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ObjectiveTo 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.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021.Review methodsTwo 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 synthesisTwo 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 measuresThe 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.Results18 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.ConclusionsA 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 registrationPROSPERO CRD42021283922.

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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

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 I 2 statistics, sources of heterogeneity were investigated using meta-regression and subgroup meta-analyses, and publication bias was qualitatively and quantitatively assessed. MAIN OUTCOMES AND MEASURESHazard ratios for all-cause mortality. RESULTSOne 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; I 2 = 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 RELEVANCEThe 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.

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Thyroid carcinoma usually presents as a neck lump. Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma (WDTC) is rare and little is known about these patients. The aim of this study is to characterize patients who present with distant metastasis as the sole initial manifestation of WDTC. Retrospective review of case records of WDTC seen at the National Cancer Centre Singapore from 2002 to 2015 was performed. Patients with no prior complaint of neck swelling and whose first presentation was distant metastatic WDTC were included. Patient demographics, disease characteristics, radiological imaging, histopathology, types of treatment administered, and survival outcomes were examined. Nineteen out of seven hundred and thirty-two cases fulfilled inclusion criteria. Mean age was 65.4 years. All patients presented with osseous (36.8%), pulmonary (31.6%), cerebral metastases (5.3%), or a combination of two out of three aforementioned sites (26.3%). Follicular thyroid carcinoma was most common (47.4%), followed by papillary (36.8%) and medullary (15.8%). More than two-thirds of patients had multiple metastatic foci. Thirteen out of nineteen patients (68.4%) underwent total thyroidectomy with or without neck dissection and adjuvant RAI, while the rest declined surgery. The mean length of follow-up was 40.1 ± 5.1 months and 5-year disease-specific survival was 48.0 ± 17.2%. Distant metastasis without a history of neck swelling as the initial presentation of WDTC is extremely rare. Osseous metastasis and follicular thyroid carcinoma are the most common metastatic site and etiology, respectively. Disease-specific survival at 5-year post-diagnosis is lower compared to patients with thyroid carcinoma diagnosed with distant metastasis on further work-up.

The novel coronavirus disease 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was declared a pandemic in March 2020. A plethora of respiratory sampling methods for SARS-CoV-2 viral detection has been used and in the current evolving situation, there is no international consensus on the recommended method of respiratory sampling for diagnosis. Otolaryngologists deal intimately with the upper respiratory tract and a clear understanding of the respiratory sampling methods is of paramount importance. This article aims to provide an overview of the various methods and their evidence till date.