshold (1.85 [95% CI: 1.03-3.32] and 2.53 [95% CI: 1.53-4.21], respectively), whereas late preterm infants were not (1.14 [95% CI: 0.73-1.78]). CONCLUSIONS: Premature infants crossed the recommended radiation threshold more often than term infants in the year after discharge from birth hospitalization.

Clinical Factors Associated With Chest Imaging Findings in Hospitalized Infants With Bronchiolitis.

Despite recommendations against routine imaging, chest radiography (CXR) is frequently performed on infants hospitalized for bronchiolitis. We conducted a review of 811 infants hospitalized for bronchiolitis to identify clinical factors associated with imaging findings. CXR was performed on 553 (68%) infants either on presentation or during hospitalization; 466 readings (84%) were normal or consistent with viral illness. Clinical factors significantly associated with normal/viral imaging were normal temperature (odds ratio = 1.66; 95% CI = 1.03-2.67) and normal oxygen saturation (odds ratio = 1.77; 95% CI = 1.1-2.83) on presentation. Afebrile patients with normal oxygen saturations were nearly 3 times as likely to have a normal/viral CXR as patients with both fever and hypoxia. Our findings support the limited role of radiography in the evaluation of hospitalized infants with bronchiolitis, especially patients without fever or hypoxia.

Risk Factors for Respiratory Decompensation Among Healthy Infants With Bronchiolitis.

BACKGROUND: Although most children with bronchiolitis only require supportive care, some decompensate and require ventilatory support. We examined predictors of respiratory decompensation among hospitalized children to identify which patients may benefit from expectant monitoring. METHODS: We examined children ≤24 months old with bronchiolitis admitted to the general infant and toddler floor. Children with pneumonia or comorbidities were excluded. Demographic and clinical characteristics were abstracted from a clinical database and medical records. Respiratory decompensation was defined as the need for initiating high-flow nasal cannula oxygen, continuous positive airway pressure, nasal intermittent mandatory ventilation, bilevel positive airway pressure, or intubation. A multivariable logistic regression model was constructed to identify independent predictors of respiratory decompensation. RESULTS: A total of 1217 children were included. The median age was 6.9 months, 41% were girls, 49% were Hispanic, 21% were black, and 18% were premature. Significant independent predictors of respiratory decompensation were age ≤3 months (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.09-5.07), age 3 to 6 months (OR: 1.76; 95% CI: 1.04-3.0), black race (OR: 1.94; 95% CI: 1.27-2.95), emergency department hypoxemia (OR: 2.34; 95% CI: 1.30-4.21), and retractions or accessory muscle use (OR: 2.26; 95% CI: 1.48-3.46). Children with 0 of 4 predictors were found to have a low risk of decompensation (3%). CONCLUSIONS: Young age, black race, emergency department hypoxemia, and retractions or accessory muscle use were associated with respiratory decompensation in children with bronchiolitis. These factors should be considered at presentation, as they identify children who require a higher level of respiratory monitoring and support and others who may not benefit.

3% Hypertonic Saline Versus Normal Saline in Inpatient Bronchiolitis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Bronchiolitis, the most common reason for hospitalization in children younger than 1 year in the United States, has no proven therapies effective beyond supportive care. We aimed to investigate the effect of nebulized 3% hypertonic saline (HS) compared with nebulized normal saline (NS) on length of stay (LOS) in infants hospitalized with bronchiolitis. METHODS: We conducted a prospective, randomized, double-blind, controlled trial in an urban tertiary care children's hospital in 227 infants younger than 12 months old admitted with a diagnosis of bronchiolitis (190 completed the study); 113 infants were randomized to HS (93 completed the study), and 114 to NS (97 completed the study). Subjects received 4 mL nebulized 3% HS or 4 mL 0.9% NS every 4 hours from enrollment until hospital discharge. The primary outcome was median LOS. Secondary outcomes were total adverse events, subdivided as clinical worsening and readmissions. RESULTS: Patient characteristics were similar in groups. In intention-to-treat analysis, median LOS (interquartile range) of HS and NS groups was 2.1 (1.2-4.6) vs 2.1 days (1.2-3.8), respectively, P = .73. We confirmed findings with per-protocol analysis, HS and NS groups with 2.0 (1.3-3.3) and 2.0 days (1.2-3.0), respectively, P = .96. Seven-day readmission rate for HS and NS groups were 4.3% and 3.1%, respectively, P = .77. Clinical worsening events were similar between groups (9% vs 8%, P = .97). CONCLUSIONS: Among infants admitted to the hospital with bronchiolitis, treatment with nebulized 3% HS compared with NS had no difference in LOS or 7-day readmission rates.

L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study.

BACKGROUND: The purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count. RESULTS: Eighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001) and from 24±8 to 40±13 nM/L (P<0.001) respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L) and increased in the placebo group (1.38±0.62 to 1.84±0.74 mmol/L; P<0.005). CONCLUSION: Our study suggests that 3 g of oral L-carnitine supplementation for 2 weeks in terminally ill HIV/AIDS patients does not improve fatigue. This study might help to determine the dose and duration of treatment used in future clinical trials, as higher doses and/or longer periods of supplementation might be needed in order to detect an improvement. The reduction in serum lactate levels suggests a potential role for L-carnitine supplementation in patients undergoing certain types of antiretroviral therapy. This study contributes evidence-based data to the field of alternative and complementary medicine, a multibillion dollar industry in which controlled studies are not the norm.

Zidovudine (AZT) overdose in a healthy newborn receiving postnatal prophylaxis.

CONTEXT: Pediatric medication dosing and administration, faced with inherent challenges of dose to body weight adjustment and variable delivery vehicles, may lead to inadvertent errors effectively resulting in overdose. Zidovudine (AZT), a nucleoside analog reverse transcriptase inhibitor (NRTI), is a commonly prescribed medication to treat HIV-exposed newborns, with limited overdose data in this patient population. Metabolic acidosis with elevated lactate is the most serious consequence of AZT toxicity in the adult population, associated with mortality. Other significant effects may include neutropenia and hepatic dysfunction. CASE REPORT: A 4-day-old male infant who received two inadvertent 10-fold overdoses of AZT while being treated for HIV postnatal prophylaxis. The newborn developed a transient metabolic acidosis with elevated lactate that resolved within 24 h, a small increase in AST, and persistent neutropenia for 5 weeks. The patient's mother cited several key factors leading to the dosing error. DISCUSSION: The paucity of AZT overdose data in newborns and infants compels this case report, which reviews the published literature and provides insight into prevention and improvement of pediatric patient safety.

A cluster of children with seizures caused by camphor poisoning.

BACKGROUND: Isolated cases of camphor-induced seizures have been reported in young children after gastrointestinal, dermal, and inhalation exposure. In 1982, after a series of unintentional ingestions of camphor products, the US Food and Drug Administration restricted the camphor content to <11% in some products intended for medicinal use. Camphor products intended for use as pesticides must be registered with the US Environmental Protection Agency. Still, many imported camphor-containing products fail to meet Food and Drug Administration and Environmental Protection Agency requirements for labeling and content. OBJECTIVE: To describe a cluster of cases of camphor-associated seizure activity resulting from the availability of imported camphor products in certain ethnic populations that use it as a natural remedy. METHODS: We present 3 cases of seizures associated with imported, illegally sold camphor in young children who presented to a large, urban children's hospital in Bronx, New York, during a 2-week period. RESULTS: The children's ages ranged from 15 to 36 months. Two children ingested camphor, and 1 child was exposed through repetitive rubbing of camphor on her skin. All 3 patients required pharmacologic intervention to terminate the seizures. One patient required bag-valve-mask ventilation for transient respiratory depression. All 3 patients had leukocytosis, and 2 patients had hyperglycemia. Exposure occurred as a result of using camphor for spiritual purposes, cold remedy, or pest control. After identification of these cases, the New York City Department of Health released a public health warning to keep camphor products away from children. Similar warnings were issued later by other state health departments. CONCLUSIONS: These cases highlight the toxicity associated with camphor usage in the community and that inappropriate use of illegally sold camphor products is an important public health issue. Camphor may be a common, yet unrecognized, source of seizures in children in certain ethnic populations that use it as a natural remedy. Efforts are needed to educate the communities about the hazards of using camphor products and to limit the illegal availability of these products.

L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study.

Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly improved FACT-An functional well-being subscale (P<0.03), and KPS (P<0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients.

Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study.

Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous L-carnitine may hold promise as a treatment for this common symptom. Little is known about L-carnitine safety, tolerability, and dose-response in patients with cancer. We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous L-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials. Adult patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 microM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score > or =50 were entered by groups of at least three into a standard maximum tolerated dose design. Each successive group received a higher dose of L-carnitine (250, 750, 1250, 1750, 2250, 2750, 3000 mg/day, respectively), administered in two daily doses for 7 days. To compare symptom outcomes before and after supplementation, patients completed validated measures of fatigue (Brief Fatigue Inventory [BFI]), depressed mood (Center for Epidemiologic Studies Depression Scale [CES-D]), quality of sleep (Epworth Sleeplessness Scale [ESS]), and KPS at baseline and 1 week later. Of the 38 patients screened for carnitine levels, 29 were deficient (76%). Twenty-seven patients participated ("intention to treat, ITT") (17 males, 10 females), and 21 completed the study ("completers"); 17 of these patients ("responders," mean+/-[SD] age=57.9+/-15) had increased carnitine levels at the end of the supplementation period. The highest dose achieved was 3000 mg/day. No patient experienced significant side effects and no toxicities were noted. Analysis of all the patients accrued (ITT, n=27) showed a total carnitine increase from 32.8+/-10 to 54.3+/-23 microM/L (P<0.001) and free carnitine increase from 26.8+/-8 to 44.1+/-17 microM/L (P<0.001). BFI decreased significantly, from 66+/-12 to 39.7+/-26 (P<0.001); ESS decreased from 12.9+/-12 to 9+/-6 (P=0.001); and CES-D decreased from 29.2+/-12 to 19+/-12 (P<0.001). A separate analysis of the 17 "responders" showed a dose-response relationship for total- (r=0.54, P=0.03), free-carnitine (r=0.56, P=0.02) levels, and fatigue (BFI) scores (r=-0.61, P=0.01). These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/day and that positive effects may be more likely at relatively higher doses in this range. This study provides the basis for the design of future placebo-controlled studies of l-carnitine supplementation for cancer-related fatigue.

The use of levo-carnitine in children with renal disease: a review and a call for future studies.

Carnitine is an amino acid derivative that has a key role in the regulation of fatty acid metabolism and ATP formation. Carnitine deficiency has been described in various conditions, including chronic kidney disease (CKD) and end stage renal disease (ESRD). The deficiency of this micronutrient is postulated to lead to adverse effects across multiple organ systems. There is a paucity of information on carnitine deficiency and its effects in the pediatric CKD and ESRD populations. Currently, there is no evidence supporting the routine use of carnitine supplementation in children with ESRD. In this article, we review the pathophysiology, pharmacokinetics and the potential effects of levo-carnitine supplementation with a focus on the pediatric CKD and ESRD populations. Finally, potential future directions of research are discussed.

Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss.

Gentamicin is a widely used ototoxic agent. In this study, we shed light on the mechanisms underlying gentamicin-induced hearing loss. More importantly, we demonstrate in vivo and in vitro the effectiveness of a strategy for preventing drug-induced hearing loss using l-carnitine (LCAR), a safe micronutrient that plays a key role in energy metabolism and detoxification [Rebouche, C. J. & Seim, H. (1998) Annu. Rev. Nutr. 18, 39-61]. We show that LCAR prevents changes in hearing threshold and cochlear damage in newborn guinea pigs exposed to gentamicin in utero. Mechanistically, gentamicin-induced apoptosis of auditory cells is mediated by the extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) pathway through up-regulation of the proapoptotic factor Harakiri (Hrk). Most important, small interfering RNA (siRNA) experiments demonstrate that Hrk up-regulation is crucial for gentamicin-induced apoptosis. LCAR, in contrast, prevents both gentamicin-induced Hrk up-regulation and apoptosis acting by means of c-Jun N-terminal kinase (JNK). Together, these results outline pathways for gentamicin-induced hearing loss and its prevention and assign a key role to Hrk in these processes. Thus, our data offer a conceptual framework for designing clinical trials using a safe micronutrient, LCAR, as a simple preventive strategy for iatrogenically induced ototoxicity.

Lack of effect of L-carnitine supplementation on weight gain in very preterm infants.

OBJECTIVE: Carnitine transfer across the placenta occurs predominantly during the third trimester. Unless L-carnitine is provided, very preterm infants develop carnitine deficiency. Although breast milk and infant formulas contain L-carnitine, parenteral nutrition solutions do not routinely provide L-carnitine. We hypothesized that prolonged L-carnitine supplementation in very preterm infants would improve weight gain and shorten length of stay in the hospital. STUDY DESIGN: The study was a double-blind parallel placebo-controlled randomized clinical trial. Eligible patients were <29 weeks of gestation, <72 hours of age, and did not have a potentially life-threatening congenital malformation or hereditary metabolic disorder. Patients were stratified by gestational age (23 to 25(6/7) and 26 to 28(6/7) weeks), and randomized to receive, either L-carnitine at a dose of 50 mumol/kg/day, or placebo. Carnitine was provided intravenously until the infants tolerated 16 ml/day of feeds. The sample size was calculated to have 80% power to detect a 10% increase in weight gain from birth until 36 weeks of postmenstrual age or discharge from the hospital. Secondary outcome variables included food efficiency (defined as weight gain divided by caloric intake), weight gain at 4 weeks of age, time to regain birth weight and length of stay. RESULTS: Among the 63 infants enrolled in the trial, 32 were randomized to L-carnitine and 31 to placebo. L-Carnitine supplementation did not significantly affect average daily weight gain from birth until 36 weeks or hospital discharge, or any of the secondary outcome variables. CONCLUSION: Prolonged supplementation of L-carnitine did not improve long-term weight gain in very preterm infants.

Cisplatin-induced apoptosis in auditory cells: role of death receptor and mitochondrial pathways.

Cisplatin, a commonly used chemotherapeutic agent, has a major limitation due to its ototoxicity. Previous studies have shown that cisplatin induces apoptosis in auditory sensory cells, but the underlying mechanisms remain to be elucidated. In this study, cisplatin was found to induce apoptosis in a cochlear cell line, in a dose- and duration-dependent manner. Specific caspase assays revealed an early (6 h) but transient increase in caspase 8 activity, and a delayed (12 h) increase in caspase 9 activity. The enhanced caspase 8 activity was preceded by upregulation of p53 expression, and coincided with cleavage of Bid to its truncated form. This was followed temporally by activation and mitochondrial translocation of Bax, induction of mitochondrial permeability transition, release of cytochrome c into the cytosol, activation of caspase 9, and entry into the execution phase of apoptosis. Our results indicate the involvement of both the death receptor mechanisms as well as mitochondrial pathways in cisplatin-induced apoptosis of auditory cells in an in vitro model system.