Elevated Comorbidity Research Articles

Sufferers from olfactory reference disorder: lonely, depressed and socially pained?

Although the few studies available on Olfactory Reference Disorder (ORD) indicate that the disorder is associated with fear of rejection, avoidance and impairment of social relationships, there are no investigations that have examined loneliness and social pain in individuals with ORD. Additionally, despite studies showing elevated comorbidity of ORD and Major Depressive Disorder (MDD), the relationship between ORD according to the ICD-11 and depressiveness has not been investigated. This exploratory pilot study examined the association of symptoms of ORD according to the ICD-11 with emotional/social loneliness, social pain and depressiveness. A total of 225 German university/college students participated in an anonymous internet-based survey. Severity of ORD symptoms were significantly associated with more severe depressiveness, greater emotional and social loneliness as well as greater social pain. In our sample, participants with self-reported ORD reported on average elevated levels of social pain and loneliness. A total of 93.3% of the participants with self-reported ORD had elevated scores of depressiveness. Emotional and social loneliness remained significantly correlated with ORD symptoms in partial correlations that adjusted for depressive symptoms. In a multiple regression analysis, olfactory concerns were associated with the total loneliness score independent of the effects of depressiveness and social pain. These preliminary results highlight the importance of considering depressive symptoms and social pain in the assessment and treatment of ORD. In addition, results suggest that individuals suffering from ORD might be at increased risk for loneliness.

An uncommon orthogeriatric syndrome: a case of Ogilvie’s syndrome

Acute colonic pseudo-obstruction (ACPO), also known as Ogilvie’s syndrome, is an uncommon postoperative complication of major orthopedic surgery that is characterized by massive colonic dilatation and the potential for substantial morbidity and mortality. Most patients who had Ogilvie’s syndrome had risk factors that could be identified preoperatively, such as immobility, elevated comorbidity, and polypharmacy, prefiguring the frail elderly patient. In modern terms, it is considered a typical orthogeriatric syndrome. In these kinds of patients, we need to be vigilant for its development and judicious in the use of epidural anesthesia. We present an ACPO case in an elderly frail patient with a hip fracture, and we review the available literature to outline clinical characteristics and outcomes. Our patient presented numerous risk factors for developing the syndrome in the preoperative period: nonautonomy in basic and daily living activities, polypharmacotherapy, spinal trauma, and hyposodiemia. In this patient, epidural anesthesia was an additional risk factor. The purpose of this case report is to emphasize the presence of this rare syndrome (1.5% of orthogeriatric patients) in orthogeriatric departments and to identify not only pharmacological, traumatic, and electrolytic risk factors but also those that can be identified even through geriatric evaluation to avoid the use of anesthesiologic techniques and drugs that may have an impact on the prognosis of these patients.

A Comparison of Veterans with Problematic Opioid Use Identified through Natural Language Processing of Clinical Notes versus Using Diagnostic Codes.

Opioid use disorder is known to be under-coded as a diagnosis, yet problematic opioid use can be documented in clinical notes, which are included in electronic health records. We sought to identify problematic opioid use from a full range of clinical notes and compare the demographic and clinical characteristics of patients identified as having problematic opioid use exclusively in clinical notes to patients documented through ICD opioid use disorder diagnostic codes. We developed and applied a natural language processing (NLP) tool that combines rule-based pattern analysis and a trained support vector machine to the clinical notes of a patient cohort (n = 222,371) from two Veteran Affairs service regions to identify patients with problematic opioid use. We also used a set of ICD diagnostic codes to identify patients with opioid use disorder from the same cohort. The NLP tool achieved 96.6% specificity, 90.4% precision/PPV, 88.4% sensitivity/recall, and 94.4% accuracy on unseen test data. NLP exclusively identified 57,331 patients; 6997 patients had positive ICD code identifications. Patients exclusively identified through NLP were more likely to be women. Those identified through ICD codes were more likely to be male, younger, have concurrent benzodiazepine prescriptions, more comorbidities, and more care encounters, and were less likely to be married. Patients in both these groups had substantially elevated comorbidity levels compared with patients not documented through either method as experiencing problematic opioid use. Clinicians may be reluctant to code for opioid use disorder. It is therefore incumbent on the healthcare team to search for documentation of opioid concerns within clinical notes.

Stress hyper-reactivity increases vulnerability to developing binge-type eating and associated anxiety-like behavior; comparison between Wistar-Kyoto and Sprague-Dawley rats.

Binge eating disorder (BED) is a widespread eating disorder that primarily affects women worldwide, and it is characterized by the presence of binge eating episodes and the absence of any compensatory behavior to prevent weight gain. BED presents elevated comorbidity with other psychiatric disorders, such as anxiety, and it has been suggested that stress sensibility could be a vulnerability factor for the development of BED and the associated anxiety comorbidity. In this study, we aim to investigate whether the Wistar-Kyoto rat strain (WKY), which has a stress hyper-reactive phenotype, could develop both binge-type eating and anxiety-like behaviors simultaneously. We also aim to compare its vulnerability to developing both behaviors with the Sprague Dawley rat strain (SD), a rat strain commonly used in binge-eating models. WKY and SD rats were subjected to the model of intermittent access to palatable food (sucrose solution 30% or shortening) without calorie restriction or stress exposure. We evaluated and compared the development of binge-type eating behavior, anxiety-like behavior, and serum corticosterone variation as an index of the stress response in both rat strains. WKY rats presented a higher percentage of binge-type eaters and required less time to develop binge-type eating behavior than SD rats. The WKY eating pattern emulated a binge-eating episode regardless of the palatable food. Although the development of sucrose binge-type eating was similar between strains, WKY developed more easily the shortening binge-type eating than SD and was more susceptible to developing anxiety-like behavior. Additionally, sucrose binge eating seems to differentially affect both strains' hypothalamic-pituitary-adrenal (HPA) axis response to stress since it facilitated its response in SD and blunted it in WKY. Our results show that high-stress sensitive phenotype is a common vulnerability factor for the development of binge-type eating and anxiety-like behavior. Regardless of the macronutrient composition of the palatable food, WKY is susceptible to developing a binge-type eating behavior and is more susceptible than SD to developing anxiety-like behavior simultaneously. In conclusion, results showed that a hyper-reactive stress phenotype predisposes the development of binge-type eating behavior and anxiety-like behavior in the absence of calorie restriction and stress exposure.

173 Electrical Stimulation Used as an Adjunct to Cervical Spine Fusion in Patients at Risk for Pseudarthrosis

INTRODUCTION: Prior studies show that pulsed electromagnetic field (PEMF) stimulation promotes bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk. The current study further evaluates the adjunct effect of PEMF in subjects undergoing cervical spinal surgery presenting with risk factors for pseudarthrosis. METHODS: A prospective multicenter clinical trial (NCT 03177473) was conducted at eleven clinical sites. Subjects undergoing cervical spinal fusion surgery with one or more risk factors for pseudarthrosis were identified for enrollment. Risk factors for pseudarthrosis included multilevel fusion, prior failed cervical spine fusion, diabetes, osteoporosis, or smoking. Subjects undergoing cervical spinal fusion were required to wear the PEMF device for 4 hours/day for 6 months post-op. Fusion status was determined at the 12-month visit using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). NDI, EQ-5D, SF-36, and VAS for neck and arm pain were collected as secondary outcome measures. RESULTS: Out of 160 subjects, 144 (90.0%) were graded as fused (all levels) at the 12-month visit. Fusion success was 91.7% (n = 55/60), 89.0% (n = 89/100), and 90.9% (n = 20/22) for subjects with 1, 2+, or 3+ risk factors, respectively. Significant improvements in NDI, SF-36, EQ-5D, VAS-arm and VAS-neck were observed compared to baseline (p < 0.001). A device compliance rate of 85.0% was observed at 3-months and 78.3% at 6-months in subjects who had successful cervical fusion. CONCLUSIONS: The PEMF bone growth stimulator device is a valuable tool to aid in fusion healing, especially in challenging populations. Subjects in this study experienced favorable fusion rates of 90% and significant improvement in patient reported outcomes despite having elevated comorbidity and/or complex surgeries.

Associations between olfactory reference disorder and social phobia - results of an internet-based study.

Despite the similar clinical features of Olfactory Reference Disorder (ORD) and Social Phobia (SP), or studies showing elevated comorbidity of the two disorders, and the conceptualization of ORD as a form of SP in the East Asian culture, to our knowledge, the relationship between ORD and SP has not been investigated. This study examined the association of ORD according to the 11th revision of the International Classification of Diseases (ICD-11) and SP in 225 German university / college students who completed self-ratings with regard to socio-demographic data and symptoms of SP and ORD within an anonymous internet-based survey. Symptoms of SP were assessed with the Social Phobia Inventory (SPIN). Symptoms of ORD according to the ICD-11 were assessed with the Olfactory Reference Disorder Questionnaire (ORDQ), developed for this study. In our sample, 86.6% of the participants who met the self-rated features for ORD also met the self-rated criteria for current SP. ORD severity scores were significantly related to SP. Participants with and without self-reported ORD differed significantly in their SP total scores. SP severity was also significantly correlated with poorer insight of ORD-related beliefs, greater ORD-related avoidance of intimate relationships and higher levels of shame and fear of rejection due to body odor. These preliminary findings indicate that ORD could be closely related to SP and highlight the need for future research on the relationship of ORD and SP in order to gain a better understanding of the development, maintenance, treatment and classification of ORD.

Regional Anesthetic Use in Trans-Hiatal Esophagectomy. Are They Worth Consideration? A Case Series.

Esophagectomy traditionally has high levels of perioperative morbidity and mortality due to surgical techniques and case complexity. While thoracic epidural analgesia (TEA) is considered first-line for postoperative analgesia after esophagectomy, complications can arise related to its sympathectomy and mobility impairment. Additionally, it has been shown that postoperative outcomes are improved with early extubation following esophagectomy. Our aim is to describe the impact of transversus abdominis plane (TAP) blocks on extubation rates following esophagectomy when uncoupled from TEA. This is a case series of 42 patients who underwent trans-hiatal esophagectomy between 2019 and 2022 who received a TAP block without TEA. The primary outcomes of interest were the rates of extubation within the operating room (OR) and reintubation. Secondary outcomes included: intensive care unit (ICU) and hospital length of stay (LOS), opioid pain medication use, post-operative hypotension, fluid administration, postoperative pain scores, development of anastomotic leak, and 30-day readmission. The mean age at operation was 63 years and 97.6% of patients were represented by American Society of Anesthesia (ASA) physical status class III or IV. Thirty-four (81%) patients immediately extubated postoperatively. Nine patients (21.4%) underwent reintubation during their hospital course. Only seven patients (16.7%) required vasopressors postoperatively. The median LOS was five days in the ICU and 10 days in the hospital. TAP block alone was found to be equivalent to TAP with additional regional blocks (TAP+) on the basis of immediate extubation, reintubation, ICU and hospital LOS, and reported postoperative pain. The results of this study demonstrated immediate extubation is possible using TAP blocks while limiting post-operative hypotension and fluid administration. This was shown despite the elevated comorbidity burden of this study's population. Overall, this study supports the use of TAP blocks as a possible alternative for primary analgesia in patients undergoing trans-hiatal esophagectomy. This study includes participants who were retrospectively registered. IRB# 037.HPB.2018.R.

IDH inhibitors or chemotherapy in relapsed or refractory IDHmut acute myeloid leukemia.

e19043 Background: Venetoclax and IDH inhibitors provide novel treatment options for acute myeloid leukemia (AML). The optimal sequencing of these therapies in the relapsed or refractory setting remains unknown. The purpose of this study was to analyze the overall survival of patients receiving IDH inhibitors, venetoclax-based lower-intensity therapy, and conventional chemotherapy with fludarabine-based regimens in patients undergoing salvage following failure of intensive chemotherapy. Methods: We identified 74 patients with IDH1mut or IDH2mut mutated AML treated from January 1, 2013 to January 1, 2022 at VCU Massey Cancer Center in this single-institution, retrospective study. Forty-eight patients were treated with front-line intensive induction, 19 of whom had relapsed or refractory disease. These were grouped into three salvage cohorts: IDH inhibitors with or without a hypomethylating agent (HMA) (N = 3), intensive fludarabine-based salvage (FLAG) (N = 9), and venetoclax + HMA (N = 7). Patients who received more than one of these salvage therapies were excluded from the analysis. Performance status, disease characteristics, and treatment regimens at salvage were recorded. Demographics of the three cohorts were compared using the Kruskal-Wallis test; we computed the overall survival with the Kaplan-Meier method, using the log-rank test for comparison. Patients alive at the end of the study or lost to follow-up were censored on the date of last contact. Results: Patients in the FLAG cohort were significantly younger than the IDH inhibitor or venetoclax cohorts ( p = 0.009). Patients in the venetoclax cohort had significantly more comorbidities assessed by the Charlson Comorbidity Index score ( p = 0.026) than the intensive chemotherapy salvage cohort. ELN 2022 genetic risk was not significantly different between cohorts ( p = 0.263). In the IDH inhibitor cohort, the median overall survival was not reached at a median follow-up time of 11.8 months. The median overall survival of the FLAG cohort was 14.3 months, and the median survival of the venetoclax cohort was 9.4 months. Overall survival significantly favored the IDH inhibitor cohort ( p = 0.030). The FLAG cohort was associated with significantly improved survival compared to the venetoclax cohort ( p = 0.048). Conclusions: Despite patients in the IDH inhibitor cohort being significantly older, the use of IDH inhibitors, with or without a hypomethylating agent, in the second line following the failure of intensive chemotherapy was associated with significantly superior overall survival compared to FLAG or venetoclax-based salvage. These findings should be interpreted with caution, given the limitations of retrospective studies and significantly elevated comorbidities in the venetoclax cohort. Prospective trial designs are needed to provide further evidence for optimal therapeutic sequencing.

Post-lumbar surgery prescription variation and opioid-related outcomes in a large US healthcare system: an observational study

BACKGROUND CONTEXTSpinal decompression and fusion procedures are one of the most common procedures performed in the United States (US) and remain associated with high postsurgical opioid burden. Despite guidelines emphasizing nonopioid pharmacotherapy strategies for postsurgical pain management, prescribing practices are likely variable and guideline-incongruent. PURPOSEThe purpose of this study was to characterize patient-, care-, and system-level factors associated with opioid, nonopioid pain medication, and benzodiazepine prescribing variation in the US Military Health System (MHS). STUDY DESIGN/SETTINGRetrospective study analyzing medical records from the US MHS Data Repository. PATIENT SAMPLEAdult patients (N=6,625) undergoing lumbar decompression and spinal fusion procedures from 2016 to 2021 in the MHS enrolled in TRICARE at least a year prior to their procedure and had at least one encounter beyond the 90-day postprocedure period, without recent trauma, malignancy, cauda equina syndrome, and co-occurring procedures. OUTCOME MEASURESPatient-, care-, and system-level factors influencing outcomes of discharge morphine equivalent dose (MED), 30-day opioid refill, and persistent opioid use (POU). POU was defined as dispensing of opioid prescriptions monthly for the first 3 months after surgery and then at least once between 90 and 180 days after surgery. METHODS(Generalized) linear mixed models evaluated multilevel factors associated with discharge MED, opioid refill, and POU. RESULTSThe median discharge MED was 375 mg (IQR 225, 580) and days’ supply was 7 days (IQR 4, 10); 36% received an opioid refill and 5%, overall, met criteria for POU. Discharge MED was associated with fusion procedures (+151–198 mg), multilevel procedures (+26 mg), policy release (-184 mg), opioid naïvty (-31 mg), race (Black -21 mg, another race and ethnicity -47 mg), benzodiazepine receipt (+100 mg), opioid-only medications (+86 mg), gabapentinoid receipt (-20 mg), and nonopioid pain medications receipt (-60 mg). Longer symptom duration, fusion procedures, beneficiary category, mental healthcare, nicotine dependence, benzodiazepine receipt, and opioid naivety were associated with both opioid refill and POU. Multilevel procedures, elevated comorbidity score, policy period, antidepressant receipt, and gabapentinoid receipt, and presurgical physical therapy were also associated with opioid refill. POU increased with increasing discharge MED. CONCLUSIONSSignificant variation in discharge prescribing practices require systems-level, evidence-based intervention.

Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.

A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden. We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA2DS2-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA2DS2-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA2DS2-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC. In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; P=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; P=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; P=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; P=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- P=0.027) but not in OptumLabs (interaction-P=0.720). ERC was not associated with an increased risk for the primary safety outcome. ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA2DS2-VASc score ≥4).

Self‐reported wellbeing and health‐related quality of life of Aboriginal and Torres Strait Islander people pre and post the first wave of the COVID‐19 2020 pandemic

ObjectiveQuantify change in wellbeing and health‐related quality‐of‐life (HRQoL) in Aboriginal and Torres Strait Islander adults pre and post Australia's initial COVID‐19 lockdown. MethodsAboriginal and Torres Strait Islander adults completed an online survey at Time 1 (October–November 2019; before the initial Australian COVID‐19 outbreak) and Time 2 (August–September 2020; after the first Australian lockdown). We assessed wellbeing using a visual analogue scale (VAS) and HRQoL using the Assessment of Quality of Life (AQoL‐4D) instrument. Participants who completed both surveys (n=42) were included to quantify change in outcomes over time and by comorbidity and demographic factors. ResultsMean reduction in wellbeing over time was 6.4 points (95%CI −14.2 to 1.4) and was associated with age (18–54yo), financial instability and mental health comorbidity. Mean reduction in HRQoL over time was 0.06 (95%CI −0.12 to 0.01) and was associated with financial instability, high physical comorbidity level and mental health comorbidity. ConclusionsAboriginal and Torres Strait Islanders aged 18–54yo, who were financially unstable or had elevated comorbidity during COVID lockdowns experienced greater reductions in wellbeing and HRQoL. Implications for public healthAs the COVID‐19 pandemic continues in Australia, both urgent and forward planning is needed, especially for the priority groups identified.

Mood, sleep and pain comorbidity outcomes in cannabis dependent patients: Findings from a nabiximols versus placebo randomised controlled trial

BackgroundMood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities. MethodsThis is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs. ResultsAmong those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12–24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes. ConclusionsParticipants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

458 Pulsed Electromagnetic Fields (PEMF) Used in Cervical Spine Fusion for Patients with Risk Factors for Non-Union

INTRODUCTION: A post market prospective study was conducted to examine the effect of the adjunctive use of a pulsed electromagnetic field (PEMF) device on cervical fusion rate in subjects with risk factors for non-union. PEMF has been shown to stimulate bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk for non-union. METHODS: Patients undergoing cervical fusion surgery were identified for enrollment from 11 investigator sites based on being classified as having one or more risk factors for non-union. Subjects were those having a multi-level (2 or more) fusion, prior cervical spine fusion, diabetes, osteoporosis, or smokers. Subjects were required to wear the PEMF device for 4 hours/day for 6 months. Compliance was measured based on usage data downloaded from the device. The primary outcome measure was fusion status at 12 month follow-up period as indicated by x-ray and CT. Fusion status was determined by the site investigator using A/P, lateral, and flexion/extension radiographs in addition to CT (without contrast). RESULTS: Out of 152 subjects, 138 (90.8%) were graded as fused (all levels) at the 12 month visit About half of the subjects (49.3%) had 3 or more levels fused. Fusion success for subjects with 2 or more risk factors was 88.5%, and was 94.4% for subjects with a single risk factor. On average, compliance rates (minutes using device/minutes prescribed) were 83.8% and 74.9% for the 3 and 6 month visit, respectively. The followup rate at the 12 month visit was 97%. CONCLUSION: The results of our study suggest that adjunctive use of PEMF is effective in cervical spine fusion patients with factors associated with non-union. Favorable fusion rates were obtained with patients having elevated comorbidity and/or complex surgeries. Further research is planned to include a control group in a real world setting to better assess the impact of the PEMF device in this population.

Healthcare resource utilization, total costs, and comorbidities among patients with myotonic dystrophy using U.S. insurance claims data from 2012 to 2019

BackgroundMyotonic dystrophy (DM) is a rare, inherited disorder with multi-systemic effects that impact the skeletal muscles, eyes, heart, skin and gastrointestinal, endocrine, respiratory, and central nervous systems. DM is divided into two subtypes: DM1 can present from early childhood through adulthood and also has a congenital form (cDM) while DM2 typically manifests during mid-adulthood. Both forms are progressive with no approved treatments, and unmet need for disease-modifying therapies remains high. This study interrogated health insurance claims data to explore the clinical experience, healthcare resource utilization (HCRU), and all-cause costs for DM.ResultsA total of 8541 patients with DM and 242 patients with cDM and their matched controls were selected from a database of over 200 million claimants. HCRU and all-cause costs, including pharmacy, outpatient, and inpatient services, were analyzed across four years in 12-month follow-up periods. Mean all-cause costs per DM patient were high in each of the four periods (range $14,640–$16,704) and showed a steady increase from 13 to 23 months on, while the control group mean costs declined from $9671 in the first 12 months after the index event, to approach the US population average ($5193) over time. For cDM, the highest mean costs were in the first 12-months ($66,496 vs. $2818 for controls), and remained high (above $17,944) across all subsequent periods, while control mean costs approached $0. For DM and cDM, HCRU was higher compared to controls across all study periods and all-cause healthcare costs were mostly driven by inpatient and outpatient encounters. Analysis of all diagnosis codes over the study period (comorbidities) demonstrated an elevated comorbidity profile consistent with the clinical profile of DM.ConclusionsThis study is among the first to utilize claims data to increase understanding of the clinical experience and health economic outcomes associated with DM. The markedly elevated HCRU patterns and comorbidity profile presented here add to the broad body of scientific and clinical knowledge on DM. These insights can inform clinical care and support the development of disease modifying and/or symptom-targeting therapies that address the multi-systemic, progressive nature of DM.

CA-125 variation in acute heart failure: a single-centre analysis.

AimsA decrease in carbohydrate antigen 125 (CA‐125) predicts survival advantage in chronic heart failure (HF); the impact of its variation in acute HF is unknown. We studied the association of CA‐125 decrease with prognosis in acute HF.Methods and resultsWe studied acute hospitalized HF patients. Predictors of admission and discharge CA‐125 were determined by linear regression. Follow‐up was 1 year; endpoint was all‐cause death. The association of admission and discharge CA‐125 with mortality was assessed using a Cox‐regression analysis. A Cox‐regression analysis was also used to assess the prognostic impact of CA‐125 decrease during hospitalization. Analysis was stratified by length of hospital stay (LOS). We studied 363 patients, 51.5% male, mean age 75 ± 12 years, 51.5% ischaemic, 30.0% with preserved ejection fraction, and 57.3% with reduced ejection fraction; patients presented elevated comorbidity burden. Median LOS was 7 (5–11) days. In the subgroup of 262 patients with CA‐125 measured both at admission and at discharge, we reported a significant increase in its levels: 56.0 (26.0–160.7) U/mL to 74.0 (32.3–195.0) U/mL. Independent predictors of admission CA‐125 were higher BNP and lower creatinine. Predictors of discharge CA‐125 were higher discharge BNP, lower discharge albumin, and younger age. Both admission and discharge CA‐125 predicted mortality. During follow‐up, 75 (31.8%) patients died. A decrease in CA‐125 predicted a 68% reduction in the 1 year death risk only in patients with LOS > 10 days.ConclusionsOur results suggest that an early re‐evaluation (>10 days) with CA‐125 measurement after an acute HF hospitalization may be of interest in patient management.

Phenotypic Disease Network Analysis to Identify Comorbidity Patterns in Hospitalized Patients with Ischemic Heart Disease Using Large-Scale Administrative Data.

Ischemic heart disease (IHD) exhibits elevated comorbidity. However, few studies have systematically analyzed the comorbid status of IHD patients with respect to the entire spectrum of chronic diseases. This study applied network analysis to provide a complete picture of physical and mental comorbidities in hospitalized patients with IHD using large-scale administrative data. Hospital discharge records from a provincial healthcare database of IHD inpatients (n = 1,035,338) and one-to-one matched controls were included in this retrospective analysis. We constructed the phenotypic disease networks in IHD and control patients and further assessed differences in comorbidity patterns. The community detection method was applied to cluster diagnoses within the comorbidity network. Age- and sex-specific patterns of IHD comorbidities were also analyzed. IHD inpatients showed 50% larger comorbid burden when compared to controls. The IHD comorbidity network consisted of 1941 significant associations between 71 chronic conditions. Notably, the more densely connected comorbidities in IHD patients were not within the highly prevalent ones but the rarely prevalent ones. Two highly interlinked communities were detected in the IHD comorbidity network, where one included hypertension with heart and multi-organ failures, and another included cerebrovascular diseases, cerebrovascular risk factors and anxiety. Males exhibited higher comorbid burden than females, and thus more complex comorbidity relationships were found in males. Sex-specific disease pairs were detected, e.g., 106 and 30 disease pairs separately dominated in males and females. Aging accounts for the majority of comorbid burden, and the complexity of the comorbidity network increased with age. The network-based approach improves our understanding of IHD-related comorbidities and enhances the integrated management of patients with IHD.

Vestibular Migraine in Adolescents

Migraine is a recurrent throbbing headache that affects one side of the head and is usually related to nausea and decreased vision. Migraine is typically seen in adolescents due to increased use of electronic devices and computers. It is a non communicable disease.10 percent patients with migraine suffer from vestibular migraine. Vertigo in children can lead to migraine and continue in adults too. Preventing the vertigo attacks in children and adolescents can help in the treatment of migraine. Behavioural therapy is an important factor in treatment of migraine in this age. 40% of migraine patients have some associated vestibular symptoms which includes dizziness and disturbed balance. An elevated comorbidity of migraine and vertigo was discovered in several patient categories and later verified at the community level, far exceeding what random chance would predict. Vertigo is substantially more commonly seen in migraine sufferers, particularly those with aura, than in headache-free controls. Migraine is one of the most disturbing diseases in USA, is nearly as common as hypertension and more common than asthma and diabetes. Migraine and vestibular symptoms can coexist with inner ear disorders. It is a difficult condition to diagnose and treat. Multiple temporal patterns are responsible for this. The most common cause of vertigo in children is vestibular migraine (VM). Clinical findings and laboratory test results have been found in a sample of children and adolescents suffering from Vestibular migraine. Recent classification criteria for dizzy children are discussed and their limitations. Migraine is typically seen in adolescents due to increased use of electronic devices and computers. It is a non-communicable disease. 10 percent patients with migraine suffer from vestibular migraine.

CML-081: Effect of Comorbidities on Response Outcomes with First-Line Tyrosine Kinase Inhibitors (TKIs), Dasatinib Versus Imatinib, in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Exploratory Post Hoc Analysis of DASISION

Background: Five-year follow-up of the open-label, phase 3 DASISION study (NCT00481247) demonstrated faster and deeper molecular responses with dasatinib versus imatinib as first-line therapy for CML-CP. NCCN guidelines recommend considering comorbidities when selecting first-line TKI therapy. This exploratory post hoc analysis of DASISION investigates the effect of comorbidities on responses with dasatinib versus imatinib. Design: Patients with newly diagnosed CML-CP were randomized to 100mg dasatinib (n=259) or 400mg imatinib (n=260) QD. Charlson Comorbidity Index (CCI) was retrospectively calculated for each patient at diagnosis; data were retrospectively stratified by CCI categories (2-4, 5-6, and ≥7 [high burden]). Major molecular response (MMR) and MR4.5 were compared between treatments using unstratified Cochran-Mantel-Haenszel tests. Time to response was evaluated using Kaplan-Meier methodology with HRs based on Cox proportional hazards models and P-values from unstratified log-rank tests. Results: Baseline characteristics were mostly balanced between treatments. Fourteen (3%) patients had CCI 2-4, 260 (50%) had 5-6, and 245 (47%) had ≥7. Responses were numerically greater with dasatinib versus imatinib for CCI 2-4 (MMR: 85.7% versus 57.1%, P=0.2542; MR4.5: 71.4% versus 14.3%, P=0.0374) and ≥7 (MMR: 70.8% versus 64.0%, P=0.2552; MR4.5: 45.0% versus 39.2%, P=0.3589), and significantly higher for CCI 5-6 (MMR: 81.1% versus 64.8%, P=0.0033; MR4.5: 42.4% versus 29.7%, P=0.0329). Median time to MMR (months) was significantly shorter with dasatinib than imatinib for CCI 5-6 (15.0 versus 24.0; HR, 1.64; P=0.0006) and ≥7 (12.0 versus 21.4; HR, 1.41; P=0.0279). Grade 3/4 treatment-related adverse events (TRAEs; dasatinib versus imatinib): 0% versus 14% (CCI 2-4), 8% versus 9% (CCI 5-6), 24% versus 13% (CCI ≥7). Frequency of grade 3/4 TRAEs leading to discontinuation was similar: 0% versus 0%, 1% versus 1%, 8% versus 7%. No deaths occurred for CCI 2-4; similar percentage of patients died between treatments for CCI 5-6 and ≥7. Conclusions: Dasatinib was effective across all CCI groups, consistent with previous findings, suggesting that comorbidities do not negatively affect TKI activity. These findings highlight the benefits of first-line dasatinib in patients with CML-CP and elevated comorbidity burden. Funding: Bristol Myers Squibb. Previous presentation: 62nd ASH Annual Meeting, December 5-8, 2020; republished with permission of Elsevier Inc.

Benchside to the bedside of frailty and cardiovascular aging: Main shared cellular and molecular mechanisms.

Due to the impact that frailty and cardiac aging have on society and health systems, the mechanisms surrounding these conditions must be known. If the frailty and cardiovascular complications are due to numerous controllable factors or not, different strategies must be considered to improve the elderly patient's prognosis and improve their quality of life. This review aimed to investigate the main shared mechanisms of cardiac aging and frailty. MEDLINE-PubMed, Cohrane and EMBASE databases were searched to perform this review. The mesh-terms used for this search was frailty, cardiovascular disease, cardiovascular aging, or heart failure (HF). Frailty frequently coexists with heart conditions since they share predisposing pathophysiological alterations, the aging process, and elevated comorbidity burden, contributing to fast functional decline and sarcopenia. Mitochondrial dysfunctions and decreased protein synthesis lead to protein degradation, denervation, atrophy, impairment in the fatty acid oxidation, resulting in cardiomyopathy. The homeostasis of muscle metabolism deteriorates with aging, leading to a reduction in muscle quality and quantity. The installation of a low-grade and chronic inflammatory process adds to an impairment in glucose, protein and lipid metabolism, endothelial dysfunction, cardiovascular conditions, sarcopenia, and HF. The exacerbated rise in inflammatory biomarkers and impaired insulin resistance leads to worsening of the patient's general condition. The good news is that frailty is a dynamic syndrome, fluctuating between different states of seriousness but still has potential for reversibility based on physical activity, cognitive training, nutrition intervention, and a plethora of other approaches that can be performed by a multi-disciplinary team.

Enhancing Health for the Growing Number of Older Cancer Survivors: Designing Innovative Behavioral Interventions

By 2040, there will be an estimated 26.1 million cancer survivors in the United States, with 73% over age 65. Compared to younger survivors and those without cancer, older adult cancer survivors have an elevated comorbidity burden. Lifestyle interventions can play a key role in preventing and managing chronic health conditions and promoting quality of life during and after cancer treatment. Yet, behavioral interventions for maximizing health are under-utilized in older adults with cancer. At times, older adults may have unique needs that require tailoring to increase accessibility, optimization, and uptake of behavioral interventions.This symposium will showcase innovative approaches for enhancing health among older adult cancer survivors during and after cancer treatment. Dr. Bluethmann will discuss design considerations for using geriatric assessment in an ongoing exercise trial to manage side effects of aromatase inhibitors. Dr. Gell will present data on older survivors’ preferences regarding text messaging to support physical activity maintenance from an intervention study. Dr. Leach will discuss the use of technology to facilitate lifestyle change in older cancer survivors, presenting data on older adults’ user preferences and benefits from an eHealth tool. The discussant, Dr. Trevino, will summarize how these interventions can be leveraged to promote engagement in managing older survivors’ health and to inform next steps in intervention development. Collectively, this multidisciplinary group of speakers will provide practical information and “lessons learned” from designing behavioral and technology-based interventions, and highlight the promise that these approaches hold for improving quality of life in aging cancer survivors. Cancer and Aging Interest Group Sponsored Symposium.