'Didn't See the Need': Misperceptions about glucagon from the perspectives of people with diabetes and their caregivers.

AIMS: Severe hypoglycaemia among people with diabetes who use insulin can be a life-threatening complication if left untreated. Although glucagon has been approved for treatment of hypoglycaemia since the 1960s, it has been underutilized. We aimed to understand the perceptions of people with diabetes and their caregivers about glucagon. METHODS: We conducted in-depth, one-on-one telephone interviews with people with diabetes and their caregivers in the United States. The interviews included questions around general awareness of glucagon, reasons for owning or not owning glucagon, and suggestions for improving understanding of glucagon as treatment for severe hypoglycaemia. Initial synopsis and inductive codebook schema were used to analyse the responses by two independent researchers. Themes were developed from the codes, and codes were re-mapped back to the themes. RESULTS: There were 60 dyads of people with diabetes and their caregivers (N = 120). Four themes developed from the interviews: (1) for most participants, the stated reasons for not owning or renewing a prescription for glucagon included unawareness of the medication, its advantages and its value; (2) misperceptions about glucagon occurred frequently; (3) caregivers often lacked confidence in administering reconstituted injectable glucagon; and (4) education and training from healthcare providers about glucagon would be welcomed. CONCLUSIONS: This study emphasizes the need for healthcare providers to discuss hypoglycaemia prevention and events at each clinical visit, including the use of glucagon in the case of severe hypoglycaemia. Healthcare providers are encouraged to assess the knowledge of people with diabetes and their caregivers regarding treatment and prevention of hypoglycaemia.

The experience of a severe hypoglycaemic event from the perspective of people with diabetes and their caregivers: "What am I going to do?"

AIMS: Among people with diabetes using insulin, severe hypoglycaemia (SH) can be a life-threatening complication, if untreated. The personal experiences during an SH event from the perspectives of people with diabetes and their caregivers are not well-characterized. This study assessed the perceptions of the event and the decision making processes of people with diabetes (T1D n = 36; T2D n = 24) and their caregivers during SH events. METHODS: In-depth one-on-one telephone interviews were conducted with dyads of people with diabetes and caregivers in the United States (n = 120). An initial synopsis and inductive codebook schema were used to analyse the data with two independent coders (kappa = 0.87-0.89). Themes were developed from the codes, and codes were re-mapped to the themes. RESULTS: Four themes were formed: (1) Caregivers scramble to do the right thing and support people with diabetes in treating SH; (2) Decision making capacity is impaired during an SH event, often a panicked time; (3) People learn to manage SH events through their own experiences and frequently make lifestyle changes to prevent and treat future events; and (4) Discussion with healthcare providers about SH, and particularly SH treatment, is limited. CONCLUSIONS: SH events are stressful and often evoke emotional reactions that can impair decision making. Thus, advance treatment planning of SH events needs to occur. Much of the knowledge about SH treatment derives from prior experience rather than healthcare provider guidance, suggesting a need for healthcare providers to initiate proactive discussions about SH treatment.

Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy.

INTRODUCTION/AIMS: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. METHODS: Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated. RESULTS: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P < .0001) and 9.5% (3.2%-15.9%) in the TA group (P = .01). CMV increased significantly in the BB and TA groups and FF decreased in the TA group. There were no consistent improvements in functional or PRO measures in either group. The most common adverse events were mild or moderate injection-site reactions. DISCUSSION: Significant increases in TMV with ACE-083 vs placebo did not result in consistent functional or PRO improvements with up to 12 months of treatment.

Reasons for treatment changes in adults with attention-deficit/hyperactivity disorder: a chart review study.

BACKGROUND: Adults with attention-deficit hyperactivity disorder (ADHD) often cycle through multiple treatments for reasons that are not well documented. This study analyzed the reasons underlying treatment changes among adults treated for ADHD in a real-world setting. METHODS: Data were collected via an online reporting form completed by eligible physicians between October and November 2020. Data for adult patients in the United States who were diagnosed with ADHD and initiated a treatment regimen within 1 to 5 years of chart abstraction were obtained. Reason for a treatment change was described for a randomly selected regimen episode, which spanned from treatment initiation until the earliest among treatment add-on/switch or discontinuation, death, or date of chart abstraction. The overall rate of ADHD/treatment-related complications were also described. Physician satisfaction with current treatment options for adult ADHD and opinions on areas for improvement were assessed. RESULTS: Data on 320 patients were reported by 152 physicians specializing in psychiatry (40.1%), pediatrics (25.0%), family medicine (21.7%), and internal medicine (13.2%). Patients had a mean age of 29.3 years; most were diagnosed with ADHD as adults (57.5%) and within the previous 5 years (56.5%). Selected treatment regimens included stimulants (79.1%), nonstimulants (14.7%), and combination therapy (5.6%) for an average duration of 1.9 years. Among patients with treatment discontinuation (N = 59), the most common reasons for discontinuation were suboptimal symptom management (55.9%), occurrence of ADHD/treatment-related complications (25.4%), and patient attitude/dislike of medication (25.4%). The main reasons for other key treatment changes were inadequate/suboptimal management of symptoms and cost considerations. Over 40% of patients had ≥ 1 documented ADHD/treatment-related complication, irrespective of whether they led to a treatment change. One in 5 physicians (19.8%) were very dissatisfied, moderately dissatisfied, or neither satisfied nor dissatisfied with current treatment options for ADHD in adults; the top 3 suggested improvements were lower risk of abuse (71.7%), longer effect duration (65.1%), and fewer ADHD/treatment-related complications (61.2%). CONCLUSIONS: The top reasons for treatment changes among adults with ADHD are lack of efficacy and ADHD/treatment-related complications, highlighting the importance of developing more effective and safer treatments to alleviate the burden of ADHD.

Incidence of Major Atherothrombotic Vascular Events among Patients with Peripheral Artery Disease after Revascularization.

BACKGROUND: Patients with peripheral artery disease (PAD) treated with lower extremity revascularization are at increased risk of major atherothrombotic vascular events (acute limb ischemia (ALI), major non-traumatic lower-limb amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular (CV)-related death). This study assessed the incidence of major atherothrombotic vascular events, venous thromboembolism (VTE) events and rates of subsequent lower extremity revascularizations in the real-world among patients with PAD after revascularization. METHODS: Patients aged ≥50 years with PAD who underwent peripheral revascularization were identified from Optum Clinformatics Data Mart claims database (Q1/2014-Q2/2019). The first lower extremity revascularization after PAD diagnosis was defined as index date. Incidence rates of major atherothrombotic vascular events (i.e., composite of ALI, major non-traumatic lower-limb amputation, MI, ischemic stroke, and CV-related death) and VTE were assessed during follow-up as the number of events divided by patient-years of observation (censored at the first event). Rates of subsequent revascularizations and VTE were estimated overall and compared between patients with major atherothrombotic vascular events and those without. RESULTS: Of the 38,439 patients included, 6,675 (17.4%) had a major atherothrombotic vascular event during a median follow-up of 1.0 year. The composite major atherothrombotic vascular and VTE incidence rates were 13.81/100 patient years and 1.77/100 patient years, respectively, and 40.2% of patients experienced subsequent revascularizations. Patients with a post-revascularization major atherothrombotic vascular event had significantly higher rates of subsequent revascularizations (64.6% vs. 35.1%, standardized difference [SD] ≥10%) and VTE (4.6% vs. 2.1%, SD ≥10%) versus those without. CONCLUSION: One-in-six PAD patients aged ≥50 years who underwent peripheral revascularization experienced a major atherothrombotic vascular event within one year, and consequently, experienced higher rates of subsequent revascularizations compared with those without a major atherothrombotic vascular event post-revascularization. These findings highlight the need to improve strategies to prevent major atherothrombotic vascular events after revascularization.

Practical guidance for managing electromyography requests and testing during the COVID-19 pandemic.

The COVID-19 pandemic has necessitated cancelation of elective or nonurgent contact with the healthcare system, including nonurgent nerve conduction studies and electromyography (electrodiagnostic [EDX] studies). The definitions of elective and nonurgent are physician judgments, and often are not straightforward. Clinical care must be provided to help our patients in a timely manner, while keeping them, healthcare personnel, and the community safe. Benefit/risk stratification is an important part of this process. We have stratified EDX studies into three categories: Urgent, Non-urgent, and Possibly Urgent, in an effort to help clinicians triage these referrals. For each category, we provide a rationale and some examples. However, each referral must be reviewed on a case-by-case basis, and the clinical situation will evolve over time, necessitating flexibility in managing EDX triaging. Engaging the referring clinician and, at times, the patient, may be useful in the triage process.

Guidance for resumption of routine electrodiagnostic testing during the COVID-19 pandemic.

As the world accommodates to the coronavirus disease 2019 (COVID-19) pandemic, routine in-person medical services are resuming. The resumption of non urgent electrodiagnostic (EDX) testing faces unique challenges due to the long duration of the procedure and direct close contact with patients, including studies with risk of exposure to oropharyngeal secretions. We provide consensus guidance for resumption of EDX testing, addressing scheduling, patient arrival and registration, use of personal protective equipment, COVID-19 screening and testing, the performance of EDX testing in outpatient and inpatient settings, cleaning and maintenance of the EDX equipment and laboratory, balancing trainee safety and training requirements, and patient care issues. These are broad recommendations that need to be adapted to local COVID-19 risks, institutional guidelines and policies, and changing federal, state, and local regulations, and to changes in the pandemic over time.

Assessing the economic burden of Alzheimer's disease patients first diagnosed by specialists.

BACKGROUND: It is not known if there is a differential impact on Alzheimer's disease (AD) diagnosis and outcomes if/when patients are diagnosed with cognitive decline by specialists versus non-specialists. This study examined the cost trajectories of Medicare beneficiaries initially diagnosed by specialists compared to similar patients who received their diagnosis in primary care settings. METHODS: Patients with ≥2 claims for AD were selected from de-identified administrative claims data for US Medicare beneficiaries (5 % random sample). The earliest observed diagnosis of cognitive decline served as the index date. Patients were required to have continuous Medicare coverage for ≥12 months pre-index (baseline) and ≥12 months following the first AD diagnosis, allowing for up to 3 years from index to AD diagnosis. Time from index date to AD diagnosis was compared between those diagnosed by specialists (i.e., neurologist, psychiatrist, or geriatrician) versus non-specialists using Kaplan-Meier analyses with log-rank tests. Patient demographics, Charlson Comorbidity Index (CCI) during baseline, and annual all-cause medical costs (reimbursed by Medicare) in baseline and follow-up periods were compared across propensity-score matched cohorts. RESULTS: Patients first diagnosed with cognitive decline by specialists (n = 2593) were younger (78.8 versus 80.8 years old), more likely to be male (40 % versus 34 %), and had higher CCI scores and higher medical costs at baseline than those diagnosed by non-specialists (n = 13,961). However, patients diagnosed by specialists had a significantly shorter time to AD diagnosis, both before and after matching (mean [after matching]: 3.5 versus 4.6 months, p < 0.0001). In addition, patients diagnosed by specialists had significantly lower average total all-cause medical costs in the first 12 months after their index date, a finding that persisted after matching ($19,824 versus $25,863, p < 0.0001). Total per-patient annual medical costs were similar for the two groups starting in the second year post-index. CONCLUSIONS: Before and after matching, patients diagnosed by a specialist had a shorter time to AD diagnosis and incurred lower costs in the year following the initial cognitive decline diagnosis. Differences in costs converged during subsequent years. This suggests that seeking care from specialists may yield more timely diagnosis, appropriate care and reduced costs among those with cognitive decline.

Acute and chronic systemic corticosteroid-related complications in patients with severe asthma.

BACKGROUND: Many patients with severe asthma require maintenance treatment with systemic corticosteroids (SCSs) to control daily symptoms and prevent serious acute exacerbations, but chronic SCS use is associated with complications. OBJECTIVE: We sought to evaluate the risk of SCS-related complications by SCS exposure and quantify the associated health care costs and resource use in patients with severe asthma. METHODS: We performed a longitudinal, open-cohort, observational study using health insurance claims data (1997-2013: Medicaid) from Florida, Iowa, Kansas, Missouri, Mississippi, and New Jersey. Eligible patients were 12 years old or older with 2 or more asthma diagnoses and had more than 6 months of continuous SCS use. An open-cohort approach was used to classify patients' follow-up into low, medium, and high SCS exposure (≤ 6, >6-12, and >12 mg/d, respectively). Multivariate generalized estimating equation models were used to estimate the adjusted risk of SCS-related complications for patients with medium and high exposure compared with patients with low exposure and quantify the resulting health care resource use and costs. RESULTS: The study included 3628 patients (mean age, 57.6 years; 68% female). Patients with medium and high SCS exposure had significantly higher risks of SCS-related complications, including infections and cardiovascular, metabolic, psychiatric, ocular, gastrointestinal, and bone-related complications (odds ratio, 1.23-2.12 by complication; P < .05 for all but one) versus those with low (reference group) SCS exposure. Medium and high SCS exposure were also associated with significantly more emergency department visits (incidence rate ratios, 1.31 [P = .0004] and 1.78 [P < .0001]) and inpatient visits (incidence rate ratios, 1.25 [P < .0001] and 1.59 [P < .0001]) versus low SCS exposure. CONCLUSIONS: A significant dose-response relationship was demonstrated between chronic SCS use and risk of SCS-related complications in patients with severe asthma. Effective SCS-sparing strategies might reduce the burden associated with SCS-related complications in patients with severe asthma.

Impact of a Telehealth and Care Management Program on All-Cause Mortality and Healthcare Utilization in Patients with Heart Failure.

BACKGROUND: Telehealth has the potential to improve chronic disease management and outcomes, but data regarding direct benefit of telehealth in patients with heart failure (HF) have been mixed. The objective of this study was to determine whether the Health Buddy Program (HBP) (Bosch Healthcare, Palo Alto, CA), a content-driven telehealth system coupled with care management, is associated with improved outcomes in Medicare beneficiaries with HF. MATERIALS AND METHODS: This was a retrospective cohort study of 623 Medicare beneficiaries with HF offered HBP enrollment compared with a propensity score-matched control group of Medicare beneficiaries with HF from the Medicare 5% sample. Associations between availability of the HBP and all-cause mortality, hospitalization, hospital days, and emergency department visits were evaluated. RESULTS: Beneficiaries offered enrollment in the HBP had 24.9% lower risk-adjusted all-cause mortality over 3 years of follow-up (hazard ratio [HR] = 0.75; 95% confidence interval [CI], 0.63-0.89; p = 0.001). Patients who used the HBP at least once (36.9%) had 57.2% lower mortality compared with matched controls (HR = 0.43; 95% CI, 0.31-0.60; p < 0.001), whereas patients who did not use the HBP had no significant difference in survival (HR = 0.96; 95% CI, 0.78-1.19; p = 0.69). Patients offered the HBP also had fewer hospital admissions following enrollment (Δ = -0.05 admissions/quarter; p = 0.011), which was primarily observed in patients who used the HBP at least once (Δ = -0.10 admissions/quarter; p < 0.001). CONCLUSIONS: The HBP, a content-driven telehealth system coupled with care management, was associated with significantly better survival and reduced hospitalization in Medicare beneficiaries with HF. Prospective study is warranted to determine the mechanism of this association and opportunities for optimization.

Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome.

The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.

Medical costs of Alzheimer's disease misdiagnosis among US Medicare beneficiaries.

INTRODUCTION: Recent developments in diagnostic technology can support earlier, more accurate diagnosis of non-Alzheimer's disease (AD) dementias. METHODS: To evaluate potential economic benefits of early rule-out of AD, annual medical resource use and costs for Medicare beneficiaries potentially misdiagnosed with AD prior to their diagnosis of vascular dementia (VD) or Parkinson's disease (PD) were compared with that of similar patients never diagnosed with AD. RESULTS: Patients with prior AD diagnosis used substantially more medical services every year until their VD/PD diagnosis, resulting in incremental annual medical costs of approximately $9,500-$14,000. However, following their corrected diagnosis, medical costs converged with those of patients never diagnosed with AD. DISCUSSION: The observed correlation between timing of correct diagnosis and subsequent reversal in excess costs is strongly suggestive of the role of misdiagnosis of AD - rather than AD comorbidity - in this patient population. Our findings suggest potential benefits from earlier, accurate diagnosis.

Public sector replacement of privately funded pharmaceutical R&D: cost and efficiency considerations.

AIMS: Economic studies have found that public support of basic medical research provides important long-term benefits. In response to suggestions that private pharmaceutical research and development (R&D) funding could be totally replaced by public funding, we investigate the economic implications of such a substitution in funding roles that maintain the recent pace of pharmaceutical innovation. MATERIALS AND METHODS: Total lifecycle R&D costs were estimated using the latest available R&D expenditures per novel molecule entering clinical trials, likelihood of approval, pre-clinical and post-approval expenditures, using a published survey and a review of publicly available financial accounts from US-listed multinational developers. This estimate was then stratified by the average number of annual FDA approvals to estimate total costs of R&D funding born by the private sector. RESULTS: We find total lifecycle R&D costs were US$2.83 billion per approved medicine. Estimated uncapitalized costs to replace private R&D funding for one year of FDA approvals were $139.6 billion. These additional costs are equivalent to 302% of the entire National Institute for Health 2022 budget of $46.2 billion, and around 25 times NIH's estimated annual $5.6 billion currently dedicated to clinical research trials for pharmaceuticals. Further assessing the policy proposition through a literature review, we found little evidence for improvements in economic efficiency via public funding substitution, while there may be additional challenges including asymmetric information, adverse selection, yardstick competition, hold-up, under-rewarding of incremental innovation and political rent-seeking. LIMITATIONS: Our calculations may undervalue full replacement costs, by excluding non-R&D expenses for manufacturing, distribution, or financing. CONCLUSIONS: The bulk of investment in R&D is underwritten by the private sector. Political discourse portraying the NIH as the central force in bringing a new drug to market may underappreciate the pivotal role of private at-risk capital. Replacing such investment while maintaining the current innovation output in terms of approved therapies would necessitate substantial increases in taxpayer financing.

Understanding the impact of slowing disease progression for individuals with biomarker-confirmed early symptomatic Alzheimer's disease.

Recent advances in development of amyloid-targeting therapies support the potential to slow the rate of progression of Alzheimer's disease. We conducted a narrative review of published evidence identified through a targeted search of the MEDLINE and EMBASE databases (2020-2023), recent presentations at disease-specific conferences, and data updates from cohort studies in Alzheimer's disease to describe the trajectory of the progression of Alzheimer's disease. Our findings enable the interpretation of clinical trial results and the value associated with slowing disease progression across outcomes of relevance to patients, care partners, clinicians, researchers and policymakers. Even at the earliest stages, Alzheimer's disease imposes a substantial burden on individuals, care partners, and healthcare systems. The magnitude of the burden increases with the rate of disease progression and symptom severity, as worsening cognitive decline and physical impairment result in loss of functional independence. Data from cohort studies also indicate that slowing disease progression is associated with decreased likelihood of needing extensive clinical care over at least 5 years, decreased care partner burden, and substantial individual and societal cost savings. Slowed disease progression is of significant benefit to individuals with Alzheimer's disease, their loved ones, and the healthcare system. As clinicians and policymakers devise strategies to improve access to treatment earlier in the disease spectrum, they should carefully weigh the benefits of slowing progression early in the disease (e.g. preservation of cognitive and functional abilities, as well as relative independence) to individuals, their loved ones, and broader society.

How I Treat Chronic Inflammatory Demyelinating Polyneuropathy Podcast.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy that typically presents with progressive or relapsing, symmetric, proximal, and distal weakness of upper and lower limbs, sensory involvement of at least two limbs, and decreased or absent deep tendon reflexes. The symptoms of CIDP can be similar to those of other neuropathies, making diagnosis difficult, which can often lead to delays in correct diagnosis and treatment. The updated European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 guideline outlines a set of diagnostic criteria that help to identify CIDP with high accuracy and provides recommendations for the treatment of CIDP. The aim of this podcast, featuring Dr. Urvi Desai (Professor of Neurology, Wake Forest School of Medicine and Atrium Health Neurosciences Institute Wake Forest Baptist, Charlotte), is to discuss how the new guideline impacts diagnosis and treatment decisions in her everyday clinical practice. Using a patient case study example, the updated guideline recommends assessing a patient for clinical, electrophysiological, and supportive criteria for CIDP, enabling a more straightforward diagnosis of either typical CIDP, a CIDP variant, or an autoimmune nodopathy. A second patient case study highlights how the new guideline no longer considers autoimmune nodopathies as CIDP, as patients with these disorders do not meet hallmark CIDP criteria. This leaves an unmet need in terms of guidance on how to treat this subset of patients. Although the new guideline has not necessarily changed treatment preference in clinical practice, the addition of subcutaneous immunoglobulin (SCIG) into the guideline now better reflects clinical practice. The guideline helps to define and categorize CIDP more simply and consistently, allowing quicker and more accurate diagnosis, leading to a positive impact on treatment response and prognosis. These real-world insights into the diagnosis and management of patients with CIDP could help guide best clinical practice and help facilitate optimization of patient outcomes.

Unintended Consequences of Increased Out-of-Pocket Costs During Medicare Coverage Gap on Anticoagulant Discontinuation and Stroke.

INTRODUCTION: This study aims to assess the risk of direct oral anticoagulant (DOAC) discontinuation among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) who reach the Medicare coverage gap stratified by low-income subsidy (LIS) status and the impact of DOAC discontinuation on rates of stroke and systemic embolism (SE) among beneficiaries with increased out-of-pocket (OOP) costs due to not receiving LIS. METHODS: In this retrospective cohort study, Medicare claims data (2015-2020) were used to identify beneficiaries with NVAF who initiated rivaroxaban or apixaban and entered the coverage gap during ≥ 1 year. DOAC discontinuation rates during the coverage gap were stratified by receipt of Medicare Part D Low-Income Subsidy (LIS), a proxy for not experiencing increased OOP costs. Among non-LIS beneficiaries, incidence rates of stroke and SE during the subsequent 12 months were compared between beneficiaries who did and did not discontinue DOAC in the coverage gap. RESULTS: Among 303,695 beneficiaries, mean age was 77.3 years, and 28% received LIS. After adjusting for baseline differences, non-LIS beneficiaries (N = 218,838) had 78% higher risk of discontinuing DOAC during the coverage gap vs. LIS recipients (adjusted hazard ratio [aHR], 1.78; 95% CI [1.73, 1.82]). Among non-LIS beneficiaries, DOAC discontinuation during coverage gap (N = 91,397; 34%) was associated with 14% higher risk of experiencing stroke and SE during the subsequent 12 months (aHR, 1.14; 95% CI [1.08, 1.20]). CONCLUSION: Increased OOP costs during Medicare coverage gap were associated with higher risk of DOAC discontinuation, which in turn was associated with higher risk of stroke and SE among beneficiaries with NVAF.

Real-World Incidence of Adverse Clinical Outcomes Among People With Coronary Artery Disease and/or Peripheral Artery Disease in Relation to Vascular Risk in the United States.

Presence of polyvascular disease, diabetes, heart failure, or renal insufficiency in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are associated with increased risks of adverse events, including major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). In this retrospective observational study using administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 2016 to September 2021, we described the incidence rates of MACEs, MALEs, and major thrombotic vascular events in patients with CAD or PAD stratified by the presence of risk factors (i.e., polyvascular disease, diabetes, heart failure, or renal insufficiency). A total of 1,435,241 patients (77% CAD and 34% PAD) met the inclusion and exclusion criteria. Patients with 0 risk factors were deemed the low-risk group (47%; n = 681,333) and patients with ≥1 risk factor were deemed the high-risk group (53%; n = 753,908). The mean age was 71.8 and 73.6 years, and 42% and 44% were female in the low- and high-risk groups, respectively. Compared with the low-risk group, the high-risk group had a 72% higher hazard of developing MACEs (adjusted hazard ratio 1.72, 95% confidence interval 1.70 to 1.74), 82% higher hazard of developing major thrombotic vascular events (1.82, 1.80 to 1.84), and 146% higher hazard of developing MALEs (2.46, 2.39 to 2.53) (all p <0.001). In conclusion, in patients with CAD or PAD, the presence of 1 or more risk factors was associated with higher risks of MACEs, MALEs, and major thrombotic vascular events, underscoring the need to improve management of underlying diseases in this population.

Real-World Racial Variation in Treatment and Outcomes Among Patients with Peripheral Artery Disease.

INTRODUCTION: Prior studies have found considerable disparities in prevalence and outcomes for patients with peripheral arterial disease (PAD). This study compared rates of diagnostic testing, treatment patterns, and outcomes after diagnosis of PAD among commercially insured Black and White patients in the United States. METHODS: Optum's de-identified Clinformatics® Data Mart Database (1/2016-6/2021) were used to identify Black and White patients with PAD; first PAD diagnosis was deemed study index date. Baseline demographics, markers of disease severity, and healthcare costs were compared between cohorts. Patterns of medical management and rates of major adverse limb events (MALE; including acute or chronic limb ischemia, lower-limb amputation) and cardiovascular (CV) events (stroke, myocardial infarction) during the available follow-up period were described. Outcomes were compared between cohorts using multinomial logistic regression models, Kaplan-Meier survival analysis, and Cox proportional hazards models. RESULTS: A total of 669,939 patients were identified, with 454,382 White patients and 96,162 Black patients. Black patients were younger on average (71.8 years vs. 74.2 years), but had higher comorbid burden, concomitant risk factors, and CV medication use at baseline. Prevalence of diagnostic testing, revascularization procedures, and medication use was numerically higher among Black patients. Black patients were also more likely than the White patients to receive medical therapy without a revascularization procedure [adjusted odds ratio with 95% confidence interval (CI) = 1.47 (1.44-1.49)]. However, Black patients with PAD had higher incidence of MALE and CV events than White patients [adjusted hazard ratio for composite event (95% CI) = 1.13, (1.11-1.15)]. Except myocardial infarction, the hazards of individual components of MALE and CV events were also significantly higher among Black patients with PAD. CONCLUSIONS: Results of this real-world study suggest that Black patients with PAD have higher disease severity at the time of diagnosis and are at increased risk of experiencing adverse outcomes following diagnosis.

Disease Progression and Longitudinal Clinical Outcomes of Lewy Body Dementia in the NACC Database.

INTRODUCTION: As the identification of Lewy body dementia (LBD) is often confirmed postmortem, there is a paucity of evidence on the progression of disease antemortem. This study aimed to comprehensively assess the course of LBD over time across cognitive, functional, and neuropsychiatric outcomes using real-world data. METHODS: Adults with at least one visit to an Alzheimer's Disease Center with a diagnosis of mild cognitive impairment/dementia (index date), indication of LBD, and at least one follow-up visit were identified in the National Alzheimer's Coordinating Center database (September 2005-June 2020). Participant characteristics, medication use, comorbidities, and changes in outcomes were assessed over a 5-year follow-up period and stratified by disease severity based on the Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB) score at index. RESULTS: A total of 2052 participants with LBD (mean age at index 73.4 years) were included (mild, 219; moderate, 988; severe, 845). Mean annualized increase over 5 years was 0.9 points for CDR-Global Score, 5.6 points for CDR-SB, 10.4 points for the Functional Activities Questionnaire, and 2.0 points for the Neuropsychiatric Inventory-Questionnaire. Disease progression was greater among participants with moderate and severe LBD at index compared with those with mild LBD. CONCLUSION: Participants with LBD experienced decline across all outcomes over time, and impairment increased with disease severity. Findings highlight the substantial clinical burden associated with LBD and the importance of earlier diagnosis and effective treatment. Further research is needed to understand the predictors of cognitive and functional decline in LBD which may help inform clinical trials.