Publications by authors named "Dorina Kallogjeri"

125 Publications

Development and Preliminary Evaluation of the Tinnitus Severity Short Form.

Am J Audiol 2021 Jun 24;30(2):404-415. Epub 2021 May 24.

Department of Psychological & Brain Sciences, Washington University in St. Louis, MO.

Purpose Tinnitus, or the perception of sounds that occur without an external sound source, is a prevalent condition worldwide. For a subset of adults, tinnitus causes significant distress and impairment. Several patient-reported outcome measures have been developed to assess severity of tinnitus distress. However, at present, the field lacks a brief measure that is sensitive to treatment change. The purpose of the current study was to develop and preliminarily validate a brief questionnaire for tinnitus severity from two existing measures of tinnitus-related distress, the Tinnitus Handicap Inventory (THI) and Tinnitus Functional Index (TFI). Method Using data from nine study samples in the United States and United Kingdom, we conducted exploratory and confirmatory factor analyses to identify a short measure with good psychometric properties. We also assessed sensitivity to treatment-related change by examining associations with change in the TFI and THI. Finally, we conducted a confirmatory factor analysis of the final short questionnaire in a new sample of adults seeking treatment for tinnitus-related distress. Results We identified 10 items from the THI and TFI that exhibited limited loadings on secondary factors. The resulting Tinnitus Severity Short Form achieved good to excellent fit, including in a unique sample of individuals seeking online treatment for tinnitus, and appeared sensitive to treatment-related change. Conclusions The Tinnitus Severity Short Form developed in the current study may be a useful tool for the assessment of subjective severity and distress associated with tinnitus, especially when patient burden is a concern. Further research is necessary to fully validate the questionnaire for the assessment of treatment-related change.
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http://dx.doi.org/10.1044/2021_AJA-20-00164DOI Listing
June 2021

Effectiveness of Prophylactic Preoperative Antibiotics in Mandible Fracture Repair: A National Database Study.

Otolaryngol Head Neck Surg 2021 Apr 13:1945998211004270. Epub 2021 Apr 13.

Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.

Objective: This is the first database study to assess the effectiveness of prophylactic preoperative antibiotics (PPAs) in mandible fracture repair.

Study Design: Retrospective cohort.

Setting: Database study using US inpatient and outpatient insurance claims submitted from July 2006 to March 2015.

Methods: The IBM MarketScan Commercial Database was queried for adults aged 18 to 64 years who had undergone first-time mandible fracture repair according to codes for open and closed repair. Primary outcomes included surgical revision, local infection, and osteomyelitis. Rates were compared between cohorts based on whether or not patients had filled antibiotic prescriptions during the preoperative period alone. The effects of drug abuse and type of mandible repair (open vs closed) were explored. Multivariate Poisson regression models were used to calculate adjusted relative risk estimates, and 95% CIs were used to determine statistically significant differences.

Results: A total of 2676 patients were included, with 847 (31.7%) filling PPAs and 1829 (68.3%) filling no antibiotics. Rates were 38.9% for revision, 5.8% for local infection, and 2.1% for osteomyelitis. After multivariate analysis, exposure to PPAs was not associated with surgical revision (adjusted relative risk, 1.04; 95% CI, 0.94-1.15), local infection (1.16; 0.82-1.64), or osteomyelitis (1.21; 0.68-2.14). Patients were more likely to fill PPAs if they underwent open repair (35.3%) versus closed (26.6%) (proportion difference, 8.7%; 95% CI, 5.2%-12.2%), but exposure to antibiotics did not predict outcomes on subgroup analysis.

Conclusion: PPAs do not improve mandible repair outcomes, regardless of repair type.
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http://dx.doi.org/10.1177/01945998211004270DOI Listing
April 2021

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction.

JAMA Otolaryngol Head Neck Surg 2021 Jun;147(6):502-509

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent.

Objective: To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging.

Design, Setting, And Participants: This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin' Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020.

Interventions: Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention.

Main Outcome And Measures: The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin' Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures.

Results: A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum.

Conclusions And Relevance: The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.
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http://dx.doi.org/10.1001/jamaoto.2021.0086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974830PMC
June 2021

Investigating the Impact of Cognitive Training for Individuals With Bothersome Tinnitus: A Randomized Controlled Trial.

Otolaryngol Head Neck Surg 2021 Mar 2:194599821994742. Epub 2021 Mar 2.

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA.

Objective: To evaluate the effectiveness of cognitive training in improving tinnitus bother and to identify predictors of patient response.

Study Design: Prospective open-label randomized controlled trial.

Setting: Online.

Methods: Participants were adults with subjective idiopathic nonpulsatile tinnitus causing significant tinnitus-related distress. The intervention group trained by using auditory-intensive exercises for 20 minutes per day, 5 days per week, for 8 weeks. The active control group trained on the same schedule with non-auditory intensive games. Surveys were completed at baseline, 8 weeks, and 12 weeks.

Results: A total of 64 participants completed the study. The median age was 63 years (range, 25-69) in the intervention group and 61 years (34-68) in the control group. Mixed model analysis revealed that within-subject change in Tinnitus Functional Index in the intervention group was not different than the control group, with marginal mean differences (95% CI): 0.24 (-11.20 to 10.7) and 2.17 (-8.50 to 12.83) at 8 weeks and 2.33 (-8.6 to 13.3) and 3.36 (-7.91 to 14.6) at 12 weeks, respectively. When the 2 study groups were compared, the control group had higher Tinnitus Functional Index scores than the intervention group by 10.5 points at baseline (95% CI, -0.92 to 29.89), 8.1 at 8 weeks (95% CI, -3.27 to 19.42), and 9.4 at 12 weeks (95% CI, -2.45 to 21.34).

Conclusion: Auditory-intensive cognitive training was not associated with changes in self-reported tinnitus bother. Given the potential for neuroplasticity to affect tinnitus, we believe that future studies on cognitive training for tinnitus remain relevant.
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http://dx.doi.org/10.1177/0194599821994742DOI Listing
March 2021

Survival Outcomes of De Novo vs Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

JAMA Otolaryngol Head Neck Surg 2021 Apr;147(4):350-359

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist.

Objective: To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC).

Data Sources: A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors.

Study Selection: Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included.

Data Extraction And Synthesis: Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model.

Main Outcomes And Measures: The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort.

Results: One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%).

Conclusions And Relevance: This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.
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http://dx.doi.org/10.1001/jamaoto.2020.5261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844698PMC
April 2021

20 pack-year smoking history as strongest smoking metric predictive of HPV-positive oropharyngeal cancer outcomes.

Am J Otolaryngol 2021 May-Jun;42(3):102915. Epub 2021 Jan 13.

Department of Otolaryngology - Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Objectives: While smoking is associated with worse outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), the magnitude of this association is unclear given the heterogenous smoking definitions and outcomes. Our objective was to investigate the association between smoking, survival, and recurrence in HPV-related OPSCC using multiple smoking metrics reported in the literature.

Materials And Methods: This was a retrospective cohort study of 375 adults with p16+ OPSCC undergoing surgical resection (n = 272) or definitive chemoradiation (n = 103) at a tertiary academic institution from 2006 to 2017. The primary outcome was overall survival (OS). Secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and recurrence. We used multiple smoking metrics commonly cited in previous studies, including ever versus never smokers, current versus former/never smokers, ≤10 versus >10 pack-year, ≤20 versus >20 pack-year, and continuous pack-year.

Results: There were 375 patients, median age 58 years, with 326 (87%) males, and median follow-up of 52 months. Of all smoking metrics, >20 pack-year history was the strongest predictor of both OS (HR 2.24, 95% CI: 1.19-4.20) and DFS (HR 1.67, 95% CI: 1.04-2.66) on univariable and multivariable analysis after adjusting for age, overall stage, and comorbidities. Patients with >20 pack-year smoking history were also more likely to have recurrence (HR 1.59, 95% CI: 0.95-2.67) after adjusting for overall stage.

Conclusion: Heavier smoking >20 pack-years was the strongest smoking metric associated with 2-times worse survival and recurrence. Our findings suggest that >20 pack-year smoking history may be a more useful cutoff for risk stratification models but requires further validation.
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http://dx.doi.org/10.1016/j.amjoto.2021.102915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096678PMC
January 2021

Validation of Hearing Loss Prediction Tool for Cisplatin Chemotherapy and Radiation in Head and Neck Cancer Treatment.

JAMA Otolaryngol Head Neck Surg 2021 02;147(2):182-189

Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine, St Louis, Missouri.

Importance: Hearing loss affects up to 88% of patients undergoing head and neck cancer treatment; however, there are few validated models to predict this outcome. A predictive posttreatment model for hearing loss will allow clinicians and patients to make well-informed decisions about treatment with cisplatin-based chemotherapies and radiotherapy.

Objective: To validate a previously created predictive model for objective hearing outcomes and to assess barriers to using the prediction nomogram in general practice for patients newly diagnosed with head and neck cancer.

Design, Setting, And Participants: This cohort study includes an evaluation of 105 patients (208 ears) and interviews with 6 clinicians. The patients were treated at a high-volume tertiary care hospital. Patient participants were newly diagnosed with head and neck cancer and treated at Siteman Cancer Center from July 1, 2018, to December 31, 2019, with radiotherapy both with and without cisplatin-based chemotherapy. Additionally, the clinicians involved in the care of patients with head and neck cancer were interviewed to assess implementation strategies.

Exposures: Radiotherapy with and without cisplatin-based chemotherapy.

Main Outcomes And Measures: Hearing defined by the audiometric pure-tone average of 1, 2, and 4 kHz.

Results: A total of 105 patients (208 ears; mean [SD] age, 61 [11] years; 82 men [78%]) were compared with the development cohort to assess the similarities and differences in case mix. All patients underwent radiation therapy, 50 (48%) received cisplatin-based chemotherapy, and 67 (64%) had a surgical resection. The mean (SD) cochlear dose of radiation was 13 (12) Gy, and the mean (SD) total cisplatin dose was 238 (83) mg/m2 for those undergoing cisplatin therapy. A calibration curve demonstrated that predicted and observed posttreatment pure-tone average were not significantly different. The model predicted a posttreatment pure-tone average greater than 35 dB (a common threshold for hearing aid consideration) with a sensitivity of 73% and specificity of 67% with an area under the curve of 0.71, showing good discrimination. Clinician interviews suggest the nomogram requires careful integration into patient counseling to clarify risks and benefits for treatment.

Conclusions And Relevance: The findings of this cohort study confirm this model's ability to predict posttreatment hearing outcomes in a unique population of patients. This model has the potential to inform pretreatment counseling and posttreatment hearing evaluations for this patient population.
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http://dx.doi.org/10.1001/jamaoto.2020.4620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729577PMC
February 2021

Predictors of Occurrence and Timing of Post-Tonsillectomy Hemorrhage: A Case-Control Study.

Ann Otol Rhinol Laryngol 2021 Jul 8;130(7):825-832. Epub 2020 Dec 8.

Department of Otolaryngology, Washington University School of Medicine, Saint Louis, MO, USA.

Objective: To describe cases and timing of pediatric post-tonsillectomy hemorrhage (PTH), to evaluate predictors of PTH, and to determine the optimal amount of postoperative care unit (PACU) monitoring time.

Study Design: Using the Pediatric Health Information System (PHIS) database and electronic medical records, a matched case-control study from 2005 to 2015 was performed.

Setting: A single, tertiary-care institution.

Subjects And Methods: Each case of PTH was matched with 1 to 4 controls for the following factors: age, sex, surgeon, and time of year. A total of 124 cases of PTH and 479 tonsillectomy controls were included. The rate and timing of postoperative bleeding were assessed, and matched pair analysis was performed using conditional logistic regression.

Results: Our institutional PTH rate of 1.9% (130 of 6949) included 124 patients; 15% (19) were primary (≤24 hours), with 50% (9) occurring within 5 hours. Twenty-one percent (4 of 19) of primary PTH patients received operative intervention. Eighty-five percent (105 of 124) of all cases were secondary PTH, and 47% (49) of those patients received operative intervention. Cold steel (OR 1.9, 95% CI 1.1-3.3) and Coblation (OR 1.9, 95% CI 1.2-3.1) techniques and tonsillectomy alone (OR 3.7, 95% CI 1.9-7.2) increased odds of PTH. Patients who developed PTH had 4 times the odds of having a preceding postoperative respiratory event than controls (OR 4.0, 95% CI 1.6-10.0).

Conclusion: We conducted a rigorous case-control study for PTH, finding that PTH was associated with use of cold steel and Coblation techniques and with tonsillectomy alone. Patients with a postoperative respiratory event may be more likely to develop a PTH and should be counseled accordingly. A PACU monitoring time of 4 hours is sufficient for outpatient tonsillectomy.
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http://dx.doi.org/10.1177/0003489420978010DOI Listing
July 2021

Comparison of Surgical Treatments for Zenker Diverticulum: A Systematic Review and Network Meta-analysis.

JAMA Otolaryngol Head Neck Surg 2021 02;147(2):190-196

Department of Otolaryngology-Head and Neck Surgery, Washington University in St Louis School of Medicine, St Louis, Missouri.

Importance: Zenker diverticulum (ZD) can cause significant dysphagia, and symptoms can return or persist after surgery. This systematic review and network meta-analysis is the first to our knowledge to compare 3 common surgical techniques for ZD.

Objective: To compare the 3 most common surgical techniques-endoscopic laser-assisted diverticulotomy, endoscopic stapler-assisted diverticulotomy, and transcervical diverticulectomy with cricopharyngeal myotomy-in adult patients with ZD.

Data Sources: The published literature was searched using strategies designed by a medical librarian (search performed September 21, 2018). Strategies were established using a combination of controlled vocabulary terms and keywords and were executed in Ovid MEDLINE (1946 to September 21, 2018), Embase (1947 to September 21, 2018), Scopus (1823 to September 21, 2018), Cochrane Library, and ClinicalTrials.gov. Results were limited to English using database-supplied filters, which generated studies from 1997 to 2017.

Study Selection: Inclusion criteria were cohort studies or randomized clinical trials. Studies that included patients needing revision surgery or undergoing an alternative technique were excluded.

Data Extraction And Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses-Network Meta-analyses (PRISMA-NMA) checklist was used to report the study findings. Two authors independently reviewed the studies.

Main Outcome And Measure: The primary outcome measure was the incidence of persistent or recurrent symptoms following surgery. The primary study outcome was planned before data collection began.

Results: The search generated 529 studies. After applying inclusion and exclusion criteria, 9 cohort studies remained, consisting of 903 patients treated with either laser-assisted diverticulotomy (n = 283), transcervical diverticulectomy (n = 150), or stapler-assisted diverticulotomy (n = 470). A network meta-analysis was performed. Between endoscopic laser-assisted diverticulotomy and open diverticulectomy, the open approach showed a statistically lower likelihood of persistent/recurrent symptoms following treatment (odds ratio [OR], 0.20; 95% CI, 0.04-0.91). Comparing laser-assisted diverticulotomy with the stapler-assisted technique, there was not a significant difference between the 2 techniques (OR, 0.83; 95% CI, 0.43-1.60). The consistency model for the network meta-analysis was supported (χ21 = 0.12; P = .73).

Conclusions And Relevance: This systematic review and meta-analysis compared 3 common techniques for treating ZD. The open approach showed a decreased likelihood of persistent or recurrent symptoms following surgery compared with the 2 other techniques.
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http://dx.doi.org/10.1001/jamaoto.2020.4091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716255PMC
February 2021

Outcomes of Patients With Single-Node Metastasis of Human Papillomavirus-Related Oropharyngeal Cancer Treated With Transoral Surgery.

JAMA Otolaryngol Head Neck Surg 2021 01;147(1):16-22

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Regional lymph node metastasis remains an important prognostic factor in patients with oropharyngeal squamous cell carcinoma (OPSCC). Although survival among patients with regional metastasis in human papillomavirus (HPV)-related OPSCC is more favorable compared with patients who are HPV negative, prognostic variables associated with failure in patients with single-node metastasis are not known.

Objective: To evaluate recurrence and survival in patients with HPV-related OPSCC with single-lymph node metastasis treated with transoral surgery.

Design, Setting, And Participants: A retrospective cohort study was conducted of 207 adults with newly diagnosed p16-positive OPSCC and pathology-confirmed single-node disease who underwent surgical resection with or without adjuvant therapy at 2 tertiary academic medical centers from January 1, 2007, to December 31, 2016. Statistical analysis was performed from September 1, 2018, to September 1, 2020.

Interventions: Surgery alone (n = 59), surgery with adjuvant radiation (n = 75), or surgery with adjuvant chemoradiation (n = 73).

Main Outcomes And Measures: The primary outcome was regional recurrence. Secondary outcomes included overall survival, any recurrence, and identification of factors associated with regional recurrence and overall survival.

Results: Among 207 patients, 178 (86%) were men, with a median age of 57 years (range, 35-82 years) at the time of surgery. Median follow-up was 36.2 months (range, 7-127 months). Regional recurrence occurred in 11 patients (5%). Of these, 1 patient (9%) was lost to follow-up after diagnosis, 1 (9%) was treated with palliative chemotherapy, and 9 (82%) were treated with curative intent. Ultimately, 7 patients received successful salvage treatment, and 3 died with disease. Overall, there were 21 patients (10%) with any recurrence, with 4 patients (19%) experiencing local recurrence, 11 (52%) experiencing regional recurrence, and 6 (29%) experiencing distant metastasis. The 5-year overall survival was 95% (95% CI, 89%-98%) for all patients. Older age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), advanced T stage (OR, 3.5; 95% CI, 0.9-14.0), and positive margins (OR, 10.9; 95% CI, 1.8-67.5) were associated with increased regional recurrence. Extranodal extension (OR, 0.2; 95% CI, 0.04-0.8), lymph node size greater than 3 cm (OR, 0.2; 95% CI, 0.1-0.7), and adjuvant therapy (OR, 0.08; 95% CI, 0.02-0.4) were associated with decreased regional recurrence. Advanced comorbidities (hazard ratio, 6.20; 95% CI, 1.4-27.7), lymphovascular invasion (hazard ratio, 4.7; 95% CI, 1.0-21.2), and regional recurrence (hazard ratio, 16.0; 95% CI, 3.1-82.0) were associated with worse overall survival.

Conclusions And Relevance: The findings of this cohort study suggest that patients with HPV-related OPSCC and single-node disease undergoing surgical resection with or without adjuvant treatment have excellent survival. Adjuvant therapy appears to improve regional control. Among patients with regional recurrence of OPSCC, there is a high rate of successful salvage treatment.
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http://dx.doi.org/10.1001/jamaoto.2020.3870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645757PMC
January 2021

Development and Validation of the Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NOSE HHT).

JAMA Otolaryngol Head Neck Surg 2020 11;146(11):999-1005

Clinical Outcomes Research Office, Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Epistaxis is the greatest cause of morbidity in patients with hereditary hemorrhagic telangiectasia (HHT); because of this, a validated epistaxis-specific quality-of-life instrument for HHT should be made available.

Objective: To develop and validate an epistaxis-specific quality-of-life patient-reported outcome measure for HHT.

Design, Setting, And Participants: This survey study focused on the development and validation of the Nasal Outcome Score for Epistaxis (NOSE) in HTT (NOSE HHT) outcome measure with data prospectively collected from December 10, 2019, to March 15, 2020. A total of 401 patients were recruited from within the Cure Hemorrhagic Telangiectasia online patient advocacy social media network, the Washington University HHT Center of Excellence, and a randomized clinical trial investigating an intranasal timolol gel for HHT-associated epistaxis.

Main Outcomes And Measures: Face and content validity, factor analysis, internal consistency as measured through Cronbach α, construct validity, responsiveness to change, and minimal clinically important difference.

Results: The NOSE HHT was developed and validated with a possible score ranging discretely from 0 to 4 for each of the 29 items and a total score ranging continuously from 0 to 4 after dividing by the total number of items answered. A total of 401 participants completed the NOSE HHT. Factor analysis identified 3 factors that matched the a priori specified subgroups of particular aspects of life affected by HHT-associated epistaxis: physical problems (mean [SD] magnitude, 1.59 [0.83]), functional limitations (mean [SD] magnitude, 1.28 [0.84]), and emotional consequences (mean [SD] magnitude, 1.95 [1.02]). The instrument had high internal consistency with an overall Cronbach α of 0.960. Convergent validity determined the total NOSE HHT score to be a strong predictor of disease severity; total NOSE HHT score can be split up into the following epistaxis severity categories: mild (0-1), moderate (1.01-2), and severe (>2). The instrument was found to be sensitive to change, and the minimal clinically important difference for the total NOSE HHT score was 0.46.

Conclusions And Relevance: Evaluation of the consistency, reliability, and responsiveness of the NOSE HHT survey found it to be a valid instrument to assess severity and change in epistaxis. Study results suggest that the NOSE HHT survey is clinically applicable and useful as an outcome measure of future HHT-associated epistaxis trials.
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http://dx.doi.org/10.1001/jamaoto.2020.3040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530813PMC
November 2020

Efficacy of Timolol in a Novel Intranasal Thermosensitive Gel for Hereditary Hemorrhagic Telangiectasia-Associated Epistaxis: A Randomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg 2020 11;146(11):1006-1014

Clinical Outcomes Research Office, Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Other than nasal moisturizers, no standard-of-care medical therapy exists for epistaxis in hereditary hemorrhagic telangiectasia (HHT). With epistaxis as the greatest cause of morbidity in patients with HHT, there is a need to identify effective topical therapies.

Objective: To determine the efficacy and safety of an intranasal timolol thermosensitive gel vs placebo thermosensitive gel in treating HHT-associated epistaxis.

Design, Setting, And Participants: This double-blind, placebo-controlled randomized clinical trial was conducted from October 29, 2019, to May 20, 2020, at a tertiary care center. A total of 27 patients with HHT and moderate-to-severe epistaxis were recruited and included in this prespecified analysis: 14 in the timolol group and 13 in the placebo group. Inclusion criteria included (1) age 18 years or older, (2) clinical or genetic diagnosis of HHT, (3) screening Epistaxis Severity Score (ESS) of 4 or greater and 2 or more nosebleeds cumulatively lasting at least 5 minutes per week, (4) stable epistaxis pattern over the preceding 3 months, and (5) no change in epistaxis treatment or nasal hygiene regimen in the preceding month. Exclusion criteria included (1) contraindications to systemic β-blocker administration, (2) use of medications interacting with timolol, (3) use of antiangiogenic medications in the last month before recruitment, and (4) use of anticoagulants, antiplatelets, or fibrinolytic therapies within the last month.

Interventions: Novel thermosensitive intranasal timolol (0.1%) gel vs placebo thermosensitive gel applied twice daily to each nostril for 8 weeks.

Main Outcomes And Measures: The primary outcome was the median change in ESS and percentage of participants reaching the minimal clinically important difference in ESS. Secondary outcomes were changes in Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores, Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia, and hemoglobin level.

Results: Of 27 participants randomized (median [range] age, 55 [20-76] years; 14 women [52%]; 25 White [93%]), a total of 23 patients with HHT completed the primary outcome measure. Within the timolol gel and placebo gel groups, respectively, the median change (range) in ESS was 2.32 (0.22 to 5.97) vs 1.96 (-0.91 to 5.98), and 9 of 11 (82%) vs 9 of 12 (75%) participants experienced a clinically meaningful improvement in ESS. Twenty-two of the 23 participants (96%) reported improvement via the Clinical Global Impression-Improvement score, with 81% vs 58% of participants reporting reduced severity of epistaxis in the timolol vs placebo group, respectively. Of participants completing the Nasal Outcome Score for Epistaxis in HHT at follow-up visit, 7 of 10 (70%) in the timolol group achieved a clinically important difference vs 5 of 10 (50%) in the placebo group. There was no change in hemoglobin level between or within groups. Zero participants in the placebo group and 2 of 13 (15%) in the timolol group withdrew because of adverse events.

Conclusions And Relevance: Thermosensitive gel, alone or in combination with timolol, was highly effective in reducing HHT-associated epistaxis. The timolol group had greater improvement in epistaxis and quality of life than the placebo group, but effect estimates were imprecise, and no definitive conclusions on the superiority of timolol can be drawn. Physicians treating patients with HHT-associated epistaxis should consider a thermosensitive gel (with or without timolol) for their patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT04139018.
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http://dx.doi.org/10.1001/jamaoto.2020.3025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499238PMC
November 2020

Cochlear Implant Outcomes Following Vestibular Schwannoma Resection: Systematic Review.

Otol Neurotol 2020 10;41(9):1190-1197

Department of Otolaryngology-Head and Neck Surgery.

Objective: Hearing loss remains a significant morbidity for patients with vestibular schwannomas (VS). A growing number of reports suggest audibility with cochlear implantation following VS resection; however, there is little consensus on preferred timing and cochlear implant (CI) performance.

Data Sources: A systematic literature search of the Ovid Medline, Embase, Scopus, and clinicaltrails.gov databases was performed on 9/7/2018. PRISMA reporting guidelines were followed.

Study Selection: Included studies reported CI outcomes in an ear that underwent a VS resection. Untreated VSs, radiated VSs, and CIs in the contralateral ear were excluded.

Data Extraction: Primary outcomes were daily CI use and attainment of open-set speech. Baseline tumor and patient characteristics were recorded. Subjects were divided into two groups: simultaneous CI placement with VS resection (Group 1) versus delayed CI placement after VS resection (Group 2).

Data Synthesis: Twenty-nine articles with 93 patients met inclusion criteria. Most studies were poor quality due to their small, retrospective design. Group 1 had 46 patients, of whom 80.4% used their CI on a daily basis and 50.0% achieved open-set speech. Group 2 had 47 patients, of whom 87.2% used their CI on a daily basis and 59.6% achieved open-set speech. Group 2 had more NF2 patients and larger tumors. CI timing did not significantly impact outcomes.

Conclusions: Audibility with CI after VS resection is feasible. Timing of CI placement (simultaneous versus delayed) did not significantly affect performance. Overall, 83.9% used their CI on a daily basis and 54.8% achieved open-set speech.
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http://dx.doi.org/10.1097/MAO.0000000000002784DOI Listing
October 2020

Prolonged time to extubation after general anaesthesia is associated with early escalation of care: A retrospective observational study.

Eur J Anaesthesiol 2021 May;38(5):494-504

From the Department of Anesthesiology - University of Mississippi Medical Center, Jackson, Mississippi (AV, LC), Department of Anesthesiology, Washington University, St. Louis (IRR, AS, DLH, LC), Department of Obstetrics & Gynecology, Washington University, St. Louis (KP), Department of Otolaryngology-Head & Neck Surgery, Washington University, St. Louis (DPL) and Research Statistician, Department of Otolaryngology, Head and Neck Surgery, Washington University in St. Louis - School of Medicine, St. Louis, Missouri, USA (DK).

Background: Prolonged time to extubation after general anaesthesia has been defined as a time from the end of surgery to airway extubation of at least 15 min. This occurrence can result in ineffective utilisation of operating rooms and delays in patient care. It is unknown if unanticipated delayed extubation is associated with escalation of care.

Objectives: To assess the frequency of 'prolonged extubation' after general anaesthesia and its association with 'escalation of care before discharge from the postanaesthesia care unit', defined as administration of reversal agents for opioids and benzodiazepines, airway re-intubation and need for ventilatory support. In addition, we tried to identify independent factors associated with 'prolonged extubation'.

Design: Single-centre retrospective study of cases performed from 1 January 2010 to 31 December 2014.

Setting: A large US tertiary academic medical centre.

Patients: Adult general anaesthesia cases excluding cardiothoracic, otolaryngology and neurosurgery procedures, classified as: Group 1 - regular extubation (≤15 min); Group 2 - prolonged extubation (≥16 and ≤60 min); Group 3 - very prolonged extubation (≥61 min).

Main Outcome Measures: First, cases with prolonged time to extubation; second, instances of escalation of care per extubation group; third, independent factors associated with prolonged time to extubation.

Results: A total of 86 123 cases were analysed. Prolonged extubation occurred in 8138 cases (9.5%) and very prolonged extubation in 357 cases (0.4%). In Groups 1, 2 and 3 respectively, naloxone was used in 0.4, 4.1 and 3.9% of cases, flumazenil in 0.03, 0.6 and 2% and respiratory support in 0.2, 0.7 and 2%, and immediate re-intubation occurred in 0.1, 0.3 and 2.8% of cases. Several patient-related, anaesthesia-related and procedure-related factors were independently associated with prolonged time to extubation.

Conclusion: Prolonged time to extubation occurred in nearly 10% of cases and was associated with an increased incidence of escalation of care. Many independent factors associated with 'prolonged extubation' were nonmodifiable by anaesthetic management.
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http://dx.doi.org/10.1097/EJA.0000000000001316DOI Listing
May 2021

Hearing and Quality-of-Life Outcomes After Cochlear Implantation in Adult Hearing Aid Users 65 Years or Older: A Secondary Analysis of a Nonrandomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg 2020 10;146(10):925-932

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Hearing loss, especially moderate to severe forms, has the potential to negatively affect an individual's physical, social, emotional, and cognitive well-being. Moreover, having ineffective binaural hearing increases difficulty understanding speech in noise and leads to a greater degree of social isolation and loneliness and a reduced quality of life (QoL).

Objective: To explore the audiometric and holistic effects of cochlear implantation in a group of adults 65 years or older compared with an optimized bilateral hearing aid condition.

Design, Setting, And Participants: This ad hoc secondary analysis of a prospective, single-subject, repeated-measures nonrandomized clinical trial included 13 cochlear implantation centers across the United States. Participants 65 years or older with postlingual bilateral moderate-to-profound sensorineural hearing loss with aided Consonant-Vowel Nucleus-Consonant (CNC) word scores in quiet of 40% or less in the ear to undergo implantation and 50% or less in the contralateral ear were included in the analysis. Baseline QoL testing was performed after 1 month of optimized bilateral hearing aid use. Participants were enrolled from February 20, 2017, to May 3, 2018, and follow-up was completed December 21, 2018. Data were analyzed from March 25, 2019, to March 31, 2020.

Interventions: Unilateral implantation with a slim, modiolar cochlear implant device. Hearing aid use in the contralateral ear was required through the 6-month primary end-point interval.

Main Outcomes And Measures: The primary objective was to evaluate speech perception before and 6 months after activation of a new cochlear implant. Secondary objectives were QoL metrics in the everyday listening condition before and 6 months after implantation.

Results: Seventy participants (51 men [73%]) with a median age of 74 (range, 65-91) years were included in the analysis. No major adverse events occurred. Mixed-model analysis with estimated marginal means and 95% CIs compared preimplantation baseline performance with 6-month postimplantation performance. A clinically important improvement in CNC words was shown in the bimodal condition, with a mean difference of 37.2% (95% CI, 32.0%-42.4%), and in the unilateral (cochlear implant only) condition, with a mean difference of 44.1% (95% CI, 39.0%-49.2%). A clinically important improvement in noise (AzBio sentences signal-to-noise ratio of +10 dB) was also shown, with a mean difference of 21.6% (95% CI, 15.7%-27.5%) in the bimodal condition and 24.5% (95% CI, 18.3%-30.7%) in the unilateral condition. The Health Utilities Index Mark 3 multiple-attribute score improved by 0.186 (95% CI, 0.136-0.234); the Speech, Spatial, and Qualities of Hearing Scale total score improved by 2.58 (95% CI, 2.18-2.99); and a novel Device Use Questionnaire reported 94% of participants were satisfied with overall hearing in the everyday listening condition.

Conclusions And Relevance: This subgroup analysis of patients 65 years or older enrolled in a within-subject clinical trial of cochlear implantation demonstrated clinically meaningful audiometric and QoL benefit with an acceptable risk profile. These findings suggest that cochlear implantation in older adults may facilitate the concept of healthy aging.

Trial Registration: ClinicalTrials.gov Identifier: NCT03007472.
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http://dx.doi.org/10.1001/jamaoto.2020.1585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453343PMC
October 2020

Assessment of Speech Understanding After Cochlear Implantation in Adult Hearing Aid Users: A Nonrandomized Controlled Trial.

JAMA Otolaryngol Head Neck Surg 2020 10;146(10):916-924

Department of Otolaryngology-Head & Neck Surgery, Washington University in St Louis, St Louis, Missouri.

Importance: Cochlear implants were approved for use in adults in the 1980s, but use remains low owing to a lack of awareness regarding cochlear implantation candidacy criteria and expected outcomes. There have been limited, small series examining the safety and effectiveness of cochlear implantation in adult hearing aid (HA) users with and without mild cognitive impairment (MCI).

Objective: To investigate the safety and effectiveness of a single-ear cochlear implant in a group of optimized adult HA users with and without MCI across a variety of domains.

Design, Setting, And Participants: In this nonrandomized controlled trial, a multicenter, prospective, repeated-measures investigation was conducted at 13 US institutions. The setting was academic and community-based cochlear implant programs. Eligible participants were 100 adults (aged >18 years) with postlinguistic onset of bilateral moderate sloping to profound or worse sensorineural hearing loss (≤20 years' duration). Fluent English speakers underwent an optimized bilateral HA trial for at least 30 days. Individuals with aided Consonant-Vowel Nucleus-Consonant (CNC) word score in quiet of 40% or less correct in the ear to be implanted and 50% or less correct in the contralateral ear were offered cochlear implants. The first participant was enrolled on February 20, 2017, and the last participant was enrolled on May 3, 2018. The final follow-up was on December 21, 2018.

Interventions: Participants received the same cochlear implant system and contralateral HA.

Main Outcomes And Measures: The primary outcome measure was speech understanding in quiet (CNC word score) using both the cochlear implant and opposite ear HA. Secondary outcome measures included the following: adverse events; speech understanding in noise (AzBio signal-to-noise ratio of +10 db [+10 SNR]) Health Utilities Index Mark 3 (HUI3); Speech, Spatial, and Qualities of Hearing Questionnaire 49 (SSQ49); and Montreal Cognitive Assessment (MoCA).

Results: The median age at cochlear implantation of the 96 patients included in the trial was 71 years (range, 23-91 years), and 62 patients (65%) were male. Three serious adverse events requiring revision surgery occurred, and all resolved without sequelae. By 6 months after activation, the absolute marginal mean change in CNC word score and AzBio +10 SNR was 40.5% (95% CI, 35.9%-45.0%) and 24.1% (95% CI, 18.9%-29.4%), respectively. Ninety-one percent (87 of 96) of participants had a clinically important improvement (>15%) in the CNC word score in the implant ear. Mild cognitive impairment (MoCA total score ≤25) was observed in 48 of 81 study participants (59%) at baseline. Speech perception marginal mean improvements were similar between individuals with and without baseline MCI, with values of 40.9% (95% CI, 35.2%-46.6%) and 39.6% (95% CI, 31.8%-47.4%), respectively, for CNC word score and 27.5% (95% CI, 21.0%-33.9%) and 17.8% (95% CI, 9.0%-26.6%), respectively, for AzBio +10 SNR. Statistically significant and clinically important improvements in the HUI3 and SSQ49 were evident at 6 months.

Conclusions And Relevance: The findings of this nonrandomized controlled trial seem to indicate that cochlear implants are safe and effective in restoring speech understanding in both quiet and noise and improve quality of life in individuals with and without MCI.

Trial Registration: ClinicalTrials.gov Identifier: NCT03007472.
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http://dx.doi.org/10.1001/jamaoto.2020.1584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453346PMC
October 2020

Assessment of Cochlear Implants for Adult Medicare Beneficiaries Aged 65 Years or Older Who Meet Expanded Indications of Open-Set Sentence Recognition: A Multicenter Nonrandomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg 2020 10;146(10):933-941

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Current indications for Medicare beneficiaries to receive a cochlear implant are outdated. Multichannel cochlear implant systems may be effective when provided to Medicare beneficiaries using expanded indications.

Objective: To examine the effectiveness of cochlear implants, as measured by improvement on the AzBio Sentence Test, for newly implanted Medicare beneficiaries who meet the expanded indications of an AzBio Sentence Test score of 41% to 60% in their best-aided condition.

Design, Setting, And Participants: A multicenter nonrandomized trial examined preoperative and postoperative speech recognition, telephone communication, hearing device benefit, health utility, and quality of life for 34 participants enrolled at 8 different centers who received a cochlear implant between September 17, 2014, and July 10, 2018. All participants were 65 years or older, had bilateral moderate to profound hearing loss, and had a best-aided preoperative AzBio Sentence Test score in quiet of 41% to 60%. Analysis was performed on an intention-to-treat basis. Statistical analysis of final results took place from July 29 to October 1, 2019.

Intervention: Multichannel cochlear implants.

Main Outcomes And Measures: The study examined the a priori hypothesis that the cochlear implant would improve the AzBio Sentence Test score in the best-aided condition by 25% or more and in the implanted ear-alone condition by 30% or more. The study additionally examined word and telephone recognition and examined device benefit, health utility, and quality of life.

Results: A total of 34 participants received a cochlear implant; 31 (23 men [74%]; median age, 73.6 years [range, 65.7-85.1 years]) completed testing through the 6-month evaluation, and 29 completed testing through the 12-month evaluation. Median preoperative AzBio Sentence Test scores were 53% (range, 26%-60%) for the best-aided condition and 24% (range, 0%-53%) for the cochlear implant-alone condition; median scores 12 months after implantation improved to 89% (range, 36%-100%) for the best-aided condition and 77% (range, 13%-100%) for the cochlear implant-alone condition. This outcome represents a median change of 36% (range, -22% to 75%) for the best-aided condition (lower bound of 1-sided 95% CI, 31%) and a median change of 53% (range, -15% to 93%) for the cochlear implant-alone condition (lower bound of 1-sided 95% CI, 45%).

Conclusions And Relevance: Intervention with a cochlear implant was associated with improved sentence, word, and telephone recognition in adult Medicare beneficiaries whose preoperative AzBio Sentence Test scores were between 41% and 60%. These findings support expansion of the Center for Medicare & Medicaid current indications for cochlear implants.

Trial Registration: ClinicalTrials.gov Identifier: NCT02075229.
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http://dx.doi.org/10.1001/jamaoto.2020.2286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453340PMC
October 2020

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.

Clin Cancer Res 2020 10 14;26(19):5140-5152. Epub 2020 Jul 14.

Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.

Purpose: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.

Patients And Methods: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684).

Results: Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.

Conclusions: Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547532PMC
October 2020

The association of smoking and outcomes in HPV-positive oropharyngeal cancer: A systematic review.

Am J Otolaryngol 2020 Sep - Oct;41(5):102592. Epub 2020 Jun 2.

Department of Otolaryngology - Head and Neck Surgery, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address:

Purpose: While smoking is linked to worse outcomes for human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC), the magnitude of this association and the amount of smoking exposure necessary to confer clinically significant differences in outcomes is unclear. Recent studies suggested that greater tobacco exposure results in higher risk of cancer progression and death. Our study objective was to perform a systematic review of the association between smoking and HPV-related OPSCC outcomes.

Materials And Methods: A literature search was conducted in April 2019 to identify relevant articles using Embase, Medline, Scopus, CENTRAL, and Cochrane databases. All studies were independently screened by two investigators to identify studies that assessed HPV-positive patients as an independent cohort, specified smoking measures, and reported locoregional recurrence (LRR), overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS) in association with smoking.

Results: Of 1130 studies identified, 10 met final inclusion criteria with 2321 total patients, mean age 57.5 years. Smoking measures included ever vs never, current vs never/former smokers, ≤10 vs >10 pack-year, and continuous pack-years. Of these studies, 8 (80%) showed a significant effect of smoking on increasing recurrence and mortality. Adjusted HRs for LRR ranged from 0.6 to 5.2, OS from 1.3 to 4.0, DSS from 2.3 to 7.2, and DFS from 1.02 to 4.2 among heavier smokers compared to lighter/non-smokers.

Conclusions: While there was significant variability in smoking metrics and reported outcomes, all studies reporting statistically significant HRs showed that smoking was associated with worse outcomes. Further studies using uniform smoking measures are necessary to better understand this association.
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http://dx.doi.org/10.1016/j.amjoto.2020.102592DOI Listing
November 2020

Randomized clinical trial to evaluate mometasone lavage vs spray for patients with chronic rhinosinusitis without nasal polyps who have not undergone sinus surgery.

Int Forum Allergy Rhinol 2020 08 29;10(8):936-943. Epub 2020 May 29.

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St. Louis, MO.

Background: There is no consensus regarding the best route of intranasal delivery of corticosteroids in the treatment of chronic rhinosinusitis (CRS). The study objective of this work was to compare the impact of mometasone furoate nasal spray (MFNS) vs mometasone nasal irrigation in the management of CRS patients who have not undergone sinus surgery.

Methods: A double-blind, placebo-controlled, randomized clinical trial was conducted in adults with CRS. Individuals with nasal polyps and/or history of sinus surgery were excluded. Patients were randomized to receive 8 weeks of either MFNS or mometasone nasal irrigation. The primary outcome measure was change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score between the 2 groups. Secondary outcome measures included patient global response to treatment and Lund-Kennedy endoscopy scores.

Results: A total of 43 participants completed the study (n = 22, MFNS; n = 21,mometasone nasal irrigation). Fourteen (64%) participants in the MFNS group and 17 (81%) in the mometasone lavage group had a clinically meaningful improvement in SNOT-22 scores with a proportion difference of 17% (95% confidence interval [CI], -9% to 44%). The least-squares (LS) mean difference between the 2 groups for SNOT-22 was -8.6 (95% CI, -17.7 to 0.58; p = 0.07), whereas the LS mean difference between the 2 groups for Lund-Kennedy endoscopy scores was 0.16 (95% CI, -0.84 to 1.15; p = 0.75). No adverse events were associated with the study.

Conclusion: Both MFNS and mometasone nasal irrigations are beneficial in symptom management of CRS. Our study suggests that patients who perform mometasone lavage do better in a clinically meaningful way, but our results are not definitive and further studies are warranted.
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http://dx.doi.org/10.1002/alr.22586DOI Listing
August 2020

Risk Factors for Patient-Reported Olfactory Dysfunction After Endoscopic Transsphenoidal Hypophysectomy.

JAMA Otolaryngol Head Neck Surg 2020 07;146(7):621-629

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Iatrogenic olfactory dysfunction after endoscopic transsphenoidal hypophysectomy (ETSH) is an overlooked complication without elucidated risk factors.

Objective: To assess the independent prognostic role of demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative parameters in patient-reported postoperative olfactory dysfunction, and to explore the association between anatomical measurements of the skull base and sinonasal cavity and postoperative olfactory dysfunction.

Design, Setting, And Participants: This retrospective cohort study in a tertiary care medical center enrolled consecutive patients with primary sellar lesions who underwent ETSH between January 1, 2015, and January 31, 2019. Patients were excluded if they underwent multiple sinonasal surgical procedures, presented with a sellar malignant neoplasm, required an expanded transsphenoidal approach, had nasal polyposis or a neurodegenerative disease, or sustained traumatic brain injury. After undergoing medical record review and telephone screening, patients were asked to participate in a 3-item telephone survey.

Main Outcomes And Measures: The primary outcome was the Clinical Global Impressions change in smell rating, a validated transitional patient-reported outcome measure. Patients rated their change in smell before and after ETSH on a 7-point Likert scale, with the following response options: (1) much better, (2) somewhat better, (3) slightly better, (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, or (7) much worse. Responses of slightly worse, somewhat worse, and much worse were surrogates for postoperative olfactory dysfunction status. Patient medical records, preoperative imaging scans, operative notes, and pathology reports were reviewed.

Results: Of the 147 patients (mean [SD] age, 54 [15] years; 79 women [54%]) who responded to the telephone survey, 42 (29%) reported olfactory dysfunction after ETSH. Median (interquartile range [IQR]) time between the ETSH completion and survey response was 31.1 (21-43) months. On multivariable analysis, abdominal fat grafting (adjusted relative risk [aRR], 2.95; 95% CI, 1.89-4.60) was associated with postoperative olfactory dysfunction, whereas smoking history (aRR, 1.54; 95% CI, 0.95-2.51) demonstrated a clinically meaningful but imprecise effect size. A more obtuse angle between the planum sphenoidale and face of the sella turcica on sagittal imaging was protective (aRR, 0.98; 95% CI, 0.96-0.99). Increased number of months after the ETSH was associated with patient-reported normosmia (aRR, 0.93; 95% CI, 0.91-0.95). In contrast, other comorbidities; intraoperative variables such as turbinate resection, nasoseptal flap, and mucosal or bone grafting; histological variables such as pathology and proliferative index; and postoperative variables such as adjuvant radiotherapy were not associated with postoperative olfactory dysfunction.

Conclusions And Relevance: This study found that abdominal fat grafting, acute skull base angle, and smoking history appeared to be clinically significant risk factors for patient-reported postoperative olfactory dysfunction. Increased time after ETSH may be associated with better olfactory outcomes.
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http://dx.doi.org/10.1001/jamaoto.2020.0673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206533PMC
July 2020

Powering the Gracilis for Facial Reanimation: A Systematic Review and Meta-analysis of Outcomes Based on Donor Nerve.

JAMA Otolaryngol Head Neck Surg 2020 05;146(5):429-436

Division of Facial Plastic & Reconstructive Surgery, Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Free gracilis transfer for dynamic reanimation in chronic facial paralysis is the gold standard, but there remains a need to better understand outcomes with respect to the donor nerve.

Objective: To characterize outcomes in adults undergoing primary gracilis transfer for facial paralysis stratified by donor nerve used for neurotization.

Data Sources: Search strategies were used in Ovid MEDLINE (1946-2019), Embase (1947-2019), Scopus (1823-2019), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (1997-2019).

Study Selection: Inclusion and exclusion criteria were designed to capture studies in adults with unilateral chronic facial paralysis undergoing single-paddle free gracilis transfer. All study types were included except case reports. Abstracts and full texts were reviewed in duplicate. Of 130 unique citations, 10 studies including 295 patients were included after applying inclusion and exclusion criteria. Data were analyzed between November 2018 and December 2019.

Data Extraction And Synthesis: PRISMA guidelines were followed. The Newcastle-Ottawa scale was used to assess study quality, and the Cochrane Risk of Bias tool was used to assess risk of bias. Independent extraction by 2 authors (P.M.V. and J.J.C.) was performed. Data were pooled using a random-effects model.

Main Outcomes And Measures: Owing to heterogeneity in reporting of facial reanimation outcomes, we first performed a systematic review, and then compiled available outcomes for meta-analysis. Outcomes studied for meta-analysis were oral commissure excursion and facial symmetry.

Results: Meta-analysis of masseteric nerve (MN) (n = 56) vs cross-facial nerve graft (CFNG) (n = 52) in 3 retrospective studies showed no statistical heterogeneity between these studies (I2 = 0%), and the standardized mean difference (SMD) was greater for MN (0.55; 95% CI, 0.17 to 0.94). Meta-analysis of angles of symmetry in 2 retrospective studies comparing MN (n = 51) to CFNG (n = 47) both at rest (-0.22; 95% CI, -0.63 to 0.18) and with smiling (-0.14; 95% CI, -0.73 to 0.46) were better with MN, though the difference was not statistically significant.

Conclusions And Relevance: Owing to heterogeneity in reported outcomes from facial reanimation, we were unable to make definitive conclusions regarding the optimal donor nerve. Establishing a reporting standard at peer-reviewed journals to improve results reporting is one method to allow for improved collaboration in the future. Standardizing follow-up times, assessing spontaneity in an objective and reproducible fashion, and use of consistent outcome measures would allow for future meta-analyses and better understanding of options for facial reanimation.
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http://dx.doi.org/10.1001/jamaoto.2020.0065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099528PMC
May 2020

Immediate and 1-Year Outcomes with a Slim Modiolar Cochlear Implant Electrode Array.

Otolaryngol Head Neck Surg 2020 May 17;162(5):731-736. Epub 2020 Mar 17.

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.

Objective: To explore the immediate and 1-year outcomes of patients who underwent implantation with the slim modiolar electrode (SME).

Study Design: Consecutive case series with chart review.

Setting: Tertiary referral academic center.

Subject And Methods: Between May 2016 and August 2018, a total of 326 cochlear implantations (CIs) were performed. Intraoperative x-rays were performed in all cases to identify tip rollovers. Scalar location was identified for 76 CIs that had postoperative computed tomography reconstructions. Speech outcomes were measured at 3, 6, and 12 months with consonant-nucleus-consonant word and AzBio sentences in quiet and noise (+10-dB signal-to-noise ratio). Preservation of hearing was defined as maintaining a low-frequency pure tone average ≤80 dB at 250 and 500 Hz.

Results: Among 326 CIs, 23 (7%) had tip rollovers. Postoperative reconstructions revealed 5 of 76 (6.6%) scalar translocations. A subset of 177 cases met criteria for evaluation of speech perception scores. The marginal mean differences between presurgery and 12 months for speech tests were as follows: consonant-nucleus-consonant, 43.7 (95% CI, 39.8-47.6); AzBio in quiet, 49.7 (95% CI, 44.9-54.4); and AzBio in noise, 29.9 (95% CI, 25.2-34.7). Sixty-one patients were identified with preservable hearing (low-frequency pure tone average ≤80 dB), and 12 of 61 (20%) preserved hearing at 1 year.

Conclusion: CI with SME provides reliable scala tympani insertion in a consistent perimodiolar position. An initially increased tip rollover rate improved with case volume and sheath design improvement. For long-term outcomes, speech performance was comparable to that of other cochlear implants. While hearing preservation for the SME may be better than prior perimodiolar electrodes, consistent outcomes are unlikely.
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http://dx.doi.org/10.1177/0194599820907336DOI Listing
May 2020

Incidence of Infectious Complications Following Cochlear Implantation in Children and Adults.

JAMA 2020 01;323(2):182-183

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

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http://dx.doi.org/10.1001/jama.2019.18611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990693PMC
January 2020

Importance of Defining and Interpreting a Clinically Meaningful Difference in Clinical Research.

JAMA Otolaryngol Head Neck Surg 2020 02;146(2):101-102

Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

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http://dx.doi.org/10.1001/jamaoto.2019.3744DOI Listing
February 2020

Predicting Hearing Loss After Radiotherapy and Cisplatin Chemotherapy in Patients With Head and Neck Cancer.

JAMA Otolaryngol Head Neck Surg 2020 02;146(2):106-112

Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Accurate, accessible predictions of posttreatment hearing loss for patients with head and neck cancer prior to the initiation of treatment are a necessary part of informed patient decision-making.

Objective: To develop a prediction model for postradiotherapy and/or post-cisplatin chemotherapy hearing loss for patients with head and neck cancer.

Design, Setting, And Participants: A retrospective cohort study was conducted at a tertiary academic medical center among 242 patients (482 ears) with head and neck cancer who were treated with radiotherapy and/or cisplatin from October 1, 2014, to July 31, 2018, and had follow-up audiometric data available.

Exposures: Radiotherapy and cisplatin chemotherapy.

Main Outcomes And Measures: Patient hearing level, as measured by the mean of pure tone audiometry at 1, 2, and 4 kHz on completion of treatment. A multivariable mixed model for predicting the posttreatment pure tone average was developed using only information available to clinicians at the beginning of treatment.

Results: A total of 242 patients (482 ears; 56 women and 186 men; mean [SD] age, 60 [10] years) were included in the analysis. All patients in the study received radiotherapy, and 105 (43.4%) received cisplatin chemotherapy. The mean (SD) total cumulative cisplatin dose was 298 (109) mg/m2. Patients' ears received a mean (SD) cochlear radiotherapy dose of 15 (13) Gy. The fixed-effects predictions from the predictive model agreed with 77% (95% CI, 73%-81%) of the variability in the posttreatment pure tone average. This predictive model also had a sensitivity of 80% and a specificity of 75% for predicting an observed posttreatment pure tone average greater than 35 dB (area under the receiver operating characteristic curve, 0.85).

Conclusions And Relevance: To our knowledge, this study develops the first accurate prediction model of posttreatment hearing in patients with head and neck cancer that is feasible for use in the clinical setting before the initiation of treatment. This research confirms that exposure of the cochlea to cisplatin chemotherapy and radiotherapy is associated with hearing loss in patients with head and neck cancer. Finally, this research motivates future studies of ototoxic effects to better understand the adverse effects of head and neck cancer treatment.
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http://dx.doi.org/10.1001/jamaoto.2019.3550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902235PMC
February 2020

Risk and Rate of Occult Contralateral Nodal Disease in Surgically Treated Patients With Human Papillomavirus-Related Squamous Cell Carcinoma of the Base of the Tongue.

JAMA Otolaryngol Head Neck Surg 2020 01;146(1):50-56

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: The optimal treatment strategy for patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) of the base of the tongue (BOT) has not been sufficiently studied.

Objective: To investigate the rate of and risk factors for occult contralateral nodal disease in patients with HPV-related BOT OPSCC undergoing transoral surgery and bilateral neck dissections.

Design, Setting, And Participants: This retrospective case series reviewed the medical records of patients with HPV-related BOT OPSCC who underwent transoral surgery and bilateral neck dissections from January 1, 2002, through December 31, 2018, at the tertiary care center of Washington University School of Medicine in St Louis. Patients had a median follow-up of 30.0 months (interquartile range, 11.0-60.4 months). Patients with recurrent disease or multiple synchronous OPSCC primary tumors were excluded for a total of 89 patients. Data were analyzed from January 1 through June 1, 2019.

Main Outcomes And Measures: The primary outcome was the rate of contralateral occult nodal disease. Secondary outcomes were potential risk factors for contralateral occult nodal disease and regional recurrence rates.

Results: Eighty-nine patients were included in the series, of whom 81 (91.0%) were men. The mean (SD) age was 60 (9) years. Overall, 34 patients (38.2%) had pathologic contralateral nodal metastases. Seventy patients had no clinical evidence of contralateral nodal disease. Of these 70, occult nodes were identified in 15 (21.4%). Risk of contralateral disease was higher when the primary tumor crossed midline (odds ratio, 6.23; 95% CI, 1.71-22.77). Of the 55 patients with no occult disease identified, only 2 (3.6%) received radiotherapy to the contralateral neck, and no regional recurrence of disease was noted.

Conclusions And Relevance: Given the rate of occult contralateral nodal disease of 21.4%, it appears that contralateral elective neck dissection or radiotherapy should be recommended in patients with HPV-related BOT OPSCC. Patients with a pathologically negative result of contralateral neck dissection may not benefit from radiotherapy to that nodal basin. Future prospective investigations should evaluate functional and oncologic outcomes of contralateral elective neck dissection compared with elective radiotherapy in the contralateral neck for HPV-related BOT OPSCC.
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http://dx.doi.org/10.1001/jamaoto.2019.3277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865237PMC
January 2020

Complications, Mortality, and Functional Decline in Patients 80 Years or Older Undergoing Major Head and Neck Ablation and Reconstruction.

JAMA Otolaryngol Head Neck Surg 2019 12;145(12):1150-1157

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Data regarding outcomes after major head and neck ablation and reconstruction in the growing geriatric population (specifically ≥80 years of age) are limited. Such information would be extremely valuable in preoperative discussions with elderly patients about their surgical risks and expected functional outcomes.

Objectives: To identify patient and surgical factors associated with 30-day postoperative complications, 90-day mortality, and 90-day functional decline; to explore whether an association exists between the type of reconstructive procedure and outcome; and to create a preoperative risk stratification system for these outcomes.

Design, Setting, And Participants: This retrospective, multi-institutional cohort study included patients 80 years or older undergoing pedicle or free-flap reconstruction after an ablative head and neck surgery from January 1, 2015, to December 31, 2017, at 17 academic centers. Data were analyzed from February 1 through April 20, 2019.

Main Outcomes And Measures: Thirty-day serious complication rate, 90-day mortality, and 90-day decline in functional status. Preoperative comorbidity and frailty were assessed using the American Society of Anesthesiologists classification, Adult Comorbidity Evaluation-27 score, and Modified Frailty Index. Multivariable clustered logistic regressions were performed. Conjunctive consolidation was used to create a risk stratification system.

Results: Among 376 patients included in the analysis (253 [67.3%] men), 281 (74.7%) underwent free-flap reconstruction. The median age was 83 years (range, 80-98 years). A total of 193 patients (51.3%) had 30-day serious complications, 30 (8.0%) died within 90 days, and 36 of those not dependent at baseline declined to dependent status (11.0%). Type of flap (free vs pedicle, bone vs no bone) was not associated with these outcomes. Variables associated with worse outcomes were age of at least 85 years (odds ratio [OR] for 90-day mortality, 1.19 [95% CI 1.14-1.26]), moderate or severe comorbidities (OR for 30-day complications, 1.80 [95% CI, 1.34-2.41]; OR for 90-day mortality, 3.33 [95% CI, 1.29-8.60]), body mass index (BMI) of less than 25 (OR for 30-day complications, 0.95 [95% CI, 0.91-0.99]), high frailty (OR for 30-day complications, 1.72 [95% CI, 1.10-2.67]), duration of surgery (OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), flap failure (OR for 90-day mortality, 3.56 [95% CI, 1.47-8.62]), additional operations (OR for 30-day complications, 5.40 [95% CI, 3.09-9.43]; OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), and surgery of the maxilla, oral cavity, or oropharynx (OR for 90-day functional decline, 2.51 [95% CI, 1.30-4.85]). Age, BMI, comorbidity, and frailty were consolidated into a novel 3-tier risk classification system.

Conclusions And Relevance: Important demographic, clinical, and surgical characteristics were found to be associated with postoperative complications, mortality, and functional decline in patients 80 years or older undergoing major head and neck surgery. Free flap and bony reconstruction were not independently associated with worse outcomes. A novel risk stratification system is presented.
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http://dx.doi.org/10.1001/jamaoto.2019.2768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802247PMC
December 2019

The metabotropic glutamate receptor 5 negative allosteric modulator fenobam: pharmacokinetics, side effects, and analgesic effects in healthy human subjects.

Pain 2020 01;161(1):135-146

Department of Anesthesiology, Washington University in Saint Louis School of Medicine, St. Louis, MO, United States.

Metabotropic glutamate receptor 5 (mGlu5) has been shown to modulate nociception in animals, but no mGlu5 antagonists have been developed commercially as analgesics. The mGlu5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl)urea] was originally evaluated for development as a nonbenzodiazepine anxiolytic. Fenobam is analgesic in numerous mouse pain models, acting exclusively through mGlu5 blockade. Furthermore, fenobam showed no signs of analgesic tolerance with up to 2 weeks of daily dosing in mice. Analgesic effects of fenobam in humans have not been reported. The purpose of this investigation was to evaluate fenobam pharmacokinetics and analgesic effects in humans. We first evaluated single-dose oral fenobam disposition in a parallel-group dose-escalation study in healthy volunteers. A second investigation tested the analgesic effects of fenobam in an established experimental human pain model of cutaneous sensitization using capsaicin cream and heat, in a double-blind placebo-controlled study. The primary outcome measure was the area of hyperalgesia and allodynia around the area applied with heat/capsaicin. Secondary outcome measures included nociception, measured as pain rating on a visual analog scale, heat pain detection threshold, and effects on cognition and mood. Fenobam plasma exposures showed considerable interindividual variability and were not linear with dose. Fenobam reduced sensitization vs placebo at a single timepoint (peak plasma concentration); we found no other difference between fenobam and placebo. Our results suggest highly variable fenobam disposition and minimal analgesic effects at the dose tested. We suggest that future studies testing analgesic effects of mGlu5 blockade are warranted, but such studies should use molecules with improved pharmacokinetic profiles.
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http://dx.doi.org/10.1097/j.pain.0000000000001695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923598PMC
January 2020