Abstract

PURPOSE Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Abstract

IMPORTANCE Obstructive sleep apnea (OSA) is associated with a rise in serum inflammatory markers, which may be attenuated by sleep surgery. OBJECTIVE To evaluate whether sleep surgery was associated with improved levels of proinflammatory markers in adults with OSA. DATA SOURCES Two authors independently searched Cochrane, Embase, and PubMed databases from inception through June 14, 2022. STUDY SELECTION Two authors searched the Cochrane, Embase, and PubMed databases for studies comparing preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery. DATA EXTRACTION AND SYNTHESIS Data were extracted from included articles into a structured proforma. Meta-analyses of the standardized mean difference (SMD) were conducted in random-effects models. To ensure relevance to clinicians and patients, the probability of benefit and number needed to treat were calculated for outcomes that demonstrated a statistically significant effect after sleep surgery. MAIN OUTCOMES AND MEASURES The primary outcome was the preoperative and postoperative levels of serum biomarkers in patients undergoing sleep surgery, including C-reactive protein (CRP), glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and interleukin-6 (IL-6). Data analysis was performed from April to May 2022. RESULTS Of the 3218 studies screened, 26 studies with 1187 patients (mean [SD] age, 42.8 [11.1] years; 932 [78.5%] men and 255 [21.5%] women) were included. Soft-tissue sleep surgery was associated with a large decrease in CRP (SMD, -0.377; 95% CI, -0.617 to -0.137), total cholesterol (SMD, -0.267; 95% CI, -0.417 to -0.116), LDL (SMD, -0.201; 95% CI, -0.344 to -0.058), IL-6 (SMD, -1.086; 95% CI, -1.952 to -0.221), tumor necrosis factor-α (SMD, -0.822; 95% CI, -1.617 to -0.027), triglyceride (SMD, -0.186; 95% CI, -0.301 to -0.071), and leptin (SMD, -0.519; 95% CI, -0.954 to -0.083) in patients with OSA. Meta-regression highlighted that increased age, higher preoperative score for cumulative sleep time percentage with oxyhemoglobin saturation less than 90% (CT90), and greater change in CT90 postoperatively were associated with a greater decrease in serum CRP levels after soft-tissue sleep surgery. A greater reduction in apnea hypopnea index (AHI) was strongly associated with a greater reduction in total cholesterol and LDL. A greater reduction in body mass index and AHI were also associated with a greater increase in HDL. CONCLUSIONS AND RELEVANCE The findings of this systematic review and meta-analysis of 26 studies suggest that sleep surgery is associated with decreased levels of CRP, total cholesterol, LDL, triglyceride, IL-6, leptin, and TNF-α, which may improve the inflammatory and cardiometabolic profile of patients who undergo sleep surgery.

Abstract

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.