Sleep disordered breathing has minimal association with retinal microvascular diameters in a non-diabetic sleep clinic cohort.

INTRODUCTION: Obstructive sleep apnea (OSA) may increase stroke risk; retinal arteriolar (central retinal arteriolar equivalent, CRAE) diameter narrowing and/or retinal venular (central retinal venule equivalent, CRVE) widening may predict stroke. We examined relationships between sleep disordered breathing (SDB) and CRAE and CRVE and in a diabetes-free sleep clinic cohort. METHODS: Patients for SDB assessment were recruited (Main Group, n = 264, age: 58.5 ± 8.9 yrs [mean ± SD]; males: 141) for in-laboratory polysomnography (standard metrics, eg apnea hypopnea index, AHI) and retinal photographs (evening and morning). A more severe SDB sub-group (n = 85) entered a 12-month cardiovascular risk factor minimisation (hypertension/hypercholesterolemia control; RFM) and continuous positive airway pressure (CPAP) intervention (RFM/CPAP Sub-Group); successfully completed by n = 66 (AHI = 32.4 [22.1-45.3] events/hour, median[IQR]). Univariate (Spearman's correlation, t-test) and multiple linear regression models examined non-SDB and SDB associations with CRAE and CRVE measures. RESULTS: Main Group: Evening CRAE predictors were: systolic blood pressure (0.18µm decrease per mmHg, p = 0.001), age (2.47µm decrease per decade, p = 0.012), Caucasian ethnicity (4.45 µm versus non-Caucasian, p = 0.011), height (0.24 µm decrease per cm increase, p = 0.005) and smoking history (3.08 µm increase, p = 0.052). Evening CRVE predictors were: Caucasian ethnicity (11.52 µm decrease versus non-Caucasian, p>0.001), diastolic blood pressure (0.34 µm increase in CRVE per mmHg, p = 0.001), hypertension history (6.5 µm decrease, p = 0.005), and smoking history (4.6 µm increase, p = 0.034). No SDB metric (all p>0.08) predicted CRAE or CRVE measures. RFM/CPAP Sub-Group: A one-unit increase in ln(AHI+1) was associated with a 0.046µm increase in CRAE (n = 85; p = 0.029). Mean evening CRAE and CRVE values did not change across the intervention (n = 66), but evening CRVE decreased ~6.0 µm for individuals with AHI >30 events/hr. CONCLUSION: No major SDB associations with CRAE or CRVE were identified, although the RFM/CPAP intervention reduced evening CRVE for severe OSA patients. Implications for cerebro-vascular disease risk remain uncertain. TRIAL REGISTRATION: The protocol was registered with the Australian New Zealand Clinical Trials Registry (Trial Id: ACTRN12620000694910).

Retinal abnormalities, although relatively common in sleep clinic patients referred for polysomnography, are largely unrelated to sleep-disordered breathing.

STUDY OBJECTIVES: There has been long-standing interest in potential links between obstructive sleep apnea (OSA) and eye disease. This study used retinal photography to identify undiagnosed retinal abnormalities in a cohort of sleep clinic patients referred for polysomnography (PSG) and then determined associations with PSG-quantified sleep-disordered breathing (SDB) severity. METHODS: Retinal photographs (n = 396 patients) were taken of each eye prior to polysomnography and graded according to validated, standardized, grading scales. SDB was quantified via in-laboratory polysomnography (PSG; n = 385) using standard metrics. A questionnaire (n = 259) documented patient-identified pre-existing eye disease. Within-group prevalence rates were calculated on a per patient basis. Data were analyzed using multivariate logistic regression models to determine independent predictors for retinal abnormalities. P < 0.05 was considered significant. RESULTS: Main findings were (1) 76% of patients reported no pre-existing "eye problems"; (2) however, 93% of patients had at least one undiagnosed retinal photograph-identified abnormality; (3) most common abnormalities were drusen (72%) and peripapillary atrophy (PPA; 47%); (4) age was the most common risk factor; (5) diabetes history was an expected risk factor for retinopathy; (6) patients with very severe levels of SDB (apnea hypopnea index ≥ 50 events/h) were nearly three times more likely to have PPA. CONCLUSION: Retinal photography in sleep clinic settings will likely detect a range of undiagnosed retinal abnormalities, most related to patient demographics and comorbidities and, except for PPA, not associated with SDB. PPA may be indicative of glaucoma, and any association with severe SDB should be confirmed in larger prospective studies.

Predictors for carotid and femoral artery intima-media thickness in a non-diabetic sleep clinic cohort.

INTRODUCTION: The impact of sleep disordered breathing (SDB) on arterial intima-media thickness (IMT), a surrogate measure for cardiovascular disease, remains uncertain, in part because of the potential for non-SDB vascular risk factor interactions. In the present study, we determined predictors for common carotid (CCA) and femoral (CFA) artery IMT in an adult, sleep clinic cohort where non-SDB vascular risk factors (particularly diabetes) were eliminated or controlled. METHODS: We recruited 296 participants for polysomnography (standard SDB severity metrics) and CCA/CFA ultrasound examinations, followed by a 12 month vascular risk factor minimisation (RFM) and continuous positive pressure (CPAP) intervention for participants with a range of SDB severity (RFM Sub-Group, n = 157; apnea hyponea index [AHI]: 14.7 (7.2-33.2), median [IQR]). Univariable and multivariable linear regression models determined independent predictors for IMT. Linear mixed effects modelling determined independent predictors for IMT change across the intervention study. P<0.05 was considered significant. RESULTS: Age, systolic blood pressure and waist:hip ratio were identified as non-SDB predictive factors for CCA IMT and age, weight and total cholesterol:HDL ratio for CFA IMT. No SDB severity metric emerged as an independent predictor for either CCA or CFA IMT, except in the RFM Sub-Group, where a 2-fold increase in AHI predicted a 2.4% increase in CFA IMT. Across the intervention study, CCA IMT decreased in those who lost weight, but there was no CPAP use interaction. CFA IMT, however, decreased by 12.9% (95%CI 6.8, 18.7%, p = 0.001) in those participants who both lost weight and used CPAP > = 4hours/night. CONCLUSION: We conclude that SDB severity has little impact on CCA IMT values when non-SDB vascular risk factors are minimised or not present. This is the first study, however, to suggest a potential linkage between SDB severity and CFA IMT values. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611000250932 and ACTRN12620000694910.

CPAP treatment in REM-related obstructive sleep apnea: a distinct clinical phenotype of sleep disordered breathing.

PURPOSE: REM-related obstructive sleep apnea (REM-OSA), as defined using revised apnea-hypopnea index (AHI) criteria, might represent a specific OSA phenotype. However, there is a lack of data on outcomes of treatment in this population. This study evaluated the effects of CPAP treatment over 12 months on clinical outcomes for patients with the polysomnography phenotype of REM-OSA. METHODS: We conducted a prospective observational study with the following inclusion criteria: subjective sleepiness and diagnostic polysomnography demonstrating AHIREM≥15 events/h, AHINREM<5 events/h, and ≥ 30 min of REM sleep. Clinical outcomes assessed included Epworth Sleepiness Scale (ESS), psychomotor vigilanc test reaction time (PVT-RT), and CPAP adherence at baseline, 1, 3, 6, and 12 months; Functional Outcomes of Sleep Questionnaire (FOSQ) and Depression Anxiety Stress Scales (DASS-21) at baseline, 1, 3 and 12 months. The reason is the first 3 outcomes (ESS, PVT, adherence) were assessed at baseline, 1, 3, 6, and 12 months, while the next 2 outcomes (FOSQ, DASS) were assessed at baseline, 1, 3, and 12 months. The edited version is not as clear in separating these outcomes into 2 groups; Functional Outcomes of Sleep Questionnaire (FOSQ); and Depression Anxiety Stress Scales (DASS-21) at baseline, 1, 3, and 12 months. Linear mixed effects models were used to investigate the joint effects of time and average CPAP adherence on our outcomes of interest. RESULTS: Twenty participants completed a minimum of 1 month of CPAP treatment and were included for analysis. During the trial, 8 participants discontinued CPAP (4 before 3 months, 1 before 6 months, 3 before 12 months), and 19 participants completed 12 months of treatment. Baseline ESS was elevated at 12.6 units. Average CPAP usage for all 27 participants over 12 months was 2.9 ± 2.4 h. There was a significant decrease in ESS and increase in FOSQ at all time points, and the decrease in ESS was only seen in the CPAP-adherent subgroup. Decreases in DASS-21 and PVT-RT were not sustained. CONCLUSIONS: CPAP treatment in sleepy patients with moderate to severe REM-OSA is associated with reduced sleepiness and improved quality of life. TRIAL REGISTRATION: The trial was registered in the Australian New Zealand Clinical Trials Registry: ACTRN12620000576921, 18/05/2020 (retrospectively registered).

Anthropometric and craniofacial sexual dimorphism in obstructive sleep apnea patients: is there male-female phenotypical convergence?

Obstructive sleep apnea (OSA) is more common in men than women. Body size is greater in males (sexual dimorphism), but large body habitus is associated with OSA for both genders. We speculated that male-female phenotypical convergence (reduced sexual dimorphism via identical phenotype acquisition) occurs with OSA and tested hypotheses: (1) phenotypical features pathogenic for OSA differ between OSA and healthy subjects irrespective of gender; and (2) such characteristics exhibit phenotypical convergence. Utilizing an existing database, we calculated male-female (group average) ratios for eight anthropometric and 33 surface cephalometric variables from 104 Caucasian OSA patients [72 males; apnea-hypopnea index (events h(-1) ): males: 42.3 ± 24.7 versus females: 42.6 ± 26.1 (P > 0.9)] and 85 Caucasian, healthy, non-OSA, community volunteers (36 males). Log-transformed data were analysed using a general linear model with post-hoc unpaired t-tests and significance at P < 0.0012 (Bonferroni multiple-comparison correction). OSA patients were older (56.9 ± 14.4 versus 38.0 ± 13.8 years), but there were no within-group gender-based age differences. All anthropometric variables (except height), plus cranial base width, mandibular breadth and retromandibular width diagonal were larger in gender-matched OSA versus healthy comparisons; thus satisfying hypothesis (1). Male-female ratios were mostly >1.0 across groups, but with no significant group × gender interactions no variable satisfied hypothesis (2). Thus, in this exploratory study, OSA patients had gender-common phenotypical differences to healthy subjects, but sexual dimorphism was preserved. Lack of complete phenotypical convergence may indicate gender-based critical phenotype-level attainment for OSA and/or gender-based OSA prevalence arises from factors other than those in this study.

Surface cephalometric and anthropometric variables in OSA patients: statistical models for the OSA phenotype.

STUDY OBJECTIVE: We used statistical modelling to probe the contributions of anthropometric and surface cephalometric variables to the OSA phenotype. DESIGN: The design is prospective cohort study. SETTING: The setting is community-based and sleep disorder laboratory. PATIENTS OR PARTICIPANTS: Study #1-Model development study: 147 healthy asymptomatic volunteers (62.6 % Caucasian; age, 18-76 years; 81 females; median multivariable apnea prediction index=0.15) and 140 diagnosed OSA patients (84.3 % Caucasian; age, 18-83 years; 41 females; polysomnography [PSG] determined apnea-hypopnea index >10 events/h). Study #2-Model test study: 345 clinic patients (age, 18-86 years; 129 females) undergoing PSG for diagnosis of OSA. INTERVENTION: We measured 10 anthropometric and 34 surface cephalometric dimensions (calipers) and calculated mandibular enclosure volumes for study #1 and recorded age and neck circumference for study #2. Statistical modelling included principal component (PC), logistic regression, and receiver-operator curve analyses. MEASUREMENTS AND RESULTS: Model development study: A regression model incorporating three identified PC predicted OSA with 88 % sensitivity and specificity. However, a simplified model based on age and NC alone was equally effective (87 % sensitivity and specificity). Model test study: The simplified model predicted OSA with high sensitivity (93 %) but poor specificity (21 %). CONCLUSION: We conclude that in our clinic-based cohort, craniofacial bony and soft tissue structures (excluding neck anatomy) do not play a substantial role in distinguishing patients with OSA from those without. This may be because craniofacial anatomy does not contribute greatly to the pathogenesis of OSA in this group or because referral bias has created a relatively homogeneous phenotypic population.

The ecology of antibiotic use in the ICU: homogeneous prescribing of cefepime but not tazocin selects for antibiotic resistant infection.

BACKGROUND: Antibiotic homogeneity is thought to drive resistance but in vivo data are lacking. In this study, we determined the impact of antibiotic homogeneity per se, and of cefepime versus antipseudomonal penicillin/ß-lactamase inhibitor combinations (APP-ß), on the likelihood of infection or colonisation with antibiotic resistant bacteria and/or two commonly resistant nosocomial pathogens (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa). A secondary question was whether antibiotic cycling was associated with adverse outcomes including mortality, length of stay, and antibiotic resistance. METHODS: We evaluated clinical and microbiological outcomes in two similar metropolitan ICUs, which both alternated cefepime with APP-ß in four-month cycles. All microbiological isolates and commensal samples were analysed for the presence of antibiotic-resistant bacteria including MRSA and P. aeruginosa. RESULTS: Length of stay, mortality and overall antibiotic resistance were unchanged after sixteen months. However, increased colonisation and infection by antibiotic-resistant bacteria were observed in cefepime cycles, returning to baseline in APP-ß cycles. Cefepime was the strongest risk factor for acquisition of antibiotic-resistant infection. CONCLUSIONS: Ecological effects of different ß-lactam antibiotics may be more important than specific activity against the causative agents or the effect of antibiotic homogeneity in selection for antibiotic resistance. This has important implications for antibiotic policy.