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Item Association of Obstructive Sleep Apnea With Calvarial and Skull Base Thinning(American Medical Association, 2018-06-01) Rabbani, Cyrus; Saltagi, Mohamad Z.; Ye, Michael J.; Patel, Janaki M.; Manchanda, Shalini; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineImportance: Spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone are associated with obesity, calvarial thinning, and obstructive sleep apnea (OSA), and the incidence has doubled in the past decade. It is currently unknown if OSA is independently associated with skull thinning. Objective: To determine if patients with OSA have thinner skulls than patients without OSA. Design, Setting, and Participants: A retrospective cohort study of patients who underwent a level 1 polysomnogram (PSG) and also had high-resolution computed tomographic (CT) imaging of the head from January 2010 to March 2017 at Indiana University was carried out. Patients with moderate to severe OSA (apnea-hypopnea index [AHI]≥25/h) and without OSA (AHI<5/h) were matched for age and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). Interventions: Measurement of calvarial thickness, extracranial zygoma thickness, skull base height and tegmen dehiscence (>4 mm) when blinded to OSA status. Main Outcomes and Measures: Primary outcomes were calvarial, skull base, and zygoma thickness differences between patients with OSA vs those without OSA. Results: A total of 22 933 patients had a PSG and 1012 also had head CT imaging. Of the 1012 patients with both PSG and CT, the mean (SD) age was 50.8 (16.2) years and 624 (61.7%) were women. Those patients with moderate to severe OSA (56) and without OSA (58) were matched for mean (SD) age (50.3 [6.5] vs 49.8 [6.1] years]) and BMI (37.4 [8.1] vs 38.6 [6.8]). Patients with OSA had thinner mean (SD) calvaria (2.73 [0.67] vs 2.47 [0.52] mm; difference, -0.26 mm; 95% CI, -0.49 to -0.04; Cohen d, 0.44) and thinner skull bases (5.03 [1.40] vs 4.32 [1.28] mm; difference, -0.71; 95% CI, -1.23 to -0.19; Cohen d, 0.53). The mean (SD) extracranial zygoma thickness was the same (4.92 [0.87] vs 4.84 [0.84] mm; difference, -0.07 mm; 95% CI, -0.39 to 0.24). The tegmen mastoideum was dehiscent in nearly twice as many patients with OSA as those without (37% vs 20%; difference, 17%; 95% CI, 0.4-32). Conclusions and Relevance: Obstructive sleep apnea was independently associated with intracranial bone (calvaria and skull base) thinning and not with extracranial (zygoma) thinning. These findings support a possible role of OSA in the pathophysiologic development of sCSF-L.Item A Feasibility Study: Testing Whether a Sleep Application Providing Objective Sleep Data to Physicians Improves Patient-Physician Communication Regarding Sleep Experiences, Habits, and Behaviors(Springer, 2022) Durrani, Sana; Cao, Sha; Bo, Na; Pai, Jennifer K.; Baker, Jarod; Rawlings, Lori; Qureshi, Zaina P.; Sigua, Ninotchka L.; Manchanda, Shalini; Khan, Babar; Medicine, School of MedicineIntroduction: Sleep tracker data have not been utilized routinely in sleep-related disorders and their management. Sleep-related disorders are common in primary care practice and incorporating sleep tracker data may help in improving patient care. We conducted a pilot study to assess the feasibility of a sleep program using the Fitbit Charge 2™ device and SleepLife® application. The main aim of the study was to examine whether a program using a commercially available wearable sleep tracker device providing objective sleep data would improve communication in primary care settings between patients and their providers. Secondary aims included whether patient satisfaction with care would improve as result of the program. Methods: A prospective, randomized, parallel group, observational pilot study was conducted in 20 primary care clinics in Indianapolis, IN from June 2018 to February 2019. Inclusion criteria included patients over the age of 18, have a diagnosis of insomnia identified by electronic medical record and/or a validated questionnaire, and were on a prescription sleep aid. The study was not specific to any sleep aid prescription, branded or generic, and was not designed to evaluate a drug or drug class. Each primary care clinic was randomized to either the SleepLife® intervention or the control arm. All patients were provided with a Fitbit Charge 2™ device. Only patients in the intervention arm were educated on how to use the SleepLife® application. Physicians in the intervention arm were set up with the SleepLife® portal on their computers. Results: Forty-nine physicians and 75 patients were enrolled in the study. Patients had a mean age of 57 (SD 12.8) years and 61% were female. Mean age of physicians was 47 (SD 10.6) years. Patients showed high rates of involvement in the program with 83% completing all survey questions. Physician survey completion rate was 55%. Only one physician logged into the SleepLife portal to check their patients' sleep status. At the end of the 6-week intervention, patients' composite general satisfaction scores with sleep health management decreased significantly in the intervention arm when compared to controls (p = 0.03). Patients' satisfaction with communication also decreased significantly in the intervention group (p = 0.01). The sleep outcomes, which were calculated on the basis of study questionnaire answers, improved significantly in the intervention group as compared to the control group (p = 0.04). Physician communication satisfaction scores remained unchanged (p = 0.12). Conclusions: SleepLife® and its related physician portal can facilitate physician-patient communication, and it captures patient sleep outcomes including behaviors and habits. Patients were highly engaged with the program, while physicians did not demonstrate engagement. The study design and questionnaires do not specifically address the reasons behind the decreased patient satisfaction with care and communication, but it was perceived to be a result of physician non-responsiveness. Sleep quality scores on the other hand showed an improvement among SleepLife® users, suggesting that patients may have implemented good sleep practices on their own. Given that it was a feasibility study, and the sample size was small, we were not able to make major inferences regarding the difference between sleep disorder types. Additionally, we excluded patients with a history of alcohol use, substance abuse, or depression because of concerns that they may affect sleep independently. To promote the growth of technology in primary care, further research incorporating results from this study and physician engagement techniques should be included.Item GABA and Glutamate Levels in Occlusal Splint-Wearing Males with Possible Bruxism(Elsevier B.V., 2015-07) Dharmadhikari, Shalmali; Romito, Laura M.; Dzemidzic, Mario; Dydak, Ulrike; Xu, Jun; Bodkin, Cynthia L.; Manchanda, Shalini; Byrd, Kenneth E.; Department of Oral Biology, IU School of DentistryObjective The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the pathophysiology of anxiety behavioural disorders such as panic disorder and post-traumatic stress disorder and is also implicated in the manifestation of tooth-grinding and clenching behaviours generally known as bruxism. In order to test whether the stress-related behaviours of tooth-grinding and clenching share similar underlying mechanisms involving GABA and other metabolites as do anxiety-related behavioural disorders, we performed a Magnetic Resonance Spectroscopy (MRS) study for accurate, in vivo metabolite quantification in anxiety-related brain regions. Design MRS was performed in the right hippocampus and right thalamus involved in the hypothalamic−pituitary−adrenal axis system, together with a motor planning region (dorsal anterior cingulate cortex/pre-supplementary motor area) and right dorsolateral prefrontal cortex (DLPFC). Eight occlusal splint-wearing men (OCS) with possible tooth-grinding and clenching behaviours and nine male controls (CON) with no such behaviour were studied. Results Repeated-measures ANOVA showed significant Group × Region interaction for GABA+ (p = 0.001) and glutamate (Glu) (p = 0.031). Between-group post hoc ANOVA showed significantly lower levels of GABA+ (p = 0.003) and higher levels of Glu (p = 0.002) in DLPFC of OCS subjects. These GABA+ and Glu group differences remained significant (GABA+, p = 0.049; Glu, p = 0.039) after the inclusion of anxiety as a covariate. Additionally, GABA and Glu levels in the DLPFC of all subjects were negatively related (Pearson's r = −0.75, p = 0.003). Conclusions These findings indicate that the oral behaviours of tooth-grinding and clenching, generally known as bruxism, may be associated with disturbances in brain GABAergic and glutamatergic systems.Item Hospital outcomes in non-surgical patients identified at risk for OSA(Elsevier, 2020) Khan, Sikandar H.; Manchanda, Shalini; Sigua, Ninotchka L.; Green, Erika; Mpofu, Philani B.; Hui, Siu; Khan, Babar A.; Medicine, School of MedicineBackground: In-hospital respiratory outcomes of non-surgical patients with undiagnosed obstructive sleep apnea (OSA), particularly those with significant comorbidities are not well defined. Undiagnosed and untreated OSA may be associated with increased cardiopulmonary morbidity. Study objectives: Evaluate respiratory failure outcomes in patients identified as at-risk for OSA by the Berlin Questionnaire (BQ). Methods: This was a retrospective study conducted using electronic health records at a large health system. The BQ was administered at admission to screen for OSA to medical-service patients under the age of 80 years old meeting the following health system criteria: (1) BMI greater than 30; (2) any of the following comorbid diagnoses: hypertension, heart failure, acute coronary syndrome, pulmonary hypertension, arrhythmia, cerebrovascular event/stroke, or diabetes. Patients with known OSA or undergoing surgery were excluded. Patients were classified as high-risk or low-risk for OSA based on the BQ score as follows: low-risk (0 or 1 category with a positive score on the BQ); high-risk (2 or more categories with a positive score on BQ). The primary outcome was respiratory failure during index hospital stay defined by any of the following: orders for conventional ventilation or intubation; at least two instances of oxygen saturation less than 88% by pulse oximetry; at least two instances of respiratory rate over 30 breaths per minute; and any orders placed for non-invasive mechanical ventilation without a previous diagnosis of sleep apnea. Propensity scores were used to control for patient characteristics. Results: Records of 15,253 patients were assessed. There were no significant differences in the composite outcome of respiratory failure by risk of OSA (high risk: 11%, low risk: 10%, p = 0.55). When respiratory failure was defined as need for ventilation, more patients in the low-risk group experienced invasive mechanical ventilation (high-risk: 1.8% vs. low-risk: 2.3%, p = 0.041). Mortality was decreased in patients at high-risk for OSA (0.86%) vs. low risk for OSA (1.53%, p < 0.001). Conclusions: Further prospective studies are needed to understand the contribution of undiagnosed OSA to in-hospital respiratory outcomes.Item Insomnia and Upper Airway Stimulation Therapy Benefit and Adherence: A Case Series(Springer, 2023-03) Stahl, Stephanie M.; Manchanda, Shalini; Parker, Noah; Chernyak, Yelena; Neurology, School of MedicineObstructive sleep apnea (OSA) and insomnia are common sleep disorders that often occur concurrently. The presence of one of these disorders often negatively impacts the other, including affecting treatment benefit and adherence. While insomnia has been shown to adversely affect positive airway pressure therapy adherence, minimal data are currently available on the effects of insomnia on upper airway stimulation (UAS) therapy for the treatment of OSA. We present two cases that highlight the negative impact of insomnia on UAS therapy usage and OSA management as well as the benefits of insomnia treatment on overall outcomes. Screening for and treatment of insomnia prior to UAS implantation are recommended.Item Novel Outcome Analysis Tool for Hypoglossal Nerve Stimulator Sensor Lead Function and Comparison by Incision Type (2 Versus 3)(Wiley, 2023) Saltagi, Mohamad Z.; Powell, Kayla; Saltagi, Abdul K.; Stahl, Stephanie; Manchanda, Shalini; Parker, Noah P.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: No reported outcome measures have been established to evaluate sensor lead function in the hypoglossal nerve stimulator (HNS). This study describes the development of novel functional outcome measures for intraoperative sensor electrode function and compares 2-incision and 3-incision outcomes for HNS. Methods: A retrospective cohort study of 100 consecutive patients who underwent HNS between June 2019 and September 2021. Demographic information, intraoperative findings, and immediate postoperative outcomes were recorded. Structured parameters were developed to compare intraoperative waveforms with six outcome measures utilized: waveform syncing, waveform amplitude, sensory current leakage, shark-fin morphology, cardiac artifact, and overall impression. Two sleep surgeons and two sleep medicine specialists compared all waveforms in a blinded fashion and assigned scores on the Likert Scale. Results: The cohort included 50 three-incision and 50 two-incision patients. Age, gender, average body mass index, comorbidity profiles, and sleep endoscopy findings did not significantly differ between the two groups. No major complications occurred. The interclass-correlation-coefficient was greater than 0.7 for all comparisons (good to very good interrater reliability). There was no difference in waveform amplitude, cardiac artifact, sensory current leakage, or shark-fin morphology between the two groups. Waveform syncing and overall impression were statistically better in the 2-incision cohort. Conclusions: This study is the first to define a structured method of HNS sensor electrode outcome measurement and showed consistent measures by surgeons and sleep medicine specialists. This article supports the transition to the 2-incision technique among surgeons for placement of the sensor lead. Consideration should be given to utilizing this novel tool in the clinical/research setting and validating these measures moving forward.Item Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes(Elsevier, 2017-10) Facco, Francesca L.; Grobman, William A.; Reid, Kathryn J.; Parker, Corette B.; Hunter, Shannon M.; Silver, Robert M.; Basner, Robert C.; Saade, George R.; Pien, Grace W.; Manchanda, Shalini; Louis, Judette M.; Nhan-Chang, Chia-Ling; Chung, Judith H.; Wing, Deborah A.; Simhan, Hyagriv N.; Haas, David M.; Iams, Jay; Parry, Samuel; Zee, Phyllis C.; Medicine, School of MedicineBACKGROUND: Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. OBJECTIVE: Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. STUDY DESIGN: This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (<7 h/night), late sleep midpoint (midpoint between sleep onset and sleep offset >5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. RESULTS: In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11-4.53; and odds ratio, 2.58; 95% confidence interval, 1.24-5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01-4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13-4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. CONCLUSION: Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.Item Obstructive Sleep Apnea, Glucose Tolerance, and β-Cell Function in Adults With Prediabetes or Untreated Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study(American Diabetes Association, 2021-04) Mokhlesi, Babak; Tjaden, Ashley H.; Temple, Karla A.; Edelstein, Sharon L.; Sam, Susan; Nadeau, Kristen J.; Hannon, Tamara S.; Manchanda, Shalini; Mather, Kieren J.; Kahn, Steven E.; Ehrmann, David A.; Van Cauter, Eve; RISE Consortium; Pediatrics, School of MedicineObjective: Obstructive sleep apnea (OSA) is associated with insulin resistance and has been described as a risk factor for type 2 diabetes. Whether OSA adversely impacts pancreatic islet β-cell function remains unclear. We aimed to investigate the association of OSA and short sleep duration with β-cell function in overweight/obese adults with prediabetes or recently diagnosed, treatment-naive type 2 diabetes. Research design and methods: Two hundred twenty-one adults (57.5% men, age 54.5 ± 8.7 years, BMI 35.1 ± 5.5 kg/m2) completed 1 week of wrist actigraphy and 1 night of polysomnography before undergoing a 3-h oral glucose tolerance test (OGTT) and a two-step hyperglycemic clamp. Associations of measures of OSA and actigraphy-derived sleep duration with HbA1c, OGTT-derived outcomes, and clamp-derived outcomes were evaluated with adjusted regression models. Results: Mean ± SD objective sleep duration by actigraphy was 6.6 ± 1.0 h/night. OSA, defined as an apnea-hypopnea index (AHI) of five or more events per hour, was present in 89% of the participants (20% mild, 28% moderate, 41% severe). Higher AHI was associated with higher HbA1c (P = 0.007). However, OSA severity, measured either by AHI as a continuous variable or by categories of OSA severity, and sleep duration (continuous or <6 vs. ≥6 h) were not associated with fasting glucose, 2-h glucose, insulin sensitivity, or β-cell responses. Conclusions: In this baseline cross-sectional analysis of the RISE clinical trial of adults with prediabetes or recently diagnosed, untreated type 2 diabetes, the prevalence of OSA was high. Although some measures of OSA severity were associated with HbA1c, OSA severity and sleep duration were not associated with measures of insulin sensitivity or β-cell responses.Item Preoperative STOP-BANG Scores and Postoperative Delirium and Coma in Thoracic Surgery Patients(Elsevier, 2018) Wang, Sophia; Sigua, Ninotchka Liban; Manchanda, Shalini; Gradney, Steve; Khan, Sikandar H.; Perkins, Anthony; Kesler, Kenneth; Khan, Babar; Psychiatry, School of MedicineBackground Obstructive sleep apnea (OSA) is associated with higher rates of postoperative delirium. The relationship between preoperative OSA risk and postoperative delirium and coma in thoracic surgery patients hospitalized in the intensive care unit (ICU) is not well understood. This study tests the hypothesis that thoracic surgery patients hospitalized in ICU with a higher preoperative risk for OSA are more likely to develop postoperative delirium and coma, resulting in longer hospital stays. Methods Preoperative OSA risk was measured using the STOP-BANG questionnaire. STOP-BANG scores of ≥ 3 were defined as intermediate-high risk for OSA. 128 patients who underwent major thoracic surgery completed the STOP-BANG questionnaire preoperatively. The Richmond Agitation and Sedation Scale was used to assess level of consciousness. The Confusion Assessment Method for the ICU was used to assess for delirium. Linear regression was used to assess the relationship between risk of OSA and outcome measures. Results were adjusted for age, gender, body mass index, Charlson Comorbidity Index, instrumental activities of daily living, and surgery type. Results 96 out of 128 patients (76%) were in the intermediate-high risk OSA group. Adjusted analyses showed that the intermediate-high risk OSA group had a longer duration of postoperative ICU delirium and coma compared to the low risk OSA group (1.4 days ± 1.3 vs 0.9 days ± 1.4; P = 0.04). Total number of hospital days was not significantly different. Conclusions Higher preoperative risk for OSA in thoracic surgery patients was associated with a longer duration of postoperative delirium and coma.Item Prevalence of insomnia and restless legs syndrome in patients with upper airway stimulation therapy and effects on treatment outcomes(Elsevier, 2022-10) Jomha, Mohammed; Dabboussi, Tarek; Parker, Noah P.; Manchanda, Shalini; Chernyak, Yelena; Stahl, Stephanie M.; Neurology, School of MedicineObjective This study aims to explore the prevalence of insomnia and restless legs syndrome (RLS) and the possible effects of these conditions on treatment adherence and outcomes in patients with upper airway stimulation (UAS) therapy for the treatment of obstructive sleep apnea. Methods Consecutive patients who underwent UAS system implantation were retrospectively studied. Patients without insomnia or RLS, insomnia, RLS, and both insomnia and RLS were compared. The apnea-hypopnea index (AHI), in-lab UAS titration data, Epworth Sleepiness Scale (ESS), and adherence to UAS therapy were compared. Results Sixty-four patients who had UAS implantation and completed post-implant in-lab UAS titration were identified. Insomnia was present in 47%, RLS in 28%, and both insomnia and RLS in 14%. During in-lab titration, the AHI improved for all groups and did not differ across groups. The arousal index on in-lab titration was higher in patients with both RLS and insomnia compared to those without these conditions. At the time of the in-lab titration, the hours of UAS therapy usage were reduced for patients with RLS (4.7 ± 1.9 h/night, p = 0.027) compared to those without RLS (6.0 ± 2.0 h/night). The ESS was higher in patients with RLS compared to those without RLS at in-lab titration. Conclusion Insomnia and RLS are common in patients using UAS therapy. A decrease in UAS usage and higher ESS were present in patients with RLS. Further research evaluating the long-term effects of insomnia and RLS in UAS therapy usage and benefit is needed.