Effects of socioeconomic status on enrollment in clinical trials for cancer: A systematic review.

BACKGROUND: To achieve equitable access to cancer clinical trials (CCTs), patients must overcome structural, clinical, and attitudinal barriers to trial enrollment. The goal of this systematic review was to study the relationship between socioeconomic status (SES), assessed either by direct or proxy measures, and CCT enrollment. METHODS: The review team and medical librarian developed search strategies for each database to identify studies for this systematic review, which was conducted according to PRISMA guidelines. Inclusion criteria were as follows: studies published in relevant scientific journals between January 2000 and July 2022, primary sources, English literature, and studies conducted in the US. Sixteen studies fulfilled the inclusion criteria and were reviewed. The risk of bias assessment was conducted independently by two reviewers using the Newcastle Ottawa scale. RESULTS: The initial search yielded 4070 citations, and 16 studies were included in our review. Four of the studies included used patient reported annual income as a measure of SES, while the remaining 12 studies used patient zip code as a proxy measurement of SES. Consistent with our hypothesis, 13 studies showed a positive association between high SES (patient-reported or proxy measurement) and CCT enrollment. Two studies showed a negative association, and one study showed no relationship. CONCLUSIONS: The existing literature suggests that low SES is associated with lower participation in CCT. The small number of studies identified on this topic highlights the need for additional research on SES and other barriers to CCT participation.

The Clinical Significance of Clinocephaly in Late-Presentation Sagittal Craniosynostosis.

The diagnosis of late-presentation sagittal suture craniosynostosis (SCS) can be challenging, especially in the setting of subtle physical exam findings. The clinical significance of clinocephaly-a retro-coronal concavity along the midvault-in this context remains unknown. The aim of this study is to evaluate the predictive value of clinocephaly in identifying late-presentation SCS.A retrospective chart review of all patients >1 year old presenting to the craniofacial clinic with a concern for SCS was performed. The presence or absence of SCS in the setting of clinocephaly was recorded following diagnostic imaging. Student's t test, Chi Square test, and multivariate logistic regression analysis were performed to determine predictors for SCS.75 patients met inclusion criteria. 32 patients (42.7%, 6% female) were diagnosed with SCS. No difference in age between patients with and without SCS was detected. Stratification of patients by age (1-2, 2-4, and >4 years) revealed a higher rate of SCS in younger patients (P = 0.04). The cephalic index (C.I.) of those with sagittal synostosis was significantly smaller but within the normal range, indicating a more scaphocephalic shape (P = 0.003). Logistic regression analysis revealed that C.I. was a strong predictor for SCS (P = 0.003). Of those with SCS, a mix of complete and partial fusion of the sagittal suture was appreciated.This study found that 42.7% of patients with clinocephaly had SCS. C.I. was the only predictor for SCS and unique suture fusion patterns were identified in those with SCS. This study suggests that clinocephaly should be considered a core component of the exam and work-up for SCS. Future studies aimed at evaluating the positive predictive value of this exam finding and identifying risk factors associated with late-presentation SCS are underway.

Embryonic medial ganglionic eminence cells survive and integrate into the inferior colliculus of adult mice.

Acoustic overexposure can lead to decreased inhibition in auditory centers, including the inferior colliculus (IC), and has been implicated in the development of central auditory pathologies. While systemic drugs that increase GABAergic transmission have been shown to provide symptomatic relief, their side effect profiles impose an upper-limit on the dose and duration of use. A treatment that locally increases inhibition in auditory nuclei could mitigate these side effects. One such approach could be transplantation of inhibitory precursor neurons derived from the medial ganglionic eminence (MGE). The present study investigated whether transplanted MGE cells can survive and integrate into the IC of non-noise exposed and noise exposed mice. MGE cells were harvested on embryonic days 12-14 and injected bilaterally into the IC of adult mice, with or without previous noise exposure. At one-week post transplantation, MGE cells possessed small, elongated soma and bipolar processes, characteristic of migrating cells. By 5 weeks, MGE cells exhibited a more mature morphology, with multiple branching processes and axons with boutons that stain positive for the vesicular GABA transporter (VGAT). The MGE survival rate after 14 weeks post transplantation was 1.7% in non-noise exposed subjects. MGE survival rate was not significantly affected by noise exposure (1.2%). In both groups the vast majority of transplanted MGE cells (>97%) expressed the vesicular GABA transporter. Furthermore, electronmicroscopic analysis indicated that transplanted MGE cells formed synapses with and received synaptic endings from host IC neurons. Acoustic stimulation lead to a significant increase in the percentage of endogenous inhibitory cells that express c-fos but had no effect on the percentage of c-fos expressing transplanted MGE cells. MGE cells were observed in the IC up to 22 weeks post transplantation, the longest time point investigated, suggesting long term survival and integration. These data provide the first evidence that transplantation of MGE cells is viable in the IC and provides a new strategy to explore treatment options for central hearing dysfunction following noise exposure.

Healthcare providers' perceived support from their organization is associated with lower burnout and anxiety amid the COVID-19 pandemic.

BACKGROUND: Professional burnout represents a significant threat to the American healthcare system. Organizational and individual factors may increase healthcare providers' susceptibility or resistance to burnout. We hypothesized that during the COVID-19 pandemic, 1) higher levels of perceived organizational support (POS) are associated with lower risk for burnout and anxiety, and 2) anxiety mediates the association between POS and burnout. METHODS: In this longitudinal prospective study, we surveyed healthcare providers employed full-time at a large, multihospital healthcare system monthly over 6 months (April to November 2020). Participants were randomized using a 1:1 allocation stratified by provider type, gender, and academic hospital status to receive one of two versions of the survey instrument formulated with different ordering of the measures to minimize response bias due to context effects. The exposure of interest was POS measured using the validated 8-item Survey of POS (SPOS) scale. Primary outcomes of interest were anxiety and risk for burnout as measured by the validated 10-item Burnout scale from the Professional Quality (Pro-QOL) instrument and 4-item Emotional Distress-Anxiety short form of the Patient Reported Outcome Measurement Information System (PROMIS) scale, respectively. Linear mixed models evaluated the associations between POS and both burnout and anxiety. A mediation analysis evaluated whether anxiety mediated the POS-burnout association. RESULTS: Of the 538 participants recruited, 402 (75%) were included in the primary analysis. 55% of participants were physicians, 73% 25-44 years of age, 73% female, 83% White, and 44% had ≥1 dependent. Higher POS was significantly associated with a lower risk for burnout (-0.23; 95% CI -0.26, -0.21; p<0.001) and lower degree of anxiety (-0.07; 95% CI -0.09, -0.06; p = 0.010). Anxiety mediated the associated between POS and burnout (direct effect -0.17; 95% CI -0.21, -0.13; p<0.001; total effect -0.23; 95% CI -0.28, -0.19; p<0.001). CONCLUSION: During a health crisis, increasing the organizational support perceived by healthcare employees may reduce the risk for burnout through a reduction in anxiety. Improving the relationship between healthcare organizations and the individuals they employ may reduce detrimental effects of psychological distress among healthcare providers and ultimately improve patient care.

The cost of cure: Examining objective and subjective financial toxicity in head and neck cancer survivors.

BACKGROUND: Little is documented regarding objective financial metrics and their impact on subjective financial toxicity in head and neck cancer (HNC) survivors. METHODS: In a cross-sectional analysis, 71 survivors with available claims data for HNC-specific out-of-pocket expenses (OOPE) completed a survey including patient-reported, subjective financial toxicity outcome tools: the Comprehensive Score for financial Toxicity (COST) and the Financial Distress Questionnaire (FDQ). RESULTS: Worse COST scores were significantly associated with lower earnings at survey administration (coefficient = 3.79; 95% CI 2.63-4.95; p < 0.001); loss of earnings after diagnosis (coefficient = 6.03; 95% CI 0.53-11.52; p = 0.032); and greater annual OOPE as a proportion of earnings [log10(Annual OOPE:Earnings at survey): coefficient = -5.66; 95% CI -10.28 to -1.04; p = 0.017]. Similar results were found with FDQ. CONCLUSION: Financial toxicity is associated with particular socioeconomic characteristics which, if understood, would assist the development of pre-treatment screening tools to detect at-risk individuals and intervene early in the HNC cancer survivorship trajectory.

Understanding financial toxicity in head and neck cancer survivors.

OBJECTIVES: (1) Describe financial toxicity (FT) in head and neck cancer (HNC) survivors and assess its association with personal/health characteristics and health-related quality of life (HRQOL); (2) examine financial coping mechanisms (savings/loans); (3) assess relationship between COmprehensive Score for financial Toxicity (COST) and Financial Distress Questionnaire (FDQ). PATIENTS AND METHODS: Cross-sectional survey from January - April 2018 of insured patients at a tertiary multidisciplinary HNC survivorship clinic who completed primary treatment for squamous cell carcinoma of the oral cavity, oropharynx, or larynx/hypopharynx. RESULTS: Of 104 survivors, 30 (40.5%) demonstrated high FT. Patients with worse FT were more likely (1) not married (COST, 25.33 ±â€¯1.87 vs. 30.61 ±â€¯1.34, p = 0.008); (2) of lower education levels (COST, 26.12 ±â€¯1.47 vs. 34.14 ±â€¯1.47, p < 0.001); and (3) with larynx/hypopharynx primaries (COST, 22.86 ±â€¯2.28 vs. 30.27 ±â€¯1.50 vs. 32.72 ±â€¯1.98, p = 0.005). Younger age (4.23, 95%CI 2.20 to 6.26, p < 0.001), lower earnings at diagnosis (1.17, 95%CI 0.76 to 1.58, p < 0.001), and loss in earnings (-1.80, 95%CI -2.43 to -1.16, p < 0.001) were associated with worse FT. COST was associated with HRQOL (0.08, p = 0.03). Most survivors (63/102, 60%) reported using savings and/or loans. Worse FT was associated with increased likelihood of using more mechanisms (COST, OR1.06, 95%CI 1.02 to 1.10, p = 0.004). Similar results were found with FDQ. CONCLUSIONS: We found differences in FT by primary site, with worst FT in larynx/hypopharynx patients. This finding illuminates potential site-specific factors, e.g. workplace discrimination or inability to return to work, that may contribute to increased risk. FDQ correlates strongly with COST, encouraging further exploration as a clinically-meaningful screening tool.

Medical and bioethical considerations in elective cochlear implant array removal.

OBJECTIVE: Cochlear explantation for purely elective (e.g. psychological and emotional) reasons is not well studied. Herein, we aim to provide data and expert commentary about elective cochlear implant (CI) removal that may help to guide clinical decision-making and formulate guidelines related to CI explantation. DATA SOURCES: We address these objectives via three approaches: case report of a patient who desired elective CI removal; review of literature and expert discussion by surgeon, audiologist, bioethicist, CI user and member of Deaf community. REVIEW METHODS: A systematic review using three scientific online databases was performed. Included articles addressed the benefits and/or complications of cochlear implantation in young children, CI explantation with or without revision surgery and the ethical debate between the medical and Deaf communities on cochlear implantation and explantation. CONCLUSIONS: The medical and audiological perspectives identify a host of risks related to implant removal without reimplantation, including risk from surgery, general anaesthesia, cochlear ossification and poor audiometric outcomes. The member of the deaf community and bioethicist argue that physicians need to guide the principles of beneficence, non-maleficence and patient autonomy. Taken together, patient desires should be seen as paramount, if the patient is otherwise fit for surgery and well informed. IMPLICATIONS FOR PRACTICE: Similar to the case of device implantation, device explantation should be a multidisciplinary and collaborative decision with the patient and the family's desires at the centre. While every case is different, we offer a CI explantation discussion to assist in clinical decision-making, patient counselling and education.

Audiologic, cVEMP, and Radiologic Progression in Superior Canal Dehiscence Syndrome.

OBJECTIVE: To assess the change in hearing, vestibular function, and size of superior canal dehiscence (SCD) in patients with SCD syndrome over time. PATIENTS: Adult patients with SCD in one or both ears with documented sign and symptom progression, as shown by the medical record, audiometry, cervical vestibular-evoked myogenic potentials (cVEMP), and computed tomography (CT). INTERVENTION: Audiometry, cVEMPs, and temporal bone CT were performed on patients with high clinical suspicion of disease progression. MAIN OUTCOME MEASURE: Audiometry (magnitude of the air-bone gap [ABG]), cVEMP (magnitude of the thresholds), and CT scans (size of the superior canal dehiscence) were analyzed. Symptoms were assessed at each clinical visit and before repeat testing. RESULTS: Retrospective review of 250 patients with SCDS showed three patients with disease progression over time with follow-up testing as outlined above. All patients presented initially with mild symptoms, ABGs, low cVEMP thresholds, and small bony defects of the arcuate eminence. Four, 6, and 8 years later, progression of SCD signs and symptoms was observed in these three patients, respectively. Audiometry showed larger ABGs and lower cVEMP thresholds compared with previous testing. CT showed an increase in bony defect size. CONCLUSION: Progression of SCD symptoms can be associated with a wider air-bone gap, lower cVEMP thresholds, and a larger bony defect. Prospective studies using validated measures of hearing loss and dizziness in patients who have not yet undergone surgery for SCD will determine the association between specific symptoms and objective test outcomes and how these change over time.

Benign paroxysmal positional vertigo commonly occurs following repair of superior canal dehiscence.

OBJECTIVES/HYPOTHESIS: Repair of superior canal dehiscence (SCD) often results in the resolution of preoperative auditory and vestibular symptoms; however, many patients experience dizziness in the postoperative period. Postoperative dizziness may be the result of new-onset benign paroxysmal positional vertigo (BPPV). This study aims to investigate the prevalence of BPPV before and following SCD repair. STUDY DESIGN: Retrospective chart review at a tertiary care center. METHODS: Electronic medical records were reviewed for patients with a diagnosis of SCD syndrome (SCDS) between January 2002 and May 2015. Collected information included demographic data, incidence of BPPV diagnosed by Dix-Hallpike maneuver before and following surgery, operative technique, repair material, and the duration of time to BPPV onset. RESULTS: A total of 180 patients with a diagnosis of SCDS were identified: 84 patients underwent surgery (operated subjects) and 96 were observed (nonoperated, control group). In operated subjects, 20 of 84 (23.8%) developed BPPV following SCD repair versus 6.2% of nonoperated (P < 0.005). Benign paroxysmal positional vertigo lateralized to the operated side in all but one subject whose laterality was unknown (P < 0.0001). There were no associations of BPPV with surgical approach (P = 0.50) or repair material (P = 0.33). The majority of subjects (58%) were diagnosed with BPPV within 3 months of surgery. CONCLUSION: New-onset BPPV occurs commonly after SCD repair and may be the result of mobilized otoliths from inner ear pressure changes. Although the exact etiology of post-SCD repair BPPV remains unknown, postoperative dizziness is important to discuss with patients during preoperative counseling. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2092-2097, 2016.

Health Utility Improves After Surgery for Superior Canal Dehiscence Syndrome.

OBJECTIVE: Health utility value (HUV) is an outcome measure used to calculate quality adjusted life years (QALYs) and to determine cost-effectiveness of medical treatments. Herein, we measure HUV in patients with superior canal dehiscence syndrome (SCDS) before and after surgical repair. Health utility values of patients with SCDS are compared to normative data of the general United States population. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENTS: Adult patients with SCDS. SETTING: Tertiary referral center. INTERVENTIONS: SCD repair via middle fossa craniotomy or transmastoid approaches. PRIMARY OUTCOME: change in HUV, as measured by the Short-Form 6-Dimension questionnaire. SECONDARY OUTCOMES: autophony index (AI), dizziness handicap inventory (DHI), and hearing handicap inventory (HHI). RESULTS: Fifty-one patients with SCDS were enrolled, 23 underwent surgical repair. Mean HUV in patients with SCDS is significantly lower than the general U.S. POPULATION: 0.68 (SD = 0.13) versus 0.80 (0.29), p < 0.01, respectively. Patients electing to undergo surgical repair had similar values relative to nonoperated patients: 0.65 (0.13) versus 0.71 (0.14), p = 0.20, respectively. At mean follow-up of 12 months (range 3-39), postoperative HUV improved to 0.79 (0.12), p < 0.01. AI decreased (improved) after repair: 32.7 (28.0) to 4.8 (8.3), p < 0.001. DHI and HHI did not change significantly after surgery, p > 0.14. Nonoperated patients had no significant change in HUV during a mean follow-up period of 21 months (range 9-39), p = 0.33. CONCLUSIONS: SCDS patients have significantly lower HUV compared with the general U.S. POPULATION: HUV demonstrated improvement after surgery. Nonoperated patients have ongoing impaired quality of life.

Auditory brainstem implant candidacy in the United States in children 0-17 years old.

OBJECTIVES: The auditory brainstem implant (ABI) is an option for hearing rehabilitation in profoundly deaf patients ineligible for cochlear implantation. Over the past decade, surgeons have begun implanting ABIs in pediatric patients who are unable to receive cochlear implants due to congenital or acquired malformations of the inner ear. No study has examined the potential population-level demand for ABIs in the United States (US). Herein, we aim to quantify the potential need for pediatric ABIs. METHODS: A systematic literature review was conducted to identify studies detailing the rates of congenital cochlear and/or cochlear nerve (CN) anomalies. Absolute indications for ABI include bilateral cochlea or CN aplasia (Group A), and relative indications for ABI include bilateral cochlea or CN hypoplasia (Group B). Data was subsequently correlated to the US Census Bureau, the National Health Interview Survey, and the Gallaudet Research Institute to provide an estimation of pediatric ABI candidates. RESULTS: Eleven studies documented rates of bilateral findings. Bilateral cochlea aplasia was identified in 0-8.7% of patients and bilateral CN aplasia in 0-4.8% of patients (Group A). Bilateral cochlea hypoplasia was identified in 0-8.7% of patients and bilateral CN hypoplasia in 0-5.4% of patients (Group B). Using population-level sensorineural hearing loss data, we roughly estimate 2.1% of potential implant candidates meet absolute indications for an ABI in the United States. CONCLUSION: Congenital cochlear and cochlear nerve anomalies are exceedingly rare. This study provides the first preliminary estimate of cochlea and CN aplasia/hypoplasia at the population level albeit with limitations based on available data. These data suggest the need for dedicated ABI centers to focus expertise and management.

Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways.

Optogenetics has become an important research tool and is being considered as the basis for several neural prostheses. However, few studies have applied optogenetics to the auditory brainstem. This study explored whether optical activation of the cochlear nucleus (CN) elicited responses in neurons in higher centers of the auditory pathway and whether it elicited an evoked response. Viral-mediated gene transfer was used to express channelrhodopsin-2 (ChR2) in the mouse CN. Blue light was delivered via an optical fiber placed near the surface of the infected CN and recordings were made in higher-level centers. Optical stimulation evoked excitatory multiunit spiking activity throughout the tonotopic axis of the central nucleus of the inferior colliculus (IC) and the auditory cortex (Actx). The pattern and magnitude of IC activity elicited by optical stimulation was comparable to that obtained with a 50dB SPL acoustic click. This broad pattern of activity was consistent with histological confirmation of green fluorescent protein (GFP) label of cell bodies and axons throughout the CN. Increasing pulse rates up to 320Hz did not significantly affect threshold or bandwidth of the IC responses, but rates higher than 50Hz resulted in desynchronized activity. Optical stimulation also evoked an auditory brainstem response, which had a simpler waveform than the response to acoustic stimulation. Control cases showed no responses to optical stimulation. These data suggest that optogenetic control of central auditory neurons is feasible, but opsins with faster channel kinetics may be necessary to convey information at rates typical of many auditory signals.

Dizziness is more prevalent than autophony among patients who have undergone repair of superior canal dehiscence.

OBJECTIVE: Studies have reported high early success rates in rectifying dizziness and autophony after primary repair of superior canal dehiscence (SCD). We sought to identify the prevalence of dizziness and autophony at later time points in patients who had undergone SCD repair. We also assessed any problems with hearing in this population, along with prevalence of headaches and decreases in overall quality of life. STUDY QUALITY DESIGN: Identification of patients via retrospective chart review, followed by administration of multiple validated surveys. SETTING: Tertiary, hospital-based neurotology practice. PATIENTS: All 62 patients who had undergone primary SCD repair at Massachusetts Eye and Ear Infirmary with follow-up time of at least 3 months were contacted, with 38 responses from 22 women and 16 men. The average follow-up was 34 months (range, 3-155 mo). INTERVENTIONS: Patient surveys. MAIN OUTCOME MEASURES: Dizziness Handicap Inventory and Autophony Index. SECONDARY OUTCOME MEASURES: Hearing Handicap Survey, MIDAS headache survey, and Short Form-36 Quality of Life Survey. RESULTS: Twenty patients reported low DHI scores, whereas 18 patients reported elevated DHI scores corresponding to moderate-to-severe dizziness. Autophony was less prevalent, as 3 patients experienced autophony in the operated ear, whereas 3 patients experienced "unmasking" of autophony in the contralateral ear. HHI scores were not significantly different between the low DHI and high DHI group. There were significantly more female subjects in the high DHI group, which was also characterized by significantly more severe MIDAS grades and significantly worse SF-36 scores. CONCLUSION: Dizziness is more prevalent than autophony among patients who have undergone SCD repair, although the majority of these patients are satisfied with their decision to undergo surgery. Female sex and migraine headaches are associated with dizziness in this patient population. Further work is necessary to determine causal relationships among these associations.