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Background Family caregivers experience psychological distress or physical strain that may lead to an increased risk of cardiovascular disease (CVD) morbidity and mortality. Objective This systematic review aimed to describe the current evidence and gaps in the literature on measures used to assess CVD outcomes in family caregivers, the association of caregiving with CVD incidence/risk outcomes, and associated factors in family caregivers of patients with chronic disease. Methods Medline, PubMed, CINAHL, Web of Science, and Google Scholar were searched for English-language, peer-reviewed studies published from 2008 to 2020 that examined CVD incidence and risk among family caregivers of adults with chronic conditions. Results Forty-one studies were included in this review. The measures used to assess CVD risk were categorized into biochemical, subclinical markers, components of metabolic syndrome, and global risk scores. Compared with noncaregivers, caregivers were more likely to have higher CVD incidence rates and objectively measured risk. Cardiovascular disease risks were also increased by their caregiving experience, including hours/duration of caregiving, caregivers' poor sleep status, psychological symptoms, poor engagement in physical/leisure activities, and care recipient's disease severity. Conclusions Although there were limited longitudinal studies in caregivers of patients with diverse health conditions, we found evidence that caregivers are at high risk of CVD. Further research for various caregiver groups using robust methods of measuring CVD risk is needed. Caregiver factors should be considered in developing interventions aimed at reducing CVD risk for caregivers.

Advances in gene sequence technology and data analysis have enabled the detection and taxonomic identification of microorganisms in vivo based on their unique RNA or DNA sequences. Standard culture techniques can only detect those organisms that readily grow on artificial media in vitro. Culture-independent technology has been used to provide a more accurate assessment of the richness (total number of species) and diversity (relative abundance of each species) of microorganisms present in a prescribed location. The microbiome has been defined as the genes and genomes of all microbial inhabitants within a defined environment. Microorganisms within a microbiome interact with each other as well as with the host. A microbiome is dynamic and may change over time as conditions within the defined environment become altered. In oral health, neither gingivitis nor periodontitis is present, and the host and microbiome coexist symbiotically without evoking an inflammatory response. The circumstances that cause a shift from immune tolerance to a proinflammatory response remain unknown, and a unified, all-encompassing hypothesis to explain how and why periodontal disease develops has yet to be described. The purpose of this review is to clarify the current understanding of the role played by the oral microbiome in dogs and cats, describe how the microbiome changes in periodontal disease, and offer guidance on the utility of systemic antimicrobial agents in the treatment of periodontitis in companion animals.

Purpose of review Sleep is intimately involved in overall health and wellbeing. We provide a comprehensive report on the interplay between systemic diseases and sleep to optimize the outcomes of systemic disorders. Recent findings Spanning the categories of endocrinologic disorders, metabolic/toxic disturbances, renal, cardiovascular, pulmonary, gastrointestinal, infectious diseases, autoimmune disorders, malignancy, and critical illness, the review highlights the prevalent coexisting pathology of sleep across the spectrum of systemic disorders. Although it is rare that treating a sleep symptom can cure disease, attention to sleep may improve quality of life and may mitigate or improve the underlying disorder. Recent controversies in assessing the cardiovascular relationship with sleep have called into question some of the benefits of treating comorbid sleep disorders, thereby highlighting the need for an ongoing rigorous investigation into how sleep interplays with systemic diseases. Summary Systemic diseases often have sleep manifestations and this report will help the clinician identify key risk factors linking sleep disorders to systemic diseases so as to optimize the overall care of the patient.

It has long been accepted that certain oral bacterial species are responsible for the development of periodontal disease. However, the focus of microbial and immunological research is shifting from studying the organisms associated with disease to examining the indigenous microbial inhabitants that are present in health. Microbiome refers to the aggregate genetic material of all microorganisms living in, or on, a defined habitat. Recent developments in gene sequence analysis have enabled detection and identification of bacteria from polymicrobial samples, including subgingival plaque. Diversity surveys utilizing this technology have demonstrated that bacterial culture techniques have vastly underestimated the richness and diversity of microorganisms in vivo, since only certain bacteria grow in vitro. Surveys using gene sequence analysis have demonstrated that the healthy oral microbiome is composed of an unexpectedly high number of diverse species, including putative pathogens. These findings support the view that coevolution microorganisms and macroscopic hosts has occurred in which certain microorganisms have adapted to survive in the oral cavity and host immune tolerance has allowed the establishment of a symbiotic relationship in which both parties receive benefits (mutualism). This review describes gene sequence analysis as an increasingly common, culture-independent tool for detecting bacteria in vivo and describes the results of recent oral microbiome diversity surveys of clinically healthy humans, dogs, and cats. Six bacterial phyla consistently dominated the healthy oral microbiome of all 3 host species. Previous hypotheses on etiology of periodontitis are reviewed in light of new scientific findings. Finally, the consideration that clinically relevant periodontal disease occurs when immune tolerance of the symbiotic oral microbiome is altered to a proinflammatory response will be discussed.

Introduction Central sleep apnea (CSA) is unique sleep breathing phenotype in patients with advanced chronic heart failure (HF) and portend poor prognosis. The prevalence of CSA in HF patients under contemporary therapy is uncertain. Methods We reviewed consecutive HF patients on optimal medical therapy who underwent clinically indicated diagnostic in-lab polysomnography at a single academic center. Age, sex and BMI matched patients without HF were selected from sleep clinic as a control. Patients with atrial fibrillation were excluded from this study. Apnea subtypes were determined after careful scoring and confirmation by sleep physicians. ‘Any CSA’ was defined by central apnea index (CAI) >5 and >1/hr. ‘True CSA’ was defined if met both CAI≥5/hr and > obstructive apnea index (OAI). Obstructive sleep apnea (OSA) was defined if apnea hypopnea index >15 and OAI>CAI. Multivariate analysis was performed using logistic regression adjusting for age, sex, HF and systolic dysfunction as appropriate. Results In patients with HF (N=95, mean age 59, female: 50%), CSA was low and was comparable to control group (N=94) (HF vs. Non-HF; CSA: 5.3 vs. 4.3%, P=NS; Any CSA 14.7 vs. 17%, P=NS). Only 3 patients with HF had true CSA. In contrast, OSA was common in both groups regardless of obesity status (52.3 vs. 55.3%). In patients with HF, Cheyne Stokes respiration was more frequent in patients with Any CSA vs. without Any CSA (13.3 vs. 3.8%, p=0.04). In multivariate analysis, presence of OSA, but not HF, was associated with Any CSA in entire cohort (Any CSA OR: 3.1 [1.3, 8.1], p=0.02). In patients with HF, male sex was associated with Any CSA (OR: 5.3 [1.1, 40.8], p=0.05). Exclusion of patients with high BMI did not change the results. Conclusion CSA was rare in patients with stable HF on contemporary optimal medical therapy. Support None

Introduction Adherence to continuous positive airway pressure (CPAP) may delay cognitive decline in older adults with obstructive sleep apnea (OSA) and amnestic mild cognitive impairment (MCI), defined as deficits in memory that do not significantly impact daily functioning. The aim of this analysis was to identify predictors of CPAP adherence in this population. Methods Data are from Memories 2, an ongoing multisite clinical trial on the effect of treatment of moderate to severe OSA on cognitive decline in older adults 65-85 years of age who have amnestic MCI. Unadjusted and adjusted linear models were used to examine predictors of mean hours of CPAP use at 3 months. Predictors were age, sex (male/female), race (White/Non-White), education (more than high school, less than high school), Apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), and CPAP Comfort and Confidence scores at 7 days. Collinearity in the adjusted model for CPAP use at 3 months was examined using the variance inflation factor. Results Of 57 participants, most were male (54%), White (72%), with a mean age of 66.3 years (SD: 6.1). Mean AHI in this sample was 35.1 (SD: 19.9), with mean daily hours of CPAP use at 3 months 5.3 hours (SD: 2.3). Adjusted linear model results demonstrated that younger age (β=-0.13, SE=0.04, p=0.0032), White race (β=2.56, SE=0.58, p Conclusion Tailored interventions to increase self-efficacy during the first 7 days of CPAP treatment, especially in Non-Whites and those older than 74 years, may improve long-term CPAP adherence in older adults with amnestic MCI. Support R01AG054435

The relationship between cardiovascular disease and abnormalities in sleep architecture is complex and bi-directional. Sleep disordered breathing (SDB) often confounds human studies examining sleep in the setting of heart failure, and the independent impact of isolated right or left heart failure on sleep is difficult to assess. We utilized an animal model of right heart failure using pulmonary artery banding (PAB) in mice to examine the causal effect of right heart failure on sleep architecture. Four weeks after PAB or sham (control) surgery, sleep was measured by polysomnography for 48 hours and right ventricular (RV) hypertrophy confirmed prior to sacrifice. PAB resulted in right ventricular hypertrophy based on a 30% increase in the Fulton Index (p < 0.01). After PAB, mice spent significantly more time in NREM sleep compared to the control group over a 24 hour period (53.5 ± 1.5% vs. 46.6 ± 1.4%; p < 0.01) and exhibited an inability to both cycle into REM sleep and decrease delta density across the light/sleep period. Our results support a phenotype of impaired sleep cycling and increased 'sleepiness' in a mouse model of RV dysfunction.

An association between restless legs syndrome (RLS) and obstructive sleep apnea (OSA) has been suggested for decades but has been questioned in recent years given the apparently similar prevalence of RLS among patients with OSA and the general population. Still, marked improvement in symptoms of RLS has been reported in patients with OSA treated with continuous positive airway pressure (CPAP). Whether the effect of OSA treatment on RLS extends to modalities of OSA treatment other than CPAP remains an open question. Here, we report the case of a patient with OSA and comorbid debilitating RLS who underwent upper airway stimulation device implantation and subsequently experienced near-resolution of her severe RLS symptoms. Upper airway stimulation devices may be an option for patients with OSA and severe RLS intolerant to conventional CPAP modalities. CITATION: Myc LA, Churnin IT, Jameson MJ, Davis EM. Treatment of comorbid obstructive sleep apnea by upper airway stimulation results in resolution of debilitating symptoms of restless legs syndrome. J Clin Sleep Med. 2018;14(10):1797–1800.

Insomnia is a common disorder that affects up to 40% of people age 65 and older. Untreated insomnia can decrease quality of life, increase healthcare use, and exacerbate cognitive problems. Individuals with cognitive impairment experience more sleep disorders than those without cognitive concerns, yet little is known about insomnia and mild cognitive impairment (MCI). Our objective was to examine predictors of insomnia in persons with MCI (PwMCI). Using data from the National Alzheimer’s Coordinating Center Uniform Data Set, a cross-sectional study of older PwMCI was conducted. Independent sample t-tests and contingency tables with chi-square tests of independence were used to examine differences between PwMCI with and without insomnia. Multivariate binary logistic modeling was performed. The total sample (N=1543) was comprised of 234 (15.1%) with clinician-reported insomnia and 1309 (84.9%) without insomnia. PwMCI and insomnia were more likely to be younger, take more medications, and smoke cigarettes (p.05). Three variables significantly predicted insomnia in PwMCI subjects in a multivariate model: active depression (OR 1.66, 95%CI 1.21, 2.27), active anxiety (OR 2.16, 95%CI 1.57, 2.99) and arthritis (OR 1.78, 95%CI 1.33, 2.39). Differences in predictors of insomnia in PwMCI highlight the need for geriatric and mental health specialists to provide specialized care to this population. Future studies should examine conversion of PwMCI with insomnia to dementia and the compounding effects of insomnia on cognition.

Recent epidemiological studies have demonstrated that significant associations exist between oral disease and diseases involving non-oral tissues. Occasionally, the roles may be reversed and the oral cavity can be severely affected by systemic disease originating in another part of the body. Renal secondary hyperparathyroidism is a common endocrinopathy that occurs as a consequence of chronic azotemic kidney disease. Renal osteodystrophy, the most dramatic clinical consequence of renal secondary hyperparathyroidism is uncommon, but can result in demineralization of maxillofacial bones, loosening of teeth, and pathological jaw fractures. The purpose of this report is to update the current understanding of the pathophysiology of this endocrine disease and to compare the oral manifestations of renal secondary hyperparathyroidism in humans and companion animals. A 50-year review of the veterinary literature was undertaken to examine the clinical presentation of renal osteodystrophy in dogs, and to determine what clinical consequences of renal secondary hyperparathyroidism have been reported in domestic cats.

OBJECTIVES Accurate preoperative staging of pancreatic cancer (Pca) is crucial to direct management. There is a perception that endoscopic ultrasound (EUS) staging should be performed before biliary decompression because of artifact caused by self-expandable metal stents (SEMS). Our aim is to determine whether placement of SEMS affects the staging of Pca. METHODS Fifty-five patients (35 men; mean age, 67 years) with newly diagnosed Pca staged in the last 5 years and captured prospectively were divided into 2 groups matched by age, sex, and final staging. The staging accuracy of EUS in patients who had a SEMS (n = 28) was compared with patients without a SEMS (n = 27). The gold standard was surgical pathology, or cytologic confirmation of metastatic disease. Multivariate analysis was effected on age, sex, presence of SEMS, and presence of metastasis to assess prediction of staging inaccuracy. RESULTS Endoscopic ultrasound correctly staged 14 (52%) of 27 patients in the no-SEMS group and 13 (46%) of 28 in the SEMS group. Logistic regression analysis identified only metastasis as a predictor of inaccuracy in EUS staging. CONCLUSIONS Endoscopic ultrasound staging of Pca does not seem to be affected by the presence of a SEMS. The major reason for misstaging in both groups was failure to detect metastatic disease.

Obesity is a primary risk factor for the development of obstructive sleep apnea in humans, but the impact of obesity on central sleep apnea is less clear. Given the comorbidities associated with obesity in humans, we developed techniques for long-term recording of diaphragmatic EMG activity and polysomnography in obese mice to assess breathing patterns during sleep and to determine the effect of obesity on apnea generation. We hypothesized that genetically obese ob/ob mice would exhibit less variability in breathing across the 24-h circadian cycle, be more prone to central apneas, and be more likely to exhibit patterns of increased diaphragm muscle activity consistent with obstructive apneas compared with lean mice. Unexpectedly, we found that obese mice exhibited a greater circadian impact on respiratory rate and diaphragmatic burst amplitude than lean mice, particularly during rapid eye movement (REM) sleep. Central apneas were more common in REM sleep (42 ± 17 h−1) than non-REM (NREM) sleep (14 ± 5 h−1) in obese mice ( P < 0.05), but rates were not different between lean and obese mice in either sleep state. Even after experimentally enhancing central apnea generation by acute withdrawal of hypoxic chemoreceptor activation during sleep, central apnea rates remained comparable between lean and obese mice. Last, we were unable to detect patterns of diaphragmatic burst activity suggestive of obstructive apnea events in obese mice. In summary, obesity does not predispose mice to increased occurrence of central or obstructive apneas during sleep, but does lead to a more pronounced circadian variability in respiration.

Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.

We previously reported the unexpected finding that 4 wk of exposure to intermittent hypoxia (IH), which simulates the hypoxic stress of obstructive sleep apnea, improved LV cardiac function in healthy, lean C57BL/6J mice. The purpose of the present study was to assess the impact of 4 wk of IH on cardiac function in a transgenic murine model that exhibits a natural history of heart failure. We hypothesized that IH exposure would exacerbate cardiac decompensation in heart failure. Adult male FVB (wild type) and transgenic mice with cardiac overexpression of tumor necrosis factor α (TNF-αTG) at 10–12 wk of age were exposed to 4 wk of IH (nadir inspired oxygen 5–6% at 60 cycles/h for 12 h during light period) or intermittent air (IA) as control. Cardiac function was assessed by echocardiography and pressure-volume loop analyses, and mRNA and protein expression were performed on ventricular homogenates. TNF-αTG mice exposed to IA exhibited impaired LV contractility and increased LV dilation associated with markedly elevated cardiac expression of atrial natriuretic peptide and brain natriuretic peptide compared with wild-type mice. When wild-type FVB mice were exposed to IH, they exhibited increases in arterial pressure and dP/d tmax, consistent with our previous report in C57BL/6J mice. Surprisingly, we found that TNF-αTG mice exposed to IH showed a reduction in end-diastolic volume (38.7 ± 3.8 to 22.2 ± 2.1 ul; P < 0.01) and an increase in ejection fraction (29.4 ± 2.5 to 41.9 ± 3.1%; P < 0.05). In contrast to our previous study in C56Bl/6J mice, neither FVB nor TNF-αTG mice exhibited an upregulation in β-adrenergic expression or cAMP in response to IH exposure. We conclude that 4 wk of exposure to IH in mice induces adaptive responses that improve cardiac function in not only healthy animals but also in animals with underlying heart failure.