As the United States approaches its 250 anniversary, this perspective examines the intertwined evolution of medicine and democracy as mutually reinforcing systems grounded in shared principles of human dignity, rights, a...As the United States approaches its 250 anniversary, this perspective examines the intertwined evolution of medicine and democracy as mutually reinforcing systems grounded in shared principles of human dignity, rights, and collective responsibility. From the nation's founding, democratic ideals, including life, liberty, and the pursuit of happiness have shaped public health infrastructure, medical ethics, and access to care. Historical figures and landmark legislation illustrate how civic values have been translated into clinical practice, scientific advancement, and population health protections. Major public health achievements reflect democratic processes requiring transparency, participation, and accountability. However, persistent disparities, rising costs, fragmented systems, and erosion of trust expose fractures in the health-democracy compact. Reinvigorating this alliance demands renewed investment in equitable access, modernized public health systems, ethical governance of data and artificial intelligence, and strengthened civic health literacy. Ultimately, both medicine and democracy are active practices requiring engagement and stewardship. Their alignment remains essential to ensuring that future progress advances both individual well-being and the collective promise of a just and democratic society.
BACKGROUND: The recombinant zoster vaccine (RZV; Shingrix) was approved in 2017. In 2018, the vaccine appeared cost-effective based on available evidence and assumptions. Since then, new evidence has become available reg...BACKGROUND: The recombinant zoster vaccine (RZV; Shingrix) was approved in 2017. In 2018, the vaccine appeared cost-effective based on available evidence and assumptions. Since then, new evidence has become available regarding long-term efficacy, completion of the 2-dose regimen, duration of immunity, and vaccine price. METHODS: We adapted a previously published Markov state-transition model to compare RZV with no vaccination among immunocompetent US adults aged 50, 60, 70 and 80 years. The model simulated annual transitions between health states including healthy, acute herpes zoster, postherpetic neuralgia, other complications, and death. Key updated parameters included age-specific efficacy, duration of immunity, completion of the 2-dose regimen, and 2025 vaccine pricing. Costs and outcomes were evaluated from a societal perspective over a lifetime horizon and discounted at 3% annually. We estimated cost-effectiveness by age to identify the optimal time to vaccinate. RESULTS: The incremental cost-effectiveness ratio (ICER) for RZV was $161,162 per QALY at age 50, and $31,465, $16,457, and $19,230 per QALY at ages 60, 70, and 80, respectively. Vaccination was cost-effective for adults aged 60 years and older but not at age 50, using a willingness-to-pay threshold of $100,000/QALY. Results were most sensitive to vaccine price, herpes zoster incidence, and waning duration. Age-specific analysis showed that vaccination became cost-effective at approximately age 54 years. CONCLUSIONS: RZV is cost-effective for adults aged 54 years and older. Continued assessment of long-term protection is needed to refine these estimates and evaluate the potential need for booster doses.
Valeriani E, Marcucci R, Di Nisio M
… +12 more, Calabrò P, Cirillo P, Gresele P, Patti G, Pengo V, Palumbo IM, Poli D, Antonucci E, Santilli F, Pannunzio A, Pignatelli P, Violi F
BACKGROUND: Aspirin is a standard therapy for secondary prevention in coronary artery disease, yet its antiplatelet effect varies and incomplete thromboxane-A₂ inhibition has been shown in older individuals. Because no a...BACKGROUND: Aspirin is a standard therapy for secondary prevention in coronary artery disease, yet its antiplatelet effect varies and incomplete thromboxane-A₂ inhibition has been shown in older individuals. Because no age threshold currently guides treatment, we investigated whether aspirin efficacy differs across predefined age cut-off in patients with coronary artery disease. METHODS: We analyzed data from START-ANTIPLATELET registry, a multicenter prospective registry of patients hospitalized for acute coronary syndrome and subsequently treated with at least one month of aspirin monotherapy. Patients were stratified by age ≥ 65 versus < 65 65 years. The primary endpoint was major adverse cardiovascular events, evaluated using Kaplan-Meier estimates and multivariable Cox regression. A systematic review and meta-analysis were conducted to evaluate the effect of aspirin for secondary prevention in older versus younger adults. Pooled risk ratios with 95% confidence intervals were calculated using a random-effects model. RESULTS: 410 patients were included in the registry, of whom 53.7% had ≥ 65 years. Patients aged ≥ 65 years exhibited a substantially higher incidence of major adverse cardiovascular events than younger patients, for an absolute increase of 5 events per 1,000 patient-months. Older age was associated with increased risk of major adverse cardiovascular events (hazard ratio 4.99, 95%CI 1.11-22.58) independently of other cardiovascular risk factors (hazard ratio 3.94, 95%CI 0.84-18.65). The meta-analysis of 58,394 participants from 19 trials confirmed the increased risk of major adverse cardiovascular events among older individuals receiving aspirin compared with younger patients (RR 1.41, 95%CI 1.141.73). CONCLUSION: The efficacy of aspirin monotherapy for secondary coronary artery disease prevention is reduced in elderly patients from 65 years of age onward.
Clinical reasoning at the bedside has historically been grounded in pathophysiological mechanism characterized by the causal understanding of what is happening in this particular patient's body. Over the past three decad...Clinical reasoning at the bedside has historically been grounded in pathophysiological mechanism characterized by the causal understanding of what is happening in this particular patient's body. Over the past three decades, two developments have displaced that tradition: the institutionalization of evidence-based medicine, which elevated population-level statistical evidence above individual clinical reasoning, and the rise of molecular biology, which relocated scientific prestige from organ-level integrative physiology to the receptor and the gene. Together, they have produced a clinical culture in which mechanistic reasoning at the level of the individual patient lacks both institutional support and epistemological standing. We argue that this displacement has been costly, that it was never adequately diagnosed, and that recovering mechanistic reasoning while preserving the genuine contributions of both evidence-based medicine and molecular biology is now an urgent task for clinical medicine and medical education alike. Individualized patient care, the explicit goal of contemporary medicine, cannot be achieved within a purely probabilistic framework. Our argument is not against evidence-based medicine; its contributions to clinical practice are genuine and irreversible. It is an argument for integration: population evidence and mechanistic reasoning working together, each supplying what the other cannot. Individualized care requires both.
BACKGROUND: Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap (ACO), contribute to significant health burdens. Understanding patient characteristics, sl...BACKGROUND: Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap (ACO), contribute to significant health burdens. Understanding patient characteristics, sleep patterns, and mortality factors is critical for improving management. METHODS: Data from the UK Biobank were used to compare the baseline characteristics, sleep patterns, and mortality rates of 14,326 COPD, asthma, and ACO patients. Multivariable logistic and linear regression analyses were conducted to identify factors affecting mortality and sleep. RESULTS: COPD patients were older, with higher smoking rates and mortality compared to ACO and asthma patients (P < 0.001). Asthma patients had the highest BMI (29.76), while ACO patients showed the highest diabetes prevalence (14.2%) and asthma patients had the highest hypertension prevalence (46.9%) (P < 0.001). Asthma patients exhibited the poorest sleep quality, with higher rates of short sleep duration, insomnia, and daytime dozing compared to COPD and ACO patients (P < 0.001). Multivariable analysis revealed that COPD patients had higher mortality risks compared to ACO patients (P < 0.001), and poor sleep scores and diabetes were significantly associated with increased mortality (P < 0.001). Asthma patients had significantly lower sleep scores than ACO patients (P < 0.001). CONCLUSION: ACO patients showed intermediate outcomes, with worse sleep than asthma patients but better than COPD patients. Poor sleep quality, along with diabetes and smoking, was linked to higher mortality. Addressing sleep disturbances may reduce mortality in ACO and COPD patients, warranting further research on targeted interventions.
Obesity is a major global health burden with profound cardiovascular implications, contributing to morbidity, mortality, and healthcare costs. Excess adiposity promotes atherosclerosis, hypertension, atrial fibrillation,...Obesity is a major global health burden with profound cardiovascular implications, contributing to morbidity, mortality, and healthcare costs. Excess adiposity promotes atherosclerosis, hypertension, atrial fibrillation, heart failure, stroke, and venous thromboembolism through entangled mechanisms, including adipose tissue dysfunction, chronic low-grade inflammation, immune dysregulation, endothelial impairment, insulin resistance, and neurohormonal activation. Dysfunctional adipose tissue, including perivascular and epicardial fat, actively contributes to vascular inflammation, cardiac remodeling, and arrhythmogenesis. Although the "obesity paradox" has been described, obesity remains strongly associated with earlier and more severe cardiovascular events. Recent therapeutic advances, particularly incretin therapies, have improved the management of obesity and its consequences by realizing notable weight loss and metabolic benefits. However, important gaps in obesity phenotyping, cardiovascular risk stratification, and individualized therapy persist, supporting integrated precision-medicine and public-health strategies to reduce obesity-related cardiovascular burden.
BACKGROUND: Circulating Apolipoprotein E (ApoE) plays key roles in lipoprotein metabolism, but its clinical utility in cardiovascular risk assessment and its relationship with incident heart failure remain unclear. This...BACKGROUND: Circulating Apolipoprotein E (ApoE) plays key roles in lipoprotein metabolism, but its clinical utility in cardiovascular risk assessment and its relationship with incident heart failure remain unclear. This study aims to evaluate the association of serum ApoE concentration with incident cardiovascular outcomes. METHODS: This retrospective cohort study used electronic health records from a multi-specialty outpatient population in Shenzhen, China. Adults who had serum ApoE measured and did not have prior ischemic heart disease, stroke, or heart failure were included (N=14,852). The outcomes were incident major adverse cardiovascular events (MACE), ischemic heart disease, stroke, and heart failure. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: During a median follow-up of 4.0 years, we observed 491 MACE, 515 ischemic heart disease, 293 stroke, and 181 heart failure incident events. Higher ApoE concentrations were significantly associated with increased risks of incident MACE (HR[95%CI] per 1mg/dL increment: 1.09[1.04-1.15]), ischemic heart disease (1.07[1.02-1.13]), and heart failure (1.14[1.07-1.22]), but not stroke (1.03[0.96-1.11]). These associations were independent of low-density lipoprotein cholesterol (LDL-C), small and dense LDL-C, high-density lipoprotein cholesterol, and neutrophil-to-lymphocyte ratio. However, adjustment for triglycerides attenuated the associations. Individuals with elevations in both ApoE and triglycerides had disproportionately higher risks of cardiovascular events. CONCLUSIONS: Elevated circulating ApoE concentrations are risk factors for incident MACE, ischemic heart disease, and heart failure, and may signal the residual risk of cardiovascular disease beyond cholesterol markers. Concurrent elevation in ApoE and triglycerides may represent a high-risk clinical phenotype, suggesting the joint assessment of ApoE and triglycerides may improve risk stratification for hypertriglyceridemic individuals.
Salt sensitivity is a major component of highly prevalent uncontrolled hypertensive disease. Multiple disease determinants, such as age, sex (biological male or female), genetic predisposition, pro-inflammatory factors,...Salt sensitivity is a major component of highly prevalent uncontrolled hypertensive disease. Multiple disease determinants, such as age, sex (biological male or female), genetic predisposition, pro-inflammatory factors, renal and vascular dysfunction, disrupted blood-brain barrier integrity, as well as gut microbiome health, effectively regulate sodium turnover and associated adverse outcomes. Salt sensitive blood pressure can be commonly observed in patients with both primary and secondary hypertension. Furthermore, patients suffering from obesity and insulin-resistant states, heart failure, chronic kidney disease, as well post-menopausal females and senior citizens, may be particularly sensitive to excessive salt exposure. Despite paramount importance, diagnosis or treatment of salt sensitive blood pressure remain challenging, often pushing clinicians into complicated management labyrinths. Significant discordance between objective findings, such as degree of thirst and edema on presentation, and results of laboratory testing, such as serum sodium, potassium, NT-proBNP, or RAAS essay, is often observed delaying the provision of appropriate care. This review offers detailed description of underlying pathophysiology, diagnosis and treatment of salt sensitive blood pressure in clinical settings, intending to ameliorate the burden of uncontrolled hypertension.
BACKGROUND: Patients receiving direct-oral anticoagulants (DOACs) often have multiple cardiovascular disorders and are frequently exposed to polypharmacy. This study aimed to identify bleeding-related drug interactions b...BACKGROUND: Patients receiving direct-oral anticoagulants (DOACs) often have multiple cardiovascular disorders and are frequently exposed to polypharmacy. This study aimed to identify bleeding-related drug interactions between DOACs and cardiovascular drugs in the context of polypharmacy using the FDA Adverse Event Reporting System (FAERS). METHODS: Individual case safety reports involving apixaban, dabigatran, edoxaban, or rivaroxaban were extracted from FAERS. DOAC-related reports were classified according to exposure to concomitant use of predefined 15 drug classes of interest-ten cardiovascular drug classes, three classes of pharmacokinetic modifiers, anti-platelets, and non-steroidal anti-inflammatory drugs-and bleeding events. Bleeding events were defined at three levels: hemorrhage-related events, actual bleeding events, and major bleeding. Major bleeding was further classified by anatomical site. Exact matching and logistic regression were performed to estimate adjusted reporting odds ratios (RORs). RESULTS: A total of 317,583 eligible reports were included. Fifteen DOAC-drug combinations were consistently identified as significant interaction signals across the three bleeding definitions, with adjusted RORs ranging from 1.06 to 2.36. Diuretics showed consistent interaction signals across DOACs and bleeding definitions, while the strongest interaction signals were observed with digitalis glycosides, non-dihydropyridine calcium channel blockers, and amiodarone analogs. Site-stratified major bleeding analyses identified 64 significant interaction signals, with rivaroxaban accounting for the largest proportion, whereas edoxaban showed a relatively less extensive interaction signal profile. CONCLUSIONS: These findings suggest that consideration of polypharmacy and potential drug interactions may improve DOAC selection and risk stratification, particularly with concomitant cardiovascular drugs and site-specific bleeding risk, supporting closer monitoring.