Olfactory Impairment and Frailty: A Systematic Review and Meta-Analysis.

Importance: Olfactory impairment (OI) and frailty are prevalent conditions associated with aging, but studies investigating their association with each other have been discordant. Objective: To summarize current evidence surrounding the association between OI and frailty. Data Sources: PubMed, Embase, Cochrane Library, SCOPUS, and CINAHL from inception to November 28, 2023. Study Selection: This study included observational studies investigating the association between objectively or subjectively assessed OI and objectively evaluated frailty among adults. Data Extraction and Synthesis: Two independent authors extracted data into a structured template. Maximally adjusted estimates were pooled using a random-effects model, and statistical heterogeneity was evaluated using I2 values. Additional prespecified subgroup and sensitivity analyses were performed. This study used the Newcastle-Ottawa Scale for bias assessment and the Grading of Recommendations Assessment, Development and Evaluation framework for overall evidence quality evaluation. Main Outcomes and Measures: The primary outcome was the cross-sectional association between OI and frailty, for which the odds of frailty were compared between participants with and without OI. The secondary outcome was the cross-sectional association between frailty and OI, for which the odds of OI were compared between participants with and without frailty. Results: This study included 10 studies with 10 624 patients (52.9% female; mean [SD] age, 62.9 [9.6] years). The Newcastle-Ottawa Scale score of studies ranged from low to moderate. Grading of Recommendations Assessment, Development and Evaluation scores ranged from low to moderate. OI was associated with a 2.32-fold (odds ratio [OR], 2.32; 95% CI, 1.63-3.31; I2 = 0%) greater odds of frailty compared with individuals with healthy olfactory function. The odds of OI was progressively greater with categorical frailty status, with a 1.55-fold (OR, 1.55; 95% CI, 1.32-1.82; I2 = 0%), 2.28-fold (OR, 2.28; 95% CI, 1.96-2.65; I2 = 0%), and 4.67-fold (OR, 4.67; 95% CI, 2.77-7.86; I2 = 0%) increase in odds for individuals with prefrailty, frailty, and the most frailty, respectively, compared with robust individuals. The results demonstrated stability in subgroup analyses (geographical continent of study, objective vs subjective olfactory assessment) and sensitivity tests. Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that there is an association between OI and frailty, with an increase in the odds of OI with worsening categorical frailty status among individuals with prefrailty, frailty, and the most frailty. OI may be a potential biomarker for frailty. Future studies could delve into whether OI may be a modifiable risk factor for frailty.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Infectious disease for the rhinologist.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent literature relating to viral, fungal and bacterial infections and their interactions within the sinonasal tract in the past 18 months. RECENT FINDINGS: Coronavirus disease 2019 (COVID-19)-associated olfactory dysfunction (OD) is variant dependent. Magnetic resonance imaging studies have found greater olfactory cleft opacification and higher olfactory bulb volume in post-COVID-19 OD. Olfactory training remains the mainstay of treatment, while platelet-rich plasma injections and ultramicronized palmitoylethanolamide and luteolin combination oral supplementation have shown early promise.Consensus statements on paranasal sinus fungal balls and acute invasive fungal sinusitis have been released.Studies on the nasal microbiome have reported Staphylococcus and Corynebacterium as the most abundant genera, with higher levels of Staphylococcus and Corynebacterium being found in patients with chronic rhinosinusitis (CRS) and healthy individuals respectively. However, there is conflicting evidence on the significance of biodiversity of the nasal microbiome found in CRS versus healthy patients. SUMMARY: While the peak of the COVID-19 pandemic is behind us, its sequelae continue to pose treatment challenges. Further studies in OD have implications in managing the condition, beyond those afflicted post-COVID-19 infection. Similarly, more research is needed in studying the nasal microbiome and its implications in the development and treatment of CRS.

Association Between Smoking and Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease of the upper airway. The impact of smoking on CRS has not been clearly established. We aim to clarify the association between first-hand cigarette smoking and the prevalence and prognoses of CRS. REVIEW METHODS: PubMed, Embase, SCOPUS, and Cochrane Library were searched from inception until May 15, 2022. Three blinded reviewers selected relevant studies, extracted data, and evaluated study bias following a PROSPERO-registered protocol (CRD42022345585). We used random-effects meta-analyses to pool the prevalence of smoking in CRS, association between smoking status and CRS, and association of smoking with quality of life (QOL) before and after functional endoscopic sinus surgery (FESS). We also performed descriptive analyses of olfactory function, CT scores, and endoscopy scores before and after FESS. RESULTS: We included 23 cross-sectional studies, 19 cohort studies, two case-control studies, and one prospective clinical trial. The pooled prevalence of ever-smokers was 40% (95% CI = 0.30-0.51) and 33% (95% CI = 0.25-0.43) in patients with and without CRS. Compared to never-smokers, active smokers and past smokers had 1.35 (95% CI = 1.18-1.55) and 1.23 (95% CI = 1.17-1.29) higher odds of having CRS. Among patients with CRS, non-smokers reported higher initial QOL than smokers (standardized mean difference [SMD] = 0.23, 95% CI = 0.11-0.35), although post-FESS QOL was similar (SMD = 0.10, 95% CI = -0.30-0.51). Descriptive analysis found no significant correlations between smoking and post-FESS olfactory function and endoscopy scores. CONCLUSIONS: Cigarette smoking is associated with higher prevalence and odds of CRS. Clinicians should be aware that smoking predisposes to CRS, but does not negatively impact the rhinologic outcomes of FESS. Laryngoscope, 134:2513-2524, 2024.

The Impact of Hearing Impairment on Health Indicators in a Multiethnic Population of Older Adults in Singapore.

Background and Objectives: To determine the impact of hearing impairment (HI) on health indicators in a multiethnic Singaporean population of older adults. Research Design and Methods: In this cross-sectional, population-based study, pure-tone averages of air-conduction thresholds at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz were calculated for each ear. Eight categories of HI were defined ranging from: 1: No HI to 8: Bilateral severe HI. Health indicators included hearing-related quality of life (H-QoL), depressive symptoms, frailty, gait speed, instrumental activities of daily living, sarcopenia, and cognitive impairment. Multivariable regression models determined the independent associations between HI and outcomes. Results: A total of 2,503 older adults (mean age ± SD 73.4 ± 8.4; 55.2% female participants) were enrolled. Of these, 289 (11.6%), 259 (10.4%), 798 (31.9%), 303 (12.1%), 515 (20.6%), 52 (2.1%), 155 (6.2%), and 115 (4.6%) had hearing levels in Cats 1 to 8, respectively; and 20 (0.8%) used a hearing aid. Compared to those with no HI, participants with unilateral mild HI (Cat 2) had a 107% reduction in H-QoL (ß: 0.63; CI: 0.18, 1.09, p = .006), increasing to a 2,816% reduction (ß: 16.78; CI: 13.25, 20.31, p < .001) in those with bilateral severe HI-Cat 8 (p-trend < .001). Those with Cat 8 also had lower gait speed and we observed a nonsignificant increase in odds of frailty as HI worsened. Discussion and Implications: H-QoL is affected across the spectrum of severity and laterality of HI. Interventions to alleviate the effects of HI and provision of QoL support are warranted. Other health indicators were only affected in late stages, suggesting that slowing disease progression is crucial in clinical management.

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves.

OBJECTIVE: To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021. REVIEW METHODS: Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery. MAIN OUTCOME MEASURES: The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste. RESULTS: 18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I2=70%, τ2=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I2=67%, τ2=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I2=0.0-77.2%, τ2=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I2=0.0-72.1%, τ2=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I2=20%, τ2=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I2=78%, τ2=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I2=10%, τ2<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I2=0%, τ2<0.001) were less likely to recover their sense of smell. CONCLUSIONS: A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021283922.

Association of Olfactory Impairment With All-Cause Mortality: A Systematic Review and Meta-analysis.

Importance: Olfactory impairment is highly prevalent and associated with multiple comorbidities, including neurodegenerative, cardiovascular, nutritional, and immune disorders. However, epidemiologic associations between olfactory impairment and mortality are discordant. Objective: To systematically clarify the epidemiologic associations between olfactory impairment and mortality. Data Sources: The PubMed, Embase, and Cochrane Library databases were searched from inception to August 13, 2021. Study Selection: Two blinded reviewers selected observational studies published as full-length, English-language articles in peer-reviewed journals that reported the presence or severity of chronic olfactory impairment, whether objectively measured or self-reported, in association with any mortality estimate, among adults aged 18 years or older. Data Extraction and Synthesis: Two reviewers independently extracted data, evaluated study bias using the Newcastle-Ottawa Scale, and appraised the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, heterogeneity was measured using I2 statistics, sources of heterogeneity were investigated using meta-regression and subgroup meta-analyses, and publication bias was qualitatively and quantitatively assessed. Main Outcomes and Measures: Hazard ratios for all-cause mortality. Results: One retrospective cohort study and 10 prospective cohort studies (with a total of 21 601 participants) from 1088 nonduplicated records were included. Ten studies had a low risk of bias, whereas 1 study had a moderate risk; exclusion of the latter did not alter conclusions. Nine studies were included in the meta-analysis. Olfactory loss was associated with a significantly higher pooled hazard of all-cause mortality (hazard ratio, 1.52; 95% CI, 1.28-1.80; I2 = 82%). Meta-regression sufficiently explained heterogeneity, with longer mean follow-up duration weakening the pooled association, accounting for 91.3% of heterogeneity. Self-reported and objective effect sizes were similar. Associations were robust to trim-and-fill adjustment and the Egger test for publication bias. The overall quality of evidence was moderate. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that olfactory impairment is associated with all-cause mortality and may be a marker of general health and biological aging. Further research is required to establish the underlying mechanisms and the scope for interventions.

Neuroradiological Basis of COVID-19 Olfactory Dysfunction: A Systematic Review and Meta-Analysis.

OBJECTIVE: Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention. METHODS: PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD. RESULTS: We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes. CONCLUSION: Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.

Adaptations of a Tertiary Otorhinolaryngology Head and Neck Surgery Department in Singapore during the COVID-19 Outbreak.

PURPOSE: The novel coronavirus 2019 (COVID-19) outbreak which was first reported in Wuhan, China has been declared a pandemic by the World Health Organization on March 11, 2020. Otorhinolaryngologists deal intimately with pathologies of the head and neck region and upper respiratory tract and have been reported as a vulnerable group of healthcare workers who may be more susceptible to COVID-19 nosocomial infection. METHODS: In this article, we provide a comprehensive overview of the adaptations of Singapore's largest tertiary Otorhinolaryngology department during the COVID-19 outbreak. This was undertaken via an evidence-based approach. The relevant medical literature and evidence underlying our adaptations are highlighted. RESULTS: A four-pronged strategy including (1) personnel segregation, (2) triaging and decantment, (3) use of personal protective equipment and (4) changes in clinical practice was employed. The strategy was bolstered by drawing upon a collective learnt experience from the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. CONCLUSION: A rigorous framework which can preserve operationality while navigating the heightened risks during this outbreak is critical for every Otorhinolaryngology department. As the pandemic continues to evolve and more scientific reports of this disease are made available, approaches will need to be morphed.

Distribution of branchial anomalies in a paediatric Asian population.

INTRODUCTION: The objective of the present study was to review the distribution and incidence of branchial anomalies in an Asian paediatric population and highlight the challenges involved in the diagnosis of branchial anomalies. METHODS: This was a retrospective chart review of all paediatric patients who underwent surgery for branchial anomalies in a tertiary paediatric hospital from August 2007 to November 2012. The clinical notes were correlated with preoperative radiological investigations, intraoperative findings and histology results. Branchial anomalies were classified based on the results of the review. RESULTS: A total of 28 children underwent surgery for 30 branchial anomalies during the review period. Two children had bilateral branchial anomalies requiring excision. Of the 30 branchial anomalies, 7 (23.3%) were first branchial anomalies, 5 (16.7%) were second branchial anomalies, 3 (10.0%) were third branchial anomalies, and 4 (13.3%) were fourth branchial anomalies (one of the four patients with fourth branchial anomalies had bilateral branchial anomalies). In addition, seven children had 8 (26.7%) branchial anomalies that were thought to originate from the pyriform sinus; however, we were unable to determine if these anomalies were from the third or fourth branchial arches. There was inadequate information on the remaining 3 (10.0%) branchial anomalies for classification. CONCLUSION: The incidence of second branchial anomalies appears to be lower in our Asian paediatric population, while that of third and fourth branchial anomalies was higher. Knowledge of embryology and the related anatomy of the branchial apparatus is crucial in the identification of the type of branchial anomaly.