Cardiovascular Comorbidities Research Articles

Incidence of Right Ventricular Dysfunction in an Echocardiographic Referral Cohort.

Incidence rates (IRs) of RV dysfunction (RVD) are unknown. We examined the rates, risk factors, and heart failure (HF) hospitalization hazard associated with incident RVD in patients referred for Transthoracic Echocardiogram (TTE). In this retrospective cohort study, we extracted tricuspid regurgitant velocity (TRV) and tricuspid annular systolic plane excursion (TAPSE) from TTEs at Vanderbilt (2010-2023). We followed patients from their earliest TTE with normal RV function (TAPSE≥17mm) and a reported TRV. The primary outcome was new RVD (TAPSE<17mm), and the secondary outcome was HF hospitalization after second TTE. Poisson regression and multivariable cox models estimated IRs and hazard ratios, adjusted for demographics, comorbidities, and TTE measures. Among 45,753 patients (63 years [IQR 50-72], 45% Male, 13% Black) meeting inclusion criteria, 13,735 (30.1%) underwent a follow up TTE and 4,198 (9.2%) developed RVD. The IR of RVD in the full cohort was 3.2/100 person/years (95%CI 3.1-3.3) and 8.2 (95%CI 8.0-8.5) in the repeat TTE cohort. IRs increased with rising RVSP. Risk factors for incident RVD were most prominently HF (HR 1.88; 95%CI 1.75-2.03), left-sided valvular disease (HR 1.68; 95%CI 1.53-1.85), and other cardiovascular comorbidities. Baseline RVSP >35 mmHg associated with TAPSE decline over time. Incident RVD increased hazard of HF hospitalization (HR 2.02; 95%CI 1.85-2.21). Hazard of HF hospitalization increased when TAPSE declined by ≥5mm. RVD incidence is substantial among patients referred for TTE. Clinical monitoring is warranted if RVSP >35mmHg. Cardiovascular comorbidities drive RVD in this population. Incident RVD associates with increased hazard of HF hospitalization.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5mg BID or rivaroxaban 10mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14-p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

6903 The Treatment May Be Worse Than The Disease: The Real-World Clinical Burden Of Disease And Treatment In Congenital Adrenal Hyperplasia

Abstract Disclosure: W. Huang: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. R. Charlton: Employee; Self; Spruce Biosciences. S. Sile: Employee; Self; Spruce Biosciences. C. Dieyi: Employee; Self; STATinMED. S. Adams: Employee; Self; STATinMED. J. Maynard: Employee; Self; STATinMED. C.N. Barnes: Employee; Self; Spruce Biosciences. A.H. Hamrahian: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. Background and Aims: Classic congenital adrenal hyperplasia (CAH) is a group of autosomal recessive conditions that affects the production of adrenal hormones, leading to deficiencies in cortisol and aldosterone, and excess in adrenal androgens. Current treatment includes mineralocorticoids and oral glucocorticoids (GCs) for physiologic cortisol replacement and hypothalamic-pituitary-adrenal (HPA) axis suppression to control androgen levels. The health impacts of hyperandrogenemia include accelerated skeletal maturation leading to adult short stature, precocious puberty, acne, hirsutism, male pattern baldness, adrenal rest tumors, and infertility. There are also serious adverse events due to the long-term use of supraphysiologic doses of GCs. The aim of this study was to explore the risks associated with CAH diagnosis and treatment. Methods: This cross-sectional study used medical administrative claims data within 2014-2021 from RWD Insights®, an all-payer claims database in the US. Adult patients were required to have a diagnosis of CAH (ICD-9/10-CM: 255.9, E25.0, E25.9) and continuous use of oral GCs (defined as a proportion of days covered of 75% or more in any given calendar year). Patients were further required to receive an average daily GC dose of ≥10mg/day hydrocortisone equivalent and be free of pituitary disorders. Non-CAH controls were also selected if they did not have a CAH diagnosis or any GC use. Demographic characteristics and comorbidity rates were compared between patients with and without CAH during the study period. For comorbidity rate comparisons, rate ratios (RR) and 95% confidence intervals (CI) were computed. Results: A total of 1,532,141 (CAH: 2,033; Non-CAH: 1,530,108) were eligible for the study. A lower proportion of the CAH cohort was elderly (i.e., 65+ years; 11% vs. 26%), and there were more females (67% vs. 57%), as compared to the non-CAH cohort. After propensity score matching (PSM) on demographic characteristics, there were 2,019 and 8,076 patients in the CAH and non-CAH cohort, respectively, and patient characteristics were balanced. There were higher rates of comorbidities in the CAH cohort. Some notable differences, RR (95%CI), include GC related comorbidities such as osteoporosis/necrosis, 3.48 (3.36, 3.60) and fractures, 2.14 (1.90, 2.39); metabolic disorders, 2.20 (2.08, 2.33), obesity, 1.35 (1.26-1.44), type 2 diabetes, 1.27 (1.18,1.36), and cardiovascular disorders, 1.24 (1.16, 1.33); and CAH related comorbidities, hirsutism, 11.70 (11.34, 12.06) and testicular hypofunction, 5.48 (5.24, 5.71). Conclusions: This study suggests the association of several comorbidities with CAH, highlighting the burden of both the disease and treatment. Novel, non-steroidal treatments that improve hormonal balance in CAH could ameliorate the systemic risks associated with hyperandrogenemia and chronic overexposure to GCs. Presentation: 6/1/2024

7281 Increased Incidence Of Fracture And Predicted Fracture Risk In Patients With Mild Autonomous Cortisol Secretion

Abstract Disclosure: R. Sagar: None. A. Saadulla: None. A. Abbas: None. Background: Mild autonomous cortisol secretion (MACS) is common in patients presenting with adrenal incidentalomas (AI) and has been associated with cardiovascular and metabolic co-morbidities. Whilst there is growing evidence to support the increased risk of cardiometabolic co-morbidity in this cohort, the bone health effects are less well characterised. Our study evaluated the prevalence of fragility fracture and fracture risk in patients with AI and MACS compared with a cohort of patients with benign, non-functional AI. Methods: Retrospective observational data were collected on 391 patients with MACS and an AI along with 626 patients with a benign, non-functional AI. Demographic, biochemical, radiological and bone health data were recorded. FRAX, a validated fracture risk stratifying tool, was used to calculated risk scores for all patients aged between 40 and 90 and risk category according to national guidance were also recorded. Results: MACS cohort (mean age 69±10 and 53% female) had a mean cortisol on overnight dexamethasone suppression test of 76.6±21nmol/l. Benign, non-functional patients had a mean age 61.4±12 and 57% female. Both cohorts had predominantly unilateral lesions (76% in MACS versus 84%). Patients with MACS had a significantly higher prevalence of all fragility fractures, 15.9% compared with 6.7% in the benign, non-functional group, p&amp;lt;0.0001. Patients with MACS had a significantly higher 10-year risk of major osteoporotic fracture (10.6±3.8% versus 7.1±5.4%, p&amp;lt;0.0001) and also hip fracture (7.2±4.1% versus 1.9±2.7%, p&amp;lt;0.0001). 17% of MACS cohort were classed as either high or very high fracture risk, with a further 28% classed as intermediate risk requiring further assessment of bone health compared with 3% high/very high risk in the non-functional group. Despite this only 31% of the MACS group had undergone DEXA scan to assess bone mineral density compared to 13% of the non-MACS group. Only 5% of MACS patients were on osteoporosis treatment (3% in non-MACS cohort). Conclusions: Patients with MACS make up a large proportion of those presenting with adrenal incidentaloma. Our study suggests an increased prevalence of fragility fractures along with increased fracture risk in patients with MACS compared to those with non-functional AI. However, we also demonstrate an unmet need, with less than 1/3 of patients with MACS undergoing formal bone health assessment and just 5% of the total cohort on treatment for osteoporosis despite a significant proportion meeting intervention thresholds. Presentation: 6/1/2024

9360 Evaluating The More Accurate Indicator Of Kidney Function In Mild Autonomous Cortisol Secretion: EGFR Creatinine Versus EGFR Cystatin

Abstract Disclosure: L. Rahimi: None. J. Saini: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) have higher prevalence of cardiovascular comorbidities including chronic kidney disease. However, considering that patients with MACS may have relative skeletal muscle atrophy, it is unclear whether the creatine-based assessment of kidney function is accurate in this population. Objective: To characterize the differences in assessing estimated glomerular filtration rate using cystatin (eGFRcys) versus creatinine (eGFRcre) in patients with MACS versus referent subjects. Methods: Cross-sectional single-center study, 2019-2022. MACS was defined as serum cortisol concentration &amp;gt;1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST). For each patient, eGFRcre, eGFRcys and eGFRcre/eGFRcys ratio were measured and compared between the two groups. Body composition was measured by DXA scan. The Kruskal-Wallis test was used to compare measurements between groups. Result: A total of 37 patients with MACS (median age 59 years (interquartile range, IQR 47-67), 25 (68%) women) and 45 referent subjects (median age 57 years (IQR 51-66), 30 (67%) women) were included. The distribution of BMI, total body fat mass and total body lean mass were similar between the two groups. In the MACS cohort, the median cortisol following 1-mg DST was 3.0 ug/dL (IQR, 2.2-4.0). While assessment of kidney function with eGFRcre showed no differences between patients with MACS and referent subjects (median 85.1 vs 87.0 ml/min/1.73m2, P=0.431), kidney function using eGFRcys was lower in MACS (median 78.0 vs 89.3 ml/min/1.73m2 in referents, P&amp;lt;0.014), resulting also in a higher eGFRcre/eGFRcys ratio (median 1.07 vs 0.97 in MACS vs referents, P=0.053). After adjusting for age, sex, and BMI, a higher 1 mg DST cortisol level in the MACS cohort was associated with a higher eGFRcre/eGFRcys ratio (Spearman correlation coefficient of 0.35, P = 0.042). Lower eGFRcys was associated with higher fat mass (Spearman correlation of -0.26, P = 0.023), and a higher eGFRcre/eGFRcys ratio showed a trend towards lower lean mass (Spearman correlation of -0.20, P = 0.081). Conclusion: Creatinine-based eGFR assessment in patients with MACS underestimates the degree of kidney dysfunction, likely due to underlying skeletal muscle atrophy. eGFRcys is a more accurate indicator of kidney function in patients with hypercortisolism. Presentation: 6/1/2024

6618 Risks for Cardiovascular Comorbidities Associated with Desiccated Thyroid Extract Administration

Abstract Disclosure: S.C. De La Torre: None. C. Godar: None. K. Flynn: None. A.A. Patel: None. D. Maxwell: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: Levothyroxine (LT4), synthetic thyroid hormone (T4), is considered the standard of care for the management of hypothyroidism based on the current American Thyroid Association (ATA) guidelines. However, there is a small subset of patients demonstrating symptomatic improvement with desiccated thyroid extract (DTE), which is composed of desiccated porcine thyroid containing T4 and triiodothyronine (T3). Limited data or studies are available exploring long-term cardiovascular effects associated with DTE use. In this retrospective review, we aim to identify possible cardiovascular comorbidities associated with DTE use. Methods: The charts of 77 patients at a tertiary hospital center (64 females and 13 males) over the age of 18 who were prescribed DTE were reviewed. Data collected include duration of treatment, dose of treatment, pre-treatment and current weight, blood pressure (BP), TSH, free T4, and total T3 levels. New cardiovascular and other events following initiation of treatment (hypertension, coronary artery disease (CAD), myocardial infarction (MI), stroke, transient ischemic attack (TIA), atrial fibrillation, type 2 diabetes, fractures) were also obtained. Averages, medians, and totals of patient data were used for analysis. Results: Average patient age was 54 years, average duration of therapy was 77.5 months, and median DTE dose was 75 milligrams per day. Review of chart documentation from DTE initiation compared to current values identified a 2.5% increase in weight, 3.6% increase in systolic BP, 0.8% decrease in diastolic BP, 60.9% decrease in TSH, 5.2% decrease in free T4, and 14.4% increase in total T3. 19.5% patients (15 total, 80% of which were female) had recorded new cardiovascular events at any time following initiation of therapy. 15 patients developed HTN, 5 developed CAD, 2 developed atrial fibrillation, 5 developed type 2 diabetes, 5 new fractures, 0 MI, 0 stroke, and 0 TIA. Conclusion: These results demonstrate new cardiovascular events in our study population following the initiation of DTE, but it is unclear whether these events were directly associated with DTE use versus other factors based on our available data. Limitations of our study include small study size, uneven gender distribution, and data significance would be improved with comparison to a control group. Additional studies are needed to further evaluate long-term cardiovascular risk factors associated with DTE use. Presentation: 6/2/2024

Multidimensional phenotyping to distinguish among central (CSA), obstructive (OSA) and co-existing central and obstructive sleep apnea (CSA-OSA) phenotypes in real-world data

PurposeWhen navigating the landscape of obstructive sleep apnea (OSA), central sleep apnea (CSA) and intersection of the two diseases (co-existing CSA-OSA), there are significant knowledge gaps. Data are scarce regarding the respective prevalence and differences in clinical presentation of the three conditions. One major issue for characterization of the prevalence of the different sleep apnea entities is the scoring of central versus obstructive hypopneas which is not included in the routine practice of many sleep laboratories. MethodWe prospectively assessed multidomain symptoms and collected data on comorbidities, medications and treatment indications in a large monocentric real-life dataset (n > 2400) of patients referred for suspicion of sleep apnea. We have systematically distinguished central versus obstructive hypopneas to define OSA, CSA and co-existing CSA-OSA. ResultsWhen CSA was defined by the proportion of central apneas (and hypopneas were considered obstructive by default), the prevalence of CSA was 4.59 % (co-existing CSA-OSA: 11.03 %, and OSA: 84.37 %). When the distinction between obstructive and central hypopneas was used to classify the sleep disordered breathing, the prevalence of CSA was fourfold higher at 19.69 % (co-existing: 19.16 %, OSA: 61.16 %). The burden of cardiovascular and metabolic comorbidities was the highest in the CSA and co-existing sleep apnea subgroups. The three sleep apnea groups exhibited different constellations of symptoms but most of the patients with CSA, co-existing and OSA were symptomatic after comprehensive evaluation. The CSA group exhibited the most severe disturbances in sleep architecture on polysomnography. Therapeutic indications differed depending on the subtype of respiratory events. ConclusionOur findings imply that not differentiating between central and obstructive hypopneas will underestimate the severity of central sleep disordered breathing abnormalities that mislead therapeutic decisions and might limit improvements in quality of life and sleepiness that are expected in appropriately treated patients with CSA.

Management of immune-checkpoint inhibitor (ICI)-related thyroid dysfunction: An avenue for quality improvement.

309 Background: Hypothyroidism is a common immune-related adverse effect (irAE) with ICI therapy, occurring in 4-9% of patients treated with PD-1 ICI, and 10-15% of patients treated with dual PD-1/CTLA-4 ICI therapy. Prolonged thyroid dysfunction increases risk for cardiovascular and cerebrovascular events. Consensus guidelines recommend weight-based dosing for thyroid repletion in younger patients and/or without cardiovascular comorbidities. We observed that patients on thyroid repletion are often underdosed compared to guideline recommendations. To formally evaluate this, we performed a retrospective study to determine the percentage of ICI-treated cancer patients who are receiving guideline-recommended thyroid repletion at an urban comprehensive cancer center. Methods: We identified patients who received PD-1 ICI, either singly or in combination with chemotherapy, TKI, or other ICI to identify patients who met the consensus guideline criteria for weight-based dosing of thyroid repletion. Analysis was restricted to ICI-treated patients who had a thyroid stimulating hormone (TSH) level above 10 mU/L following initiation of therapy. For each patient, we collected the patient’s age, weight, and initial prescribed dose of levothyroxine. We also obtained the date of abnormality and normalization for TSH and free thyroxine (T4). Results: 402 patients received ICI, either singly or in combination. 55 patients had TSH &gt; 10 mU/L. 15 patients who did not have documentation of hypothyroidism or developed it prior to immunotherapy were excluded. The proportion of patients who were eligible for, and who received weight-based repletion is summarized in the table. The proportion of patients who received guideline-recommended thyroid repletion was: 6/17 (35%) SITC-guideline recommended dose, 18/27 (67%) NCCN-guideline recommended dose and 6/22 (28%) ASCO-guideline recommended dose. The median time to free T4 normalization was 9 weeks (IQR 6-15 weeks) and TSH normalization was 13 weeks (IQR 9-30 weeks). Conclusions: At an urban comprehensive cancer center, the incidence of hypothyroidism in ICI-treated cancer patients is 10%. The compliance with guideline recommended weight-based dosing is low, with 33-72% of patients not receiving appropriate therapy, translating into prolonged time to thyroid function normalization. We aim to develop a quality improvement intervention to improve thyroid dosing in this patient population. Proportion of patients receiving guideline-recommended thyroid repletion. Criteria Per SITC Guidelines Per NCCN Guidelines (if lower end of dosing range) Per ASCO Guidelines Patients eligible for weight-based dosing 17 27 22 # of patients who received appropriate initial dosing 6 (35%) 18 (67%) 6 (28%) Average initial dose prescribed 81 mcg 78 mcg 76 mcg Average initial dose per guidelines (based on ideal body weight) 107 mcg 71 mcg 109 mcg

Proteasome inhibitors and risk of cardiovascular events in patients with multiple myeloma.

300 Background: Proteasome inhibitors (PI) represent a significant advancement in the treatment of multiple myeloma (MM). While recent studies have stressed the cardiovascular (CV) risk associated with carfilzomib (CARF) use, the risk with ixazomib (IXA) is underreported and no large comparative analysis is available. This study aims to compare CV and dose-limiting toxicities in MM patients treated with CARF and IXA. Methods: We conducted a retrospective cohort study analyzing TriNetX electronic medical records, including MM patients age 18 years and older who initiated CARF or IXA between January 1, 2016 to December 31, 2023. Patients with a prior history of heart failure (HF) or arrhythmias were excluded. We evaluated the incidence of new onset of HF and arrhythmia within three months of initiating PIs. Secondary outcomes included the incidence of diarrhea, nausea and vomiting during this period. Propensity score matching (PSM) was performed using 1:1 nearest neighbor matching to balance baseline characteristics. Matching covariates included patients’ demographics (age, sex, race/ethnicity), cardiovascular comorbidities and medications (cardiovascular and chemotherapy). Hazard ratios (HRs) for the outcomes were calculated using Cox proportional hazards models with a significance threshold of p&lt;0.05. Results: We identified 950 and 2,872 patients in the IXA- and CARF-treated cohorts, respectively. After PSM, each cohort included 753 patients, with a mean age of 65 years, 52% male and 65% white. Matched populations had no significant differences with respect to matching criteria. The new onset of HF within three months was 2.8% in the IXA group and 5.4% in the CARF group (HR: 0.50, 95% CI: 0.30–0.85, p=0.009). The new onset of arrhythmias was also significantly lower in the IXA group (4.3%) compared to the CARF group (6.6%) (HR:0.63, 95% CI:0.40–0.98, p=0.04). There was no significant difference in the incidence of diarrhea (HR: 0.92, 95% CI: 0.68–1.26, p=0.61), while nausea/vomiting was significantly lower in the IXA group (HR:0.71, 95% CI:0.54–0.93, p=0.013). Conclusions: Our study indicates that ixazomib is associated with a significantly lower risk of cardiac side effects compared to carfilzomib in the treatment of MM, with similar gastrointestinal side effects. Enhanced cardiac monitoring may be necessary for patients on carfilzomib. Further research is needed to validate these cardiovascular risk differences.

Comparing outcomes of patients with early active rheumatoid arthritis initially treated on an inpatient or outpatient basis: a posthoc analysis of the CORRA trial

ObjectiveTreatment strategies of patients with active rheumatoid arthritis (RA) vary within and between countries. While most patients in Germany are treated on an outpatient basis, some are hospitalised (inpatients). In...

Pseudo polyarthrite rhizomélique : mise au point

Polymyalgia rheumatica (PMR) is a rheumatologic condition characterized by inflammatory pain of the pelvic and scapular girdles associated with a biological inflammatory syndrome in patients > 50 years old. It is associated with giant cell arteritis (GCA) in 16-21% of cases. There is no specific biological test for PMR. The diagnosis is based on the exclusion of diseases that could mimic PMR. In recent years, imaging has undergone significant development helping clinicians for the diagnostic. Treatment of PMR is based on glucocorticoid therapy, which is gradually tapered over 12 months. Over the last few years, assessment of glucocorticoid-sparing agents has been developed, to reduce the occurrence of glucocorticoid associated side effect in an elderly population, who often has cardiovascular, metabolic and/or fracture-related comorbidities. The aim of this review is to provide clinicians an overview of the epidemiological, clinical, imaging and therapeutic features of PMR.

A timeline study on vascular co-morbidity induced cerebral endothelial dysfunction assessed by perfusion MRI

Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction. This study primarily aimed to identify which among various perfusion MRI methodologies could be effectively utilized to non-invasively identify early pathological alterations as a result of endothelial dysfunction. We compared these perfusion MRI measurements to invasive immunohistochemistry to detect early pathological alterations in the cerebral vasculature of a rat model of multiple cardiovascular co-morbidities (the ZSF1 Obese rat) at several stages of the cerebrovascular pathology. We observed cerebral hyperperfusion, expressed by increased Cerebral Blood Flow (CBF) and increased BBB permeability in the ZSF1 Obese rats, at an early stage of disease development. The increase in CBF observed with Arterial Spin Labeling (ASL) was lost during later stages of disease progression. These findings are in line with recent clinical findings in early stages of Alzheimer's disease (AD), that also show early increases in CBF.

A Retrospective Analysis of Disease Epidemiology, Comorbidity Burden, Treatment Patterns, and Healthcare Resource Utilization of Migraine in the United Arab Emirates.

Migraine is a recurrent, disabling neurological disorder with a substantial global disease burden. However, limited real-world data are available on the patient characteristics, treatment patterns, comorbidities, and economic burden of migraine in the United Arab Emirates (UAE). In this study, we evaluated the disease burden, comorbidities, treatment patterns, specialties involved in migraine diagnosis, and healthcare resource utilization (HCRU) and associated costs in patients with migraine in Dubai, UAE. A retrospective, secondary database cohort study was conducted from 01 January 2014 to 31 March 2022 using the Dubai Real-World Database. Patients aged ≥ 18years with at least one diagnosis claim for migraine with continuous enrollment during the study period were included. Patients were stratified into treatment sub-cohorts. Outcomes were evaluated in terms of clinical characteristics, comorbidities, specialists visited, treatment patterns, and HCRU. The study included 203,222 patients (mean age: 40years), with male predominance (55.4%). About 13.4% of patients had specific cardiovascular comorbidities. Frequently prescribed drug classes were nonsteroidal anti-inflammatory drugs (84.4%), triptans (29.8%), and beta-blockers (12.8%), while only 1.0% of patients with migraine were prescribed newer medications like calcitonin gene-related peptide antagonists. General medicine was the most frequently visited specialty on the index date (51.5%). The all-cause and migraine-specific median gross costs during the 12-month post-index period were US $1252.6 (2.4-564,740.7) and US $198.1 (0-168,903.3) respectively, with maximum contribution from inpatients. The contribution of migraine-specific median costs to all-cause median costs was highest for the diagnosis-related group (64.9%), followed by consumables (35.2%), medications (32.0%), procedures (24.5%), and services (24.5%). Migraine significantly impacts healthcare costs in the UAE. The role of newer therapies in migraine management should be explored to reduce the associated socioeconomic burden and improve patients' quality of life.

Clinical characteristics and outcomes in middle-aged Fontan patients

BackgroundMiddle-aged Fontan patients are underrepresented in contemporary studies. The purpose of this study was to describe the clinical characteristics and outcomes in middle-aged patients with Fontan palliation. MethodsAll adults with Fontan palliation were divided into ‘middle-aged’ group (>40 years of age at baseline encounter), and ‘young adult’ group. Clinical characteristics were assessed across multiple domains (atrial arrhythmias, heart failure, and hepatorenal function). Clinical outcomes were assessed as composite outcome of death/heart transplant. ResultsOf 455 adults (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, and worse hepatorenal function. Of 63 patients in the middle-aged group, 26 (41 %) patients died, and 4 (6 %) patients underwent heart transplant. The middle-aged group had a higher 5-year cumulative incidence of death/transplant (45 % versus 21 %, p < 0.001), and 10-year cumulative incidence of death/transplant (64 % versus 29 %, p < 0.001) compared to the young adult group. Higher pulmonary artery wedge pressure (hazard ratio 1.18 [1.09–1.27]), and higher model for end-stage liver disease excluding international normalized ratio score (hazard ratio 1.07, [1.03–1.14]), were associated with death/transplant. ConclusionsAbout 14 % of adults with Fontan palliation were middle-aged, and these patients had higher prevalence of cardiovascular comorbidities, hepatorenal dysfunction, and mortality. These data underscore the need for better risk stratification strategies to identify patients at risk for adverse outcomes and allow for early referral for transplant evaluation in this emerging subpopulation. Clinical summaryThe purpose of this study was to describe the clinical characteristics (comorbidities and end-organ dysfunction) and outcomes (death/transplant) in middle-aged patients with Fontan palliation. Of 455 patients (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, worse hepatorenal function, and higher risk of death/transplant. The correlates of death/transplant were higher pulmonary artery wedge pressure and hepatorenal dysfunction. These data underscore the need for better risk stratification in this emerging population.

AGING GRACEFULLY IN OSTEOARTHRITIS: IMPACT OF COMORBIDITIES

Background: Osteoarthritis (OA) is a prevalent musculoskeletal disorder, often complicated by comorbid conditions such as cardiovascular diseases, metabolic syndromes, and mental health issues. These comorbidities significantly impact the progression of OA and the effectiveness of its management, posing challenges for comprehensive patient care. Objectives: This review examines the relationship between OA and its common comorbidities, focusing on cardiovascular diseases, metabolic conditions, and mood disorders. We also explore the impact of pharmacological and non-pharmacological treatments in these patients, emphasizing the importance of integrated care strategies. Methods: Data from multiple studies were analyzed to assess the association between OA and comorbid conditions. The studies examined mortality risk, cardiovascular incidents, metabolic syndrome, diabetes, obesity, and mood disorders, while considering the effects of various OA treatment modalities, particularly non-steroidal anti-inflammatory drugs (NSAIDs). Results: Cardiovascular comorbidities, including coronary heart disease, are significantly linked to OA, with functional limitations such as impaired mobility being major contributors to increased cardiovascular risks and mortality. NSAIDs, commonly prescribed for OA, present substantial cardiovascular and renal risks, complicating their use in patients with pre-existing cardiovascular conditions. Metabolic comorbidities, particularly obesity and diabetes, are highly prevalent in OA patients and are associated with reduced quality of life and exacerbation of OA symptoms. Furthermore, mood disorders like depression and anxiety are common among OA patients, leading to a vicious cycle of pain and psychological distress that worsens functional outcomes. Conclusions: OA is closely related to various comorbidities, necessitating a holistic, multimodal approach to treatment. Beyond pharmacologic interventions, lifestyle changes, psychosocial support, and careful management of comorbid conditions are essential for improving outcomes in OA patients.

Evaluating the Femoral Atherosclerotic Plaque in Psoriasis Patients and Controls: A Case-Control Study.

Psoriasis is a chronic inflammatory disease that can affect the skin or the cardiovascular system. The presence of femoral atherosclerotic plaque could be a promising sign in predicting cardiovascular risk for these patients. The study aims to evaluate the prevalence of femoral atherosclerotic plaque between psoriasis and control individuals. This case-control study involved 40 patients diagnosed with vulgaris psoriasis and 40 non-psoriasis individuals matched by age group and gender. We used clinical signs and symptoms to diagnose psoriasis and evaluated the disease's severity using the Psoriasis Area and Severity Index (PASI). The atherosclerotic plaque on the femoral artery was detected using Doppler ultrasound to measure the femoral artery intima-media thickness (fIMT). Data were analyzed by SPSS 25. Male patients accounted for the proportion of 72.5%. In the psoriatic group, the mean value of PASI was 12.91 ± 6.73 (points). The proportion of femoral atherosclerotic plaque was significantly higher in the psoriasis compared to the controls (32.5% vs 10%; P = 0.014). Some factors associated with the femoral atherosclerotic plaque include age, smoking, and hypertension (P < 0.05). Hypertension was an independent risk factor for femoral atherosclerotic after regression analysis. Femoral atherosclerotic plaque is higher in psoriasis patients. This result emphasizes the need to screen for cardiovascular comorbidities in these patients.

Comparative efficacy, safety and benefit/risk of alerting agents for excessive daytime sleepiness in patients with obstructive sleep apnoea: a network meta-analysis

Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA. In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640. Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150mg; effect size [ES]=0.66 [95% CI: 0.36, 0.96]), pitolisant (20mg; ES=0.66 [95% CI: 0.44, 0.88]), and modafinil (200mg; ES=0.54: [95% CI: 0.33, 0.74]); 400mg; ES=0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200mg, modafinil 400mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400mg and modafinil 200mg for benefit-risk ratio. Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities. Bioprojet.

An Italian Delphi Consensus on the Triple inhalation Therapy in Chronic Obstructive Pulmonary Disease.

The management of chronic obstructive pulmonary disease (COPD) lacks standardization due to the diverse clinical presentation, comorbidities, and limited acceptance of recommended approaches by physicians. To address this, a multicenter study was conducted among Italian respiratory physicians to assess consensus on COPD management and pharmacological treatment. The study employed the Delphi process using the Estimate-Talk-Estimate method, involving a scientific board and expert panel. During a 6-month period, the scientific board conducted the first Delphi round and identified 11 broad areas of COPD management to be evaluated while the second Delphi round translated all 11 items into statements. The statements were subsequently presented to the expert panel for independent rating on a nine-point scale. Consensus was considered achieved if the median score was 7 or higher. Consistently high levels of consensus were observed in the first rating, allowing the scientific board to finalize the statements without requiring further rounds. Topics generating substantial discussion included the pre-COPD phase, patient-reported outcomes, direct escalation from a single bronchodilator to triple therapy, and the role of adverse events, particularly pneumonia, in guiding triple therapy prescriptions. Notably, these topics exhibited higher standard deviations, indicating greater variation in expert opinions. The study emphasized the significance that Italian pulmonologists attribute to managing mortality, tailoring treatments, and addressing cardiovascular comorbidities in COPD patients. While unanimous consensus was not achieved for all statements, the results provide valuable insights to inform clinical decision-making among physicians and contribute to a better understanding of COPD management practices in Italy.

Adolescents and Young Adults With Respiratory Failure in U.S. PICUs: A Pediatric Health Information System Database Study, 2011–2022

Objectives: To examine the clinical characteristics, outcomes, and resource use of adolescents and young adults (AYAs) admitted to PICUs in the United States with respiratory failure. Design: Retrospective cohort study. Setting: De-identified data from 48 U.S. children’s hospitals contributing to the Pediatric Health Information System (PHIS) database. Patients: All patients older than 30 days old with respiratory failure, defined as encounters with clinical transaction codes for noninvasive or invasive mechanical ventilation, admitted to PHIS database PICUs from January 2011 to December 2022. Patients were categorized into five cohorts (&lt; 15, 15–18, 19–21, 22–25, and &gt; 25 yr old). Interventions: None. Measurements and Main Results: A total of 430,238 patients were identified. AYA (≥ 15 yr old) accounted for 15% (65,740) of all PICU admissions with respiratory failure. Forty-nine percent (32,232/65,740) of AYA older than 25 years had medical technology dependence compared with 39% in those younger than 15 years (p &lt; 0.001). Sixty-one percent of AYA older than 25 years had a cardiovascular comorbidity compared with 35% of those younger than 15 years (p &lt; 0.001). Forty percent of AYA older than 25 years had a neurologic comorbidity, and 27% a gastrointestinal comorbidity, compared with 27% and 31%, respectively, in those younger than 15 years (all p &lt; 0.001). Compared with those younger than 15 years, AYA median hospital crude mortality rate was higher at 7.7% compared with 5.2%, as were median hospital charges per encounter at $163K (interquartile range [IQR], $77K–$350K) vs. $121K (IQR, $53K–$278K; all p &lt; 0.001). Median ventilator days and hospital length of stay in survivors were similar for all age cohorts. Conclusions: AYA represent a substantial proportion of patients admitted to the PICU with respiratory failure. These individuals have unique comorbidities and are at risk for increased mortality and resource utilization compared with younger patients during hospitalization. Medical complexity and sequelae of pediatric illness may delay the transition of AYA to adult care, necessitating collaboration between adult and pediatric critical care physicians to increase research across the age spectrum and develop and implement appropriate evidence-based guidelines.

Nonseizure Response to ECT in Older Adults with Bipolar Depression on Bumetanide

Abstract: Psychiatric presentations in older adults are complicated by chronic comorbidities, polypharmacy, and older age-related psychosocial changes. This case report discusses an unusual treatment response to ECT in a 75-year-old man with chronic bipolar disorder. There was no seizure activity on EEG and upon direct observation in 3 out of 7 ECT sessions. After an in-depth medication review of its impact on ECT, we propose that bumetanide could likely have contributed to the nonseizure response. Bumetanide was proposed as a potential antiepileptic agent, but the evidence for its effect on ECT is sparse. A proportion of older adults receiving ECT are likely to be on this FDA-approved diuretic for cardiovascular comorbidities. This case highlights the need for further studies to test for ECT-modifying of bumetanide.