Search Results (331)

Background/Objectives: To inform policy making for the German breast cancer (BC) screening program, we systematically evaluated the long-term benefits and harms of extended age limits compared to the current standard of biennial mammography at ages 50–69 years using a decision-analytic approach. Methods: We developed and applied a Markov state-transition model for mammography screening in Germany to systematically assess the benefit–harm trade-offs of various screening strategies varying in age at start and end of screening as well as in screening frequency. The model was populated with international data for sensitivity and specificity of mammography along with German epidemiological, clinical and age-specific quality-of-life data. In deterministic analyses, the following outcomes were projected: detected ductal carcinoma in situ (DCIS) and invasive BC, BC-related deaths, life years (LY), and quality-adjusted life years (QALY), number of positive, false-positive, and total mammograms, overdiagnosis, and the incremental harm–benefit ratio (IHBR). Results: In the base-case analysis, mammography at ages 45–79 (annual, age 45–49; biennial, 50–79) achieved the highest gain in LY (10.0 life years gained [LYG] per 100 women) compared with current screening. Biennial mammography at ages 45–74 resulted in the highest benefits considering both life expectancy and quality of life (3.5 QALYs gained/100 women). Compared to current biennial mammography screening at ages 50–69, lowering the start age from 50 to 45 years resulted in an IHBR of 47 additional mammograms/LYG. Compared to biennial mammography at ages 45–69, biennial mammography at age 45–74 results in 96 additional mammograms/LYG. Further extended screening results in substantially less favorable IHBRs. Conclusions: Based on our results, extending biennial mammography screening to women aged 45 to 74 years may prevent additional BC deaths and increase remaining life expectancy at an acceptable benefit–harm ratio, and improve quality-adjusted life expectancy. Full article

Anti-amyloid therapy (AAT) with monoclonal antibodies (mAbs) modestly slow cognitive and functional decline in early Alzheimer’s disease (AD). However, both the magnitude of clinical benefit and the risk of treatment-related complications vary substantially even among patients with similar biomarker profiles. Frailty, both brain and systemic, is highly prevalent in older adults with AD and affects a large proportion of those considered for AAT. Despite this, it has been largely absent from current decision frameworks. Brain frailty, defined by structural and microvascular damage (e.g., small-vessel disease, microbleeds, and atrophy), limits the clinical benefit of amyloid clearance and increases susceptibility to amyloid-related imaging abnormalities. In contrast, systemic frailty, reflecting reduced physiological reserve, mainly affects treatment tolerance and recovery from adverse events. In this narrative, conceptual review, we synthesize evidence that both forms of frailty act as biologically grounded modifiers of AAT efficacy and safety and may limit the clinical benefit while increasing susceptibility to complications and decompensation. Importantly, the precise empirical thresholds at which frailty begins to exert harmful effects remain unknown. We further outline how MRI-based markers of brain frailty, combined with brief systemic frailty measures, could support risk stratification, patient selection, monitoring intensity, and shared decision-making, including deferring treatment when the benefit–risk balance is unfavorable, while avoiding exclusion of patients who may still benefit. Taken together, we propose that future studies should incorporate frailty measures and perform precise assessments of both brain and systemic frailty, as this may improve patient stratification and better characterize the effects of AAT. Full article

Prostate biopsy is among the most frequently performed diagnostic procedures in men, and two shifts have reshaped it over the past decade: the incorporation of multiparametric MRI (mpMRI) with targeted sampling, and migration from the transrectal to the transperineal route. Because these changes are usually adopted together, the practical choice facing many units is between a contemporary transperineal MRI-targeted pathway and the historical transrectal systematic one. This narrative review weights cancer detection, procedure-related harms, and implementation approximately equally, drawing on evidence that isolates route from targeting wherever possible. Across randomized trials and meta-analyses, the two pathways achieve broadly comparable detection of clinically significant cancer (ISUP grade group ≥ 2), although the transperineal route samples anterior and apical tumors more effectively and the largest randomized comparison reported a modest transperineal advantage. The principal transperineal benefit is a marked reduction in infectious complications, enabling reduced antibiotic prophylaxis and improved stewardship; its main cost is greater procedural discomfort. We review mpMRI and PI-RADS with illustrative examples, fusion technique, cost-effectiveness, special populations, emerging adjuncts, and divergent guidelines, concluding that route and targeting decisions are best individualized, with infection risk and lesion location dominant. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly encountered in pain practice, but reported pain improvement may reflect direct antinociception, weight loss, metabolic change, or disease-specific effects. This structured narrative review examined these possibilities and relevant safety issues. Methods: PubMed/MEDLINE, Embase, and Web of Science Core Collection were searched through 15 May 2026. Peer-reviewed human studies, key mechanistic preclinical studies, systematic reviews and meta-analyses, and professional guidance relevant to pain outcomes or procedural safety were considered. Metabolic-only and non-peer-reviewed reports were excluded, and human pain-primary evidence was prioritized. Results: Preclinical data support plausible mechanisms involving spinal microglia, interleukin-10, beta-endorphin, neuroinflammation, and sensory-neuron signaling, but direct analgesic efficacy at systemic clinical doses has not been demonstrated. In STEP 9 (n = 407), mean WOMAC pain scores at 68 weeks changed from baseline by −41.7 points with semaglutide 2.4 mg and −27.5 points with a placebo; body weight changed by −13.7% and −3.2%, respectively. Liraglutide produced additional weight loss without superior knee-pain reduction. Diabetic peripheral neuropathy evidence was mainly structural or neurophysiologic; idiopathic intracranial hypertension and ROSE-010-treated irritable bowel syndrome showed disease-specific signals, whereas fibromyalgia- and opioid-related findings remained observational or hypothesis-generating. Gastrointestinal dysmotility, reduced intake, and lean-mass loss may offset functional benefits. Conclusions: GLP-1RAs are not established analgesics. Current human signals are best interpreted as indirect metabolic–functional or disease-specific effects. Future trials should use validated pain-primary outcomes, control for weight loss, and monitor treatment-related harms. Full article

Background: Vaccine hesitancy (VH) is a complex global public health threat requiring validated tools for its assessment globally. This study aimed to evaluate an extended adult Vaccine Hesitancy Scale (aVHS) among Greek-speaking adults. Methods: This study evaluated a newly developed extended version of a widely used aVHS, incorporating five additional items on long-term safety, risk–benefit evaluation, vaccine-related harm, scientific credibility, and perceived alternatives, on a cross-sectional sample of 491 adults in Greece and Cyprus. Cross-cultural adaptation of the extended aVHS involved translation, back-translation, and pilot testing. Structural validity was assessed using parallel analysis, exploratory factor analysis (EFA), and reliability using Cronbach’s α and McDonald’s ω. Criterion validity was assessed against focus-group classification using ROC analysis in 68 participants. Results: A one-factor EFA solution appeared the most parsimonious, showing strong loadings for the original and extended aVHS (0.67–0.86 and 0.65–0.87), with similar explained variance (60.31% and 60.06%). The one-factor solution was confirmed by parallel analysis for both scales. Internal consistency was excellent, and slightly higher for the extended than the original aVHS (α = 0.95; ω = 0.95 vs. α = 0.92; ω = 0.93). The five newly added items performed strongly, with item–rest correlations of 0.69–0.85 and loadings of 0.72–0.87. Criterion validity was excellent, with a slightly higher AUC (0.991 vs. 0.981) and numerically higher classification performance for the extended than the original aVHS. Conclusions: The extended aVHS is a psychometrically coherent tool that improves the performance of the original scale among Greek-speaking individuals. This scale may enhance VH surveillance, aiding targeted vaccination communication strategies. Full article

Technological developments in transportation have moved quickly, often faster than the frameworks used to evaluate their broader societal and environmental implications. This study examines the extent to which Tesla’s automotive activities contribute to long-term societal well-being from a consequentialist utilitarian perspective, focusing on two related developments: (1) vehicles equipped with advanced driver assistance systems (ADAS) and (2) vehicles powered by electricity. Tesla provides a useful focal case in that it brings these two developments together in a single, highly visible setting. Using Tesla as an exploratory qualitative case, the analysis assesses both technologies within a single ethical and sustainability framework, examining how their effects combine across safety, environmental, and broader societal outcomes. Because the two technologies act on many of the same outcomes and stakeholders, they interact: they reinforce one another in some respects and offset one another in others. In the case of road safety, for example, the additional mass of an electric vehicle raises the severity of collisions even as driver assistance works to reduce their frequency. The analysis suggests an overall net positive societal impact, while recognizing the uncertainties and trade-offs that remain. This assessment rests mainly on two considerations: the likely reduction in traffic-related injuries and fatalities associated with wider adoption of ADAS-equipped vehicles, and the expectation that, in most contexts, electric vehicles provide a net environmental benefit, particularly through lower levels of harmful air pollutants relative to internal combustion engines. These benefits are not automatic, however, but depend on broader system conditions, including whether electrification and automation move transportation beyond established patterns of car dependence or reinforce them. The paper concludes by outlining the implications of these findings, while acknowledging the limits of the analysis and pointing to areas for future research. Full article

Background/Objectives: Social Prescribing (SP) seeks to address non-medical needs by connecting individuals to community-based resources through a person-centered “social prescription”, such as group activities or support services. SP is increasingly being implemented internationally and has demonstrated potential benefits for wellbeing. However, potential harms and negative or unintended consequences (HNUCs) remain poorly understood. This scoping review aims to synthesize evidence on HNUCs reported in the literature. Methods: A systematic search of EMBASE, MEDLINE, and APA PsycInfo was conducted through September 2024 to identify full-text studies published in English or German that report HNUCs associated with SP for adults in health- or social care settings. Backward reference searches of relevant reviews identified additional studies. Two reviewers screened and extracted data independently, with disagreements resolved by a third reviewer. Study characteristics and HNUCs were categorized using the Consequences of Public Health Interventions (CONSEQUENT) framework, by level (service users, stakeholders, or system level) and degree of certainty (explicit, implicit, or potential). We followed the Joanna Briggs Institute manual and the PRISMA Reporting Guidelines for Scoping Reviews. Results: Of 2097 records identified, 18 primary studies met the inclusion criteria. In addition, 87 studies, identified through 35 included reviews, were analyzed. A total of 776 unique HNUCs were identified across the CONSEQUENT framework’s domains. Most were related to the domains of “Health System”, “Health” and “Acceptability and Adherence”, and predominantly affected SP participants. Conclusions: SP may be associated with potential HNUCs affecting users, stakeholders, and systems. Identifying and addressing these risks is essential for designing, implementing, and evaluating SP programs, and guiding future research to mitigate potential HNUCs. Our findings underscore the importance of policymakers and practitioners incorporating the routine monitoring of unintended consequences and using this evidence to inform program refinement, resource allocation, and harm mitigation strategies. Full article

Background: Adverse drug reactions (ADRs) represent a major and often underestimated source of morbidity, hospitalization, and functional decline in older adults. The convergence of age-related pharmacokinetic and pharmacodynamic changes, multimorbidity, polypharmacy, and frailty creates a clinical environment in which ADR risk is not static but evolves along progressive trajectories—from mild, early manifestations toward severe, potentially irreversible outcomes. Understanding these trajectories is essential for rational geriatric prescribing. Methods: This narrative review synthesizes evidence from epidemiological studies, systematic reviews, Cochrane analyses, and clinical trials published between 2000 and 2025, focusing on adults aged 65 years and older with two or more chronic conditions. Sources were identified through a structured, non-systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus using the terms ‘adverse drug reactions’, ‘polypharmacy’, ‘multimorbidity’, ‘frailty’, ‘deprescribing’, and ‘pharmacokinetics’ in older adults, alone and in combination. Evidence quality was assessed narratively, distinguishing trial evidence from observational and expert consensus data. Results: ADRs in older adults are best classified using complementary frameworks—the augmented Type A to withdrawal Type E and failure-of-therapy Type F taxonomy (Types A–F), the Dose-Time-Susceptibility (DoTS) classification, and the EIDOS mechanistic scheme—which together capture the heterogeneity of drug-related harm in this population. Age-related pharmacokinetic changes (altered absorption, increased volume of distribution of lipophilic drugs, reduced hepatic and renal clearance) and pharmacodynamic shifts (heightened receptor sensitivity, baroreflex impairment, increased blood–brain barrier permeability) interact with polypharmacy and frailty to amplify ADR trajectories from mild to severe. Anticholinergic burden, prescribing cascades, and inappropriate polypharmacy function as structural accelerators of these trajectories. Medication review and deprescribing improve prescribing quality but evidence for hard outcome benefits remains of low to very low certainty. Emerging AI-enabled digital tools show promising accuracy for identifying frailty and pharmacological vulnerability, but this performance relates to frailty classification and has not yet been shown to prevent ADR trajectories; they require validation for routine clinical use. Conclusions: Recognizing ADRs in older adults as dynamic trajectories rather than isolated events repositions prescribing review and deprescribing from optional to essential clinical acts. An integrated approach combining pharmacological vigilance, comprehensive geriatric assessment, structured deprescribing, and emerging digital decision-support tools offers the most realistic pathway to reduce the trajectory-related burden of drug-related harm in complex older patients. Full article

Type 2 diabetes (T2D) is a prevalent disease worldwide that increases the risk of cardiovascular (CV) complications, disability and mortality. While excessive alcohol consumption is harmful, the effects of moderate wine consumption remain debated. This review evaluates whether moderate wine intake affects the risk of developing T2D and its impact on subjects with T2D. Twenty-eight studies were analysed. Evidence suggests an association between moderate wine consumption and the risk of developing T2D, with a J-shaped relationship, and reduced risk observed at low levels. This effect appears more pronounced with red wine, likely related to its higher polyphenol content, and when consumed with meals. On the other side, in patients with T2D, moderate wine consumption has been associated with a reduced risk of CV complications, nephropathy and mortality. It has also been linked to improved lipid profiles and reduced inflammatory markers, without adversely affecting body weight or glycaemic control in well-managed patients. These effects may be enhanced within a Mediterranean dietary pattern, suggesting synergistic actions. However, alcohol intake may increase the risk of hypoglycemia, particularly in patients receiving glucose-lowering therapies. It should be avoided by vulnerable individuals, and those with comorbidities such as MASLD and other significant liver diseases, peripheral neuropathy or other severe conditions. In conclusion, moderate wine consumption may be associated with a reduction in the risk of developing T2D and with several CV benefits in patients with T2D. Vulnerable patients should abstain and individuals who currently do not drink alcohol should not start drinking. If wine is consumed, intake should always remain moderate (as low as possible), within healthy meals and only after individual clinical assessment. Full article

Mitochondrial reactive oxygen species (mtROS) are central regulators of cellular function, yet their biological roles are often reduced to an oxidative-stress/antioxidant dichotomy. This review reframes mtROS through the concept of mitohormesis, in which outcomes are neither inherently harmful nor beneficial but are determined by a defined set of contextual variables. We present a mechanistic framework in which mtROS effects depend on chemical species identity, sub-mitochondrial site of production, temporal dynamics, redox-buffering capacity, and metabolic state; together, these variables determine whether mtROS promote adaptive eustress or pathological distress. We then show that, across polyphenols, isothiocyanates, terpenoids, alkaloids, and quinones, the biologically relevant effects of natural redox-modulating compounds are mediated less by direct radical scavenging than by pro-hormetic mechanisms, including mild electron transport chain perturbation, nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1) activation, modulation of mitochondrial membrane potential, mitochondrial quality control, and NAD⁺/NADPH regulation. Applying this framework to disease reveals strong tissue and state dependence: neurodegeneration favors buffering expansion and mitophagy; metabolic disease may benefit from exercise-mimetic and NRF2-activating strategies; cardiovascular disease illustrates mitohormesis through ischemic preconditioning and CoQ10 supplementation; and cancer requires distinction between prevention and therapy because redox buffering can either protect normal tissue or support tumor survival. Finally, we argue that the failure of non-specific antioxidant supplementation is mechanistically predictable and propose context-aware, biomarker-guided, temporally optimized, and compartment-targeted redox interventions as a more rational translational path. Full article

Precision medicine in prostate cancer (PCa) is increasingly best understood as a continuum linking risk-adapted detection, multimodal diagnosis and phenotyping, and implementation-ready decision pathways. Contemporary clinical guidelines emphasize structured diagnostic strategies, appropriate use of advanced imaging, and selective deployment of biomarkers when results can alter management. Upstream risk enrichment using polygenic risk scores and multivariable prediction models may improve the yield of clinically significant disease while mitigating harms related to overdiagnosis. At the point of suspicion, magnetic resonance imaging-first pathways and reflex biomarker testing provide practical tools to reduce unnecessary biopsy while maintaining safeguards for the detection of clinically important disease. Beyond diagnosis, prostate-specific membrane antigen positron emission tomography refines disease-state phenotyping in initial staging, biochemical recurrence, and limited-burden presentations, while standardized acquisition and reporting improve reproducibility and multidisciplinary communication. Germline and tumor-based molecular profiling should be operationalized as a longitudinal care process with clear consent, turnaround targets, and test-to-action rules that define what each result enables at specific decision nodes. Finally, longitudinal monitoring approaches, including liquid biopsy and artificial intelligence-enabled pathology, are evolving rapidly and require transparent reporting and rigorous risk-of-bias appraisal before broad clinical adoption. This narrative review synthesizes key evidence across the precision continuum and outlines a decision-node-based, test-to-action framework for maximizing clinical benefit, maintaining quality, and ensuring equitable access. Full article

Environmental change, accelerated by increasing global temperatures, has become a defining economic, ecological, and public health issue of the twenty-first century. This study presents an economic evaluation of early mortality associated with air pollution, a major factor underlying worldwide patterns of illness and premature mortality, through which climate change affects global population health. Using secondary global mortality estimates and an economic valuation framework, both tangible costs (e.g., economic output and income losses) and quality-of-life loss (e.g., welfare loss associated with premature mortality) are estimated. The paper contributes to planetary health scholarship by integrating established economic valuation approaches with harm-reduction and systems-based perspectives to reinterpret air pollution as an interconnected environmental, economic, and societal challenge rather than solely a public health issue. Air pollution is associated with reduced life expectancy and approximately 3 million premature deaths annually worldwide. The estimated annual tangible economic burden is approximately US$940.9 billion (range: US$550.5 billion–US$1.65 trillion), while intangible costs are estimated at US$37.8 trillion annually (range: US$13.3 trillion–US$48.8 trillion). The findings suggest that air pollution should be understood not merely as a health-related challenge but also as a broader planetary health challenge with implications for environmental sustainability, economic resilience, and long-term societal well-being. Targeted air quality interventions and pollution reduction strategies may therefore generate substantial public health and societal co-benefits worldwide. Full article

Background/Objectives: Artificial intelligence (AI) is increasingly being integrated into dental diagnostics, promising improved detection, efficiency, and patient communication. While these developments offer potential clinical benefits, emerging commercial applications raise important ethical concerns. This study explores how providers of diagnostic AI systems frame their technologies in marketing materials, with particular attention to features designed to influence patient acceptance and increase revenue. Methods: An exploratory qualitative thematic analysis was conducted on publicly available promotional content from leading dental AI companies between September and October 2025. Materials were analyzed for recurring rhetorical strategies related to commercialization, persuasion, technological authority, and representations of objectivity. Ethical interpretation was guided by principlism, professional ethics, and virtue-based perspectives. Results: The findings show that AI is frequently marketed not only as a diagnostic aid but also as a tool for boosting case acceptance, return on investment, and practice expansion. Visualizations and performance metrics are used rhetorically to position AI as authoritative and objective, encouraging patient compliance while downplaying uncertainty and potential harm. These practices risk undermining patient autonomy, promoting diagnostic inflation and overtreatment, and compromising professional integrity by shifting attention from patient welfare toward commercial outcomes. Conclusion: Pervasive marketing of diagnostic AI amplifies existing tensions between professional integrity and commercial incentives in dentistry. Without appropriate safeguards, AI risks reinforcing a transactional model of care in which patients are treated as consumers and diagnostics become instruments of persuasion. To preserve trust and ethical practice, dentists and professional organizations must ensure that AI remains a supportive clinical tool rather than a commercial device, prioritizing transparency, informed consent, and patient-centered care. Full article

Despite advances in septic shock management, optimal vasopressor strategies remain understudied. Norepinephrine (NE) is recommended as the first-line vasopressor for restoring arterial pressure; however, excessive catecholamine exposure has been associated with adverse events, including arrhythmias, ischemia, and poor clinical outcomes. While the early initiation of NE is increasingly recognized as important, uncertainty persists regarding the optimal starting dose and escalation strategy. In septic shock, particularly refractory septic shock, reduced vascular responsiveness may limit the effectiveness of escalating NE doses and increase the risk of dose-related complications. Vasopressin (AVP), a non-adrenergic vasopressor, provides complementary mechanisms to NE and may reduce catecholamine requirements. Randomized trials have not consistently demonstrated a survival benefit; AVP may improve hemodynamic stability and renal perfusion. Emerging evidence suggests the potential advantages of earlier AVP initiation at lower NE doses than those currently recommended. Collectively, the current evidence supports a strategy that prioritizes early and adequately dosed NE to achieve rapid hemodynamic stabilization, followed by the timely initiation of AVP once moderate NE requirements are reached, rather than the continued escalation of NE alone. Such an integrated approach may help balance efficacy and safety, and minimize catecholamine-related harm while optimizing perfusion in septic shock cases. Full article

Background: Neuropathy and neuropathic pain (NP) are globally prevalent, remain difficult to manage, and are often exacerbated by underlying lifestyle factors. Alcohol use, particularly in the context of chronic consumption or dependence, is a recognized contributor to peripheral nerve damage, yet its association with neuropathy/NP has not been systematically evaluated. This systematic review synthesizes the current evidence on alcohol exposure, including quantity, frequency, and dependency, and its association with the incidence, prevalence, and severity of neuropathy/NP. Methods: This systematic review included observational studies assessing alcohol consumption patterns or dependence in relation to neuropathy/NP outcomes and was conducted in accordance with PRISMA guidelines. Exposure types were analyzed independently, and pooled odds ratios and relative risks were generated when sufficient data were available. The review was registered with PROSPERO number CRD42023484158. Results: Following de-duplication and exclusions, 76 studies were included, comprising cohort (n = 15), case–control (n = 12), and cross-sectional (n = 49) designs. While associations varied by study design and exposure category, alcohol dependence and consumption were more consistently linked with increased neuropathy incidence and severity, including electrophysiological evidence of compromised function. Notably, in studies examining alcohol cessation, abstinence was linked to clinical improvements in neuropathy/NP symptoms such as hypoesthesia and muscle weakness. While heterogeneity and risk of bias were present, largely due to the subjective classification of alcohol exposure and a lack of universally applied objective neuropathy measurement tools, multiple pooled estimates reached statistical significance. Conclusions: Evidence from observational studies supports an association between alcohol use, especially dependence, and the development and progression of neuropathy/NP, although causality remains unproven. Abstinence may offer therapeutic benefit, though further abstinence- and/or harm reduction-related interventional studies are required to clarify causality and guide low-cost, adjunctive strategies for alcohol-related neuropathy/NP. Full article