A peer-to-peer handoff tool to ease clerkship transitions.

EDUCATIONAL CHALLENGE: Frequent transitions between core clinical rotations in medical school increase anxiety and cognitive load. Few formalized programs exist to ease these transitions. Our institutional needs-assessment found that approximately 85% of students believed that additional rotation-specific information prior to starting a new rotation would reduce anxiety and increase success. PROPOSED SOLUTION AND IMPLEMENTATION OF SOLUTION: We developed a novel web-based peer-to-peer handoff tool available to all clerkship students at a single, large academic institution. The tool contains the names and contact information of students who most recently completed rotations on each service for all clerkships. A handoff checklist was also created with suggested discussion points for handoffs. Students were encouraged to schedule a handoff 1-2 weeks before starting a new rotation. LESSONS LEARNED: Overall, 83 students (66%) utilized the handoff tool, with use and efficacy decreasing with time during the clinical year. Of tool users, 65% expressed that having access to the tool prior to starting a new rotation helped to reduce anxiety, and 74% felt that the information gained helped to ease transitions. Our peer-to-peer handoff tool may help students feel more prepared to start a new rotation, decrease anxiety during clerkship year, and ease transitions. NEXT STEPS: This low-resource intervention may be implemented at other institutions to provide students with equal opportunities to receive valuable information prior to starting new rotations, regardless of pre-existing peer connections. An automated update system, which we are implementing at our institution, could greatly decrease the time required to maintain a handoff tool and improve sustainability.

Prevalence of Chronic Constipation and Chronic Diarrhea in Diabetic Individuals in the United States.

INTRODUCTION: Diabetic individuals commonly report disordered bowel habits. This study aims to report the prevalence and associated factors of chronic diarrhea (CD) and chronic constipation (CC) in diabetics using a nationally representative sample of US adults. METHODS: Analyses were performed using data from subjects in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) dataset who completed the Bowel Health Questionnaire. The NHANES dataset provides medical comorbidities, demographics, and dietary habits of a nationally representative group of adult survey participants in the United States. CC and CD were defined by Bristol Stool Form Scale (BSFS) Types 1 & 2 and BSFS Types 6 & 7 as the "usual or most common stool type," respectively, and frequent laxative users were also defined as having CC. Co-variables for all subjects included demographic and lifestyle factors, and co-variables evaluated only in diabetics included treatment and severity markers for diabetes. RESULTS: We identified 661 diabetic subjects and 4488 non-diabetic subjects. Diabetic subjects (25.8%) reported disordered bowel habits. In unadjusted analysis, CD was more prevalent in diabetics than in non-diabetics (11.2% vs. 6.0%; p < 0.0001); however, the prevalence of CC was not significantly different between groups (14.6% vs. 11.2%; p = 0.126). When adjusting for covariates (e.g., BMI, gender, age, race/ethnicity, education level, etc.), diabetes itself remained associated with CD. Diabetic individuals with CD more frequently used drugs to lower blood sugar, and diabetic subjects with CC more frequently had poor kidney function. CONCLUSIONS: CD is significantly more prevalent in diabetics than in non-diabetics, whereas CC is not, and the association between CD and diabetes remains significant when adjusting for covariates. Use of medications that lower blood sugar is associated with CD in diabetic individuals, whereas poor kidney function is associated with CC in diabetics.

Significant Morbidity and Mortality Associated with Fecal Impaction in Patients Who Present to the Emergency Department.

BACKGROUND: Fecal impaction (FI) is defined as a large mass of stool in the rectum and/or colon that is unable to be evacuated. No study to date details demographics and outcomes in a sizeable sample of FI patients in the USA. AIMS: The present study aims to develop knowledge of FI by reporting descriptive measures and outcomes of patients presenting to a US emergency department (ED) with FI. METHODS: Medical charts coded with FI at Beth Israel Deaconess Medical Center from 2016 or 2017 were identified retrospectively. Patients diagnosed with FI in the ED or subsequent to direct hospital admission from the ED were included. Patient-specific demographics, visit-specific details, medical and medication histories, and hospital treatment and outcome measures were included in a database and analyzed. RESULTS: Thirty-two patients (mean age of 72.9 years, 62.5% female) had a total of 42 ED visits with FI. Patients had an average of 8.7 diagnoses and 11.2 medications listed in their charts. 54.8% of patients were taking at least one commonly prescribed constipating medication. The median total length of stay for admitted patients was 3 days, with nearly 90% of the ED visits with FI requiring hospital admission. 40.6% of patients experienced serious FI-related morbidities, and 21.9% of patients with FI died in the hospital. CONCLUSION: Patients presenting with FI had high risk of morbidity and mortality, complex medical histories, and large numbers of active treatment regimens. Patients with FI should receive immediate treatment and close monitoring for morbidities and complications.

Risk Factors for Fecal Urgency Among Individuals With and Without Diarrhea, Based on Data From the National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Fecal urgency is a common symptom among patients with gastrointestinal disorders, but can also occur in healthy individuals with normal bowel habits. There have been few studies of fecal urgency in the general population. We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) to analyze the prevalence of and risk factors for this symptom. METHODS: We analyzed data from 4676 persons who completed the Bowel Health Questionnaire from the NHANES, from 2009 through 2010. The NHANES sampled a nationally representative group of adults in the United States and provides information on demographics, medical comorbidities, and dietary habits of survey participants. The Bowel Health Questionnaire provided additional information about bowel symptoms such as urgency, incontinence, constipation, and diarrhea. We identified individuals with fecal urgency and calculated differences in fecal urgency among subgroups using chi-squared analysis. We used logistic regression to identify factors associated with urgency. RESULTS: In our study population, the prevalence of fecal urgency was 3.3%; 29.5% of individuals with fecal urgency had diarrhea. The prevalence of fecal urgency was significantly higher in individuals who had diarrhea (14.8%) than in individuals without diarrhea (3.1%). Older age, female sex, poverty, urinary urge incontinence, diarrhea, and increased stool frequency were all associated with fecal urgency on multivariable analysis. Decreased fiber intake and increased carbohydrate intake were associated with urgency among individuals with diarrhea. CONCLUSIONS: In an analysis of data from 4676 individuals who completed a Bowel Health Questionnaire from the NHANES, we found a significantly higher proportion of individuals with diarrhea to have fecal urgency. However, most individuals with fecal urgency do not have diarrhea. Factors associated with fecal urgency vary among individuals with and without diarrhea.

Factors Associated With Response to Placebo in Patients With Irritable Bowel Syndrome and Constipation.

BACKGROUND & AIMS: A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trial of patients with IBS. METHODS: We performed a retrospective analysis of 599 women with IBS with constipation who were in the placebo group of a 12-week, randomized, double-blind, phase 3 trial of the experimental medication renzapride. Primary analyses evaluated frequency of abdominal pain in patients who received placebo, defined as ≥30% pain improvement from baseline for ≥6 of the 12 study weeks. We performed backward elimination regression with bootstrapping to identify factors associated with response to placebo. RESULTS: In the placebo group, 29.0% of the patients had an abdominal pain response. Factors associated with a response to placebo were baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week 3 (OR, 3.69). Factors associated with lack of response to placebo were number of baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final baseline pain ratings (OR, 0.73; P < .001). CONCLUSIONS: We identified factors associated with a response in abdominal pain to placebo using original data from an IBS clinical trial. Baseline factors associated with the placebo response in women with IBS and constipation included variation in baseline pain symptoms, severity of baseline symptoms, and early improvement of abdominal pain. These findings have significant implications for clinical trial design.

Demographic and Dietary Associations of Chronic Diarrhea in a Representative Sample of Adults in the United States.

OBJECTIVES: No studies to date estimate the prevalence of chronic diarrhea in the United States using the Bristol stool form scale (BSFS). This study aims to report the prevalence and associated factors of chronic diarrhea using BSFS scores in a nationally representative sample of US adults. METHODS: We identified 5,246 adult participants (age ≥20 years) who completed the bowel health questionnaire in the National Health and Nutrition Examination Survey 2009-2010 data set. Chronic diarrhea was defined as type 6 or 7 rating on the BSFS (mushy or liquid consistency) as the "usual or the most common stool type." Co-variables included age, race, education, poverty income ratio, body mass index, number of medications, feeling depressed, physical activity, and dietary intake. Prevalence estimates and prevalence odds ratios (PORs) were analyzed in adjusted multivariable models using appropriate sampling weights. RESULTS: We found a prevalence of chronic diarrhea of 6.6% (95% confidence interval (CI) 5.8, 7.4) in the nationally representative data set. High daily carbohydrate intake (POR 1.56, 95% CI 1.02, 2.40), obesity (POR 2.04, 95% CI 1.44, 2.89), feeling depressed (POR 1.84, 95% CI 1.21, 2.80), older age (POR 1.02, 95% CI 1.01, 1.02), and female sex (POR 1.68, 95% CI 1.28, 2.21) were positively correlated with chronic diarrhea. Non-Hispanic White race (POR 0.49, 95% CI 0.29, 0.81) and higher education (POR 0.60, 95% CI 0.43, 0.83) were negatively correlated with chronic diarrhea. CONCLUSIONS: In a nationally representative sample of the US adults, the prevalence of chronic diarrhea was 6.6%. We identified demographic, lifestyle, and dietary factors associated with chronic diarrhea.

Sleep Disturbances Are Commonly Reported Among Patients Presenting to a Gastroenterology Clinic.

BACKGROUND: Poor sleep quality is common among patients with gastrointestinal (GI) disorders. However, few studies have assessed the presence of insomnia or reported circadian preferences and none have directly compared sleep between common GI conditions. AIMS: To compare clinical sleep characteristics in patients presenting to a tertiary care GI clinic for irritable bowel syndrome (IBS), functional dyspepsia (FD), inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and celiac disease (CD). METHODS: Validated sleep measures were administered to consecutive patients if they were diagnosed with IBS, IBD in clinical remission, CD, FD, or GERD. Healthy Controls (HCs) with no reported GI diagnoses or symptoms were also recruited. RESULTS: A total of 212 eligible respondents completed this survey, 161 GI clinic patients (IBS (n = 48), GERD (n = 29), IBD in clinical remission (n = 44), CD (n = 40)), and 41 HCs. Only, 10 respondents had a diagnosis of FD, and these were excluded. The IBS group had the highest frequency of poor sleep (72%) followed by CD (61%), GERD (60%), IBD (54%), and HC (39%). IBS patients also had the highest frequency of clinical insomnia (51%), followed by GERD (37%), CD (35%), IBD (27%), and HC (18%). 40% of IBS patients reported taking sleep medications at least once per week, compared to 32% of GERD, 23% IBD, 13% CD, and 15% HC. CONCLUSIONS: Patients presenting to a tertiary care GI clinic report poorer sleep than healthy controls. In general, patients with IBS report the highest rates of sleep difficulties compared to patients with other diagnoses.

Intensity-dependent timing and precision of startle response latency in larval zebrafish.

KEY POINTS: Using high-speed videos time-locked with whole-animal electrical recordings, simultaneous measurement of behavioural kinematics and field potential parameters of C-start startle responses allowed for discrimination between short-latency and long-latency C-starts (SLCs vs. LLCs) in larval zebrafish. Apart from their latencies, SLC kinematics and SLC field potential parameters were intensity independent. Increasing stimulus intensity increased the probability of evoking an SLC and decreased mean SLC latencies while increasing their precision; subtraction of field potential latencies from SLC latencies revealed a fixed time delay between the two measurements that was intensity independent. The latency and the precision in the latency of the SLC field potentials were linearly correlated to the latencies and precision of the first evoked action potentials (spikes) in hair-cell afferent neurons of the lateral line. Together, these findings indicate that first spike latency (FSL) is a fast encoding mechanism that can serve to precisely initiate startle responses when speed is critical for survival. ABSTRACT: Vertebrates rely on fast sensory encoding for rapid and precise initiation of startle responses. In afferent sensory neurons, trains of action potentials (spikes) encode stimulus intensity within the onset time of the first evoked spike (first spike latency; FSL) and the number of evoked spikes. For speed of initiation of startle responses, FSL would be the more advantageous mechanism to encode the intensity of a threat. However, the intensity dependence of FSL and spike number and whether either determines the precision of startle response initiation is not known. Here, we examined short-latency startle responses (SLCs) in larval zebrafish and tested the hypothesis that first spike latencies and their precision (jitter) determine the onset time and precision of SLCs. We evoked startle responses via activation of Channelrhodopsin (ChR2) expressed in ear and lateral line hair cells and acquired high-speed videos of head-fixed larvae while simultaneously recording underlying field potentials. This method allowed for discrimination between primary SLCs and less frequent, long-latency startle responses (LLCs). Quantification of SLC kinematics and field potential parameters revealed that, apart from their latencies, they were intensity independent. We found that increasing stimulus intensity decreased SLC latencies while increasing their precision, which was significantly correlated with corresponding changes in field potential latencies and their precision. Single afferent neuron recordings from the lateral line revealed a similar intensity-dependent decrease in first spike latencies and their jitter, which could account for the intensity-dependent changes in timing and precision of startle response latencies.

Fecal Impaction in the Emergency Department: An Analysis of Frequency and Associated Charges in 2011.

GOALS: The aim of this study was to analyze the incidence and associated charges of fecal impaction for trends in hospital and patient demographics in emergency departments (ED) across the United States. BACKGROUND: In 2010, an ICD-9-CM code (560.32) for fecal impaction was introduced, allowing for assessment of fecal impaction incidence. STUDY: Data were obtained from the National Emergency Department Sample records in which fecal impaction (ICD-9-CM code 560.32) was first listed as a diagnosis in 2011. RESULTS: In 2011, there were 42,481 [95% confidence interval (CI), 39,908-45,054] fecal impaction ED visits, with an overall rate of 32 fecal impaction visits per 100,000 ED visits. Adjusted for inflation in 2014 dollars, the associated mean charge of a fecal impaction ED visit was $3060.47 (95% CI, $2943.02-$3177.92), with an aggregate national charge in the US of $130,010,772 (95% CI, $120,688,659-$139,332,885). All charges were adjusted for inflation and reported in 2014 dollars. Late elders (85+ y) had the highest rate of fecal impaction ED visits, followed by early elders (65 to 84 y). Medicare was the primary payer for the greatest number of fecal impaction ED visits accounting for nearly two thirds of visit payments. CONCLUSION: This study reports previously unexplored statistics on the number, frequency, and associated charges of ED visits with a primary diagnosis of fecal impaction, a condition found most commonly among elders.

Emergency department burden of constipation in the United States from 2006 to 2011.

OBJECTIVES: Although constipation is typically managed in an outpatient setting, there is an increasing trend in the frequency of constipation-related hospital visits. The aim of this study was to analyze trends related to chronic constipation (CC) in the United States with respect to emergency department (ED) visits, patient and hospital characteristics, and associated costs. METHODS: Data from 2006 to 2011, in which constipation (The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes 564.00-564.09) was the primary discharge diagnosis, were obtained from the National Emergency Department Sample (NEDS). RESULTS: Between 2006 and 2011, the frequency of constipation-related ED visits increased by 41.5%, from 497,034 visits to 703,391 visits, whereas the mean cost per patient rose by 56.4%, from $1,474 in 2006 to $2,306 in 2011. The aggregate national cost of constipation-related ED visits increased by 121.4%, from $732,886,977 in 2006 to $1,622,624,341 in 2011. All cost data were adjusted for inflation and reported in 2014 dollars. Infants (<1 year old) had the highest rate of constipation-related ED visits in both 2006 and 2011. The late elders (85+ years) had the second highest constipation-related ED visit rate in 2006; however, the 1- to 17-year-old age group experienced a 50.7% increase in constipation-related ED visit rate from 2006 to 2011 and had the second highest constipation-related ED visit rate in 2011. CONCLUSIONS: The frequency of and the associated costs of ED visits for constipation are significant and have increased notably from 2006 to 2011.

Changes in physical activity around the time of major adverse cardiac events in patients with implantable cardioverter-defibrillators.

BACKGROUND: With modern implantable cardioverter-defibrillators (ICDs), biometric measures including physical activity have become readily available to physicians. However, despite the increased availability, applications of these data to the clinical setting remain poorly studied. We sought to investigate whether changes in physical activity occur preceding and following cardiac events in patients with ICDs. METHODS: We reviewed the electronic medical records of patients with ICDs implanted for any indication in 2018 and 2019 in the University of Pennsylvania health system. Patients with ICDs that reported physical activity were included in the study only if they experienced major adverse cardiac event(s) (MACE) that were preceded by at least 6 months without MACE after device implantation. RESULTS: Seventy-four of the 827 charts reviewed met inclusion criteria. Baseline activity levels from 6 to 2 months prior to MACE were 2.18-2.21 h/day. In the month prior to MACE, average activity decreased significantly to 2.09 h/day, and subsequently decreased again during the calendar month in which MACE occurred to 1.96 h/day. The lowest average monthly activity levels occurred in the month after MACE, with incremental but non-significant recovery occurring over the subsequent 2 months. CONCLUSIONS: In a cohort of ICD recipients, a significant decrease in physical activity was observed in the month preceding MACE. To our knowledge, this is the first study that observes time-dependent changes in activity in relation to MACE in a generalizable cohort of ICD recipients. ICD activity monitoring in patients at high risk for MACE may enhance patient care.

Clinical Characteristics and Outcomes of COVID-19 Acute Respiratory Distress Syndrome (ARDS) Survivors in Early Pandemic: A Single Healthcare System Retrospective Study.

INTRODUCTION:  Acute respiratory distress syndrome (ARDS) management in the intensive care unit (ICU) has attracted strong interest since the start of the COVID-19 pandemic. Our retrospective study aims to describe the outcomes and predictors of mortality of ARDS associated with COVID-19 within one university-based healthcare system. METHODS:  We identified 165 patients within our healthcare system during the months of April 2020 through July 2020, who were admitted to our medical ICUs and eligible for our study. Baseline patient characteristics, ICU and hospital course information, ICU interventions, ventilator settings, and hospital complications were collected and analyzed using descriptive statistical techniques. RESULTS:  Our cohort had an average age of 64. No significant difference in mortality was identified with male vs. female gender or BMI. Most of the patient cohort was identified as black (68.2%). The overall mortality of our cohort was 38.2%. Hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease were all associated with higher mortality. There was a significant difference in mortality between those with higher observed ventilator plateau pressures at 24 hours and higher driving pressures at 24 hours. CONCLUSION:  COVID-19-associated ARDS is associated with significant mortality. Physicians should be aware of pre-existing conditions potentially related to worse outcomes so that they receive an appropriate level of care in a timely manner. Ventilator management should focus on maintaining low intra-thoracic pressure changes. Prospective studies are needed to guide COVID-19-associated ARDS management.

Randomized Clinical Trial: Crofelemer Treatment in Women With Diarrhea-Predominant Irritable Bowel Syndrome.

INTRODUCTION: Crofelemer, the active compound purified from latex of Croton lechleri, has been shown to improve HIV and traveler's diarrhea and improve pain in women with irritable bowel syndrome-diarrhea (IBS-D). This trial evaluated the effect of crofelemer on abdominal pain in women with IBS-D. METHODS: Women with IBS-D were randomized to crofelemer (125 mg) or placebo twice daily for 12 weeks. The primary efficacy endpoint was overall change in percentage of abdominal pain/discomfort-free days. Post hoc analysis for Food and Drug Administration (FDA) monthly responders was performed for stool consistency, abdominal pain, and combined stool consistency and abdominal pain. RESULTS: A total of 240 women were enrolled. There was no significant difference in overall percentage of pain/discomfort-free day between the groups. In post hoc analysis, FDA abdominal pain monthly responders were significantly more likely during months 1 through 2 (58.3% vs 45.0%, P = 0.030) as well as during the entire 3 months (54.2% vs 42.5%, P = 0.037) in the crofelemer group when compared with placebo. However, there was no significant difference in the percentage of FDA stool consistency monthly responders or combined stool consistency and pain monthly responders between the groups. Crofelemer had a safety profile similar to placebo. DISCUSSION: Crofelemer did not significantly improve abdominal pain over placebo by the primary endpoint. However, it did based on the FDA abdominal pain monthly responder endpoint. This suggests that crofelemer may have a role in the treatment of abdominal pain associated with IBS-D. Further studies are warranted to evaluate the potential of crofelemer as a visceral analgesic.

Emergency department visits for depression in the United States from 2006 to 2014.

BACKGROUND: Patients with depression frequently seek care in the emergency department (ED), especially in the context of suicidal ideation (SI) and self-harm (SH). However, the prevalence and trends in the United States (US) of ED visits for depression have not yet been characterized using a nationally representative sample. This study evaluates ED trends for depression in the US from 2006 to 2014. METHODS: Data was obtained from the Nationwide Emergency Department Sample (NEDS) in 2006 and 2014 using a primary ICD-9 diagnosis of depression or a primary diagnosis of suicidal ideation (SI) and a secondary diagnosis of depression. RESULTS: Between 2006 and 2014, there was a 25.9% increase in visits to the ED for depression, which was higher than the 14.8% increase in total ED visits during this time period. The mean inflation adjusted charges associated with depression-related ED visits increased by 107.7%, which was higher than the increase in mean charges for all ED visits in the same time period (40.47%). Visit rates were bimodally distributed with respect to age, with peaks in adolescence and middle age. Notably there was a 61.3% increase in ED visits for depression in individuals younger than 20 between 2006 and 2014. Over half of patients were admitted for inpatient care with a mean length of stay of 5.6 days in both years. Inpatient charges increased 71.8% between 2006 and 2014. CONCLUSIONS: ED visits for depression in the United States rose 25.9% between 2006 and 2014, which was higher than the 14.8% increase in total ED visits during this time period. Over half of ED depression visits were admitted to inpatient stay (mean 5.6 days both years).

Clinical and manometric characteristics of women with paradoxical puborectalis syndrome.

BACKGROUND: A subset of patients with functional defecation disorders have predominance of the puborectalis muscle (PRM) on three-dimensional high definition anorectal manometry (HDARM), known as paradoxical puborectalis syndrome (PPS). The aim of this study was to assess clinical and manometric differences between patients with and without PPS. METHODS: A total of 227 women with functional defecation disorders undergoing HDARM between December 2012 and October 2016 at a single center were included in this study. All completed the Rome III constipation module and Pelvic Floor Distress Inventory 20 (PFDI-20). RESULTS: Eighty-seven out of 227 women had a 3D pressure topographic profile consistent with PPS. They had higher mean PDFI-20 scores for straining and incomplete evacuation symptoms than those without PPS. In addition, they demonstrated higher mean resting anal pressure, a more negative mean anorectal pressure differential, and a greater proportion with prolonged balloon expulsion test. These findings were more pronounced in a subgroup of 58 PPS patients with a distinct pattern of both posterior and posterolateral wall indentation. CONCLUSION: Among female patients with functional defecation disorders, those with PPS demonstrated clinical and manometric differences compared to those without PPS. These differences may be driven by predominant posterolateral wall indentation in a subgroup of PPS patients.

Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity.

Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment.