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Background: United States rural community-based practices are increasingly participating in undergraduate and graduate medical education to train the workforce of the future, and are required or encouraged to provide academic appointments to physicians who have typically not held an academic appointment. Mechanisms to identify faculty and award academic appointments across an entire health system have not been reported., Methods: Our rural community regional practice identified academic appointments as important for participating in medical education. Over a three-year period, our regional leadership organized a formal education committee that led a variety of administrative changes to promote the adoption of academic rank. Data on attainment of academic appointments was obtained from our Academic Appointment and Promotion Committee, and cross referenced with data from our regional human resources department using self-reported demographic data., Results: We describe a successful adoption strategy for awarding academic rank in a rural regional practice in which the percentage of physician staff with academic rank increased from 41.1 to 92.8% over a 3-year period., Conclusions: Our experience shows that process changes can rapidly increase and then sustain academic appointments for physicians over time. More rural health systems may want to consider the use of academic rank to support educational programs while enhancing physician satisfaction, recruitment and retention., (© 2024. The Author(s).)

Background: Ocular ischemic syndrome (OIS) is a rare presentation of atherosclerotic carotid artery stenosis that can result in permanent visual loss. This severely disabling syndrome remains under diagnosed and undertreated due to lack of awareness; especially since it requires expedited multidisciplinary care. The relevance of early diagnosis and treatment is increasing due to an increasing prevalence of cerebrovascular disease., Methods: The long-term visual and cerebrovascular outcomes following intervention for nonarteritic OIS, remain poorly described and were the objective of this concise review. We conducted a PubMed search to include all English language publications (cohort studies and case reports) between 2002 and 2023., Results: A total of 33 studies (479 patients) report the outcomes of treatment of OIS with carotid endarterectomy (CEA, 304 patients, 19 studies), and carotid artery stenting (CAS, 175 patients, 14 studies). Visual outcomes were improved or did not worsen in 447 patients (93.3%). No periprocedural stroke was reported. Worsening visual symptoms were rare (35 patients, 7.3%); they occurred in the immediate postoperative period secondary to ocular hypoperfusion (3 patients) and in the late postoperative period due to progression of systemic atherosclerotic disease. Symptomatic recurrence due to recurrent stenosis after CEA was reported in 1 patient (0.21%); this was managed successfully with CAS. None of these studies report the results of transcarotid artery revascularization, the long-term operative outcome or stroke rate., Conclusions: OIS remains to be an underdiagnosed condition. Early diagnosis and prompt treatment are crucial in reversal or stabilization of OIS symptoms. An expedited multidisciplinary approach between vascular surgery and ophthalmology services is necessary to facilitate timely treatment and optimize outcome. If diagnosed early, both CEA and CAS have been associated with visual improvement and prevention of progressive visual loss., (Copyright © 2024 Elsevier Inc. All rights reserved.)

BACKGROUND Inherited deficiencies in the FBN1 gene, which encodes fibrillin-1, result in Marfan syndrome, an autosomal dominant connective tissue disorder that is associated with aortic root dilatation and predisposes to aortic dissection. This report is of a 37-year-old woman presenting at 39 weeks of pregnancy with acute thoracic aortic dissection due to previously undiagnosed FBN1-related Marfan syndrome. This case report aims to illustrate the challenges in the diagnosis and in the peri-operative management of acute aortic dissection during pregnancy. CASE REPORT A healthy 37-year-old woman at 39 weeks of gestation presented to our hospital with dyspnea and chest pain. Initial evaluation for pulmonary embolism with chest computed tomography was unrevealing. The patient was admitted to the intensive care unit for further management. Overnight, her clinical conditions deteriorated, and a transthoracic echocardiography was obtained, demonstrating an acute ascending aortic dissection. She emergently underwent a successful combined cesarean section and ascending aortic dissection repair, with no immediate complications. On postoperative day 4 she developed cardiac tamponade, for which she underwent emergent mediastinal exploration. She was discharged home on postoperative day 10. A month later she completed genetic testing, which revealed a pathogenic mutation in the FBN1 gene, consistent with a molecular diagnosis of Marfan syndrome. CONCLUSIONS This report has shown that FBN1-related Marfan's syndrome has a variable clinical presentation that can include life-threatening aortic dissection during pregnancy. Successful diagnosis and management of these patients is challenging and requires multidisciplinary expertise, including confirmation of the diagnosis by a clinical geneticist.

Background: Amiodarone is the most effective and commonly used antiarrhythmic medication. Given its risk of toxicity, routine monitoring is recommended but is challenging to ensure in clinical practice., Methods: We created an intelligent application, built within our electronic health record, that identified every living patient with an active outpatient prescription by a clinician in our health system. The application was designed to identify patients with lapses in recommended monitoring and facilitate scheduling of overdue testing., Results: The percentage of patients with overdue monitoring tests decreased with use of the application, with greatest improvement in pulmonary function testing., Discussion: Implementing a program to monitor and mitigate adverse reactions to amiodarone by using programable features of an electronic health record is feasible., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza pericarditis and myopericarditis cases according to PRISMA guidelines using the PubMed search engine of the Medline database. Seventy-five cases of influenza myopericarditis and isolated pericarditis were identified from 1951 to 2021. Influenza A was reported twice as often as influenza B; however, influenza type did not correlate with outcome. Men and elderly patients were more likely to have isolated pericarditis, while women and younger patients were more likely to have myopericarditis. All included patients had pericardial effusion, while 36% had tamponade. Tamponade was more common in those with isolated pericarditis (41.2%) than myopericarditis (13.8%). Cardiogenic shock was more common in patients with myopericarditis (64%), with an overall mortality rate of 14.7%. Nearly 88% of the recovered patients remained without long-term complications reported. Conclusion: Influenza A appears a more common cause of pericarditis and myopericarditis. Isolated pericarditis was more commonly associated with tamponade but without reported deaths, whereas myopericarditis was more commonly associated with cardiogenic shock and death (19%).

Competing Interests: None.

Background: Although the consequences of sleep deficiency for obesity risk are increasingly apparent, experimental evidence is limited and there are no studies on body fat distribution., Objectives: The purpose of this study was to investigate the effects of experimentally-induced sleep curtailment in the setting of free access to food on energy intake, energy expenditure, and regional body composition., Methods: Twelve healthy, nonobese individuals (9 males, age range 19 to 39 years) completed a randomized, controlled, crossover, 21-day inpatient study comprising 4 days of acclimation, 14 days of experimental sleep restriction (4 hour sleep opportunity) or control sleep (9 hour sleep opportunity), and a 3-day recovery segment. Repeated measures of energy intake, energy expenditure, body weight, body composition, fat distribution and circulating biomarkers were acquired., Results: With sleep restriction vs control, participants consumed more calories (P = 0.015), increasing protein (P = 0.050) and fat intake (P = 0.046). Energy expenditure was unchanged (all P > 0.16). Participants gained significantly more weight when exposed to experimental sleep restriction than during control sleep (P = 0.008). While changes in total body fat did not differ between conditions (P = 0.710), total abdominal fat increased only during sleep restriction (P = 0.011), with significant increases evident in both subcutaneous and visceral abdominal fat depots (P = 0.047 and P = 0.042, respectively)., Conclusions: Sleep restriction combined with ad libitum food promotes excess energy intake without varying energy expenditure. Weight gain and particularly central accumulation of fat indicate that sleep loss predisposes to abdominal visceral obesity. (Sleep Restriction and Obesity; NCT01580761)., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health grant HL 114024 and a Clinical and Translational Science Award (UL1 TR002377). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr Somers serves as a consultant for Baker Tilly, Jazz Pharmaceuticals, Bayer, Sleep Number, and Respicardia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In the expanding era of antibiotic resistance, new strains of Staphylococcus aureus have emerged which possess resistance to traditionally used antibiotics (MRSA). Our review aimed to systematically synthesize information on previously described MRSA pericarditis cases. The only criterion for inclusion was the isolation of MRSA from the pericardial space. Our review included 30 adult and 9 pediatric patients (aged: 7 months to 78 years). Comorbid conditions were seen in most adult patients, whereas no comorbidities were noted amongst the pediatric patients. Pericardial effusion was found in 94.9% of cases, with evidence of tamponade in 83.8%. All cases isolated MRSA from pericardial fluid and 25 cases (64.1%) had positive blood cultures for MRSA. Pericardiocentesis and antibiotics were used in all patients. The mortality rate amongst adults was 20.5%, with a mean survival of 21.8 days, and attributed to multi-organ failure associated with septic shock. No mortality was observed in the pediatric population. In adult patients, there was no statistical difference in symptom duration, antibiotic duration, presence of tamponade, age, and sex in relation to survival. Conclusion: MRSA pericarditis often presents with sepsis and is associated with significant mortality. As such, a high clinical suspicion is needed to proceed with proper tests such as echocardiography and pericardiocentesis. In more than one third of the cases, MRSA pericarditis occurs even in the absence of documented bacteremia.

Cardiac involvement in drug reaction with eosinophilia and systemic symptoms (DS) is rare but associated with high mortality. The aim of this research was to systematically review case reports by PRISMA guidelines in order to synthetize the knowledge of cardiac manifestations of DS. We identified 42 cases from 36 case reports. Women were two times more affected than men. Two-thirds of patients had cardiac manifestation in the initial phase of the disease, while in one-third of cases cardiac manifestations developed later (mean time of 70 ± 63 days). The most common inciting medications were minocycline (19%) and allopurinol (12%). In 17% of patients, the heart was the only internal organ affected, while the majority (83%) had at least one additional organ involved, most commonly the liver and the kidneys. Dyspnea (55%), cardiogenic shock (43%), chest pain (38%), and tachycardia (33%) were the most common cardiac signs and symptoms reported. Patients frequently had an abnormal ECG (71.4%), and a decrease in left ventricular ejection fraction was the most common echocardiographic finding (45%). Endomyocardial biopsy or histological examination at autopsy was performed in 52.4%, with the predominant finding being fulminant eosinophilic myocarditis with acute necrosis in 70% of those biopsied. All patients received immunosuppressive therapy with intravenous steroids, while non-responders were more likely to have received IVIG, cyclosporine, mycophenolate, and other steroid-sparing agents (60%). Gender and degree of left ventricular systolic dysfunction were not associated with outcomes, but short latency between drug exposure and the first DRESS symptom onset (<15 days) and older age (above 65 years) was associated with death. This underscores the potential importance of heightened awareness and early treatment.

Background: Ambulatory overnight oximetry (OXI) has emerged as a cost-effective initial test for sleep disordered breathing. Obesity is closely associated with obstructive sleep apnea (OSA); however, whether body mass index (BMI) or waist-to-hip ratio (WHR) predicts abnormal overnight OXI remains unknown. Methods: We performed a retrospective cross-sectional study of 393 men seen in the Executive Health Program at Mayo Clinic in Rochester, Minnesota who underwent ambulatory overnight OXI ordered by preventive medicine physicians between January 1, 2004 through December 31, 2010. We compared participant/spouse-reported symptoms (sleepiness, snoring), physician indications for OXI (obesity, fatigue), Epworth Sleepiness Scale scores, anthropomorphic measurements (WHR, BMI), and comorbid medical conditions (hypertension, diabetes) with OXI results. Results: 295 of the 393 men who completed OXI had abnormal results. During multivariate analysis, the strongest independent predictor of abnormal OXI for men was WHR (≥1.0, OR = 5.59) followed by BMI (≥30.0 kg/m 2 , OR = 2.75), age (≥55 yrs, OR = 2.06), and the presence of snoring (OR = 1.91, P < 0.05 for all). A strong association was observed between WHR and abnormal OXI in obese (BMI ≥ 30.0 kg/m 2 , OR = 6.28) and non-obese (BMI < 29.9 kg/m 2 , OR = 6.42, P < 0.01 for both) men. Furthermore, 88 men with abnormal OXI underwent polysomnography with 91% being subsequently diagnosed with OSA. Conclusions: In ambulatory, predominantly middle-aged men undergoing preventive services evaluation many physician indications for OXI were not predictors of abnormal results; however, WHR strongly predicted abnormal OXI in obese and non-obese men. As such, we suggest middle-aged men who snore and have a WHR ≥1.0 should be directly referred to a sleep clinic for polysomnography., Competing Interests: VS has consulted for Baker Tilly, Sleep Number Corporation, Bayer, Jazz Pharmaceuticals and Respicardia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bock, Rodysill, Calvin, Vungarala, Sahakyan, Cha, Svatikova, Lopez-Jimenez and Somers.)

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A pioneering surgeon at the University of Minnesota, Dr C. Walton Lillehei, is still considered the "father of open-heart surgery". Dr Lillehei and his surgical team performed the first open-heart operations utilizing cross-circulation, including the first successful ventricular septal defect closure on a 3-year-old boy. Before his death at age 67, this patient arranged to donate his body to the University of Minnesota's Anatomy Bequest program. We describe this patient's medical history, and present unique images of internal/external cardiac anatomies and implanted devices obtained via direct visualizations, computed tomography, and fluoroscopy post-mortem. Additionally, we present computational models and 3-dimensional printed models., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the cardiovascular (CV) prognostic value of adipokines in a large prospective cohort of patients participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial., Patients and Methods: The effects of the adipokine levels at baseline and change from baseline on the composite outcome (CV death, myocardial infarction, and stroke) were analyzed using unadjusted and fully adjusted Cox models in 2330 patients with type 2 diabetes and coronary artery disease who had participated in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (from January 1, 2001, through December 1, 2008)., Results: In a fully adjusted model, baseline leptin and change from baseline leptin were protective for CV events, whereas baseline adiponectin, baseline tumor necrosis factor α (TNF-α), change from baseline TNF-α, baseline C-reactive protein (CRP), and change from baseline CRP were harmful. The effect of baseline leptin on CV events depended on the body mass index (BMI), such that the hazard ratios (HRs) varied between 0.6 and 1.4 across the BMI quintiles (interaction P=.03). The same was true for baseline adiponectin (HR varied from 0.7 to 1.7; interaction P=.01), change from baseline monocyte chemoattractant protein-1 (HR varied from 0.8 to 1.8; interaction P=.03), change from baseline TNF-α (HR varied from 0.9 to 1.4; interaction P=.02), and change from baseline IL-6 (HR varied from 0.7 to 1.8; interaction P=.005)., Conclusion: Adipokines are independent predictors of CV events in patients with type 2 diabetes and coronary artery disease. The association between the specific adipokines and CV outcome varies depending on BMI. This reflects the complex pathophysiology of CV disease in obesity and may help explain the "obesity paradox.", Trial Registration: clinicaltrials.gov Identifier: NCT00006305., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: To determine the effects of insulin sensitization (IS) and insulin provision (IP) treatment strategies on adipokines associated with cardiovascular disease in patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI 2D)., Methods and Results: Changes in adipokine levels were compared in patients with type 2 diabetes mellitus and coronary artery disease randomized to IS (n = 1037) versus IP (n = 1019) treatment strategies in BARI 2D. Circulating concentrations of leptin, adiponectin, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin 6 and C-reactive protein were evaluated at baseline and one year. IS and IP treatment strategies exerted significant (p < 0.0001) differential effects on: leptin (IS: 0.02% decrease, p = 0.01; IP: 13% increase, p < 0.0001); adiponectin (IS: 73% increase, p < 0.0001; IP: no change, p = 0.52); interleukin 6 (IS: 14% decrease, p < 0.0001; IP: no change, p = 0.68). Changes in monocyte chemoattractant protein-1 and tumor necrosis factor-alpha were not statistically different between groups. C-reactive protein decreased, but the effect was significantly greater in the IS group (-32%, p < 0.0001) than in the IP group (-5%, p = 0.0005)., Conclusion: The IS and IP treatment strategies exerted divergent effects on adipokine and inflammatory profile in patients with type 2 diabetes mellitus and coronary artery disease. The IS treatment strategy-induced changes may be more favorable than the IP treatment strategy regarding cardiovascular pathophysiology., (© The European Society of Cardiology 2014.)

Study Objectives: To assess etiology of ischemic stroke in patients with obstructive sleep apnea (OSA) compared with controls. This information may aid in determining how OSA increases stroke risk and facilitate recurrent stroke prevention in patients with OSA., Design: Retrospective, case-control study., Setting: Academic tertiary referral center., Patients: Consecutive patients who underwent polysomnography and had an ischemic stroke within 1 year were identified. Stroke subtype was determined using two validated algorithms. Polysomnographic results were used to separate patients into OSA cases and controls. Information regarding cardiovascular risks, neuroimaging, and echocardiographic data were collected., Interventions: N/A., Measurements and Results: In 53 subjects, cardioembolic (CE) strokes were more common among OSA cases than controls (72% versus 33%, P = 0.01). The majority of CE strokes occurred in those with moderate to severe OSA. Atrial fibrillation (AF) was more frequent in OSA cases (59% versus 24%, P = 0.01). The association between OSA and CE stroke remained significant after controlling for AF (P = 0.03, odds ratio 4.5)., Conclusions: There appears to be a strong association between obstructive sleep apnea (OSA) and cardioembolic (CE) stroke. In patients with OSA presenting with cryptogenic stroke, high clinical suspicion for CE is warranted. This may lead to consideration of diagnostic studies to identify CE risk factors such as paroxysmal atrial fibrillation (AF). CE strokes are more common in patients with OSA even after adjusting for AF. This finding may reflect a high rate of occult paroxysmal AF in this population; alternatively, OSA may lead to CE strokes through mechanisms independent of AF., (© 2015 Associated Professional Sleep Societies, LLC.)

Purpose: Obstructive sleep apnea (OSA) has been implicated in both cardiovascular and cerebrovascular diseases. Systemic inflammation and coagulation may be related to cardiovascular pathophysiology in patients with OSA. Fibrinogen is a major coagulation protein associated with inflammation, and long-term elevated plasma fibrinogen is associated with an increased risk of major cardiovascular diseases. We assessed whether severity of OSA is associated with levels of fibrinogen in newly diagnosed, untreated, and otherwise healthy OSA patients., Methods: We studied 36 men with OSA and 18 male control subjects (apnea-hypopnea index [AHI]<5 events/h). OSA patients were divided into mild (AHI≥5<15 events/h) and severe (AHI≥15 events/h) OSA groups. Morning fibrinogen levels in OSA patients were compared to those in control subjects of similar age, body mass index, blood pressure, smoking habits, and alcohol consumption., Results: Fibrinogen levels were significantly elevated in patients with severe OSA compared to both control (P=0.003) and mild OSA (P=0.02) subjects after adjustment for covariates. However, there were no significant differences in fibrinogen levels between mild OSA and control subjects. Fibrinogen levels were directly related to AHI and arousal index and inversely related to mean and lowest oxygen saturation during sleep., Conclusions: Severity of OSA was associated with increased fibrinogen level independent of other factors, suggesting that apneic events and oxygen desaturation during sleep are mechanisms for increased fibrinogen levels in patients with OSA.

Background: Epidemiologic evidence suggests a link between short sleep duration and cardiovascular risk, although the nature of any relationship and mechanisms remain unclear. Short sleep duration has also been linked to an increase in cardiovascular events. Endothelial dysfunction has itself been implicated as a mediator of heightened cardiovascular risk. We sought to determine the effect of 8 days/8 nights of partial sleep restriction on endothelial function in healthy humans., Methods and Results: Sixteen healthy volunteers underwent a randomized study of usual sleep versus sleep restriction of two-thirds normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcome was endothelial function measured by flow-mediated brachial artery vasodilatation (FMD). Those randomized to sleep restriction slept 5.1 hours/night during the experimental period compared with 6.9 hours/night in the control group. Sleep restriction was associated with significant impairment in FMD (8.6±4.6% during the initial pre-randomization acclimation phase versus 5.2±3.4% during the randomized experimental phase, P=0.01) whereas no change was seen in the control group (5.0±3.0 during the acclimation phase versus 6.73±2.9% during the experimental phase, P=0.10) for a between-groups difference of -4.40% (95% CI -7.00 to -1.81%, P=0.003). No change was seen in non-flow mediated vasodilatation (NFMD) in either group., Conclusion: In healthy individuals, moderate sleep restriction causes endothelial dysfunction., Clinical Trial Registration Url: ClinicalTrials.gov. Unique identifier: NCT01334788., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Central sleep apnea (CSA) is common among patients with heart failure (HF) and is promoted by elevated CO2 chemosensitivity. Left atrial size is a marker of the hemodynamic severity of HF. The aim of this study was to determine if left atrial size predicts chemosensitivity to CO2 and CSA in patients with HF., Methods: Patients with HF with left ventricular ejection fraction ≤ 35% underwent polysomnography for detection of CSA, echocardiography, and measurement of CO2 chemosensitivity. CSA was defined as an apnea-hypopnea index (AHI) ≥ 15/h with ≥ 50% central apneic events. The relation of clinical and echocardiographic parameters to chemosensitivity and CSA were evaluated by linear regression, estimation of ORs, and receiver operator characteristics., Results: Of 46 subjects without OSA who had complete data for analysis, 25 had CSA. The only parameter that significantly correlated with chemosensitivity was left atrial volume index (LAVI) (r = 0.40, P < .01). LAVI was greater in those with CSA than those without CSA (59.2 mL/m2 vs 36.4 mL/m2, P < .001) and significantly correlated with log-transformed AHI (r = 0.46, P = .001). LAVI was the best predictor of CSA (area under the curve = 0.83). A LAVI ≤ 33 mL/m2 was associated with 22% risk for CSA, while LAVI ≥ 53 mL/m2 was associated with 92% risk for CSA., Conclusions: Increased LAVI is associated with heightened CO2 chemosensitivity and greater frequency of CSA. LAVI may be useful to guide referral for polysomnography for detection of CSA in patients with HF.

Background & Aims: Common risk factors for obstructive sleep apnea (OSA) and Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). The aims of this study were to assess the association between OSA and BE and to determine whether the association is independent of GERD and body mass index (BMI)., Methods: Patients who had undergone a diagnostic polysomnogram and esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester, Minnesota) databases from January 2000-November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed by using a multiple variable logistic model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking history., Results: Subjects with OSA had an 80% increased risk for BE compared with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P = .03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured by using the apnea-hypopnea index, was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03)., Conclusions: In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Poor fidelity to practice guidelines in the care of people with multiple chronic conditions (MCC) may result from patients and clinicians struggling to apply recommendations that do not consider the interplay of MCC, socio-personal context, and patient preferences., Objective: The objective of the study was to assess the quality of guideline development and the extent to which guidelines take into account 3 important factors: the impact of MCC, patients' socio-personal contexts, and patients' personal values and preferences., Research Design: We conducted a systematic search of clinical practice guidelines for patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two reviewers working independently selected studies, extracted data, and evaluated the quality of the guidelines., Results: We found 28 eligible guidelines, which, on average, had major methodological limitations (AGREE II mean score 3.8 of 7, SD=1.6). Patients or methodologists were not included in the guideline development process in 20 (71%) and 24 (86%) guidelines, respectively. There was a complete absence of incorporating the impact of MCC, socio-personal context, and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines, respectively. When mentioned, MCC were considered biologically, but not as contributors of complexity or patient work or as motivation to focus on patient-centered outcomes., Conclusions: Extant clinical practice guidelines for one chronic disease sometimes consider the context of the patient with that disease, but only do so narrowly. Guideline panels must remove their contextual blinders if they want to practically guide the care of patients with MCC.

Background: Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin., Methods: We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin., Results: Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P=.006) and decreased in the control group by -118 kcal/d (SD, 386 kcal/d, P=.51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P=.014). Sleep restriction was not associated with changes in activity energy expenditure (P=.62). No change was seen in levels of leptin (P=.27) or ghrelin (P=.21)., Conclusions: Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction., Trial Registration: ClinicalTrials.gov; No.: NCT01334788; URL: www.clinicaltrials.gov.

Several studies have suggested that epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD). However, the role of EAT as a potential risk factor for, and predictor of, long-term cardiovascular outcomes in patients with CAD requires additional investigation. We investigated the relation among EAT, cardiovascular events, and measures of adiposity in patients with CAD. The study was a prospective cohort study of 194 consecutive patients with CAD who entered a phase II cardiac rehabilitation program at the Mayo Clinic. EAT was measured using echocardiography. The primary outcome was the long-term recurrence of major adverse cardiovascular events (MACE). The outcomes were assessed using the Mayo Clinic electronic medical records. The mean age was 59.4 ± 10.8 years, the body mass index was 28.7 ± 4.6 kg/m(2), 80% were men, and 21% of the patients underwent coronary artery bypass grafting. The mean follow-up period was 3.6 ± 1.3 years, and 52 MACE occurred. EAT was not a predictor of MACE (hazard ratio 1.32, 95% confidence interval 0.75 to 2.31; p = 0.33) when used as a continuous variable and correlated poorly with the measures of adiposity. However, a nonsignificant trend was seen for a greater incidence of cardiovascular events when EAT was stratified by tertile (hazard ratio for third tertile 1.77, 95% confidence interval 0.84 to 3.32; p = 0.11), after statistical adjustments for age, gender, body mass index, and other covariates. In conclusion, the results of the present longitudinal study suggest that EAT, as measured using echocardiography, does not strongly predict for MACE and is poorly associated with measures of obesity in patients with CAD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF., Methods: We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB., Results: Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m(2), and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R(2) = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively., Conclusions: Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.

Background: Central sleep apnea (CSA) is frequent among patients with heart failure (HF) and associated with increased morbidity and mortality. Elevated cardiac filling pressures promote CSA and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. We hypothesized that circulating natriuretic peptide concentrations predict CSA., Methods: Consecutive patients with HF (n = 44) with left ventricular ejection fraction (LVEF) ≤ 35% underwent polysomnography for detection of CSA. CSA was defined as an apnea-hypopnea index ≥ 15 with ≥ 50% central apneic events. The relation of natriuretic peptide concentrations to CSA was evaluated by estimation of ORs and receiver operator characteristics (ROCs)., Results: Twenty-seven subjects (61%) had CSA, with men more frequently affected than women (73% vs 27%; OR, 7.1; P = .01); given that only three women had CSA, further analysis was restricted to men. Subjects with CSA had higher mean ANP (4,336 pg/mL vs 2,510 pg/mL, P = .03) and BNP concentrations (746 pg/mL vs 379 pg/mL, P = .05). ANP and BNP concentrations were significantly related to CSA (OR, 3.7 per 3,000 pg/mL, P = .03 and OR, 1.5 per 200 pg/mL, P = .04, respectively), whereas age, LVEF, and New York Heart Association functional class were not. Concentrations of ANP and BNP were predictive of CSA as ROC demonstrated areas under the curve of 0.75 and 0.73, respectively., Conclusions: Risk of CSA is related to severity of HF. ANP and BNP concentrations performed similarly for detection of CSA; low concentrations appear associated with low risk for CSA in men.

Background: The Berlin Questionnaire (BQ) has been used to identify patients at high risk for sleep-disordered breathing (SDB) in a variety of populations. However, there are no data regarding the validity of the BQ in detecting the presence of SDB in patients after myocardial infarction (MI). The aim of this study was to determine the performance of the BQ in patients after MI., Methods: We conducted a cross-sectional study of 99 patients who had an MI 1 to 3 months previously. The BQ was administered, scored using the published methods, and followed by completed overnight polysomnography as the "gold standard." SDB was defined as an apnea-hypopnea index of ≥ 5 events/h. The sensitivity, specificity, and positive and negative predictive values of the BQ were calculated., Results: Of the 99 patients, the BQ identified 64 (65%) as being at high-risk for having SDB. Overnight polysomnography showed that 73 (73%) had SDB. The BQ sensitivity and specificity was 0.68 and 0.34, respectively, with a positive predictive value of 0.68 and a negative predictive value of 0.50. Positive and negative likelihood ratios were 1.27 and 0.68, respectively, and the BQ overall diagnostic accuracy was 63%. Using different apnea-hypopnea index cutoff values did not meaningfully alter these results., Conclusion: The BQ performed with modest sensitivity, but the specificity was poor, suggesting that the BQ is not ideal in identifying SDB in patients with a recent MI.

Obesity has been associated with increased cardiac sympathetic activation during wakefulness, but the effect on sleep-related sympathetic modulation is not known. The aim of this study was to investigate the effect of fat gain on cardiac autonomic control during wakefulness and sleep in humans. We performed a randomized, controlled study to assess the effects of fat gain on heart rate variability. We recruited 36 healthy volunteers, who were randomized to either a standardized diet to gain ≈4 kg over 8 weeks followed by an 8-week weight loss period (n=20) or to serve as a weight-maintainer control (n=16). An overnight polysomnogram with power spectral analysis of heart rate variability was performed at baseline, after weight gain, and after weight loss to determine the ratio of low-frequency to high-frequency power and to examine the relationship between changes in heart rate variability and changes in insulin, leptin, and adiponectin levels. Mean weight gain was 3.9 kg in the fat gain group versus 0.1 kg in the maintainer group. Low frequency/high frequency increased both during wakefulness and sleep after fat gain and returned to baseline after fat loss in the fat gain group and did not change in the control group. Insulin, leptin, and adiponectin also increased after fat gain and fell after fat loss, but no clear pattern of changes was seen that correlated consistently with changes in heart rate variability. Short-term fat gain in healthy subjects is associated with increased cardiac sympathetic activation during wakefulness and sleep, but the mechanisms remain unclear.

Contrast-induced acute kidney injury (CIAKI) is a leading cause of iatrogenic renal failure. Multiple studies have shown that patients with diabetic nephropathy are at high risk of CIAKI. This Review presents an overview of the pathogenesis of CIAKI in patients with diabetic nephropathy and discusses the currently available and potential future strategies for CIAKI prevention.

Aims: Central sleep apnoea (CSA) and increased serum erythropoietin (EPO) concentration have each been associated with adverse prognosis in heart failure (HF) patients. The aim of this study was to examine the relationship between nocturnal hypoxaemia due to CSA and the serum EPO concentration in patients with HF., Methods and Results: Heart failure subjects (n = 33) and healthy controls (n = 18) underwent polysomnography (PSG) for diagnosis of CSA and identification and quantification of hypoxaemia. Blood collection for measurement of EPO was performed immediately post-PSG. For the analysis, HF subjects were dichotomized into subgroups defined by the presence or absence of CSA and by HF severity. Multivariate analyses were performed to evaluate the relationships of hypoxaemia and advanced HF to EPO concentration. Mean EPO concentration was 62% higher for HF subjects with CSA than for healthy controls (P = 0.004). The magnitude of nocturnal hypoxaemia was significantly and positively related to EPO concentration (r = 0.45, P = 0.02). Advanced HF was also significantly and positively related to EPO concentration (r = 0.43, P = 0.02). On multivariate analysis, the presence of combined nocturnal hypoxaemia and advanced HF yielded greater correlation to EPO concentration than either factor alone (r = 0.57, P = 0.04 and P = 0.05, respectively). Linear regression demonstrated that the combination of New York Heart Association Class and CSA was strongly associated with EPO concentration (P < 0.0001)., Conclusion: In non-anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.

Obstructive sleep apnea (OSA) exerts several effects that may be particularly deleterious in patients with heart failure (HF). OSA should be considered especially in HF patients who are obese or have the metabolic syndrome, systemic hypertension, or pulmonary hypertension. HF patients in whom OSA is suspected should undergo a full evaluation by a sleep specialist, including a polysomnogram, to diagnose OSA and differentiate this disease from central sleep apnea. Those found to have OSA should then receive continuous positive airway pressure and/or other interventions, and standard disease management strategies should be used to maximize compliance. Those who cannot tolerate continuous positive airway pressure may be candidates for mandibular advancement devices or surgical therapies including tracheostomy. Standard HF medications should be used to treat HF, and optimization of fluid balance may help minimize OSA severity. However, it is still unknown whether treatment of OSA in HF patients will reduce hospitalizations or mortality.

Objective: The negative results of two randomized controlled trials (RCTs) have challenged current guideline recommendations for using aspirin for primary prevention of cardiovascular events among patients with diabetes. We therefore sought to determine if the effect of aspirin for primary prevention of cardiovascular events and mortality differs between patients with and without diabetes., Research Design and Methods: We conducted a systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus since their inceptions until November 2008 for RCTs of aspirin for primary prevention of cardiovascular events. Blinded pairs of reviewers evaluated studies and extracted data. Random-effects meta-analysis and Bayesian logistic regression were used to estimate the ratios of relative risks (RRs) of outcomes of interest among patients with and without diabetes. A 95% CI that crosses 1.00 indicates that the effect of aspirin does not differ between patients with and without diabetes., Results: Nine RCTs with moderate to high methodological quality contributed data to the analyses. The ratios of RRs comparing the benefit of aspirin among patients with diabetes compared with patients without diabetes for mortality, myocardial infarction, and ischemic stroke were 1.12 (95% CI 0.92-1.35), 1.19 (0.82-1.17), and 0.70 (0.25-1.97), respectively., Conclusions: Whereas estimates of benefit among patients with diabetes remain imprecise, our analysis suggests that the relative benefit of aspirin is similar in patients with and without diabetes.

A 64-year-old woman presented eight days following pericardiectomy with a 2-day history of progressive dyspnea and new crushing chest pain. Chest x-ray revealed development of interval "cardiomegaly." Bedside echocardiography revealed a large accumulation of pericardial fluid despite absence of pericardium. Diagnostic and therapeutic mediastinocentesis was performed and confirmed the diagnosis of mediastinal hemorrhage. Subsequent to pericardiectomy, mediastinal hemorrhage can masquerade as cardiomegaly and may require urgent intervention.

Purpose of Review: To update the reader on the most recent developments linking obstructive sleep apnea to cardiovascular disease., Recent Findings: Significant progress has been made in defining the relationship between obstructive sleep apnea and cardiovascular disease. However, much work remains to be done to clarify the pathophysiologic mechanisms and the potential role of treatment of sleep apnea in the prevention of cardiovascular morbidity and mortality., Summary: At present there is only limited evidence to recommend the routine treatment of obstructive sleep apnea specifically for the prevention of cardiovascular disease.

The combination of metabolic syndrome and obstructive sleep apnea (OSA) has been termed "syndrome Z." The prevalence of both OSA and metabolic syndrome is increasing worldwide, in part linked to the epidemic of obesity. Beyond their epidemiologic relationship, growing evidence suggests that OSA may be causally related to metabolic syndrome. We are only beginning to understand the potential mechanisms underlying the OSA-metabolic syndrome interaction. Although there is no clear consensus, there is growing evidence that alterations in the hypothalamic-pituitary axis, generation of reactive oxygen species (ROS) due to repetitive hypoxia, inflammation, and generation of adipokines may be implicated in the changes associated with both OSA and metabolic syndrome. Whether some or all of these metabolic alterations mechanistically link OSA to metabolic syndrome remains to be proven, but it is an area of intense scientific interest.

Contrast-induced acute kidney injury (CIAKI) is the most-common form of in-hospital drug-induced acute kidney injury and occurs in 1 to over 50% of patients undergoing intravascular contrast media (CM) administration. Numerous risk factors for CIAKI have been described, the most prominent among them is pre-existing kidney disease such as diabetic nephropathy. The pathogenesis of CIAKI appears to be caused, at least in part, by renal vasoconstriction and renal ischemia leading to the generation of reactive oxygen species (ROS). Diabetes is associated with increased sensitivity to renal vasoconstrictors including CM agents and is also associated with dysfunctional renal handling of ROS, making diabetics particularly susceptible to CIAKI. At present, there are limited srtategies for the prevention of CIAKI among them the administration of the antioxidant N-acetylcysteine (NAC) and intravenous hydration. In light of the rising prevalence of diabetes worldwide and the high risk it represents for the development of CIAKI and CIAKI-associated cardiovascular mortality, a lucid understanding of the pathogenesis of CIAKI and diabetic nephropathy is indispensable. The current review addresses the role of ROS in the pathogenesis of CIAKI in the diabetic renal milieu and discusses current and potential novel treatment modalities for the prevention of CIAKI in diabetic patients.

Obstructive sleep apnea (OSA) is common among patients with cardiovascular disease; however, the association between OSA and risk of cardiovascular events is not clear. Valham and colleagues studied the effect of OSA on incident stroke, acute myocardial infarction, and death in patients with angina pectoris who were referred for coronary angiography. Patients with OSA were not more likely to die or experience a myocardial infarction than were individuals without OSA, but, after adjusting for potential confounders, patients with OSA were approximately three times more likely to experience a new stroke. Furthermore, there was a dose-response effect, with patients who had mild OSA and those who had severe OSA being 2.4 times and 3.6 times more likely to experience stroke, respectively. While this study contributes to our understanding of the interactions between OSA and the risk of both cardiovascular and cerebrovascular events, it also raises several important questions.

There is increasing awareness of sleep-disordered breathing, which may manifest as obstructive sleep apnea, central sleep apnea (CSA), or a mixture of the two. Obstructive sleep apnea and CSA are strongly associated with heart failure (HF) and risk factors for developing HF. CSA may be considered a manifestation of the pathophysiology of HF; hence, approaches to optimize pharmacologic and nonpharmacologic treatment of HF should help to ameliorate CSA. However, if CSA also contributes to HF progression, CSA may represent a potential therapeutic target. There was hope that CSA prevalence would decline with better HF therapies. However, contemporary studies of HF patients on optimal medical therapy have shown that CSA prevalence remains 30% to 40%. Treating CSA poses significant challenges. Presently, the role of routine continuous positive airway pressure remains unclear, although newer ventilatory strategies may prove effective. Currently, CSA treatment involves standard optimal HF therapies, although growing evidence indicates that newer ventilation modes and cardiac resynchronization therapy may prove to be useful.

Objective: Describe the pharmacoepidemiology of sedative medications and nurse-rated patients' behavior and sedation adequacy., Design: Cohort study, 2001-2003., Patients: Patients ventilated for >36 hrs in a medical or surgical intensive care unit at a university-affiliated hospital. Proxies for 312 eligible subjects were approached for consent, 277 subjects enrolled, and data from 274 subjects were analyzed., Interventions: None., Measurements and Main Results: Distribution of Arousal and Motor Activity levels, proportion of inadequate sedation and factors associated with inadequate sedation, variation of sedative therapy intensity, and behavior over time were measured. Sedatives were administered in 85% of 18,050 four-hour intervals during mechanical ventilation. Sedation was judged as adequate in 83% of 12,414 sedation assessments; patients were judged to be undersedated in 13.9% and oversedated in 2.6% of the assessments. Patients were unarousable or minimally arousable 32% of the time and had no spontaneous motor activity (during a 10-min observation period) 21.5% of the time. There was little variation in level of consciousness or motor activity or drug dose over 24 hrs, but daytime caregivers were more likely to judge patients as oversedated (3.7%) compared with nighttime caregivers (1.6%, p<.001). Inadequate sedation was associated with sedative drug intensity and patient behavior as measured by a two-domain sedation scale. Sedative drug intensity and behavior varied during the course of respiratory failure, and survivors received 13% more sedation per 4-hr interval of mechanical ventilation than nonsurvivors (p<.001)., Conclusions: Although patients were minimally arousable or nonarousable in 32% and motionless in 21% of the sedation assessments, surprisingly, an oversedation rating occurred in <3%. This discrepancy, along with findings that time of day influences the interpretation of sedation adequacy and that patients' behavior change over time suggests that collaborative research is needed to define adequate sedation.

Nicotine is a teratogen in rats and possibly in humans. Vaccination against nicotine is being studied as a possible treatment for nicotine dependence. The safety of maternal vaccination against nicotine during or prior to pregnancy is not known. In this study, female rats were vaccinated and then administered acute or chronic nicotine during pregnancy at doses simulating nicotine exposure in smokers. Maternal vaccination reduced nicotine distribution to both maternal brain (44-47%) and fetal brain (17-39%) for up to 25 min after a single maternal nicotine dose administered on gestational day (GD) 20, but had a smaller effect on nicotine distribution to brain after continuous nicotine infusion. Nicotine distribution to maternal or fetal brain after repeated nicotine bolus doses was reduced immediately following an individual dose in vaccinated rats, but the chronic accumulation of nicotine in fetal brain was not altered. Nicotine distribution to whole fetus, in contrast to fetal brain, was generally not altered by vaccination. Nicotine-specific antibody concentration in fetal serum was 10% that of maternal serum, and in fetal brain was <1% of maternal serum. Although nicotine transfer to the whole fetus was not reduced by vaccination, protein binding data suggest that nicotine-specific antibody transferred from mother to fetus served to bind nicotine in fetal serum, reduce the unbound nicotine concentration, and thereby reduce nicotine distribution to fetal brain. These data comment on the safety of vaccination against nicotine during pregnancy, and suggest that vaccination may reduce the distribution of nicotine to fetal brain under some nicotine dosing conditions.