Simethicone use in drug-induced sleep endoscopy improves visibility.

PURPOSE: To assess the effect of simethicone, a defoaming agent, on improving visibility during drug-induced sleep endoscopy (DISE) in obstructive sleep apnea (OSA). METHODS: The study was a retrospective case-series study on patients with OSA who failed positive airway pressure (PAP) treatment. Patient parameters were recorded including age, BMI, neck and abdominal circumference, and apnea-hypopnea index (AHI). Comparisons were made between DISE procedures performed with and without the administration of simethicone. Visibility during DISE was independently graded by two surgeons, and inter-rater reliability was assessed. RESULTS: Simethicone significantly improved DISE visibility (p = 0.03). "Best visibility" was achieved in 55% of cases with simethicone compared to 27% without simethicone (p = 0.02). Sub-analysis showed that only simethicone administration had a significant effect on visibility (p = 0.02). Inter-rater reliability between the grading surgeons was strong (Cohen-Kappa score 0.7, p < 0.001). CONCLUSION: The findings suggest that simethicone enhances DISE visibility for OSA surgical planning. Further research should explore optimizing simethicone administration timing and the potential clinical implications for surgical outcomes and patient care.

A machine learning approach for the diagnosis of obstructive sleep apnoea using oximetry, demographic and anthropometric data.

Introduction: Obstructive sleep apnoea (OSA) is a serious but underdiagnosed condition. Demand for the gold standard diagnostic polysomnogram (PSG) far exceeds its availability. More efficient diagnostic methods are needed, even in tertiary settings. Machine learning (ML) models have strengths in disease prediction and early diagnosis. We explored the use of ML with oximetry, demographic and anthropometric data to diagnose OSA. Methods: A total of 2,996 patients were included for modelling and divided into test and training sets. Seven commonly used supervised learning algorithms were trained with the data. Sensitivity (recall), specificity, positive predictive value (PPV) (precision), negative predictive value, area under the receiver operating characteristic curve (AUC) and F1 measure were reported for each model. Results: In the best performing four-class model (neural network model predicting no, mild, moderate or severe OSA), a prediction of moderate and/or severe disease had a combined PPV of 94%; one out of 335 patients had no OSA and 19 had mild OSA. In the best performing two-class model (logistic regression model predicting no-mild vs. moderate-severe OSA), the PPV for moderate-severe OSA was 92%; two out of 350 patients had no OSA and 26 had mild OSA. Conclusion: Our study showed that the prediction of moderate-severe OSA in a tertiary setting with an ML approach is a viable option to facilitate early identification of OSA. Prospective studies with home-based oximeters and analysis of other oximetry variables are the next steps towards formal implementation.

The association of obstructive sleep apnea with blood and cerebrospinal fluid biomarkers of Alzheimer's dementia - A systematic review and meta-analysis.

Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation of tau proteins. Obstructive Sleep Apnea (OSA) is associated with increased AD risk. We hypothesize that OSA is associated with higher levels of AD biomarkers. The study aims to conduct a systematic review and meta-analysis of the association between OSA and levels of blood and cerebrospinal fluid biomarkers of AD. Two authors independently searched PubMed, Embase, and Cochrane Library for studies comparing blood and cerebrospinal fluid levels of dementia biomarkers between patients with OSA and healthy controls. Meta-analyses of the standardized mean difference were conducted using random-effects models. From 18 studies with 2804 patients, meta-analysis found that cerebrospinal fluid amyloid beta-40 (SMD:-1.13, 95%CI:-1.65 to -0.60), blood total amyloid beta (SMD:0.68, 95%CI: 0.40 to 0.96), blood amyloid beta-40 (SMD:0.60, 95%CI: 0.35 to 0.85), blood amyloid beta-42 (SMD:0.80, 95%CI: 0.38 to 1.23) and blood total-tau (SMD: 0.664, 95% CI: 0.257 to 1.072, I2 = 82, p<0.01, 7 studies) were significantly higher in OSA patients compared with healthy controls. These findings suggest that OSA is associated with an elevation of some biomarkers of AD.

Obstructive sleep apnoea and glaucoma: a systematic review and meta-analysis.

INTRODUCTION: Obstructive sleep apnoea (OSA) has been thought to be associated with glaucoma, however there are many conflicting studies on this topic. With many new studies having been published since the previous meta-analysis, we believe it is important to clarify this association. Hence, in this study we meta-analyse the recent literature regarding the association between OSA and glaucoma. METHODS: Pubmed, Embase, Scopus and Cochrane Library were searched from inception till the 28th February 2022 for observational as well as cross-sectional studies examining the association between OSA and glaucoma. Two reviewers selected studies, extracted data, graded the quality of included non-randomized studies using the Newcastle-Ottawa scale. The overall quality of evidence was assessed using GRADE. Random-effects models were used to meta-analyse the maximally covariate- adjusted associations. RESULTS: 48 studies were included in our systematic review, with 46 suitable for meta-analysis. Total study population was 4,566,984 patients. OSA was associated with a higher risk of glaucoma (OR 3.66, 95% CI 1.70 to 7.90, I2 = 98%, p < 0.01). After adjustment for various important confounders including age, gender and patient comorbidities such as hyperlipidaemia, hypertension, cardiovascular diseases and diabetes, patients with OSA had up to 40% higher odds of glaucoma. Substantial heterogeneity was eliminated through subgroup and sensitivity analyses after consideration of glaucoma subtype, OSA severity and adjustment for confounders. CONCLUSIONS: In this meta-analysis, OSA was associated with higher risk of glaucoma, as well as more severe ocular findings characteristic of the glaucomatous disease process. We suggest more clinical studies looking into the effects of OSA treatment on the progression of glaucoma to help clinical decision making for patients.

Association between obstructive sleep apnea and floppy eyelid syndrome: A systematic review and metaanalysis.

RATIONALE: Obstructive sleep apnoea (OSA) has been linked to various ocular disorders, including floppy eyelid syndrome (FES). Previous studies have hypothesised the underlying association between the 2 , but results are currently still inconclusive. OBJECTIVE: To investigate the association between OSA and FES. METHODS: Four databases (Pubmed, Embase, Scopus, and Cochrane Library) were searched from inception until 28 February 2022 for observational studies and randomized controlled trials assessing the association between OSA and FES. Two reviewers selected studies, extracted data, graded the risk of bias using the Newcastle-Ottawa scale and the quality of assessment using the Grading of Recommendations Assessment, Development, and Evaluation system. Random-effects models were used to metaanalyze the associations. RESULTS: Twelve studies were included in the systematic review, of which nine were suitable for metaanalysis, with a combined cohort of 1,109 patients. Risk of bias was low to moderate. The overall analysis showed a significant positive association between OSA and FES (OR = 1.89, 95% CI = 1.27-2.83, I 2 = 44%). Further analysis revealed that the more severe the OSA was, the higher the risk of developing FES. Patients with severe OSA had the nominally highest risk of developing FES (OR = 3.06, 95% CI = 1.62-5.78, I 2 = 0%), followed by moderate OSA (OR = 2.53, 95% CI = 1.29-4.97, I 2 = 0%), and patients with mild OSA had the lowest risk (OR = 1.76, 95% CI = 0.85-3.62, I 2 = 0%). CONCLUSION: Our metaanalysis reports a positive association between OSA and FES, with increasing severity of OSA correlating with a significantly higher risk of FES. More longitudinal studies with sufficient duration of follow-up are needed to better characterise the relationship between OSA and FES.

The long-term results of modified maxillomandibular advancement in Asian OSA patients.

OBJECTIVE: Maxillomandibular advancement (MMA) surgery is considered a highly successful treatment for obstructive sleep apnea (OSA). Various modifications to the technique have been described. We aim to study the long-term results in Asian patients who underwent a modified MMA procedure intended to avoid bimaxillary protrusion and which involved four-quadrant bicuspid extractions with posterior maxillary alveolar setback. METHOD: A review of operative logs from 2000 to 2003 was conducted to identify Asian patients who underwent modified MMA during that period, for treatment of moderate and severe OSA. Sleep indices and psychometric performances were prospectively analyzed. RESULTS: Eight Asian patients were included. The mean length of follow-up was 14.4 years (range: 13.0-16.5). Mean preoperative apnea-hypopnea index (AHI) was 48.9 (range: 19.0 to 84.8). Mean post-operative AHI was 31.6 (range: 6.2 to 79.5). This reduction was statistically significant (p<0.05). Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire (FOSQ) revealed that majority of the patients (75%) did not have excessive daytime somnolence and all patients had high FOSQ totalled scores (mean 17.7, range 11.8 to 20), indicating good functional performance. CONCLUSION: This series is the longest follow-up of an Asian cohort who underwent modified MMA. With a mean follow-up of 14.4 years, improvement in AHI is still observed but not at a degree as large as prior studies with shorter lengths of follow-up. The purported efficacy of MMA for Caucasian patients may not be reproducible in Asian patients and long-term sustainability of this treatment's efficacy requires rigorous evaluation.

Practising transoral robotic surgery in a middle-income country: surgical outcomes and early challenges.

Transoral robotic surgery is a minimally invasive surgical technique that recently debuted in Malaysia. However, there are concerns over its cost, practicality, and feasibility in local settings. Our study aims to evaluate the surgical outcomes of transoral robotic surgery and discuss its learning curves. The clinical records of all patients who underwent transoral robotic surgery in a university hospital were reviewed. 25 patients were identified with a mean age of 43.9 years. The commonest indication was obstructive sleep apnoea (OSA) (76%), followed by base of tongue carcinoma (16%), recurrent tonsilitis and Wharton's duct cyst (4% each). For excision of tongue base in obstructive sleep apnoea without epiglottectomy, the mean operating time was 2.3(±0.9) hours with an average of 2.8(±0.4) days of hospital stay. The success rate for OSA surgery was seen in 78.9% of cases. The mean operating time for transoral excision of tongue base carcinoma was 4.3(±2.5) hours, whereas the mean hospital stay was 9(±3.6) days. All surgical margins were cleared with no recurrence except for one patient. The recurrent tumour was successfully excised via transoral robotic surgery, and he remained disease free after one year. The most frequent post-operative complaints were dysphagia, post-nasal drip, and hypogeusia. Transoral robotic surgery in Malaysia is in the commencement phase, where some pitfalls are expected. Opportunities should be given for more surgeons to acquire this technique so that minimally invasive surgery for head and neck diseases is readily available for patients in middle-income countries.

Improved Inflammatory and Cardiometabolic Profile After Soft-Tissue Sleep Surgery for Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.

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.

Asian Pacific Society of Cardiology Consensus Statements on the Diagnosis and Management of Obstructive Sleep Apnoea in Patients with Cardiovascular Disease.

Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of 'agree' or 'neutral.' The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region.

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 obstructive sleep apnea with thyroid cancer incidence: a systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a postulated carcinogen based on epidemiological associations with all-cancer incidence and non-thyroid biological models. However, associations with thyroid carcinoma are unclear. METHODS: We included observational/randomized studies of associations of OSA with thyroid carcinoma incidence/mortality in adults, from four databases. Random-effects meta-analyses and the population attributable fraction (PAF; from published global OSA prevalence estimates) were computed. RESULTS: We included four observational studies (N = 2,839,325), all with moderate/low risk of bias. OSA diagnosis was associated with twofold incidence of thyroid carcinoma (pooled HR 2.32, 95% CI 1.35-3.98, I2 = 95%), after multi-adjustment for demographics, BMI, smoking, alcohol, and comorbidities. Subgroup analysis of studies with at least 5 years of follow-up showed a stronger association of OSA with thyroid cancer incidence (pooled HR 3.27, 95% CI 2.80-3.82, I2 = 0%). Up to 14.5% (95% CI 4.29-27.6%) of incident thyroid carcinomas globally may be associated with OSA. Thyroid carcinoma mortality data was unavailable. CONCLUSIONS: OSA is associated with higher thyroid carcinoma incidence, though this does not prove causation. Biological/clinical studies should investigate OSA severity in relation to thyroid carcinoma progression and mortality, stratified by tumor histology.

The Association of Obstructive Sleep Apnea With Breast Cancer Incidence and Mortality: A Systematic Review and Meta-analysis.

PURPOSE: Emerging evidence from animal models suggests that intermittent hypoxia due to obstructive sleep apnea (OSA) is a risk factor for breast cancer. Despite their biological plausibility, human epidemiological studies have reported conflicting results. Therefore, we conducted a meta-analysis to delineate this relationship. METHODS: We searched the PubMed, Embase, Scopus, and Cochrane Library databases for eligible studies from inception until June 6, 2021. Two reviewers selected randomized trials or observational studies reporting the association between OSA and breast cancer incidence compared with those without OSA. Two reviewers extracted relevant data and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and Newcastle-Ottawa Scale (NOS). We pooled the maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse variance-weighted meta-analysis and performed pre-specified subgroup analyses. RESULTS: We included six studies out of 1,707 records, comprising a combined cohort of 5,165,200 patients. All studies used the International Classification of Diseases codes to classify OSA and breast cancer. OSA patients had a 36% increased breast cancer risk (HR, 1.36; 95% confidence interval [CI], 1.03-1.80; N = 6, I² = 96%) compared to those without OSA. Most studies adjusted for confounders, such as age, sex, obesity, diabetes mellitus, alcohol use, and hypertension. Subgroup analyses for studies with (1) multivariate adjustment and (2) at least five years of follow-up yielded HRs of 1.35 (95% CI, 0.98-1.87; N = 5, I² = 96%) and 1.57 (95% CI, 1.14-2.18; N = 4; I² = 90%), respectively. One Mendelian randomization study suggested a causal relationship, with a two-fold increase in the odds of breast cancer in patients with OSA. CONCLUSION: This meta-analysis suggested that OSA is a risk factor for breast cancer. Future studies should explore the dose-response relationship between OSA and breast cancer, and whether treatment may mitigate breast cancer risk or progression.

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.

Association of obstructive sleep apnea and nocturnal hypoxemia with all-cancer incidence and mortality: a systematic review and meta-analysis.

STUDY OBJECTIVES: Biological models suggest that obstructive sleep apnea (OSA) is potentially carcinogenic. We aimed to clarify the inconsistent epidemiological literature by considering various traditional and novel OSA severity indices. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane Library for observational or randomized studies of associations of OSA, measured by diagnostic codes or any index, each with all-cancer incidence or mortality in adults, compared with participants with no/mild OSA. Two reviewers independently selected studies, extracted data, and evaluated study bias using the Newcastle-Ottawa scale and quality of evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). We performed inverse variance-weighted, random-effects meta-analyses and sensitivity analyses. RESULTS: We included 20 observational studies (5,340,965 participants), all with moderate/low bias, from 1,698 records. Based on T90 (sleep duration with oxygen saturation < 90%), patients with OSA who had moderate (T90 > 1.2%, hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.07-1.54) and severe nocturnal hypoxemia (T90 > 12%, HR = 1.43, 95% CI = 1.16-1.76) experienced 30%-40% higher pooled all-cancer risk than normoxemic patients, after multiple adjustment for covariates including obesity. Furthermore, severe nocturnal hypoxemia nearly tripled all-cancer mortality (HR = 2.66, 95% CI = 1.21-5.85). Patients with apnea-hypopnea index-defined severe OSA, but not moderate OSA, had higher all-cancer risk (HR = 1.18, 95% CI = 1.03-1.35) but similar all-cancer mortality as patients without OSA. An OSA diagnosis was not associated with all-cancer risk. Evidence quality ranged from low to moderate. Insufficient evidence was available on the oxygen desaturation index, lowest/median saturation, and arousal index. CONCLUSIONS: In patients with OSA, nocturnal hypoxemia is independently associated with all-cancer risk and mortality. Future studies should explore if risk differs by cancer type, and whether cancer screening and OSA treatment are beneficial. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220836; Identifier: CRD42021220836. CITATION: Tan BKJ, Teo YH, Tan NKW, et al. Association of obstructive sleep apnea and nocturnal hypoxemia with all-cancer incidence and mortality: a systematic review and meta-analysis. J Clin Sleep Med. 2022;18(5):1427-1440.

Obstructive Sleep Apnea and Lung Cancer: A Systematic Review and Meta-Analysis.

Rationale: In 2020, lung cancer was the leading cause of cancer deaths and the most common cancer in men. Although obstructive sleep apnea (OSA) has been postulated to be carcinogenic, epidemiological studies are inconclusive. Objectives: To investigate the associations between OSA and the incidence and mortality of lung cancer. Methods: Four electronic databases (PubMed, Embase, Cochrane Library, and Scopus) were searched from inception until 6 June 2021 for randomized controlled trials and observational studies examining the association between sleep apnea and incident lung cancer. Two reviewers selected studies, extracted data, graded the risk of bias using the Newcastle-Ottawa scale and the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Random-effects models were used to meta-analyze the maximally covariate-adjusted associations. Results: Seven studies were included in our systematic review, among which four were suitable for meta-analysis, comprising a combined cohort of 4,885,518 patients. Risk of bias was low to moderate. OSA was associated with a higher incidence of lung cancer (hazard ratio, 1.25; 95% confidence interval, 1.02-1.53), with substantial heterogeneity (I2 = 97%). Heterogeneity was eliminated, with a stable pooled effect size, when including the three studies with at least 5 years of median follow-up (hazard ratio, 1.32; 95% confidence interval, 1.27-1.37; I2 = 0%). Conclusions: In this meta-analysis of 4,885,518 patients from four observational studies, patients with OSA had an approximately 30% higher risk of lung cancer compared with those without OSA. We suggest more clinical studies with longer follow-up as well as biological models of lung cancer be performed to further elucidate this relationship.

Obstructive sleep apnea and the incidence and mortality of gastrointestinal cancers: a systematic review and meta-analysis of 5,120,837 participants.

Background: Emerging evidence has shown higher overall cancer incidence in patients with obstructive sleep apnea. Gastrointestinal cancers, including esophageal, stomach, liver, pancreas, and colorectal cancers account for 26% of incident cancers. However, the link between gastrointestinal cancers and obstructive sleep apnea is still unclear. We performed a systematic review and meta-analysis (registered PROSPERO CRD42021220836) to investigate the association between obstructive sleep apnea and incidence of gastrointestinal cancer. Methods: We searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) and included studies published from inception till 15th November 2020 reporting the association of obstructive sleep apnea with gastrointestinal cancer incidence. Extracted data was meta-analyzed in a random-effects model. Results: A total of seven studies were included, forming a combined cohort of 5,120,837 patients. Studies which adjusted for demographics and comorbidities were included in meta-analysis. Among four studies with 7-11 years of median follow-up, patients with obstructive sleep apnea experienced increased incidence of colorectal cancer (HR 1.70, 95% CI: 1.48-1.96, I2=22%). Pancreatic cancer incidence was nominally increased in three studies (HR 1.36, 95% CI: 0.88-2.09, I2=96), though this was not statistically significant. There was no association between obstructive sleep apnea and liver cancer incidence among three studies (HR 0.99, 95% CI: 0.81-1.22, I2=84). However, the lack of a statistically significant relationship between obstructive sleep apnea and pancreatic cancer in our meta-analysis does not necessarily imply the true absence of an association. Conclusions: An increased risk of colorectal cancer was seen in patients with obstructive sleep apnea among studies with long-term follow-up. Further research is required to explore the utility of incorporating obstructive sleep apnea screening into colorectal cancer screening guidelines to identify high-risk individuals and to confirm a possible association of obstructive sleep apnea with pancreatic cancer. PROSPERO Registration: CRD42021220836.

The association of obstructive sleep apnea with melanoma incidence and mortality: a meta-analysis of 5,276,451 patients.

BACKGROUND: Melanoma is the most aggressive and lethal form of skin cancer. While emerging in-vivo evidence suggests that intermittent hypoxia, a hallmark feature of obstructive sleep apnea (OSA), may induce melanoma tumorigenesis, the epidemiological association between OSA and melanoma has been inconsistent. METHODS: We performed a literature search of PubMed, Embase, Scopus and Cochrane Library from inception until 6 June 2021. Two reviewers independently selected randomized trials or observational studies that reported the association of OSA with melanoma incidence or mortality in adults, in comparison to participants with no OSA. Two reviewers independently extracted relevant data and assessed the quality of evidence using the GRADE framework and the Newcastle-Ottawa Scale (NOS). We pooled data using an inverse variance-weighted meta-analysis and ran pre-specified subgrourp analyses. RESULTS: The meta-analysis included six studies out of 1897 records, comprising a combined cohort of 5,276,451 patients. All studies were adjusted for covariates, with majority of studies adjusting for age (N=5) and sex (N = 4). Compared to those without OSA, patients with OSA had 71% higher pooled hazards of melanoma (HR = 1.71; 95% CI: 1.08-2.69, I2 = 99%). Subgroup analyses for studies with (1) median follow-up duration of at least five years, (2) prospective study design, (3) adjustment for obesity yielded HRs of 1.88 (95%CI:1.32-2.67, N = 5), 1.11 (95%CI:0.77-1.60, N = 2) and 1.52 (95%CI:0.75-3.08, N = 3) respectively. One study investigating the relationship between OSA and melanoma mortality detected no association. There were insufficient studies to assess publication bias. CONCLUSIONS: Meta-analysis of mainly retrospective observational studies, with significant heterogeneity, suggests increased melanoma incidence in OSA patients. Future studies should prospectively explore the differential risk of melanoma for varying OSA severity, and whether timely OSA treatment may mitigate this risk.