Research & Scholarship
Opioid Prescribing Patterns Following Pediatric Tonsillectomy in the United States, 2009-2017.
OBJECTIVES: Assess national trends in opioid prescription following pediatric tonsillectomy: 1) overall percentage receiving opioids and mean quantity, 2) changes during 2009-2017, and 3) determinants of prescription patterns.METHODS: Cross-sectional analysis using 2009-2017 Optum claims data to identify opioid-naive children aged 1-18 with claims codes for tonsillectomy (n = 82,842). Quantities of opioids filled in outpatient pharmacies during the perioperative period were extracted and converted into milligram morphine equivalents (MMEs) for statistical comparison. Demographic, clinical, and socioeconomic predictors of opioid fill rate and quantity were determined using regression analyses.RESULTS: In 2009, 83.3% of children received opioids, decreasing to 58.3% by 2017. Rates of all-cause readmissions and post-tonsillectomy hemorrhages were similar over time. Mean quantity received was 153.47MME (95% confidence intervals [95%CI]: 151.19, 155.76) and did not significantly change during 2009-2017. Opioids were more likely in older children and those with higher household income, but less likely in children with obstructive sleep apnea, other comorbidities, and Hispanic race. Higher quantities of opioids were more likely in older children, while lower quantities were associated with female sex, Hispanic race, and higher household income. Outpatient steroids were prescribed to 8.04% of patients, who were less likely to receive opioids.CONCLUSION: While the percentage of children receiving post-tonsillectomy opioids decreased during 2009-2017, prescribed quantities remain high and have not decreased over time. Prescription practices were also influenced by clinical and sociodemographic factors. These results highlight the need for guidance, particularly with regard to opioid quantity, in children after tonsillectomy.LEVEL OF EVIDENCE: N/A Laryngoscope, 2020.
View details for DOI 10.1002/lary.29159
View details for PubMedID 33026683
Effects of Pregnancy on Otosclerosis.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
The effect of pregnancy on otosclerosis is controversial. If pregnancy physiologically increases the risk of progression, females with children would be expected to receive stapedectomy earlier than childless females and males. Here, we seek to determine whether sex moderates the relationship between number of children and age at stapedectomy.Retrospective observational study of national health care claims.2003 to 2016 Optum Clinformatics Data Mart.In total, 6025 privately insured US adults (3553 females, 2472 males) who received stapedectomy for otosclerosis were queried for age and number of children at the time of initial surgery.The average age at stapedectomy was significantly lower in females than males (46.8 vs 48.1 years; t test, P < .0001). Females with children had a significantly lower age at surgery compared to childless females (39.3 vs 49.9 years; t test, P < .0001). Males with children similarly had a significantly lower age at surgery compared to childless males (40.5 vs 51.3 years; t test, P < .0001). A higher number of children was correlated with lower age for both females (Pearson, r = -0.3817, P < .0001) and males (Pearson, r = -0. 3675, P < .0001). Linear regression showed that younger age of surgery could be predicted by female sex and number of children (F(3, 6021) = 336.93, P < .001, R2 = 0.1437) with no significant interaction between sex and number of children (P = .186).Sex does not moderate the effect of increasing number of children on decreasing age at stapedectomy. Social, rather than biological, factors surrounding parenthood such as increased overall health care utilization may explain prior associations between pregnancy and otosclerosis.
View details for DOI 10.1177/0194599820907093
View details for PubMedID 32093549
Impact of lymph node sampling on survival in cN0 major salivary gland adenoid cystic carcinoma.
Head & neck
BACKGROUND: The role of elective neck dissection in the management of major salivary gland adenoid cystic carcinoma is unclear.METHODS: Data were retrospectively extracted from the National Cancer Center Database. The study cohort included 1504 patients with adenoid cystic carcinoma of major salivary glands with clinical N0 necks who were treated with surgery between 2004 and 2014. The cohort was divided into four groups based on number of lymph nodes (LNs) examined on pathology: 0, 1-8, 9-17, and ≥18 LNs.RESULTS: The rate of occult nodal metastasis was 9.0%. Number of LNs removed was not associated with survival (Reference, 0 LNs; HR= 0.98, 95% CI 0.73-1.32 for 1-8 LNs; HR= 1.22, 95% CI 0.80-1.88 for 9-17 LNs; HR= 0.94, 95% CI 0.61-1.46 for ≥18 LNs) after adjusting for important covariates.CONCLUSIONS: LN sampling is not associated with survival in cN0 major salivary gland ACC.
View details for PubMedID 30620437
Pediatric Thyroid Cancer Incidence and Mortality Trends in the United States, 1973-2013.
JAMA otolaryngology-- head & neck surgery
The incidence of thyroid cancer is increasing by 3% annually. This increase is often thought to be attributable to overdiagnosis in adults. A previous study reported a 1.1% annual increase in the incidence of pediatric thyroid cancer. However, the analysis was limited to the period from 1973 to 2004 and was performed in a linear fashion, which does not account for changes in incidence trends over time.To analyze trends in pediatric thyroid cancer incidence based on demographic and tumor characteristics at diagnosis.This cross-sectional study included individuals younger than 20 years who had a diagnosis of thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) 9 database from 1973 to 2013. Cases of thyroid cancer were identified using the International Classification of Diseases for Oncology, Third Edition and were categorized by histologic type, stage, and tumor size.Annual percent change (APC) in the incidence rates was calculated using joinpoint regression analysis.Among 1806 patients included in the analysis, 1454 (80.5%) were female and 1503 (83.2%) were white; most patients were aged 15 to 19 years. The overall incidence rates of thyroid cancer increased annually from 0.48 per 100 000 person-years in 1973 to 1.14 per 100 000 person-years in 2013. Incidence rates gradually increased from 1973 to 2006 (APC, 1.11%; 95% CI, 0.56%-1.67%) and then markedly increased from 2006 to 2013 (APC, 9.56%; 95% CI, 5.09%-14.22%). The incidence rates of large tumors (>20 mm) gradually increased from 1983 to 2006 (APC, 2.23%; 95% CI, 0.93%-3.54%) and then markedly increased from 2006 to 2013 (APC, 8.84%; 95% CI, 3.20%-14.79%); these rates were not significantly different from incidence rates of small (1-20 mm) tumors. The incidence rates of regionally extended thyroid cancer gradually increased from 1973 to 2006 (APC, 1.44%; 95% CI, 0.68%-2.21%) and then markedly increased from 2006 to 2013 (APC, 11.16%; 95% CI, 5.26%-17.40%); these rates were not significantly different from the incidence rates of localized disease.The incidence rates of pediatric thyroid cancer increased more rapidly from 2006 to 2013 than from 1973 to 2006. The findings suggest that there may be a co-occurring increase in thyroid cancer in the pediatric population in addition to enhanced detection.
View details for DOI 10.1001/jamaoto.2019.0898
View details for PubMedID 31120475
Increases in the Rate of Age-Related Hearing Loss in the Older Old
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
2017; 143 (1): 41-45
There is a critical disparity in knowledge regarding the rate and nature of hearing loss in the older old (80 years and older).To determine if the rate of age-related hearing loss is constant in the older old.We performed a retrospective review that began on August 1, 2014, with audiometric evaluations at an academic medical center of 647 patients aged between 80 and 106 years, of whom 141 had multiple audiograms.From a population perspective, the degree of hearing loss was compared across the following age brackets: 80 to 84 years, 85 to 89 years, 90 to 94 years, and 95 years and older. From an individual perspective, the rate of hearing decrease between 2 audiograms was compared with age.Changes in hearing among age brackets were higher during the 10th decade of life than the 9th decade at all frequencies (5.4-11.9 dB hearing level [dB HL]) for the 647 patients (mean [SD] age, 90 [5.5] years). Correspondingly, the annual rate of low-frequency hearing loss was faster during the 10th decade by the 3.8 dB HL per year at 0.25 kHz, 3.8 dB HL per year at 0.5 kHz, and 3.2 dB HL per year at 1 kHz. Despite the universal presence of hearing loss in our sample, 382 patients (59%) used hearing aids.There is a significant increase in the rate of hearing loss in patients during the 10th decade of life compared with the 9th decade that represents a fundamental change in the mechanistic process of presbycusis. Despite the potential benefit of hearing aids, they remain underused in the older old. Use may be improved by changing the method of hearing rehabilitation counseling from a patient-initiated model to a chronic disease example.
View details for DOI 10.1001/jamaoto.2016.2661
View details for Web of Science ID 000394441000007
View details for PubMedID 27632707
Hearing Aid Use is Associated with Better Mini-Mental State Exam Performance.
American journal of geriatric psychiatry
2016; 24 (9): 694-702
Hearing loss is associated with cognitive decline in the elderly. However, it is unknown if the use of hearing aids (HAs) is associated with enhanced cognitive function.In a cross-sectional study at an academic medical center, participants underwent audiometric evaluation, the Mini-Mental State Exam (MMSE), and the Trail Making Test, Part B (TMT-B). The impact of use versus disuse of HAs was assessed. Performance on cognitive tests was then compared with unaided hearing levels.HA users performed better on the MMSE (1.9 points; rank-sum, p = 0.008) despite having worse hearing at both high frequencies (15.3-dB hearing level; t test, p < 0.001) and low frequencies (15.7-dB hearing level; t test p < 0.001). HA use had no effect TMT-B performance. Better performance on the MMSE was correlated with both low frequency (ρ = -0.28, p = 0.021) and high frequency (ρ = -0.21, p = 0.038) hearing level, but there was no correlation between performance on the TMT-B and hearing at any frequency.Despite having poorer hearing, HA users performed better on the MMSE. Better performance on cognitive tests with auditory stimuli (MMSE) but not visual stimuli (TMT-B) suggests that hearing loss is associated with sensory-specific cognitive decline rather than global cognitive impairment. Because hearing loss is nearly universal in those older than 80 years, HAs should be strongly recommended to minimize cognitive impairment in the elderly.
View details for DOI 10.1016/j.jagp.2016.03.005
View details for PubMedID 27394684
Management of benign middle ear tumors: A series of 7 cases.
Ear, nose, & throat journal
; 96 (10-11): 426–32
Benign middle ear tumors represent a rare group of neoplasms that vary widely in their pathology, anatomy, and clinical findings. These factors have made it difficult to establish guidelines for the resection of such tumors. Here we present 7 unique cases of these rare and diverse tumors and draw from our experience to recommend optimal surgical management. Based on our experience, a postauricular incision is necessary in nearly all cases. Mastoidectomy is required for tumors that extend into the mastoid cavity. Whenever exposure or hemostasis is believed to be inadequate with simple mastoidectomy, canal-wall-down mastoidectomy should be performed. Finally, disarticulation of the ossicular chain greatly facilitates tumor excision and should be performed early in the procedure.
View details for PubMedID 29121375
Cerebral volume and diffusion MRI changes in children with sensorineural hearing loss.
2020; 27: 102328
Sensorineural hearing loss (SNHL) is the most prevalent congenital sensory deficit in children. Information regarding underlying brain microstructure could offer insight into neural development in deaf children and potentially guide therapies that optimize language development. We sought to quantitatively evaluate MRI-based cerebral volume and gray matter microstructure children with SNHL.We conducted a retrospective study of children with SNHL who obtained brain MRI at 3 T. The study cohort comprised 63 children with congenital SNHL without known focal brain lesion or structural abnormality (33 males; mean age 5.3 years; age range 1 to 11.8 years) and 64 age-matched controls without neurological, developmental, or MRI-based brain macrostructure abnormality. An atlas-based analysis was used to extract quantitative volume and median diffusivity (ADC) in the following brain regions: cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. SNHL patients were further stratified by severity scores and hearing loss etiology.Children with SNHL showed higher median ADC of the cortex (p = .019), thalamus (p < .001), caudate (p = .005), and brainstem (p = .003) and smaller brainstem volumes (p = .007) compared to controls. Patients with profound bilateral SNHL did not show any significant differences compared to patients with milder bilateral SNHL, but both cohorts independently had smaller brainstem volumes compared to controls. Children with unilateral SNHL showed greater amygdala volumes compared to controls (p = .021), but no differences were found comparing unilateral SNHL to bilateral SNHL. Based on etiology for SNHL, patients with Pendrin mutations showed higher ADC values in the brainstem (p = .029, respectively); patients with Connexin 26 showed higher ADC values in both the thalamus (p < .001) and brainstem (p < .001) compared to controls.SNHL patients showed significant differences in diffusion and volume in brain subregions, with region-specific findings for patients with Connexin 26 and Pendrin mutations. Future longitudinal studies could examine macro- and microstructure changes in children with SNHL over development and potential predictive role for MRI after interventions including cochlear implant outcome.
View details for DOI 10.1016/j.nicl.2020.102328
View details for PubMedID 32622314
COVID-19 and the otolaryngologist - preliminary evidence-based review.
The SARS-CoV-2 virus which causes coronavirus disease 2019 (COVID-19) has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID-19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/lary.28672
View details for PubMedID 32219846
- Harms of Pediatric Thyroid Cancer Overdiagnosis-Reply. JAMA otolaryngology-- head & neck surgery 2019
- Impact of lymph node sampling on survival in cN0 major salivary gland adenoid cystic carcinoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 2019; 41 (6): 1903–7
An association between marijuana use and tinnitus.
American journal of otolaryngology
While some advocates have argued for marijuana as a treatment for tinnitus, the relationship between marijuana use and tinnitus is unknown. The objective of this study was to evaluate associations between marijuana use and the prevalence, severity, and rate of occurrence of tinnitus.Cross-sectional analysis of nationally representative data.National Health and Nutrition Examination Survey 2011-2012.Statistical analysis was performed on data collected from 2705 non-institutionalized adults aged 20-69 who underwent audiometric testing and were administered questionnaires about hearing, drug use, current health status, and medical history.The use of marijuana at least once per month for the previous 12 months was significantly associated with experiencing tinnitus during that 12-month month (X2(1) = 19.41, p < 0.001). Subjects who used marijuana were more likely to experience tinnitus after accounting for covariables including age, gender, audiometric hearing loss, noise exposure history, depression, anxiety, smoking, salicylate use, cardiovascular disease, hypertension, and diabetes (OR = 1.75, 95% CI 1.02-3.01, p = 0.043). There were no associations between the severity or frequency of tinnitus occurrence and the quantity or frequency of marijuana use. Use of other substances such as alcohol, cocaine, methamphetamine, and heroin was not associated with tinnitus.Regular marijuana use is associated with prevalent tinnitus. However, no dose response between marijuana use and tinnitus was observed. The relationship between marijuana use and tinnitus is complex and is likely modulated by psychosocial factors.
View details for DOI 10.1016/j.amjoto.2019.102314
View details for PubMedID 31732310
A Prospective Evaluation of Postoperative Opioid Use in Otologic Surgery.
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
To prospectively evaluate opioid consumption following adult outpatient otologic surgery.Prospective observational.Single-tertiary referral center.Patients scheduled for otologic surgery who did not have a history of chronic opioid use were recruited between February 2018 and February 2019.Opioid consumption was queried using telephone or in-person surveys administered between postoperative days 5 and 15. Patient demographics, surgical details, and opioid prescription patterns were abstracted from medical records. Opioid distribution was determined by querying records maintained by the California Department of Justice through a state-wide prescription drug monitoring program mandated since 2016.Seventy patients were prescribed an average of 68.9 ± 31.8 mg of morphine equivalents (MME) and consumed 47.3 ± 42.9 MME over 2.4 ± 2.3 days postoperatively. Patients who received a postauricular incision were prescribed significantly more than those who underwent transcanal procedures (86.2 vs 55.9 MME; t test, p < 0.001), consumed significantly more (72.2 vs 28.6 MME; t test, p < 0.001), and for a significantly longer duration (3.4 vs 1.6 days; t test, p = 0.001). In the postauricular group, there was no significant difference in consumption between mastoidectomy and nonmastoidectomy subgroups (64.9 vs 89.2 MME; t test, p = 0.151). Eighty percent of transcanal patients consumed 50 MME (10 pills) or less, while 80% of postauricular patients consumed 80 MME (16 pills) or less.Patients in our cohort consumed approximately 3/4 of the prescribed opioids. Those with postauricular incisions used significantly more than those with transcanal incisions. Postoperative opioid prescription recommendations should be tailored according to the extent of surgery.
View details for DOI 10.1097/MAO.0000000000002364
View details for PubMedID 31469798
Association of Cardiovascular Comorbidities With Hearing Loss in the Older Old.
JAMA otolaryngology-- head & neck surgery
In the United States, the population of individuals older than 80 years is expected to double in the next 40 years. Cardiovascular comorbidities are prevalent in this older old population, and their relationship with hearing loss has not been well characterized.To investigate the association of cardiovascular disease (CVD)-related risk factors with auditory function among the older old (>80 years).Audiological data and medical records from 2001 through 2014 of 433 patients aged 80 to 106 years at an academic medical center were analyzed in 2017.The degree of low- and high-frequency hearing loss of participants with coronary artery disease, diabetes, hypertension, history of cerebrovascular accident, and smoking status was compared with that of disease-free individuals. Rate of hearing loss was also determined.Among the 433 patients (67% female; mean [SD] age, 89 [5.8] years), the presence of at least 1 cardiovascular morbidity was associated with elevated mean (SD) low-frequency pure-tone average (LFPTA) of 42.4 (1.6) vs 36.9 (3.5) decibels hearing loss (dB HL), a difference of 5.47 (95% CI, 4.15-9.49) dB HL. Among the 96 patients with 2 audiograms performed at age 80 years or older from which the rate of hearing loss could be calculated, 32 patients had CVD or related risk factors and 64 were healthy controls. Those with at least 1 disease had accelerated hearing loss. Patients with cardiovascular morbidity experienced a faster mean (SD) decline in LFPTA of 1.90 (0.27) vs 1.18 (0.42) dB HL/y, a difference of 0.72 (95% CI, 0.08-1.36) dB HL/y. Of the conditions studied, coronary artery disease had the highest association with audiometric thresholds and was associated with hearing loss at all frequencies tested and with poor word recognition score. Hearing loss was more strongly associated with CVD risk factors in men than in women.In this study of the older old, cardiovascular risk factors and disease were associated with worse hearing and a greater rate of hearing deterioration. Hearing loss in women was less associated with the presence of CVD, possibly owing to the cardioprotective effects of estrogen. The association of hearing with CVD severity and management remains to be determined.
View details for PubMedID 29902313
A novel method of quantifying brain atrophy associated with age-related hearing loss.
2017; 16: 205–9
A growing body of evidence has shown that a relationship between age-related hearing loss and structural brain changes exists. However, a method to measure brain atrophy associated with hearing loss from a single MRI study (i.e. without an interval study) that produces an independently interpretable output does not. Such a method would be beneficial for studying patterns of structural brain changes on a large scale. Here, we introduce our method for this. Audiometric evaluations and mini-mental state exams were obtained in 34 subjects over the age of 80 who have had brain MRIs in the past 6 years. CSF and parenchymal brain volumes (whole brain and by lobe) were obtained through a novel, fully automated algorithm. Atrophy was calculated by taking the ratio of CSF to parenchyma. High frequency hearing loss was associated with disproportional temporal lobe atrophy relative to whole brain atrophy independent of age (r = 0.471, p = 0.005). Mental state was associated with frontoparietal atrophy but not to temporal lobe atrophy, which is consistent with known results. Our method demonstrates that hearing loss is associated with temporal lobe atrophy and generalized whole brain atrophy. Our algorithm is efficient, fully automated, and able to detect significant associations in a small cohort.
View details for PubMedID 28808617
View details for PubMedCentralID PMC5544491
Prophages mediate defense against phage infection through diverse mechanisms
2016; 10 (12): 2854-2866
The activity of bacteriophages poses a major threat to bacterial survival. Upon infection, a temperate phage can either kill the host cell or be maintained as a prophage. In this state, the bacteria carrying the prophage is at risk of superinfection, where another phage injects its genetic material and competes for host cell resources. To avoid this, many phages have evolved mechanisms that alter the bacteria and make it resistant to phage superinfection. The mechanisms underlying these phentoypic conversions and the fitness consequences for the host are poorly understood, and systematic studies of superinfection exclusion mechanisms are lacking. In this study, we examined a wide range of Pseudomonas aeruginosa phages and found that they mediate superinfection exclusion through a variety of mechanisms, some of which affected the type IV pilus and O-antigen, and others that functioned inside the cell. The strongest resistance mechanism was a surface modification that we showed is cost-free for the bacterial host in a natural soil environment and in a Caenorhabditis. elegans infection model. This study represents the first systematic approach to address how a population of prophages influences phage resistance and bacterial behavior in P. aeruginosa.
View details for DOI 10.1038/ismej.2016.79
View details for Web of Science ID 000394508000008
View details for PubMedID 27258950
View details for PubMedCentralID PMC5148200
Asymmetric Hearing Loss Is Common and Benign in Patients Aged 95 Years and Older
2016; 126 (7): 1630-1632
The objective of our study was to investigate age-specific auditory function in the patient population aged 95 years and older.Retrospective chart review at a tertiary medical center.Medical records of 51 patients older than 95 years (82% female, 18% male) who underwent audiologic testing were reviewed. The following information was collected: age at time of most recent audiogram and prior audiograms; results of pure tone, immittance, and speech audiometry; and findings on radiologic imaging.None of the subjects had hearing in the normal range. For the poorer hearing ear, average low-frequency, high-frequency, and overall pure tone averages (PTA) for the population were 67.9, 82.1, and 74.9 dB hearing level, respectively. Mean word recognition score (WRS) was 57.6% and deteriorated with increasing PTA (P = .0002). Asymmetry, defined by a 10-dB difference at two frequencies, was present in 39.2% of the sample, and WRS asymmetry, defined as a difference of 12% in WRS between ears, was present in 33.0% of the sample. Retrocochlear evaluation did not identify pathology in any of the cases tested. In the poorer hearing ear, average decline in PTA per year was 2.9 dB.In individuals >95 years of age, hearing loss was universal, moderately severe to profound in magnitude, and associated with substantial loss of speech recognition. Hearing loss progresses at a rate greater than for younger cohorts. In this "oldest old" population, asymmetry of loss and WRS was common and is not indicative of retrocochlear pathology.4 Laryngoscope, 126:1630-1632, 2016.
View details for DOI 10.1002/lary.25503
View details for Web of Science ID 000379983800032
View details for PubMedID 27040356
Microperforations Significantly Enhance Diffusion Across Round Window Membrane
OTOLOGY & NEUROTOLOGY
2015; 36 (4): 694-700
Introduction of microperforations in round window membrane (RWM) will allow reliable and predictable intracochlear delivery of pharmaceutical, molecular, or cellular therapeutic agents.Reliable delivery of medications into the inner ear remains a formidable challenge. The RWM is an attractive target for intracochlear delivery. However, simple diffusion across intact RWM is limited by what material can be delivered, size of material to be delivered, difficulty with precise dosing, timing, and precision of delivery over time. Further, absence of reliable methods for measuring diffusion across RWM in vitro is a significant experimental impediment.A novel model for measuring diffusion across guinea pig RWM, with and without microperforation, was developed and tested: cochleae, sparing the RWM, were embedded in 3D-printed acrylic holders using hybrid dental composite and light cured to adapt the round window niche to 3 ml Franz diffusion cells. Perforations were created with 12.5-μm-diameter needles and examined with light microscopy. Diffusion of 1 mM Rhodamine B across RWM in static diffusion cells was measured via fluorescence microscopy.The diffusion cell apparatus provided reliable and replicable measurements of diffusion across RWM. The permeability of Rhodamine B across intact RWM was 5.1 × 10(9-) m/s. Manual application of microperforation with a 12.5-μm-diameter tip produced an elliptical tear removing 0.22 ± 0.07% of the membrane and was associated with a 35× enhancement in diffusion (P < 0.05).Diffusion cells can be applied to the study of RWM permeability in vitro. Microperforation in RWM is an effective means of increasing diffusion across the RWM.
View details for Web of Science ID 000351000600021
View details for PubMedID 25310125