Association Between Hearing Loss and Cardiovascular Disease: A Meta-analysis.

OBJECTIVE: Hearing loss (HL) has been postulated to be linked to cardiovascular diseases (CVDs) via vascular mechanisms, but epidemiological associations remain unclear. The study aims to clarify the association between HL and stroke, coronary artery disease (CAD), and any CVD. DATA SOURCES: PubMed, Embase, and SCOPUS from inception until April 27, 2022. REVIEW METHODS: Three blinded reviewers selected observational studies reporting stroke, CAD, and any CVD in patients with HL, compared to individuals without HL. We extracted data, evaluated study bias using the Newcastle-Ottawa scale, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and a PROSPERO-registered protocol (CRD42022348648). We used random-effects inverse variance meta-analyses to pool the odds ratios (ORs) for the association of HL with stroke, CAD, and any CVD. RESULTS: We included 4 cohort studies (N = 940,771) and 6 cross-sectional studies (N = 680,349). Stroke, CAD, and any CVD were all strongly associated with HL. The overall pooled OR of the association between HL and stroke was 1.26 (95% confidence interval [CI] = 1.16-1.37, I2 = 78%), and was 1.33 (95% CI = 1.12-1.58) and 1.29 (95% CI = 1.14-1.45) for low- and high-frequency HL, respectively. Minimal publication bias was observed, with minimal change to pooled effect size following trim and fill. Similarly, the pooled OR of the association between HL and CAD was 1.36 (95% CI = 1.13-1.64, I2 = 96%), while that between HL and any CVD was 1.38 (95% CI = 1.07-1.77, I2 = 99%). CONCLUSION: Our findings suggest that HL and CVD are closely related. Physicians treating patients with HL should be cognizant of this association and view HL in the broader context of general health and aging.

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.

Treatment and mortality of hemophagocytic lymphohistiocytosis in critically ill children: A systematic review and meta-analysis.

OBJECTIVE: Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed. DATA SOURCES: PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022. STUDY SELECTION: Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU. DATA EXTRACTION: Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed. DATA SYNTHESIS: Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47). CONCLUSION: Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.

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.

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.