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Assessing comorbidities and predicting risk: A primer for APRNs.

Today's clinical environments are rife with tools designed to comprehensively account for medical complexity and comorbidities while predicting risk for a host of adverse health-related outcomes. Therefore, it is imperative that advanced practice registered nurses (APRNs) understand the structure and function of these tools, their similarities and differences, their limitations, and strategies for appropriate incorporation into practice. This article offers a practical overview for APRNs, emphasizing clinical implications and guidance for aligning assessment tools with the clinical population of interest to improve care delivery, quality, and patient outcomes.

Humans

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

Effectiveness of physical activity intervention for depression, anxiety and comorbid symptoms during the perinatal period among Chinese primiparas.

BACKGROUND: To examine the effectiveness of a physical activity (PA) programme incorporating partner support and enjoyment in preventing perinatal depression, anxiety, and comorbid anxiety and depression (CAD) among Chinese primiparas. METHODS: A total of 120 eligible primiparas were randomised into intervention or control groups. The intervention group received the 13-week PA programme and the control group received the usual care. The outcomes were depression, anxiety, and CAD assessed at baseline, post-intervention, and 6 weeks after delivery. Differences were examined using generalised linear mixed models with intention-to-treat. RESULTS: A significant group&#x2009;&#xd7;&#x2009;time interaction was observed for depression score, anxiety score, anxiety incidence, and CAD incidence (all p&#x2009;<&#x2009;0.05). However, no significant interaction was found for depression incidence. Compared to the control, the intervention substantially reduced the scores of depression (MD: -2.67 (-4.16 to -1.17); -2.63 (-4.15 to -1.11)) and anxiety (MD: -4.95 (-9.23 to -0.67); -7.33 (-11.85 to -2.82)), as well as the rates of depression (OR: 0.40 (0.18 to 0.85); 0.44 (0.21 to 0.93)) and CAD (OR: 0.35 (0.14 to 0.87); 0.26 (0.11 to 0.62)) at post-intervention and 6-week postpartum. Notably, anxiety incidence showed significant reduction only at 6-week postpartum (OR: 0.34 (0.16 to 0.74)) (all p&#x2009;<&#x2009;0.05). Within the intervention group, no significant changes occurred in most outcomes from baseline to post-intervention and 6-week postpartum, except depression scores (MD:-1.60 (-2.79 to -0.41); -1.23 (-2.44 to -0.03); p&#x2009;<&#x2009;0.05). CONCLUSIONS: The PA programme (including partner support and enjoyment) may be effective in reducing perinatal depression, anxiety and CAD among primiparas.

Adult

Executive function in alcohol use disorder with low psychiatric comorbidity: Comparison with a non-clinical sample and predictive value for treatment outcome.

BACKGROUND: Executive functions (EF) encompass abilities such as planning, decision-making, and inhibitory control, critical for learning, establishing and maintaining behavioral change. The association between alcohol use disorder (AUD) and impairments in EF are well established. However, prior research is dominated by studies on convenience samples including individuals with severe AUD with high levels of psychiatric comorbidity, which limits generalizability. The present study therefore aimed to investigate the degree of impairment and predictive ability of EF, on alcohol consumption, among individuals with moderate AUD with low levels of psychiatric comorbidity. METHODS: Adults with moderate AUD (n&#x2009;=&#x2009;147) were recruited at three specialized addiction outpatient clinics in Stockholm, to a randomized controlled trial investigating the efficacy of two psychological treatments. Participants underwent neuropsychological testing before treatment. Eight tests from the CANTAB&#xae; battery were administered at baseline, assessing mental flexibility, sustained attention, visuospatial working memory, response inhibition, and delay discounting. Assessments of alcohol use and related symptoms were conducted at baseline, the 12- and 26-weeks follow-up. A non-clinical reference sample (n&#x2009;=&#x2009;72) completed corresponding CANTAB&#xae; tests. The two groups were compared regarding EF using descriptive statistics and t-tests, and the predictive value of EF for reduction in alcohol consumption, was investigated using multiple regression models. RESULTS: Individuals with AUD did not perform worse on any of the tests on executive function (CANTAB&#xae;) as compared to the non-clinical reference sample. Measures of EF were not significant predictors for reduction in alcohol use for the 12-week, or the 26-week follow-up. CONCLUSIONS: EFs were not impaired and were not a clinically relevant predictor of treatment outcomes in this population with AUD. Future research on EF as a predictor in AUD treatment, needs to corroborate the present findings, and include other populations, e.g., with different socio-economic backgrounds and by including other methodologies for measuring EF.

Humans

Association of the Charlson Comorbidity Index With 1-Year Outcomes in Patients With Macular Edema Secondary to Retinal Vein Occlusion.

OBJECTIVE: To determine the predictive value of the Charlson Comorbidity Index (CCI) for outcomes in patients with macular edema secondary to retinal vein occlusion (RVO). DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients seen between 2013 and 2023 at the Cole Eye Institute, Cleveland Clinic, were included. All patients were >18, diagnosed with RVO (International Classification of Diseases (ICD)-9 and 10 codes), had a complete CCI score, and had at least 1 year of ophthalmic follow-up data after their first intravitreal injection (baseline). Patients with ocular surgery, trauma, or panretinal photocoagulation were excluded. METHODS: Age-adjusted CCI scores were calculated for each patient from chart review. For patients with bilateral RVO, one eye was selected randomly. Patients were stratified into tertiles by CCI distribution: tertile 1 (CCI 0-5; mean 3.4), tertile 2 (age-CCI 4.1-6; mean 4.9), and tertile 3 (CCI &#x2265; 8; mean 9.6). Multivariable linear regression was performed to determine the predictive value of CCI and other covariates on visual and anatomical outcomes. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 1-year follow-up. RESULTS: A total of 972 patients met all criteria, with an average age-adjusted CCI score of 6.2. Each one-point increase in CCI predicted 0.38 fewer letters in BCVA at follow-up (P < .001). Baseline BCVA was a significant predictor of follow-up BCVA in all tertiles (P < .001). In the third tertile, each one-point increase in CCI was associated with a 0.72 letter reduction in follow-up BCVA (P < .001). For CST, baseline CST was strongly predictive of final CST (P < .001), while CCI was only significant in the first tertile, where each point increase in CCI predicted a 13.7 &#xb5;m increase in CST (P = .02). In RVO subtype interaction models, the age-adjusted CCI &#xd7; CRVO interaction was not statistically significant for either 1-year BCVA (P = .269) or 1-year CST (P = .695). CONCLUSIONS: Higher CCI scores are significantly associated with worse visual outcomes in patients with RVO, particularly in the combined population and most comorbid patients (tertile 3). CCI was significantly associated with higher (thicker) CST only among the least comorbid patients (tertile 1).

Humans

[Efficacy and safety of acute-phase transcutaneous auricular vagus nerve stimulation for herpes zoster-related pain in middle-aged and elderly patients with comorbid depression and anxiety].

Objective: To evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) during the acute phase in middle-aged and elderly patients with herpes zoster (HZ) comorbid depressive and anxiety states. Methods: This was a randomized controlled trial. Forty middle-aged and elderly patients with acute-phase HZ who attended the Department of Dermatology at Xuanwu Hospital, Capital Medical University, from June 2024 to June 2025 were enrolled and randomly assigned in a 1&#x2236;1 ratio using a random number table to receive either taVNS (n=20) or sham stimulation (n=20) for 5 consecutive days. Both groups received antiviral therapy and on-demand rescue analgesia. Pain, anxiety/depression, and sleep quality were evaluated using the Visual Analog Scale (VAS), the 4-item Patient Health Questionnaire (PHQ-4), and the Insomnia Severity Index (ISI), respectively. The primary outcome was the incidence of subacute pain at 30 days post-rash onset. Secondary outcomes included cumulative analgesic consumption at 1 and 2 weeks after treatment, the changes from baseline (&#x394; values) in PHQ-4 and ISI scores at 2 weeks, and the incidence of postherpetic neuralgia (PHN) at 90 days post-rash onset. Results: In the taVNS group, 7 patients (35%) were female, with a mean age of (64.1&#xb1;9.7) years; in the sham group, 10 patients (50%) were female, with a mean age of (61.5&#xb1;8.5) years. There were no statistically significant differences between the two groups in baseline VAS, PHQ-4, or ISI scores (all P>0.05). The incidence of subacute pain was significantly lower in the taVNS group than in the sham group [5% (1/20) vs 35% (7/20), RD=-30.0% (95%CI:-52.1%--4.9%); RR=0.14 (95%CI: 0.02-1.06); P=0.044]. At 2 weeks after treatment, the &#x394; values of PHQ-4 and ISI in the taVNS group were significantly greater than those in the sham group. The proportion of patients taking Lofentadine and the cumulative Lofentadine consumption at weeks 1 and 2 were both lower in the taVNS group than in the sham group (all P<0.05). No serious adverse events occurred in either group, and the difference in PHN incidence between groups was not statistically significant (P>0.05). Conclusions: Acute-phase taVNS appears to be feasible and safe in middle-aged and elderly patients with HZ and comorbid depressive and anxiety, effectively reducing subacute pain and improving emotional and sleep outcomes.

Humans

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316&#x2008;131 participants and 11&#x2008;822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3&#xb7;9% (95% CI 3&#xb7;0-5&#xb7;1). The prevalence of UIAs in individuals with atherosclerosis was 5&#xb7;5% (4&#xb7;7-6&#xb7;4; 2229 of 40970 participants) and the adjusted PR was 1&#xb7;3 (95% CI 0&#xb7;8-2&#xb7;0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7&#xb7;9% (5&#xb7;6-11&#xb7;1; 412 of 4252 participants) and the adjusted PR was 2&#xb7;4 (0&#xb7;5-11&#xb7;2). For connective-tissue disorder, the UIA prevalence was 10&#xb7;3% (6&#xb7;5-16&#xb7;0; 94 of 879 participants) and the adjusted PR was 3&#xb7;9 (2&#xb7;0-7&#xb7;6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12&#xb7;8% (9&#xb7;2-17&#xb7;6; 293 of 1990 participants) and the adjusted PR was 4&#xb7;4 (1&#xb7;5-12&#xb7;6). RRs were for current smoking 1&#xb7;4 (1&#xb7;2-1&#xb7;6; 798 of 27911 participants), for having hypertension 1&#xb7;6 (1&#xb7;5-1&#xb7;7, 4043 of 83053 participants), and for female sex 1&#xb7;9 (1&#xb7;8-2&#xb7;0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6&#xb7;6% (6&#xb7;3-6&#xb7;8; 2904 of 41191 participants). The adjusted PR was 1&#xb7;8 (1&#xb7;1-2&#xb7;8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0&#xb7;7% (0&#xb7;6-0&#xb7;8) in 2002-2015 and 1&#xb7;4% (1&#xb7;0-1&#xb7;9) in 2016-2022. The UIA prevalence did not differ between countries. &#x3c4;2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans

Clinical insights into catathrenia: A real-world analysis from a tertiary sleep center.

INTRODUCTION: Catathrenia is a rare sleep-related breathing disorder marked by groaning during prolonged expiration, often underrecognized or misdiagnosed as obstructive or central sleep apnoea (OSA or CSA) or parasomnia. Understanding its clinical and polysomnographic features is essential for accurate diagnosis and management. MATERIALS AND METHODS: We performed a retrospective observational study of adult patients diagnosed with catathrenia at Servi&#xe7;o de Medicina do Sono de Coimbra. Diagnosis was established by attended overnight polysomnography (PSG) with synchronised audio-video recording. Demographic data, symptoms, comorbidities, PSG variables, treatment modalities, and outcomes were reviewed. Catathrenia events were defined as deep inhalation followed by prolonged exhalation with monotonous groaning. RESULTS: Ten patients were included. Median age was 46&#x2009;years (range 27-78), mostly female (70%). Common comorbidities included obesity (n&#x2009;=&#x2009;4), depression (n&#x2009;=&#x2009;2), Parkinson's disease (n&#x2009;=&#x2009;1), and restless legs syndrome (n&#x2009;=&#x2009;1). Six patients (60%) had concomitant obstructive sleep apnoea (OSA). Seven patients had excessive daytime sleepiness (Epworth Sleepiness Scale&#x2009;>&#x2009;10). All catathrenia episodes occurred exclusively during REM sleep. Continuous positive airway pressure (CPAP) therapy was the most frequently used treatment and was associated with objective or subjective improvement in most patients. Two patients experienced spontaneous remission. CONCLUSION: Catathrenia remains underdiagnosed and can mimic other sleep disorders. Recognition of its REM-sleep predominance and PSG pattern is essential. Individualised treatment, often involving PAP therapy, may improve symptoms and patient outcomes.

Humans

Embedding cardiovascular risk assessment into routine BTK inhibitor management in chronic lymphocytic leukemia.

INTRODUCTION: Cardiovascular (CV) toxicities remain a major challenge during Bruton tyrosine kinase inhibitor (BTKi) therapy for chronic lymphocytic leukemia (CLL). Selecting the optimal BTKi based solely on a history of overt CV disease may underestimate underlying cardiovascular vulnerability. AREAS COVERED: We performed a targeted, non-systematic review of PubMed and MEDLINE to examine the association between baseline CV comorbidities and BTKi-related CV toxicities in CLL. Current evidence indicates that preferential use of BTKis with more favorable CV safety profiles, coupled with appropriate cardio-oncology surveillance, reduces the risk of CV adverse events in patients with pre-existing CV disease. In patients without established CV disease, the Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (SCORE2-OP) may help identify clinically meaningful latent CV risk, enabling early optimization of modifiable risk factors in line with the proactive cardiovascular management strategy endorsed by the 2026 European Hematology Association (EHA) CLL guidelines. EXPERT OPINION: A structured, risk-adapted approach integrating standardized CV risk assessment, early management of modifiable risk factors, individualized BTKi selection, and multidisciplinary cardio-oncology collaboration may improve the safety and tolerability of BTKi therapy in CLL. Pending prospective validation, SCORE2 and SCORE2-OP should complement, rather than replace, dedicated cardio-oncology evaluation.

Humans

Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies.

BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged &#x2265; 50&#x2009;years (n&#x2009;=&#x2009;7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g&#x2009;=&#x2009;1.60, 95% CI: 0.95-2.25) and 8-OHdG (g&#x2009;=&#x2009;2.64, 95% CI: 2.13-3.14) were markedly elevated (p&#x2009;<&#x2009;0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g&#x2009;=&#x2009;5.24). In PD, 8-OHdG was moderately elevated (g&#x2009;=&#x2009;0.78, 95% CI: 0.18-1.39; p&#x2009;=&#x2009;0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g&#x2009;=&#x2009;0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.

Humans

Integrative multi-omics reveals a fibroblast-centered, ZFHX3-prioritized regulatory framework linking sick sinus syndrome and atrial fibrillation.

OBJECTIVE: To define shared genetic and multi-scale mechanisms underlying comorbidity between sick sinus syndrome (SSS) and atrial fibrillation (AF). METHODS: We integrated genome-wide association study (GWAS) summary statistics for SSS and AF with Genotype-Tissue Expression (GTEx) expression and splicing quantitative trait loci (eQTL/sQTL), atrial single-cell and spatial transcriptomics, and epigenomics. We identified trait-relevant tissues and pathways, prioritized shared cell types, quantified genome-wide and local genetic sharing, detected joint loci by cross-trait meta-analysis, and linked loci to regulatory programs via colocalization and cell-prioritized co-expression networks. RESULTS: Both traits showed strongest enrichment in cardiac tissue, especially Heart Atrial Appendage. Fibroblasts from the left atrial appendage were consistently prioritized as the key shared cell population. SSS and AF displayed significant positive genome-wide genetic correlation, with multiple locally shared regions, including six major loci. Cross-trait meta-analysis identified eight joint-phenotype SNPs implicating four susceptibility genes. ZFHX3 was the leading tissue-cell-gene candidate, acting as a hub in fibroblast co-expression modules and colocalizing with cardiac regulatory signals. CONCLUSION: Shared liability for SSS and AF is highly tissue- and cell-specific, converging on regulatory networks in atrial appendage fibroblasts, with ZFHX3 serving as a central mechanistic and biomarker node.

Humans

Relationships Between Risky Substance Use and Irritable Bowel Syndrome (IBS) Severity, Mental Health, and Smoking-Related Processes in Adults with IBS Who Smoke.

Objective: Irritable Bowel Syndrome (IBS) is a debilitating chronic pain condition that presents a major and growing public health burden. Combustible cigarette smoking plays a role in the maintenance of IBS, and the co-occurrence of these conditions warrants greater focus. Moreover, given that smoking co-occurs with other substance use behaviors, the impact of these comorbid behaviors on physical and mental health-related outcomes among individuals with IBS who smoke is warranted. The goal of the present cross-sectional study was to assess relationships of risky alcohol, cannabis, and opioid use with IBS severity, anxiety and depression, and smoking-related processes among adults with IBS who smoke. Methods: In total, 263 adults who met Rome IV criteria for IBS and who smoked combustible cigarettes were included in the study. Hierarchical regression analyses were conducted to examine the influence of risky substance uses on IBS symptom severity, IBS-related quality of life, anxiety, depression, perceived barriers for smoking cessation, and cigarette dependence. Results: Results indicated that opioid use was statistically related to all criterion variables, whereas alcohol use was specifically associated with depression and anxiety. Cannabis use showed a statistically significant association only with anxiety symptoms. Conclusions: The present investigation is among the first to explore the role of risky substance use in terms of a wide array of IBS, mental health, and smoking processes among adults with IBS who smoke. The findings suggest that substance use should be a focal point of screening and intervention for the IBS population to optimize outcomes beyond the reach of medical therapies.

Irritable bowel syndrome

Psychiatric Diagnoses and Psychotropic Medications Among Military-Affiliated Adolescents and Young Adults With Polycystic Ovary Syndrome.

PURPOSE: To study rates of psychiatric diagnoses and psychotropic medication prescription among U.S. military-affiliated adolescents and young adults (AYA) with polycystic ovary syndrome (PCOS). METHODS: This retrospective matched cohort study included U.S. military-affiliated AYA (aged 15-21 years) enrolled in TRICARE Prime for at least 6 months during the surveillance period (January 2016 to October 2023). Military-affiliated AYA were grouped into three categories: individuals diagnosed with PCOS (N = 6,911), age-matched individuals with no diagnosed PCOS symptoms (N = 35,814), and individuals with diagnosed symptoms suggestive of PCOS (N = 2,136). The presence of a psychiatric diagnoses and prescriptions for psychotropic medications were obtained via the International Classification of Diseases, 10th Revision, Clinical Modification codes and National Drug codes, respectively. RESULTS: AYA with diagnosed PCOS had higher odds of having a psychiatric diagnosis and being prescribed a psychotropic medication compared to an age-matched comparison group (psychiatric diagnosis odds ratio [OR] = 2.48 [2.35-2.62], medication OR = 2.14 [2.03-2.25]) and individuals with symptoms suggestive of PCOS (psychiatric diagnosis OR = 1.11 [1.003-1.23], medication OR = 1.16 [1.05-1.28]). DISCUSSION: The odds of psychiatric comorbidities and psychotropic medication prescription were more than twice as high as among U.S. military-affiliated AYA with PCOS. More research is needed to determine whether health-care utilization and military-related factors impact mental health outcomes among AYA with PCOS. Additionally, tailored, multidisciplinary mental health services for AYA with PCOS are needed.

Humans

Bioepidemiology of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, primarily due to immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid, is an increasingly recognized cause of heart failure. Modern diagnostic advances suggest that ATTR, particularly in older adults, may be more prevalent than historically reported. METHODS: All Olmsted County decedents aged &#x2265;40 years from 1970 to 1976 were identified. Available ventricular myocardium from retained paraffin blocks was screened histologically for amyloid using sulfated Alcian blue staining; positive cases underwent grading and proteomic typing by laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Beyond prevalence estimation, this analysis characterizes amyloid type, deposition grade and distribution, associated comorbidities, and cause-of-death patterns, comparing amyloid-positive decedents with age- and sex-matched controls. RESULTS: Of 2,566 eligible deaths, 1,028 autopsy cases with evaluable myocardium formed the study cohort (mean age 70.5 years; 61.1% male; 97% White). Cardiac amyloid was present in 52 cases giving an overall prevalence of 5.1% (95% CI: 3.8-6.6, which rose from 0% under age 60 to 37.5% (95% CI: 21.1-56.3) in those &#x2265;90 years (p < 0.001). While prevalence estimates were higher in men above age 80 compared to women, there was no evidence of an interaction of age and sex (p = 0.90). The quantity of amyloid was sufficient for typing in 38 cases: ATTR (84.2%), AL (7.9%), serum amyloid A (5.3%), and apolipoprotein A-IV (2.6%). Adjusted estimates assuming untyped mild cases were ATTR-type increased ATTR prevalence to 4.5% (95% CI: 3.3-5.9) overall. Comorbidity profiles were similar between amyloid-positive and negative groups, though syncope and leg weakness were more common in amyloid-positive decedents. CONCLUSIONS: In an unselected autopsy cohort, cardiac amyloid was common, particularly ATTR in older adults. Prevalence increased steeply after age 80. These findings suggest that ATTR amyloidosis is not rare and is likely underdiagnosed and has similar prevalence in women and men, despite the male predominance reported in the literature.

Humans

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans

The co-existence of Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome: A systematic review of the literature.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3&#xa0;years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Humans

Genetic risk stratification of common diseases in breast cancer survivors: a population-based cohort study.

IMPORTANCE: Patients diagnosed with breast cancer (BCa) are at increased risk of multiple common diseases; however, the spectrum of these diseases and the contribution of inherited genetic susceptibility remain incompletely characterized. METHODS: We evaluated 15 common diseases and tested their associations with BCa exposure and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N&#x2009;=&#x2009;254,736). Analyses were performed using cause-specific Cox proportional hazards models within a full-cohort framework, with time-updated BCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS: After recruitment, incident BCa was diagnosed in 11,386 women (4.47%), including 2,742 (24.08%) with metastatic BCa. Patients with BCa had an increased risk of nine diseases spanning cardiovascular, metabolic, and neuropsychiatric domains (P<0.003, Bonferroni-corrected). Elevated risks were generally observed among patients with both early staged and advanced BCa. Inherited susceptibility further stratified disease risk, with the highest risks observed among patients with BCa with elevated disease-specific PRS. For example, compared with women without BCa, the hazard ratio (HR; 95% CI) for osteoporosis was 2.33 (2.15-2.52) among women with any BCa, 2.38 (2.18-2.59) among those with non-metastatic BCa, and 2.12 (1.78-2.54) among those with metastatic BCa; the HR was 4.48 (3.99-5.02) among patients with BCa in the highest quartile of osteoporosis-specific PRS (all P<0.001). In contrast, BCa was not significantly associated with risk of coronary artery disease. CONCLUSION: BCa and inherited genetic susceptibility jointly contribute to increased risk of multiple common diseases, supporting the integration of genetic risk stratification into survivorship care.

Complications

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N&#xa0;=&#xa0;54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms &#x2265; 2-3&#xa0;days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64&#xa0;years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65&#xa0;years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans