Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

BACKGROUND: Growth hormone (GH)-secreting pituitary adenoma is a severe endocrine disease. Surgery is the currently recommended primary therapy for patients with GH-secreting tumours. However, non-surgical therapy (pharmacological therapy and radiation therapy) may be performed as primary therapy or may improve surgical outcomes. OBJECTIVES: To assess the effects of surgical and non-surgical interventions for primary and salvage treatment of GH-secreting pituitary adenomas in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases was 1 August 2022. We did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of more than 12 weeks' duration, reporting on surgical, pharmacological, radiation, and combination interventions for GH-secreting pituitary adenomas in any healthcare setting. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance, screened for inclusion, completed data extraction, and performed a risk of bias assessment. We assessed studies for overall certainty of the evidence using GRADE. We estimated treatment effects using random-effects meta-analysis. We expressed results as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) for continuous outcomes, or in descriptive format when meta-analysis was not possible. MAIN RESULTS: We included eight RCTs that evaluated 445 adults with GH-secreting pituitary adenomas. Four studies reported that they included participants with macroadenomas, one study included a small number of participants with microadenomas. The remaining studies did not specify tumour subtypes. Studies evaluated surgical therapy alone, pharmacological therapy alone, or combination surgical and pharmacological therapy. Methodological quality varied, with many studies providing insufficient information to compare treatment strategies or accurately judge the risk of bias. We identified two main comparisons, surgery alone versus pharmacological therapy alone, and surgery alone versus pharmacological therapy and surgery combined. Surgical therapy alone versus pharmacological therapy alone Three studies with a total of 164 randomised participants investigated this comparison. Only one study narratively described hyperglycaemia as a disease-related complication. All three studies reported adverse events, yet only one study reported numbers separately for the intervention arms; none of the 11 participants were observed to develop gallbladder stones or sludge on ultrasonography following surgery, while five of 11 participants experienced any biliary problems following pharmacological therapy (RR 0.09, 95% CI 0.01 to 1.47; 1 study, 22 participants; very low-certainty evidence). Health-related quality of life was reported to improve similarly in both intervention arms during follow-up. Surgery alone compared to pharmacological therapy alone may slightly increase the biochemical remission rate from 12 weeks to one year after intervention, but the evidence is very uncertain; 36/78 participants in the surgery-alone group versus 15/66 in the pharmacological therapy group showed biochemical remission. The need for additional surgery or non-surgical therapy for recurrent or persistent disease was described for single study arms only. Surgical therapy alone versus preoperative pharmacological therapy and surgery Five studies with a total of 281 randomised participants provided data for this comparison. Preoperative pharmacological therapy and surgery may have little to no effect on the disease-related complication of a difficult intubation (requiring postponement of surgery) compared to surgery alone, but the evidence is very uncertain (RR 2.00, 95% CI 0.19 to 21.34; 1 study, 98 participants; very low-certainty evidence). Surgery alone may have little to no effect on (transient and persistent) adverse events when compared to preoperative pharmacological therapy and surgery, but again, the evidence is very uncertain (RR 1.23, 95% CI 0.75 to 2.03; 5 studies, 267 participants; very low-certainty evidence). Concerning biochemical remission, surgery alone compared to preoperative pharmacological therapy and surgery may not increase remission rates up until 16 weeks after surgery; 23 of 134 participants in the surgery-alone group versus 51 of 133 in the preoperative pharmacological therapy and surgery group showed biochemical remission. Furthermore, the very low-certainty evidence did not suggest benefit or detriment of preoperative pharmacological therapy and surgery compared to surgery alone for the outcomes 'requiring additional surgery' (RR 0.48, 95% CI 0.05 to 5.06; 1 study, 61 participants; very low-certainty evidence) or 'non-surgical therapy for recurrent or persistent disease' (RR 1.22, 95% CI 0.65 to 2.28; 2 studies, 100 participants; very low-certainty evidence). None of the included studies measured health-related quality of life. None of the eight included studies measured disease recurrence or socioeconomic effects. While three of the eight studies reported no deaths to have occurred, one study mentioned that overall, two participants had died within five years of the start of the study. AUTHORS' CONCLUSIONS: Within the context of GH-secreting pituitary adenomas, patient-relevant outcomes, such as disease-related complications, adverse events and disease recurrence were not, or only sparsely, reported. When reported, we found that surgery may have little or no effect on the outcomes compared to the comparator treatment. The current evidence is limited by the small number of included studies, as well as the unclear risk of bias in most studies. The high uncertainty of evidence significantly limits the applicability of our findings to clinical practice. Detailed reporting on the burden of recurrent disease is an important knowledge gap to be evaluated in future research studies. It is also crucial that future studies in this area are designed to report on outcomes by tumour subtype (that is, macroadenomas versus microadenomas) so that future subgroup analyses can be conducted. More rigorous and larger studies, powered to address these research questions, are required to assess the merits of neoadjuvant pharmacological therapy or first-line pharmacotherapy.

Post-operative surveillance for somatotroph, lactotroph and non-functional pituitary adenomas after curative resection: a systematic review.

CONTEXT: Pituitary tumors are the third most common brain tumor and yet there is no standardization of the surveillance schedule and assessment modalities after transsphenoidal surgery. EVIDENCE ACQUISITION: OVID, EMBASE and the Cochrane Library databases were systematically screened from database inception to March 5, 2020. Inclusion and exclusion criteria were designed to capture studies examining detection of pituitary adenoma recurrence in patients 18 years of age and older following surgical resection with curative intent. EVIDENCE SYNTHESIS: A total of 7936 abstracts were screened, with 812 articles reviewed in full text and 77 meeting inclusion criteria for data extraction. A pooled analysis demonstrated recurrence rates at 1 year, 5 years and 10 years for non-functioning pituitary adenomas (NFPA; N = 3533 participants) were 1%, 17%, and 33%, for prolactin-secreting adenomas (PSPA; N = 1295) were 6%, 21%, and 28%, and for growth-hormone pituitary adenomas (GHPA; N = 1257) were 3%, 8% and 13%, respectively. Rates of recurrence prior to 1 year were 0% for NFPA, 1-2% for PSPA and 0% for GHPA. The mean time to disease recurrence for NFPA, PSPA and GHPA were 4.25, 2.52 and 4.18 years, respectively. CONCLUSIONS: This comprehensive review of the literature quantified the recurrence rates for commonly observed pituitary adenomas after transsphenoidal surgical resection with curative intent. Our findings suggest that surveillance within 1 year may be of low yield. Further clinical trials and cohort studies investigating cost-effectiveness of surveillance schedules and impact on quality of life of patients under surveillance will provide further insight to optimize follow-up.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas.

PURPOSE: The objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective. METHODS: We developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively. CONCLUSIONS: Using standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.

Cost-effectiveness of Endoscopic Polypectomy in Clinic compared to Endoscopic Sinus Surgery: A modelling study.

OBJECTIVE: To compare costs and quality-adjusted life years of patients receiving endoscopic polypectomy in the clinic those receiving endoscopic sinus surgery from the perspective of Canada's health system. METHOD: We developed a Markov model to simulate costs and quality-adjusted life years among a cohort of patients with chronic rhinosinusitis with polyps who received endoscopic polypectomy in clinic or endoscopic sinus surgery, over a patient's lifetime. Our study focused on patients with chronic rhinosinusitis with polyps who have the predominant symptom of bilateral nasal obstruction. Cost data were obtained from Canadian sources. Health utility values were derived from Sino-nasal Outcome Test (SNOT-22) scores reported in the published literature. A cycle length of six months was used. Both costs and quality-adjusted life years were discounted using an annual rate of 1.5%. We conducted one-way and probabilistic sensitivity analyses to assess the robustness of the study findings. RESULTS: Endoscopic polypectomy in clinic was a cost-saving option as it had a lower cost (C$736 vs. C$6,728) and produced more quality-adjusted life years (13.85 vs 13.06) compared to endoscopic sinus surgery. Our findings were, however, highly sensitive to health utility values. Results from probabilistic sensitivity analysis showed that endoscopic polypectomy in clinic had a lower cost and was more effective compared to endoscopic sinus surgery in 99.86% of iterations. CONCLUSION: From the perspective of the publicly funded healthcare system, endoscopic polypectomy in clinic was economically attractive compared to endoscopic sinus surgery for chronic rhinosinusitis with polyps patients who have a primary symptom of bilateral nasal obstruction. The cost-effectiveness results are, however, highly dependent on the relative impact of endoscopic polypectomy in the clinic and endoscopic sinus surgery on post-surgery health utility values.

Patient and Public Outreach Initiatives in Chronic Rhinosinusitis from the Canadian Sinusitis Working Group: Support for Affected Patients and Extending an Understanding of CRS to the General Public.

Chronic rhinosinusitis is an important disease entity that affects patients worldwide, yet there is limited public awareness regarding the disease. The Canadian Rhinosinusitis Working Group, a group of diverse medical professionals, has made a multitude of efforts to help improve the health literacy of patients and important stakeholders, as well as the quality of life of patients with chronic rhinosinusitis. This review will aim to outline these initiatives.

Direct costs of adult chronic rhinosinusitis by using 4 methods of estimation: Results of the US Medical Expenditure Panel Survey.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease that affects 2% to 16% of the US population. Despite its increasing prevalence, there are currently limited data in the literature evaluating the economic burden of this disease. OBJECTIVE: This study aimed to determine the direct health care costs of CRS from the perspective of the US government. METHODS: A prevalence-based approach was used to estimate cost of illness for CRS from the 2011 Medical Expenditure Panel Survey database by using a 4-part model: (1) an estimated sum of all health care expenditures, (2) an attribution model for disease-specific estimation of expenditures, (3) an estimation based on a propensity score model, and (4) estimated disease-specific expenditure by using a linear regression-based approach. A disease prevalence of 3.5% was used. RESULTS: The mean CRS-specific annual expenditure was $5955 (95% CI, $5087-$6823) by using method 1 compared with $5560 (95% CI, $4689-$6431) by using method 2 and $5560 (95% CI, $4653-$6467) by using method 3. The annual expenditure, as estimated by using method 4, was $5589 (95% CI, $4986-$6192). Ambulatory expenses accounted for the largest proportion of expenditures, followed by prescription and in-hospital expenses. CONCLUSIONS: This study provided a range of estimates of the direct medical expenditures associated with CRS. We demonstrated that the economic burden attributable to this disease was an estimated $60.2 to $64.5 billion US dollars in 2011, with a wide variation in the total and incremental direct expenditures depending on the type of estimation model used and the prevalence assumed.

Medical ID use by international patients with Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Patients widely use medical identification (ID) to indicate their food and drug allergies, and chronic medical conditions. One chronic condition for which patients are recommended to use a form of medical ID is Aspirin-Exacerbated Respiratory Disease (AERD), a disease characterized by the presence of asthma, chronic rhinosinusitis with nasal polyps and sensitivity to aspirin and other COX-1 inhibitors, including nonsteroidal anti-inflammatory drugs (NSAIDs). The uptake of medical ID use in AERD is unknown and has not been widely studied in this population. METHODS: We conducted a cross-sectional survey study to measure the perception of the need to use a medical ID and its use by patients with AERD internationally. RESULTS: 245 members of an online AERD support group completed an online survey. The majority (80%, n = 198) of the participants did not use any form of medical ID. The participants reported that the lack of knowledge and awareness about the importance of using a medical ID was the most common reason for not using it. CONCLUSION: This international survey found that the majority of the AERD patient respondents did not use a medical ID. The most common reasons for nonuse were not knowing that it is recommended for their condition and that the patients did not consider it necessary. The results highlight the need for further patient and health care provider education.

Cost-effectiveness analysis of biologics for the treatment of chronic rhinosinusitis with nasal polyps in Canada.

BACKGROUND: Dupilumab, omalizumab, and mepolizumab are the three biologics currently approved for use in CRSwNP in Canada. Despite evidence of efficacy, their cost-effectiveness, which is a key factor influencing prescribing patterns, has not yet been compared to each other. METHODS: A cost-effectiveness model using quality-adjusted life years (QALYs) was constructed using a Decision Tree Markov analysis. A third-party healthcare payer perspective and a 10-year time horizon was used. A willingness-to-pay (WTP) threshold of 50,000 Canadian dollars (CAD) per QALY was used to determine cost-effectiveness. Dupilumab, omalizumab, and mepolizumab were each compared to each other. RESULTS: Omalizumab was the most cost-effective biologic using current estimates of cost and efficacy in CRSwNP. Using omalizumab as a baseline, dupilumab had an ICER of $235,305/QALY. Mepolizumab was dominated by omalizumab and dupilumab at the current drug prices and estimates of efficacy. Sensitivity analyses determined that when increasing the WTP threshold to $150,000/QALY, dupilumab became cost-effective compared to omalizumab in 22.5% of simulation scenarios. Additionally, altering dosing frequency had a significant effect on cost-effectiveness. CONCLUSION: When comparing the relative cost-effectiveness of biologics in recalcitrant CRSwNP, omalizumab currently appears to be the most cost-effective option. Future reductions in drug prices, adjustments to currently approved dosing regimens, better patient selection, and improvements in sinus surgery outcomes will challenge the current cost-effectiveness models and necessitate reassessment as treatments for CRSwNP continue to evolve.

Cost-effectiveness of postoperative imaging surveillance strategies for nonfunctional pituitary adenomas after resection with curative intent.

OBJECTIVE: The aim of this study was to determine an optimal follow-up imaging surveillance strategy in terms of cost-effectiveness after resection of nonfunctioning pituitary adenomas with curative intent. METHODS: An individual-level state-transition microsimulation model was used to simulate costs and outcomes associated with three postoperative imaging strategies over a lifetime time horizon: 1) annual MRI surveillance, 2) tapered MRI surveillance (annual surveillance for 5 years followed by surveillance every 2 years), and 3) personalized surveillance (annual surveillance for 5 years followed by surveillance every 2 years when MRI shows remnant disease/postoperative changes, and surveillance at 7, 10, and 15 years for disease-free MRI). Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually. Model outcomes included lifetime costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, annual surveillance yielded higher costs and lower health effects (QALYs) compared with the tapered and personalized surveillance strategies (dominated). Personalized surveillance demonstrated an additional 0.1 QALY at additional cost ($1298) compared with tapered surveillance (7.7 QALYs at a cost of $12,862). The ICER was $11,793/QALY. The optimal decision was most sensitive to the probability of postoperative changes on MRI after surgery and MRI cost. Accounting for parameter uncertainty, personalized surveillance had a higher probability of being a cost-effective surveillance option compared with the alternative strategies at 79%. CONCLUSIONS: Using standard cost-effectiveness thresholds in the US ($100,000/QALY), personalized surveillance that accounted for remnant disease or postoperative changes on MRI was cost-effective compared with alternative surveillance strategies.

Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Canadian guidelines for rhinosinusitis: practical tools for the busy clinician.

Acute bacterial rhinosinusitis (ABRS) and chronic rhinosinusitis (CRS) frequently present in clinical practice. Guidelines for management of these conditions have been published extensively in the past. However, a set of guidelines that addressed issues specific to the Canadian environment while offering clear guidance for first-line clinicians was needed, and resulted in the recent publication of Canadian clinical practice guidelines for ABRS and CRS. In addition to addressing issues specific to Canadian physicians, the presented guidelines are applicable internationally, and offer single algorithms for the diagnosis and management of ABRS and CRS, as well as expert opinion in areas that do not have an extensive evidence base. This commentary presents major points from the guidelines, as well as the intended impact of the guidelines on clinical practice.See guidelines at: http://www.aacijournal.com/content/7/1/2.

Canadian real-world study of access and clinical results using dupilumab for chronic rhinosinusitis with polyps.

BACKGROUND: Dupilumab is the first monoclonal antibody therapy to be approved in Canada for the treatment of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The goal of the study was to assess its effectiveness and efficacy in a real-world setting. This study aims to assess how clinical outcomes of biologic therapy in real-world application (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness gap. METHODS: A retrospective study evaluating disease specific sinonasal outcomes routinely collected for clinical care. This study included patients who were evaluated for coverage of dupilumab at a tertiary care rhinology clinic for the treatment of CRSwNP in the first year since dupilumab was approved in Canada for this indication. Sinonasal outcomes were be evaluated by collecting data on the Sino-Nasal Outcome Test (SNOT)-22 questionnaire. RESULTS: Eighty-five patients were considered for dupilumab therapy during the study period, 49% patients were able to attain coverage for the requested therapy. The mean SNOT-22 score at baseline was 60.56 (SD 21.63). After 16 weeks of treatment the mean SNOT-22 score decreased by 37 points to 23.36; at 28 weeks the mean SNOT-22 was 23.47. After 1 year, the mean SNOT-22 score was 14.37. CONCLUSION: Patients treated with dupilumab for CRSwNP at out tertiary rhinology clinic showed substantial clinical symptom improvement that is similar to that observed in prior randomised clinical trials. No serious adverse effects related to dupilumab were reported in this cohort. Long-term follow-up is needed to inform effectiveness analyses beyond the 1 year clinical trial duration.

Recovery of Cranial Nerve Deficits in Patients Presenting with Pituitary Apoplexy: A Case Series.

Background Pituitary apoplexy (PA) is a rare complication of pituitary tumors that can present with a myriad of symptoms, including sudden onset cranial nerve deficits. After patient stabilization and hormone replacement, surgical decompression is often recommended. The timing of surgical decompression remains controversial. In this case series, we describe our institutional experience pertaining to the cranial nerve recovery in patients who underwent endoscopic endonasal transsphenoidal (EETS) surgery for PA while evaluating outcome based on tumor stage using the suprasellar infrasellar parasellar anterior posterior (SIPAP) classification. Design Present study is a single-institution retrospective cohort. Methods A retrospective review of all EETS cases for pituitary tumor resection between November 2009 and August 2018. Queries of the hospital database were completed by trained personnel to identify cases of PA treated using the EETS approach. Baseline characteristics, tumor type, endocrine data, and SIPAP classification based on preoperative magnetic resonance imaging (MRI) and operation characteristics were extracted from medical records. Postoperative results were extracted for the duration of the follow-up period available for each patient. Results Fifteen cases of PA were identified. Patient follow-up period was a mean of 30 months. The cranial nerve deficits present at admission were visual deficit (33%); unilateral third nerve palsy (47%) and unilateral sixth nerve palsy (27%). No fourth nerve palsies were observed. Following EETS, 60% of patients with preoperative visual deficit had normal visual fields. For those with third and sixth nerve palsies preoperatively, 43 and 75%, respectively, had return to normal function postoperatively. SIPAP tumor characteristics were not related to postoperative cranial nerve recovery. Conclusion In this series of surgically treated patients with pituitary apoplexy, all cranial nerve deficits normalized or improved following surgery. The tumor SIPAP classification was not associated with patient outcome. Though in a small series, the presented results suggest surgical treatment is beneficial for these patients.

Socioeconomic status: a disease modifier of chronic rhinosinusitis?

INTRODUCTION: The Lund-MacKay score (LMS) correlates poorly with chronic rhinosinusitis (CRS) symptom severity. Patients with CRS also tend to report relatively lower levels of mental wellbeing. Our purpose was to determine if there is a correlation between socio-economic status (SES) and CRS severity as measured by the LMS, and if there is an association between depression symptoms and the severity of CRS using the LMS. METHODS: A total of 127 patients diagnosed with CRS were prospectively recruited and assessed with a sinonasal assessment questionnaire (SNAQ-11), and the Patient Health Questionnaire (PHQ-9) for depression. Each patient`s education level, family income, and smoking behavior were determined. The sinus CT scan was scored using the LMS. The data were analyzed using ordinary least squares (OLS) regression techniques. RESULTS: Having a highschool education or less was associated with higher SNAQ-11 scores while being a daily smoker was associated with higher SNAQ-11 scores. There was no significant relationship between educational attainment, financial income or daily smoking and sinus CT score. Including depression scores in the SNAQ-11, regression equations indicated a significant and positive relationship between depression severity and SNAQ-11 score. CRS with polyps was negatively associated with SNAQ-11 scores but, as expected, it was positively associated with a higher LMS. CONCLUSIONS: Lower SES status is a negative modifying factor of subjective CRS severity but it has no impact on the LMS. Depression symptoms are associated with increased subjective CRS severity but they have no effect on the LMS. How SES and depression impact on a patient`s self-reported disease severity requires further study.

Olfactory recovery following infection with COVID-19: A systematic review.

Olfactory loss has been identified as one of the common symptoms related to COVID-19 infection. Although olfactory loss is recognized, our understanding of both the extent of loss and time to olfactory recovery following infection is less well known. Similarly, knowledge of potential impactful patient factors and therapies that influence olfactory recovery is desirable but is not overtly clear in the literature. Our systematic review sought to fill this knowledge gap. We included studies that: involved either an observational or an interventional design that reported data on patients with olfactory dysfunction due to Reverse Transcription Polymerase Chain Reaction (RT-PCR) diagnosed COVID-19 infection; and reported data regarding olfactory recovery measured by an objective olfactory test, Likert scale and/or visual analog scale (VAS). The study methods were determined a priori and registered in PROSPERO (Registration Number CRD42020204354). An information specialist searched Medline, Embase, LitCovid and the Cochrane Register of Controlled Trials up to March 2021, and two reviewers were involved in all aspects of study selection and data collection. After screening 2788 citations, a total of 44 studies of assorted observational designs were included. Patients had undergone objective COVID-19 testing, and most were adult patients with mild to moderate COVID-19. Olfactory recovery was found to occur as early as 7 days, with most patients recovering olfaction within 30 days. Few studies included prolonged follow-up to 6 months or longer duration. Poor olfaction at initial presentation was associated with poor recovery rates. Only a small number of studies assessed olfactory retraining and steroid therapy. Additional trials are underway.

What is the optimal outcome after endoscopic sinus surgery in the treatment of chronic rhinosinusitis? A consultation of Canadian experts.

OBJECTIVES: Many experts feel that in the absence of well-defined goals for success, they have an easier time identifying failure. As success ought to not be defined only by absence of failure, we aimed to define optimal outcomes for endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) by obtaining expert surgeon perspectives. METHODS: A total of 12 surgeons participated in this targeted consultation. Face to face semi-structured interviews were performed with expert surgeons in the field of CRS and ESS. General impressions and personal definitions of acceptable operative success and optimal operative outcomes were compiled and summarized. RESULTS: According to an expert survey, patients' main objectives are an improvement in their chief complain, a general improvement in quality of life (QoL), and a better overall symptomatic control. The most important aspects of endoscopy for defining a successful intervention were an adequate mucus circulation, a healthy mucosa, minimal edema, and patency of all explored cavities or ostia. In the assessment of surgical outcomes, it was determined that both objective and patient reported data must be carefully examined, with more attention given to subjective outcomes. CONCLUSIONS: According to data gathered from a Canadian expert consultation, a definition of success must be based on both subjective data and nasal endoscopy. We propose to define an acceptable outcome as either a subjective improvement of at least the minimal clinically improvement difference of a validated patient reported outcome questionnaire, along with a satisfactory endoscopic result (1) or a complete subjective resolution with a sub-optimal endoscopy (2).

Choosing Wisely Canada rhinology recommendations.

The Choosing Wisely Canada campaign is an initiative that aims to involve physicians and patients in collaborative decision making to avoid unnecessary tests and treatments. The Rhinology Subspecialty Group of the Canadian Society of Otolaryngology - Head & Neck Surgery developed a list of five evidence-based recommendations for the management of acute rhinosinusitis and nasal fractures: (1) don't prescribe antibiotics to patients with acute sinusitis who do not meet the diagnostic criteria for acute bacterial rhinosinusitis; (2) don't order a CT scan for uncomplicated acute rhinosinusitis; (3) don't order plain film sinus x-rays; (4) don't swab the nasal cavity as part of the work up for rhinosinusitis; and (5) don't order a plain film x-ray in the evaluation of nasal fractures.

Clinical Outcomes of Endoscopic Endonasal Odontoidectomy: A Single-Center Experience.

BACKGROUND: Odontoidectomy for basilar invagination and craniovertebral junction pathology traditionally has been performed using a transoral route. However, the endoscopic endonasal approach to the anterior craniovertebral junction may offer safer and more effective access when compared with transoral approaches. The objective of this study is to review the surgical outcomes and complications associated with endoscopic endonasal odontoidectomy. METHODS: This study is a retrospective chart review of all adult patients who underwent an endoscopic endonasal odontoidectomy at a single tertiary care center between January 2011 and May 2019. RESULTS: Seventeen patients who underwent endoscopic endonasal odontoidectomy were included. The median age at admission was 67 years (range: 33-84 years) and 65% of the patients were female. One patient (1/17, 6%) had vertebral artery injury, which had to be coiled with no neurologic deficits, and 4 patients (4/17, 24%) had intraoperative CSF leaks with no postoperative leak. Fourteen (14/17, 82%) patients were extubated by postoperative day 1. Three patients (3/17, 18%) developed postoperative sinus infections and required antibiotics. Eight patients (8/17, 47%) developed transient postoperative dysphagia. One patient (1/17, 6%) had postoperative epistaxis and 1 patient (1/17, 6%) had postoperative lower cranial nerve symptoms. The median length of hospital stay was 13 days (range: 2-44 days). CONCLUSIONS: Although the transoral approach has been the traditional route for anterior decompression of the craniovertebral junction, endoscopic endonasal odontoidectomy is a feasible and well-tolerated procedure associated with satisfactory patient outcomes and low morbidity.

Pharmacologic and surgical therapies for patients with Meniere's disease: A systematic review and network meta-analysis.

BACKGROUND: Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs). METHODS: Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes. RESULTS: We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002). CONCLUSION: To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.