Background and aim : Straining during bowel movements (BMs) is a common in constipation but has been relatively understudied as a modifiable therapeutic target. This study aimed to characterize patient perceptions, behaviors, and beliefs surrounding straining. Methods: Adults with self-reported constipation were recruited nationwide via an online research panel (Cint USA, Inc.). Participants completed a structured survey assessing symptoms, toileting behaviors, attitudes, and beliefs related to straining. Results : A total of 124 participants with self-reported constipation completed the survey with 54.0% reporting constipation for >1 year, and 8.1% met Rome IV criteria for chronic constipation. Straining in at least 25% of BM was common (49.6%), but only moderately effective (mean helpfulness score 5.3 ± 2.6 on 10-point scale). Despite only 23% expressing concern about long-term consequences of straining, 75.0% would like to reduce straining. Participants who strained during more than 50% of BMs demonstrated significantly longer toilet sitting times (p = 0.031), were more likely to attempt defecation in the absence of urge (p = 0.026), and reported more acute physiological symptoms of straining (p < 0.001). No differences were observed between frequent and infrequent strainers in perceived helpfulness of straining or concern about long-term effects. Conclusion : Straining is a common and burdensome symptom, but not very helpful in producing BM. Most participants showed interest in interventions to reduce straining. These findings highlight an important opportunity to advance treatment approaches that address straining as a modifiable component of constipation, informed by both psychological drivers and defecatory mechanics.
Background: Elevated lipoprotein(a) [Lp(a)] is an independent, genetically determined cardiovascular risk factor. Nucleic acid-based agents targeting LPA, including the siRNAs olpasiran, lepodisiran, and zerlasiran, and the antisense oligonucleotide pelacarsen, have demonstrated substantial Lp(a) lowering in phase 2 trials. Research Question: Which nucleic acid-based LPA targeting therapy and dose regimen achieves the greatest Lp(a) reduction, and how do they rank relative to one another in the absence of head-to-head trials? Methods: Four phase 2 randomized placebo-controlled trials were included: OCEAN(a)-DOSE (olpasiran, n=281), ALPACA (lepodisiran, n=320), ALPACAR-360 (zerlasiran, n=178), and AKCEA-APO(a)-LRx (pelacarsen, n=286). Only three monthly (Q4W) pelacarsen arms were included; Q2W and weekly regimens were excluded to maintain dosing interval homogeneity. Comparable dose regimens were selected across studies, yielding 11 active treatment nodes plus placebo and a total analyzed population of 864 participants. A random effects NMA was conducted using placebo as the common comparator. Treatments were ranked using SUCRA-derived scores, with lower values indicating greater efficacy. A sensitivity analysis excluding pelacarsen was performed because standard errors were indirectly derived. Results: All active regimens reduced Lp(a) levels compared with placebo. The largest reductions were observed with olpasiran 225 mg (MD –100.5 mg/dL, 95% CI –105.5 to –95.5), lepodisiran 400 mg (MD –97.6, 95% CI –113.8 to –81.4), and olpasiran 75 mg (MD –97.4, 95% CI –102.5 to –92.3). Zerlasiran also produced substantial reductions (450 mg Q24W: MD –85.6; 300 mg Q24W: MD –81.4). Pelacarsen reductions ranged from –29.0 mg/dL (20 mg Q4W) to –66.0 mg/dL (60 mg Q4W). SUCRA rankings identified olpasiran 225 mg as the highest-ranked regimen (28.1%), followed by lepodisiran 400 mg (29.7%) and olpasiran 75 mg (30.4%). Higher-dose zerlasiran regimens ranked above pelacarsen. Sensitivity analysis rankings were consistent: olpasiran 225 mg (30.4%), lepodisiran 400 mg (32.5%), and olpasiran 75 mg (33.4%). No major inconsistency was identified. Conclusions: Among nucleic acid-based Lp(a)-targeting therapies, olpasiran 225 mg and lepodisiran 400 mg achieved the greatest reductions in Lp(a), each exceeding 97 mg/dL compared with placebo. Higher dose zerlasiran regimens also achieved substantial lowering, whereas monthly pelacarsen produced more modest reductions. Rankings were robust in sensitivity analyses. These findings provide a comparative assessment of phase 2 LPA-targeting therapies and may help inform the design and interpretation of planned and ongoing cardiovascular outcomes trials
Background: Atrial fibrillation (AFib) complicates millions of hospitalizations annually. However, the independent acute clinical predictors and socioeconomic determinants of in-hospital cardiac arrest (IHCA) in this population remain incompletely characterized. Identifying these factors is critical for targeted risk stratification and addressing disparities in acute cardiovascular care. Research Question: What are the independent acute clinical predictors and socioeconomic determinants of in-hospital cardiac arrest among adults hospitalized with atrial fibrillation? Methods: We performed a retrospective observational analysis of the 2016-2023 National Inpatient Sample (NIS). Adult hospitalizations with a primary or secondary diagnosis of AFib were identified using ICD-10-CM codes. The primary outcome was IHCA. Survey-weighted multivariable logistic regression was utilized to identify independent predictors of IHCA, adjusting for demographics, hospital characteristics, and clinical comorbidities. Results: Among 37.7 million weighted AFib hospitalizations, IHCA was associated with significantly longer length of stay (9.46 vs. 6.04 days) and higher hospitalization charges ($189,954 vs. $79,545; p<0.001). After multivariable adjustment, some acute clinical conditions demonstrated the strongest association with IHCA. Electrolyte and acid-base disorders (aOR 2.89, 95% CI 2.85-2.94) and sepsis/septic shock (aOR 2.84, 95% CI 2.79-2.88) were the strongest predictors, followed by conduction disorders (aOR 1.97, 95% CI 1.93-2.01). Furthermore, significant racial and socioeconomic disparities were observed; compared with White patients, Black (aOR 1.56, 95% CI 1.52-1.59), Asian/Pacific Islander (aOR 1.40), and Hispanic patients (aOR 1.37) had significantly higher odds of IHCA. Disadvantaged financial status increased risk, with Medicaid (aOR 1.36) and self-pay (aOR 1.61) patients facing higher odds than Medicare beneficiaries. Higher income quartiles were incrementally protective (Q4 vs Q1: aOR 0.83). Conclusions: IHCA among hospitalized AFib patients is driven predominantly by acute, potentially modifiable physiologic derangements, particularly electrolyte abnormalities and sepsis. Significant racial and socioeconomic disparities persist independently of clinical acuity. Optimizing inpatient survival requires prompt correction of metabolic triggers, alongside systemic interventions that address health inequities. Limitations include the administrative nature of the dataset and the potential influence of the COVID-19 pandemic on hospitalization patterns.
BACKGROUND:Acetaminophen overdose remains one of the leading causes of both intentional and unintentional medication-related liver injury and acute liver failure in both adults and children. Although N-acetylcysteine remains the standard of care and is highly effective when administered early, massive ingestions and delayed presentation cases may exceed its ability to prevent hepatocellular injury. Fomepizole, a CYP2E1 inhibitor traditionally used for toxic alcohol poisoning, has emerged as a potential adjunctive therapy for high-risk acetaminophen overdoses. OBJECTIVE:This article reviews the mechanism of action of acetaminophen, the pathophysiology of acetaminophen-induced hepatotoxicity, outlines current management strategies, and examines the emerging role of fomepizole as an adjunctive therapy. Added focus is given to implications for nursing practice, including safe preparation, administration, and monitoring. SUMMARY:Acetaminophen toxicity develops when glutathione stores become depleted, leading to accumulation of the toxic metabolite N-acetyl-p-benzoquinone imine. N-acetylcysteine replenishes glutathione and mitigates early injury; however, extremely high acetaminophen concentrations can overwhelm detoxification pathways. Fomepizole inhibits CYP2E1 and reduces conversion of acetaminophen to N-acetyl-p-benzoquinone imine, potentially limiting hepatic damage. Evidence from animal studies and small human case series suggests benefit in massive ingestions, although large, randomized-controlled trials are lacking. IMPLICATIONS:Further research is needed to establish and standardize protocols and further clarify the role of fomepizole in the management of acetaminophen overdose cases.
