Effects of common lifestyle factors on obstructive sleep apnea: precautions in daily life based on causal inferences.

Background: This study aimed to evaluate the causal impact of common modifiable lifestyles on obstructive sleep apnea (OSA), which is beneficial for recommendations to prevent and manage OSA. Method: Published genome-wide association study (GWAS) summary statistics were used to perform two-sample Mendelian randomization (MR). Variants associated with each exposure of smoking, drinking, and leisure sedentary behaviors at the genetic level were used as instrumental variables (IVs). Then, inverse-variance weighting (IVW) was considered the primary result for causality. Moreover, several complimented approaches were also included to verify the observed associations. MR-PRESSO and MR-Egger intercept were applied to test the horizontal pleiotropy. To assess heterogeneity, Cochran's Q test by IVW and MR-Egger were applied. Results: Regular smoking history increased OSA risk in all applied approaches [OR (95% CI)IVW = 1.28 (1.12, 1.45), p = 1.853 × 10-4], while the causality of lifetime smoking index [OR (95% CI)IVW = 1.39 (1.00, 1.91), p = 0.048], alcohol intake frequency [outliers removed OR (95% CI)IVW = 1.26 (1.08, 1.45), p = 0.002], and coffee intake behavior [OR (95% CI)IVW = 1.66 (1.03, 2.68), p = 0.039] on OSA risk were not always consistent in other approaches. In addition, no robust causal associations were observed for the effect of sedentary leisure behaviors on OSA risk. In sensitivity analysis, we observed no sign of horizontal pleiotropy or heterogeneity. Conclusion: Ever regularly smoking has a robust causal role in increasing OSA risk, which should be discouraged as precautions from developing OSA.

Clinical Characteristics and Treatment Efficacy for Co-Morbid Insomnia and Sleep Apnea (COMISA): Evidence from Qualitative and Quantitative Analysis.

OBJECTIVES: A multitude of physical and mental challenges are being faced in the population with Co-morbid Insomnia and Sleep Apnea (COMISA). Unfortunately, research about clinical characteristics and management of COMISA based on quantitative evidence is lacking. METHOD: Standard procedures for literature retrieval, selection and quality assessment, data extraction, analysis, and interpretation were conducted step by step. For studying the sleep characteristics, common complications and widely recognized treatment options for COMISA, Weighted Mean Difference (WMD) and Odds Ratio (OR) were applied to assess the mean and risk differences between compared groups. Outcomes included sleep health parameters and secondary impairments in physical and mental well-being. RESULTS: COMISA showed worse sleep quality than OSA only by PSQI (WMD = 3.38 point) and heavier sleep fragmentation (WMD = 11.46 min) than insomnia only. Besides, COMISA patients showed a higher risk for depression (OR [95%CI] = 5.03[2.31, 10.93]) and PTSD (OR [95%CI] = 3.96[1.85, 8.46]) in comparison with OSA alone. Compared to insomnia alone, COMISA patients suffered from more than two times higher risk of cardiovascular diseases, hypertension, and diabetes. In treating COMISA patients, combining CBTI with PAP treatment can enhance the improvement of insomnia severity (ISI, WMD [95%CI] =-3.26[-4.51, -2.00] point) and sleep efficiency (WMD [95%CI] = 6.39[1.97, 10.81] %) compared to PAP alone. CONCLUSIONS: Impaired sleep domains in COMISA cover sleep quality and sleep structure. Also, COMISA has a higher risk for cardiometabolic diseases and mental disorders. Combining CBTI with PAP can be a recommended treatment to relieve sleep impairments for COMISA.

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis. METHODS: With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis. RESULTS: By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR 0.81, P = 0.033) and Prevotella9 (OR 0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR 0.65, P = 0.03), Bacteroidales (OR 0.65, P = 0.03), and Ruminococcaceae UCG002 (OR 0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR 1.22, P = 0.033), Pasteurellaceae (OR 1.22, P = 0.033), Blautia (OR 1.46, P = 0.014), Methanobrevibacter (OR 1.27, P = 0.026), and Eubacterium fissicatena group (OR 1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E. fissicatena group is a possible risk factor for psoriasis (OR 1.22, P = 0.00018). After false discovery rate (FDR) correction, E. fissicatena group remains a risk factor for psoriasis (PFDR = 0.03798). CONCLUSION: We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E. fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.

Outcome data from >10 000 multiple myeloma patients in the Danish and Swedish national registries.

OBJECTIVE: We describe real-world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM). METHOD: First line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005-2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse. RESULTS: We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high-risk MM in a real- world-population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches. CONCLUSION: National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs.

The Platelet microRNA Profile of Kawasaki Disease: Identification of Novel Diagnostic Biomarkers.

Challenging diagnosis and unknown etiology of Kawasaki disease (KD) increase the coronary artery lesions incidence. microRNAs (miRNAs) are the most promising biomarkers because of their stability in peripheral blood and noninvasive measurement procedure, whose potential utility have been proved in cancers. To explore the utility of differentially expressed (DE) miRNAs as early diagnostic markers, 44 patients (25 incomplete KD and 19 complete KD) and 31 febrile controls were recruited for small RNA sequencing. From all the 1922 expressed miRNA, 210 DE miRNAs were found between KD and febrile control groups. Though platelet miRNA profiles of complete KD incomplete KD were much similar through cluster analysis, the DE miRNAs were not identical. Eight DE miRNAs were validated by real-time quantitative PCR (qRT-PCR) in complete or incomplete KD groups using a normalizer, miR-126-3p, which was identified by geNorm and NormFinder tools. The expression level of miRNAs continuous changed over time was observed and the function analysis showed the potential role of miRNAs as therapeutic biomarkers. Additionally, the prediction model for KD showed a sensitivity of 78.8% and a specificity of 71.4%, respectively. This study used small RNA sequencing to identify miRNA biomarkers KD diagnosis based on a large sample size. Our findings shine a light on the understanding of molecular pathogenesis of KD and may improve the accuracy of KD diagnosis and prognosis in clinical.