Depression influences fatigue in inflammatory bowel disease amongst other factors: a structural modelling approach.

Objectives: Fatigue is common in people with inflammatory bowel disease (IBD) and is associated with IBD activity, sleep disturbance, anxiety and depression. The relative contribution of these factors to fatigue is unclear. This study aimed to investigate the relationship between fatigue and these factors through a novel approach using structural equation modelling. Design: Online questionnaire circulated via three tertiary IBD centres and Crohn's Colitis Australia. Methods: Fatigue was assessed using the Functional assessment of chronic illness measurement system fatigue subscale. Validated measures of sleep, anxiety, depression and IBD activity were included. Following correlation analyses, a structural equation model was developed for the outcome of the fatigue score. Direct and indirect effects were calculated. Results: There were 630 complete responses to the online questionnaire. The median age of respondents was 41 with the majority female and over half (52%) on biologic medication. Structural equation models for Crohn's disease and ulcerative colitis demonstrated a good fit. In Crohn's disease, the relationship between IBD activity and fatigue was mostly mediated indirectly through the influence of IBD activity on sleep, anxiety and primarily depression. Sleep quality mediated the influence of IBD activity and the indirect effects of depression on fatigue, but not anxiety. Unlike in Crohn's disease, the direct influence of IBD activity on fatigue in ulcerative colitis was non-negligible, although remained of lesser magnitude than the indirect effect of IBD activity on fatigue. Depression was the primary indirect mediator of the influence of IBD activity on fatigue in ulcerative colitis. Conclusion: In Crohn's disease, IBD activity leads to fatigue through its influence on sleep quality and mental health. The data suggest treatment of clinically significant depression, in both ulcerative colitis and Crohn's disease, may result in the largest decline in fatigue score compared to other variables. Treatment algorithms for fatigue should consider depression a priority.

Depression influences fatigue in inflammatory bowel disease Fatigue is common in people with inflammatory bowel disease. Studies investigating the causes of fatigue in people with inflammatory bowel disease have consistently identified depression, anxiety, sleep quality and IBD activity as factors associated with fatigue. People with inflammatory bowel disease were asked about their fatigue levels, sleep quality, depression, anxiety and inflammatory bowel disease activity. These responses were used to generate a model to explain the interaction between these factors and how they influence fatigue. The contribution of each of these factors to fatigue was then determined. Depression had the largest overall contribution. The influence of inflammatory bowel disease activity on fatigue occurred mostly through its impact on other factors such as depression and sleep quality. Consideration should be given to screening for and treating depression in people with inflammatory bowel disease and fatigue.

Sleep quality is associated with reduced quality of life in inflammatory bowel disease through its interaction with pain.

Background and Aim: Quality of life is reduced in people with inflammatory bowel disease (IBD) and poor sleep is prevalent in people with IBD. This study aimed to investigate the influence of sleep on quality of life (QoL) in people with inflammatory bowel disease. Methods: An online questionnaire was administered through three tertiary IBD centers, social media, and through Crohn's Colitis Australia. The questionnaire included the EQ-5D-5L measures of health-related QoL, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index (PSQI), and validated IBD activity and mental health scores. Results: There were 553 responses included with a diagnosis of Crohn's disease (62.2%), with over half on biologic therapy (53.1%). Poor sleep and clinically significant insomnia were associated with lower QoL (EQ-5D-5L scores: EQVAS, utility score, P < 0.001 for all). Sleep quality scores correlated with the EQ-5D-5L domains of "pain" (ρ 0.35, P < 0.001), "usual activities" (ρ 0.32, P < 0.001), and "depression-anxiety" (ρ 0.37, P < 0.001). After adjusting for demographic variables, IBD activity, and depression and anxiety via multivariate regression, the "pain" domain continued to be associated with PSQI components "sleep quality" (P < 0.001), "sleep disturbance" (P < 0.001), and "sleep duration" (P < 0.001). Clinically significant insomnia was associated with a reduction in QoL (EQVAS, utility score) independent of IBD activity (P < 0.001) and of a similar magnitude to that seen with IBD activity. Conclusion: Health-related QoL in IBD is influenced by aspects of sleep quality irrespective of IBD activity and mental health conditions. The presence of insomnia is associated with a reduction in health-related QoL. Consideration should be given to sleep targeting interventional studies in an IBD population.

Retraction notice to "PEITC: A resounding molecule averts metastasis in breast cancer cells in vitro by regulating PKCδ/Aurora A interplay" [HLY 8 (2021) e11656].

[This retracts the article DOI: 10.1016/j.heliyon.2022.e11656.].

Sleep health primary care clinical resource.

BACKGROUND: Obstructive sleep apnoea (OSA) and insomnia are the two most common sleep disorders and are frequent reasons for presentation in Australian general practice. OBJECTIVE: This article describes the development, content and suggested uses of the online sleep health primary care clinical resource, which provides general practitioners and other primary healthcare professionals with evidence-based information on the aetiology, assessment, management, referral and ongoing care for OSA and chronic insomnia. DISCUSSION: The Royal Australian College of General Practitioners-accepted clinical resource for the management of OSA and chronic insomnia in primary care was developed by the Australian National Centre for Sleep Health Services Research. The resource is designed to be used during consultations (eg following the steps in assessment and management and the use of online questionnaires for the assessment of OSA [Epworth Sleepiness Scale/OSA50/STOP-Bang] and insomnia [Sleep Condition Indicator/and Insomnia Severity Index]) and as an education/training tool (eg evidence on the role of continuous positive airway pressure/mandibular advancement splints for management of OSA and brief behavioural therapy for insomnia/cognitive behavioural therapy for insomnia for the management of insomnia).

Active Inflammatory Bowel Disease Is Associated with Short Sleep Duration via Objective Measures.

INTRODUCTION: Poor sleep quality has been associated with inflammatory bowel disease (IBD) activity, although studies incorporating actigraphy suggest that the perception of sleep differs rather than objective difference in sleep quality. Short sleep duration has been associated with increased pro-inflammatory cytokines that have been implicated in the pathogenesis of IBD. METHODS: An observational study incorporated home-based polysomnography that was conducted within twelve weeks of an objective assessment of IBD activity such as calprotectin, colonoscopy, or MRI. Participants completed a survey on subjective measures of sleep quality, clinical IBD activity, depression, and anxiety. Polysomnography results were normalized by standardized results for a healthy population matched by gender and age. RESULTS: Twenty participants were included in the final analysis. Those with objective evidence of active IBD had shorter stage 2 sleep duration, leading to shorter NREM sleep and total sleep time. Sleep latency was also longer in those with active IBD, leading to worse sleep efficiency-despite no difference in time available for sleep between the two groups. These changes persisted after normalization of polysomnography results by health population age and gender matched norms. Depression scores correlated with sleep latency and stage 2 sleep duration and were associated with objectively active IBD. CONCLUSIONS: Objectively confirmed active IBD was associated with shorter sleep duration. Observed sleep changes may, in part, relate to coexistent depression. Further research should consider the utility of changes in sleep duration and quality as a means of longitudinally assessing objective IBD activity.

Latent profiles of fatigue in inflammatory bowel disease.

INTRODUCTION: Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis. METHODS: An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated. RESULTS: In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile. CONCLUSION: Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Glucocorticoid receptor: a harmonizer of cellular plasticity in breast cancer-directs the road towards therapy resistance, metastatic progression and recurrence.

Recent therapeutic advances have significantly uplifted the quality of life in breast cancer patients, yet several impediments block the road to disease-free survival. This involves unresponsiveness towards administered therapy, epithelial to mesenchymal transition, and metastatic progression with the eventual appearance of recurrent disease. Attainment of such characteristics is a huge adaptive challenge to which tumour cells respond by acquiring diverse phenotypically plastic states. Several signalling networks and mediators are involved in such a process. Glucocorticoid receptor being a mediator of stress response imparts prognostic significance in the context of breast carcinoma. Involvement of the glucocorticoid receptor in the signalling cascade of breast cancer phenotypic plasticity needs further elucidation. This review attempted to shed light on the inter-regulatory interactions of the glucocorticoid receptor with the mediators of the plasticity program in breast cancer; which may provide a hint for strategizing therapeutics against the glucocorticoid/glucocorticoid receptor axis so as to modulate phenotypic plasticity in breast carcinoma.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Insomnia is common in inflammatory bowel disease (IBD) and is associated with mental health conditions as well as IBD activity.

BACKGROUND/AIMS: Insomnia is common in people with chronic medical conditions, such as inflammatory bowel disease (IBD), and is readily treatable through cognitive behavioral therapy for insomnia. This study aimed to describe the associations with insomnia in people with IBD and its relationship to IBD-related disability. METHODS: An online questionnaire was administered through 3 tertiary IBD centers, social media, and Crohn's Colitis Australia. The questionnaire included the Insomnia Severity Index (ISI), a validated assessment of insomnia. Measures of anxiety, depression, physical activity, and disability were also included. IBD activity was assessed using validated patient reported scores. A multivariate model was constructed for clinically significant insomnia and ISI scores. Subpopulations of Crohn's disease and ulcerative colitis were considered. RESULTS: In a cohort of 670 respondents the median age was 41 years (range, 32-70 years), with the majority female (78.4%), the majority had Crohn's disease (57.3%). Increasingly severe disability was associated with worse insomnia score. Clinically significant insomnia was associated with clinically active IBD, abdominal pain, anxiety, and depression, in a multivariate model. In an ulcerative colitis population, Simple Clinical Colitis Activity Index components of general well-being and urgency were associated with worse ISI score in a model including depression and anxiety. In those with Crohn's disease, the multivariate model included Harvey Bradshaw Index score in addition to depression and anxiety. CONCLUSIONS: Insomnia is common in people with IBD and is associated with increased disability. Abdominal pain and mental health conditions should prompt consideration for screening for insomnia and referral for cognitive behavioral therapy for insomnia.

Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long-term dietary administration.

The incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole-body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long-term dietary consumption of DEP in adipocytes. DEP-treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator-activated receptor γ and its downstream insulin-sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c-Apaf1-caspase 9-caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.

Machine learning and deep learning predictive models for long-term prognosis in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Machine learning and deep learning models have been increasingly used to predict long-term disease progression in patients with chronic obstructive pulmonary disease (COPD). We aimed to summarise the performance of such prognostic models for COPD, compare their relative performances, and identify key research gaps. METHODS: We conducted a systematic review and meta-analysis to compare the performance of machine learning and deep learning prognostic models and identify pathways for future research. We searched PubMed, Embase, the Cochrane Library, ProQuest, Scopus, and Web of Science from database inception to April 6, 2023, for studies in English using machine learning or deep learning to predict patient outcomes at least 6 months after initial clinical presentation in those with COPD. We included studies comprising human adults aged 18-90 years and allowed for any input modalities. We reported area under the receiver operator characteristic curve (AUC) with 95% CI for predictions of mortality, exacerbation, and decline in forced expiratory volume in 1 s (FEV1). We reported the degree of interstudy heterogeneity using Cochran's Q test (significant heterogeneity was defined as p≤0·10 or I2>50%). Reporting quality was assessed using the TRIPOD checklist and a risk-of-bias assessment was done using the PROBAST checklist. This study was registered with PROSPERO (CRD42022323052). FINDINGS: We identified 3620 studies in the initial search. 18 studies were eligible, and, of these, 12 used conventional machine learning and six used deep learning models. Seven models analysed exacerbation risk, with only six reporting AUC and 95% CI on internal validation datasets (pooled AUC 0·77 [95% CI 0·69-0·85]) and there was significant heterogeneity (I2 97%, p<0·0001). 11 models analysed mortality risk, with only six reporting AUC and 95% CI on internal validation datasets (pooled AUC 0·77 [95% CI 0·74-0·80]) with significant degrees of heterogeneity (I2 60%, p=0·027). Two studies assessed decline in lung function and were unable to be pooled. Machine learning and deep learning models did not show significant improvement over pre-existing disease severity scores in predicting exacerbations (p=0·24). Three studies directly compared machine learning models against pre-existing severity scores for predicting mortality and pooled performance did not differ (p=0·57). Of the five studies that performed external validation, performance was worse than or equal to regression models. Incorrect handling of missing data, not reporting model uncertainty, and use of datasets that were too small relative to the number of predictive features included provided the largest risks of bias. INTERPRETATION: There is limited evidence that conventional machine learning and deep learning prognostic models demonstrate superior performance to pre-existing disease severity scores. More rigorous adherence to reporting guidelines would reduce the risk of bias in future studies and aid study reproducibility. FUNDING: None.

Refashioning of the drug-properties of fluoroquinolone through the synthesis of a levofloxacin-imidazole cobalt (II) complex and its interaction studies on with DNA and BSA biopolymers, antimicrobial and cytotoxic studies on breast cancer cell lines.

Levofloxacin (HLVX), a quinolone antimicrobial agent, when deprotonated (LVX-) behaves as a bidentate ligand, and it coordinates to Co2+ through the pyridone oxygen and the carboxylate oxygen. Along with two imidazole (ImH) ligands, levofloxacin forms a Co(II)-Levofloxacin-imidazole complex, [CoCl(LVX)(ImH)2(H2O)]·3H2O (abbreviated henceforth as CoLevim) which was isolated and characterized by 1H and 13C NMR spectroscopy, UV-visible and FT-IR spectroscopy, powder X-ray diffraction and thermal analysis methods. CoLevim shows promise in its antimicrobial activities when tested against microorganisms (Bacillus cereus, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli). Fluorescence competitive studies with ethidium bromide (EB) revealed that CoLevim can compete with EB and displace it to bind to CT-DNA through intercalative binding mode. In addition, CoLevim exhibited a good binding propensity to BSA proteins with relatively high binding constants. The antioxidant activities of the free ligands and CoLevim were determined in vitro using ABTS+ radical (TEAC assay). The Co-complex showed a better antioxidant capacity with inhibitory concentrations (IC50) of 40 µM than the free ligands. CoLevim also showed noteworthy apoptotic potential and behaved as an efficient resistant modifying agent when its antiproliferative potential was examined by MTT assay using the breast cancer cell lines (MCF7, MCF7Dox/R and MCF7Pacli/R cells).

Multi-night measurement for diagnosis and simplified monitoring of obstructive sleep apnoea.

Substantial night-to-night variability in obstructive sleep apnoea (OSA) severity has raised misdiagnosis and misdirected treatment concerns with the current prevailing single-night diagnostic approach. In-home, multi-night sleep monitoring technology may provide a feasible complimentary diagnostic pathway to improve both the speed and accuracy of OSA diagnosis and monitor treatment efficacy. This review describes the latest evidence on night-to-night variability in OSA severity, and its impact on OSA diagnostic misclassification. Emerging evidence for the potential impact of night-to-night variability in OSA severity to influence important health risk outcomes associated with OSA is considered. This review also characterises emerging diagnostic applications of wearable and non-wearable technologies that may provide an alternative, or complimentary, approach to traditional OSA diagnostic pathways. The required evidence to translate these devices into clinical care is also discussed. Appropriately sized randomised controlled trials are needed to determine the most appropriate and effective technologies for OSA diagnosis, as well as the optimal number of nights needed for accurate diagnosis and management. Potential risks versus benefits, patient perspectives, and cost-effectiveness of these novel approaches should be carefully considered in future trials.

General practitioner management of comorbid insomnia and sleep apnoea.

BACKGROUND: Insomnia and obstructive sleep apnoea are the two most common sleep disorders and frequently co-exist. Patients with comorbid insomnia and sleep apnoea experience worse daytime function, mental health and physical health than patients with either disorder alone. General practitioners may face unique challenges in the assessment and management of this prevalent and debilitating condition. OBJECTIVE: This article aims to provide an overview of the prevalence, consequences, assessment and management of patients with comorbid insomnia and sleep apnoea in Australian general practice. DISCUSSION: Patients with either insomnia or sleep apnoea should be assessed for both conditions. Treatments for both disorders should be offered to patients with both conditions. The recommended treatment for insomnia is cognitive behavioural therapy, whereas the recommended first-line treatment for moderate and severe obstructive sleep apnoea is lifestyle/weight management advice (where relevant) and continuous positive airway pressure therapy.

Stepwise Add-On and Endotype-informed Targeted Combination Therapy to Treat Obstructive Sleep Apnea: A Proof-of-Concept Study.

Rationale: Oral appliance therapy (OAT) is an effective treatment for many people with obstructive sleep apnea (OSA). However, OSA pathogenesis is heterogeneous, and, in ∼50% of cases, OAT does not fully control OSA. Objectives: This study aimed to control OSA in individuals with an incomplete response to OAT alone by using additional targeted therapies informed by OSA endotype characterization. Methods: Twenty-three people with OSA (apnea-hypopnea index [AHI], 41 ± 19 events/h) not fully resolved (AHI, >10 events/h) with OAT alone were prospectively recruited. OSA endotypes were characterized pretherapy during a detailed physiology study night. Initially, an expiratory positive airway pressure (EPAP) valve and supine avoidance device therapy were added to target the impaired anatomical endotype. Those with residual OSA (AHI, >10 events/h) then received one or more nonanatomical interventions based on endotype characterization. This included O2 (4 L/min) to reduce high loop gain (unstable respiratory control) and 80/5 mg atomoxetine-oxybutynin to increase pharyngeal muscle activity. Finally, if required, OAT was combined with EPAP and continuous positive airway pressure (CPAP) therapy. Results: Twenty participants completed the study. OSA was successfully controlled (AHI, <10 events/h) with combination therapy in all but one participant (17 of 20 without CPAP). OAT plus EPAP and supine avoidance therapy treated OSA in 10 (50%) participants. OSA was controlled in five (25%) participants with the addition of O2 therapy, one with atomoxetine-oxybutynin, and one required O2 plus atomoxetine-oxybutynin. Two participants required CPAP for their OSA, and another was CPAP intolerant. Conclusions: These novel prospective findings highlight the potential of precision medicine to inform targeted combination therapy to treat OSA. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001995268).

Does OSA Increase Risk for Cancer?: A Large Historical Sleep Clinic Cohort Study.

BACKGROUND: The relationship between OSA and cancer is unclear. RESEARCH QUESTION: What is the association between OSA and cancer prevalence and incidence in a large Western Australian sleep clinic cohort (N = 20,289)? STUDY DESIGN AND METHODS: OSA severity was defined by apnea-hypopnea index (AHI) and nocturnal hypoxemia (duration and percentage at oxygen saturation < 90%) measured by in-laboratory polysomnogram. Measures of potential confounding included age, sex, BMI, smoking status, socioeconomic status, and BP. Outcomes were determined from the Western Australian cancer and death registries. Analyses were confined within periods using consistent AHI scoring criteria: January 1, 1989, to July 31, 2002 (American Sleep Disorders Association criteria), and August 1, 2002, to June 30, 2013 (Chicago criteria). We examined associations of AHI and nocturnal hypoxemia with cancer prevalence using logistic regression and cancer incidence using Cox regression analyses. RESULTS: Cancer prevalence at baseline was 329 of 10,561 in the American Sleep Disorders Association period and 633 of 9,728 in the Chicago period. Nocturnal hypoxemia but not AHI was independently associated with prevalent cancer following adjustment for participant age, sex, BMI, smoking status, socioeconomic status, and BP. Of those without prevalent cancer, cancer was diagnosed in 1,950 of 10,232 (American Sleep Disorders Association) and 623 of 9,095 (Chicago) participants over a median follow-up of 11.2 years. Compared with the reference category (no OSA, AHI < 5 events per hour), univariable models estimated higher hazard ratios for cancer incidence for mild (AHI 5-15 events per hour), moderate (AHI 15.1-30 events per hour), and severe (AHI > 30 events per hour) OSA. Multivariable analyses consistently revealed associations between age and, in some cases, sex, BMI, and smoking status, with cancer incidence. After adjusting for confounders, multivariable models showed no independent association between OSA severity and increased cancer incidence. INTERPRETATION: Nocturnal hypoxemia is independently associated with prevalent cancer. OSA severity is associated with incident cancer, although this association seems secondary to other risk factors for cancer development. OSA is not an independent risk factor for cancer incidence.

Simple Novel Screening Tool for Obstructive Sleep Apnea in Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) has been associated with an increased risk of obstructive sleep apnea (OSA). We aimed to examine the associations of obstructive sleep apnea, sleepiness, and IBD-related data and comorbidities, with the aim of developing a screening tool for sleep apnea in this population. Methods: An online survey of adults with IBD was administered which included measures of assessment of the risk of OSA, and measures of IBD activity, IBD-related disability, anxiety, and depression. Logistic regression was performed to investigate the associations between the risk of OSA and IBD data, medications, demographics, and mental health conditions. Further models were built for an outcome of severe daytime sleepiness and a combined outcome of risk of OSA and at least mild daytime sleepiness. A simple score was constructed for the purpose of screening for OSA. Results: There were 670 responses to the online questionnaire. The median age was 41 years, the majority had Crohn's disease (57%), the median disease duration was 11.9 years, and approximately half were on biologics (50.5%). Moderate-high risk of OSA was demonstrated in 22.6% of the cohort. A multivariate regression model for moderate-high risk of OSA included increasing age, obesity, smoking, and abdominal pain subscore. For a combined outcome of moderate-high risk of OSA and at least mild daytime sleepiness, a multivariate model included abdominal pain, age, smoking, obesity, and clinically significant depression. A simple score was constructed for screening for OSA utilizing age, obesity, IBD activity, and smoking status with an area under the receiver-operating curve of 0.77. A score >2 had a sensitivity of 89% and a specificity of 56% for moderate-high risk of OSA and could be utilized for screening for OSA in the IBD clinic. Conclusions: Over one-fifth of an IBD cohort met significantly high-risk criteria for OSA to warrant referral for a diagnostic sleep study. The risk of OSA was associated with abdominal pain, along with more traditional risk factors such as smoking, increasing age, and obesity. Consideration should be given for screening for OSA in IBD patients utilizing a novel screening tool that utilizes parameters typically available in IBD clinic.

Examining the influence of inflammatory bowel disease medications on sleep quality.

Background and Aim: Inflammatory bowel disease (IBD) can disrupt sleep, leading to poor sleep quality. This may in part be due to the symptoms of IBD and the influence of pro-inflammatory cytokines on sleep. This study aimed to investigate the potential influence of IBD medications on sleep quality. Methods: An online survey of adults with IBD was conducted, which included measures of sleep quality, IBD activity, anxiety, depression, and physical activity. Logistic regression was used to investigate possible associations between IBD medications (corticosteroids, immunomodulators, biologics, aminosalicyate) and outcome of poor sleep. A generalized linear model was built for outcome of sleep quality score. Results: There were 544 participants included in the final analysis, median age of 42, and 61% with Crohn's disease. Increased odds of poor sleep were seen in those taking opioids, medications for anxiety or depression, corticosteroids, vitamin D, methotrexate, and infliximab. A multivariate model was built incorporating demographic and IBD variables with opioids present in the final model and associated with increased odds of poor sleep. This was in addition to medications for sleep, depression, anxiety, IBD activity, and body weight. In a multivariate generalized linear model, opioids and methotrexate were associated with worse sleep quality scores. Conclusions: Opioids were associated with increased odds of poor sleep independent of other factors. This provides further support for avoiding these medications in people with IBD. Infliximab was associated with increased body weight and consequently increased odds of poor sleep.

Adipose tissue macrophages and their role in obesity-associated insulin resistance: an overview of the complex dynamics at play.

Obesity, a major global health concern, is characterized by serious imbalance between energy intake and expenditure leading to excess accumulation of fat in adipose tissue (AT). A state of chronic low-grade AT inflammation is prevalent during obesity. The adipose tissue macrophages (ATM) with astounding heterogeneity and complex regulation play a decisive role in mediating obesity-induced insulin resistance. Adipose-derived macrophages were broadly classified as proinflammatory M1 and anti-inflammatory M2 subtypes but recent reports have proclaimed several novel and intermediate profiles, which are crucial in understanding the dynamics of macrophage phenotypes during development of obesity. Lipid-laden hypertrophic adipocytes release various chemotactic signals that aggravate macrophage infiltration into AT skewing toward mostly proinflammatory status. The ratio of M1-like to M2-like macrophages is increased substantially resulting in copious secretion of proinflammatory mediators such as TNFα, IL-6, IL-1ß, MCP-1, fetuin-A (FetA), etc. further worsening insulin resistance. Several AT-derived factors could influence ATM content and activation. Apart from being detrimental, ATM exerts beneficial effects during obesity. Recent studies have highlighted the prime role of AT-resident macrophage subpopulations in not only effective clearance of excess fat and dying adipocytes but also in controlling vascular integrity, adipocyte secretions, and fibrosis within obese AT. The role of ATM subpopulations as friend or foe is determined by an intricate interplay of such factors arising within hyperlipidemic microenvironment of obese AT. The present review article highlights some of the key research advances in ATM function and regulation, and appreciates the complex dynamics of ATM in the pathophysiologic scenario of obesity-associated insulin resistance.