Modest Reduction In Risk Research Articles

Association of aerobic and muscle-strengthening activity with chronic low back pain: population-based study

BACKGROUND CONTEXTChronic low back pain (CLBP) is a significant global health burden, primarily affecting the middle-aged and older; However, there is a lack of clear, evidence-based guidelines for leisure-time physical activity aimed at preventing CLBP. PURPOSEThis study sought to delineate the association between aerobic physical activity (APA) and muscle strengthening activities (MSA) and the prevalence of CLBP. STUDY DESIGNThis was a population-based study conducted across the United States. PATIENT SAMPLEThis nationwide study utilizes deidentified data from 22 consecutive rounds of the National Health Interview Survey (NHIS) from 1997 to 2018. OUTCOME MEASURESThe primary outcome was self-reported CLBP. METHODSWe analyzed the prevalence of CLBP in a representative sample of 324,793 middle-aged and older people. Among 263,871 individuals, we used multiple logistic regression to investigate individual and joint association between the amount of APA and MSA with CLBP. RESULTSIn total, 263,871 participants (mean age, 59.0 years; SD, 9.7) were included in the final analysis. From 1997 to 2018, the prevalence of CLBP was approximately 32%, with an annual increase. Engaging in APA for 75 to 150 minutes weekly was associated with a modest reduction in CLBP risk (OR [95% CI] = 0.97 [0.97–0.98]). Similar benefits were seen with 150 to 225, 225 to 300, and >300 minutes. Engaging in MSA 2 to 3 times and 4 to 5 times weekly also reduced CLBP risk (0.98 [0.98–0.99] and 0.98 [0.97–0.99], respectively). Optimal reductions of CLBP risk may be associated with balanced levels of APA and MSA, with recommended amounts being 225 to 300 min/w of APA and 4 to 5 times/w of MSA (0.92 [0.89–0.95]). CONCLUSIONSThe study found engaging in over 75 minutes of APA and 2 to 5 weekly MSA sessions is associated with a reduced risk of CLBP. Furthermore, a balanced combination of APA and MSA may correspond to the greatest reduction in CLBP risk.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R ) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes. AIM To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation. METHODS Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions. RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders. CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Frailty and Clinical Outcomes of Ticagrelor Versus Clopidogrel in Older Adults With Acute Myocardial Infarction.

Ticagrelor is recommended over clopidogrel in acute coronary syndrome based on the results of the PLATO (Study of Platelet Inhibition and Patient Outcomes) trial. We aimed to emulate PLATO in older adults with and without frailty and with acute coronary syndrome treated with percutaneous coronary intervention. We created a new-user cohort of Medicare fee-for-service beneficiaries aged ≥65 years hospitalized for acute coronary syndrome from 2014 to 2018 and initiated ticagrelor or clopidogrel following percutaneous coronary intervention. Frailty was defined using a validated claims-based frailty index ≥0.25. Coprimary outcomes were major adverse cardiovascular events and major bleeding. Follow-up began on the date of first outpatient prescription for ticagrelor or clopidogrel and ended on the earliest date for an outcome event, death, discontinuation of the index drug, or disenrollment from Medicare. The study included 42 843 older adults; 23% were frail. After propensity score matching, the rates of major adverse cardiovascular events per 100 person-years comparing ticagrelor versus clopidogrel groups were 7.8 and 7.3 in the frail cohort (hazard ratio [HR], 1.07 [95% CI, 0.84-1.36]) and 3.7 and 4.2 in the nonfrail cohort (HR, 0.87 [95% CI, 0.75-1.02]). The corresponding rates of major bleeding were 4.3 and 3.8 in the frail cohort (HR, 1.12 95% CI, [0.80-1.56]) and 2.2 and 1.8 in the nonfrail cohort (HR, 1.22 [95% CI, 0.98-1.51]). There was a trend toward a modest reduction in risk of major adverse cardiovascular events and a trend toward a modest increase in risk of major bleeding with ticagrelor compared with clopidogrel in the nonfrail cohort. There was insufficient evidence for the benefit of ticagrelor in frail older adults.

Routine, prospective DPYD genotyping guided dose-individualisation for patients receiving fluoropyrimidines: Implementation, prevalence and patient safety outcomes from a multi-institutional clinical trial.

12121 Background: Prospective data regarding the prevalence of DPYD variant alleles and the impact of genotype guided dosing on safety and efficacy of fluoropyrimidines (FP) remains limited. We assessed the feasibility and safety impact of routine, prospective, DPYD genotype guided FP dosing. Methods: Adult patients (>18 years), commencing FP for the first time were enrolled. Sanger PCR sequencing was designed to target DPYD variants NM_000110.4:c.1905+1G>A (DPYD*2A), NM_000110.4:c.1679T>G (DPYD*13), NM_000110.4:c.1236G>A and NM_000110.4:c.2846A>T. Dose reductions were implemented as per current international pharmacogenomic guidelines. Gr3/4 toxicity, dose reductions/delays and hospital admissions were reviewed for the first 60 days after commencement. For comparison purposes, a retrospective review of patients receiving FP without testing in a prior year was completed. Results: Between July 2021 – May 2023, 334 patients were enrolled for testing. 95% ECOG 0-1. 57% curative treatment intent. Mean time from phlebotomy to result 6.9 days (range 2-15). Clinician/patient acceptance was high (>95% of eligible patients starting FP were enrolled). 20 (6.0%) variant DPYD allele carriers were detected. 11 heterozygous for c.1236G>A, 5 heterozygous for C.1905+1G>A, 3 heterozygous for c.2846A>T and 1 homozygous for c.1236G>A. 295 of patients tested proceeded to receive FP. 62% received Infusional-FP, 38% Capecitabine. 39 patients commenced treatment prior to DPYD result being available (treating clinician decision). Dose modification recommendations were followed in all but two patients. 24% experienced FP related Grade 3/4 toxicity within 60 days. (23% DPYD wild type, 37% DPYD variant) versus 35% in the retrospective cohort. 16% had FP related dose delays (16% DPYD wild type, 12% DPYD variant) versus 25% retrospective cohort. 14% had FP related dose reductions (13% DPYD wild type, 25% DPYD variant) versus 12% retrospective cohort. 13% had FP related hospital admissions (13% DPYD wild type, 19% DPYD variant) versus 17% retrospective cohort. 1 death in the DPYD wild type cohort was deemed potentially related to FP. Conclusions: Prospective DPYD genotype guided dosing was feasible in clinical practice, with prevalence of variant alleles comparable to published literature. There was a modest reduction in risk of FP related severe toxicity, dose delays, and hospital admissions with DPYD guided dosing compared to a historical, untested cohort. Clinical trial information: ACTRN12621001117808.

Antidepressant drugs and risk of developing glioma: a national registry-based case-control study and a meta-analysis.

Whether use of antidepressants is related to the risk of developing lower-grade (WHO grades 2-3) and higher-grade (WHO grade 4) glioma was investigated in this study. A registry-based case-control study was performed with 1283 glioma case patients and 6400 age-, sex-, and geographically matched control participants who were diagnosed in Sweden during 2009-2013. Conditional logistic regression was used to analyze whether selective serotonin reuptake inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the data set from the present study was combined with results from 2 previous epidemiologic studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (odds ratio = 0.90; 95% CI, 0.83-0.97) when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma.

Impact of metformin on melanoma: a meta-analysis and systematic review

BackgroundThere is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.MethodsSelection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using ‘Melanoma’ and ‘Metformin’ as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and I2 statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.ResultsA total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I2 = 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I2 = 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I2 = 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I2 = 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.DiscussionThe improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.

Abstract 2239: Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data

Abstract Background: More than 60,000 U.S. adults are diagnosed with non-muscle invasive bladder cancer (NMIBC) each year. These patients are recommended to undergo surveillance via repeated cystoscopies. However, the ideal frequency of post-diagnostic cystoscopy surveillance remains unknown, and efforts are underway to de-escalate surveillance given uncertainty regarding its effect on mortality. We therefore aimed to compare the effectiveness of different post-diagnostic cystoscopy surveillance strategies on bladder cancer specific mortality. Methods: We used observational data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage to emulate a target trial, i.e., a hypothetical, pragmatic randomized trial that would answer our causal question. Eligible individuals were aged 66 years or older, diagnosed with NMIBC (Ta, Tis, or T1) classified as urothelial carcinoma between January 1, 2000 and December 31, 2017, and had completed their first post-diagnostic cystoscopy. We compared 10-year risks of bladder cancer specific mortality under cystoscopy surveillance every 3, 6, and 12 months separately among individuals at low, intermediate, and high risk. We estimated mortality risks using inverse probability weighted pooled logistic regression. Results: Among 58,004 eligible individuals, the median age at diagnosis was 77 years (interquartile range: 72, 82) and 75.6% were male. Over the 10 year follow-up period, 4,977 bladder cancer deaths occurred. Among individuals at high risk, the estimated 10-year bladder cancer mortality risks were 24.5% under the 3 month strategy, 26.6% under the 6 month strategy, and 27.3% under the 12 month strategy. Compared with cystoscopy every 3 months, the risk differences were 2.1% (95% confidence interval [CI]: -0.3, 3.8) for cystoscopy every 6 months, and 2.8% (95% CI: 1.0, 4.4) for cystoscopy every 12 months. For patients in the intermediate risk group, 10-year bladder cancer mortality risks were 14.4% under the 3 month strategy, 15.1% under the 6 month strategy, and 15.9% under the 12 month strategy. The risk differences were 0.7% (95% CI: -0.6, 2.0) for 6 vs. 3 months and 1.6% (95% CI: 0.3, 2.7) for 12 vs. 3 months. Among individuals at low risk, these mortality risks were 8.3% under the 3 month strategy, 9.2% under the 6 month strategy, and 9.6% under the 12 month strategy. Risk differences were 1.1% (95% CI: -0.1, 2.5) for 6 vs. 3 months and 1.5% (95% CI: 0.2, 3.0) for 12 vs. 3 months. Conclusions: We estimated that more frequent cystoscopy may result in clinically meaningful reductions in bladder cancer mortality among high risk patients. Among low and intermediate risk patients, more frequent cystoscopy may result in modest absolute risk reductions. Decision-makers should also consider the clinical and financial burden and risk of complications associated with more frequent surveillance. Citation Format: Emma E. McGee, Xabier García de Albéniz, A. Heather Eliassen, Kendrick Yim, Barbra A. Dickerman, Mark A. Preston, Miguel Hernán. Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2239.

Smoking, Drinking, and Dietary Risk Factors for Head and Neck Cancer in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Participants

There is a paucity of large-scale prospective studies evaluating the risk of developing head and neck cancer (HNC) associated with smoking, drinking, and dietary habits. To determine the association of smoking, drinking, and dietary habits with the risk of developing HNC. A nested cohort survival analysis of Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants was performed. Participants were between 55 and 74 years of age and recruited at 10 centers across the US from November 1993 to July 2001. Participants who developed HNC were matched with controls based on demographics and family history of HNC for analysis of smoking habits; for the analysis of drinking and dietary habits, matching was performed on smoking status and duration in addition to demographics and family history of HNC. Data analysis was performed from January to November 2023. Smoking, drinking, and dietary habits. Diagnosis of HNC. In total, 139 926 participants (51% female; mean [SD] age, 62.6 [5.4] years) were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.1 (10.3-13.6) years, 571 of whom developed HNC. HNC risk associated with smoking increased the closer the proximity of the head and neck subsite to the lungs, with the greatest risk associated with smoking observed in laryngeal cancer (current smoker hazard ratio [HR], 9.36; 95% CI, 5.78-15.15 compared to a nonsmoker). For analysis of drinking and dietary habits, 94 466 participants were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.2 (10.5-13.6) years, 264 of whom developed HNC. HNC risk increased with heavy drinking (HR, 1.85; 95% CI, 1.44-2.38) and decreased with consumption of whole grains (HR, 0.78; 95% CI, 0.64-0.94/oz per day), whole fruits (HR, 0.90; 95% CI, 0.82-0.98/cup per day), and overall healthy eating, as scored by Healthy Eating Index 2015 (HR, 0.87; 95% CI, 0.78-0.98/10 points). In this nested cohort study, the risk of HNC associated with smoking was higher for subsites that were closer to the lungs; heavy drinking was associated with greater HNC risk, while healthy eating was associated with a modest reduction in HNC risk.

The prospective association between psychological strengths and incident musculoskeletal injury in active duty Army soldiers.

Extensive training, overuse, overexertion, and repetitive movements put Soldiers at increased risk for musculoskeletal injuries (MSIs). The present study investigated the prospective association between psychological strengths, physiological and social factors, and non-combat-related MSI in a sample of 24,746 active duty Army Soldiers. Over a mean follow-up period of 21.07 months (SD = 16.07), 65.42% of the Soldiers examined were treated for an MSI. Applying survival analysis techniques and adjusting for relevant physiological and social factors, we found greater baseline Optimism, Positive Affect, Coping, and Adaptability were each associated with a modest reduction in risk of MSI (4-8%). Additionally, being older, female, married, and having a higher BMI were each associated with an increased MSI risk, whereas being an officer (relative to enlisted) and obtaining post-secondary education were each associated with a decreased MSI risk. Future research should examine the mechanisms through which psychological-based interventions may impact Soldiers' risk of MSI.

Phytosterol intake and risk of coronary artery disease: Results from 3 prospective cohort studies

BackgroundPhytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary artery disease (CAD) risk remains to be elucidated. ObjectivesThis study aimed to prospectively assess the associations between total and individual phytosterol intake and CAD risk in United States health professionals. MethodsThe analysis included 213,992 participants from 3 prospective cohorts—the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study—without cardiovascular disease or cancer at baseline. Diet was assessed using a validated food frequency questionnaire every 2–4 y since baseline. Associations between phytosterol intake and the risk of CAD, such as nonfatal myocardial infarction and fatal CAD, were evaluated using Cox proportional hazards regression models. ResultsMore than 5,517,993 person-years, 8725 cases with CAD were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CAD were 0.93 (0.86, 1.01; P-trend = 0.16) for total phytosterols, 0.89 (0.82, 0.96; P-trend = 0.05) for campesterol, 0.95 (0.88, 1.02; P-trend = 0.10) for stigmasterol, and 0.92 (0.85, 1.00; P-trend = 0.09) for β-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and β-sitosterol: the risk reduction plateaued at intakes above ∼180, 30, and 130 mg/d, respectively (P-nonlinearity < 0.001). In a subset of participants (N range between 11,983 and 22,039), phytosterol intake was inversely associated with plasma concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and IL-6 and positively associated with adiponectin, whereas no significant associations were observed for low-density lipoprotein cholesterol or C-reactive protein concentrations. ConclusionsHigher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CAD risk, displaying a nonlinear relationship that plateau at moderate intake levels. The role of phytosterols in preventing CAD warrants further investigation.

Effects of continuous positive airway pressure on cardiac events and metabolic components in patients with moderate to severe obstructive sleep apnea and coronary artery disease: a meta-analysis.

This meta-analysis aimed to systematically assess the effects of continuous positive airway pressure (CPAP) in secondary prevention of major cardiovascular events (MACEs) in patients with moderate-to-severe obstructive sleep apnea and coronary artery disease. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for observational studies and randomized controlled trials that compared CPAP with usual care in patients with moderate-to-severe obstructive sleep apnea with coronary artery disease. The primary outcomes were MACEs, all-cause death, acute coronary syndrome, rehospitalization for heart failure, repeat revascularization, and arrhythmia. A total of 11 studies (5 randomized controlled trials and 6 observational studies) with 5,410 patients reported outcomes of MACEs. Treatment with CPAP was associated with a modest risk reduction in MACEs (risk ratio [RR] 0.87, 95% confidence interval [CI] 0.78 to 0.98; P = .02). Similarly, CPAP significantly reduced the risk of all-cause and cardiovascular death by 23% (RR 0.77, 95% CI 0.60 to 0.99; P = .04; I2 = 0%). Subgroup analysis revealed that CPAP adherence time ≥ 4 hours/night had a greater benefit on MACEs by 42% (RR 0.58, 95% CI 0.42 to 0.79; P < .001; I2 = 0%) and repeat revascularization by 44% (RR 0.56, 95% CI 0.34 to 0.92; P = .02; I2 = 0%). Also, CPAP had a positive effect on systolic and diastolic blood pressure. CPAP therapy might prevent subsequent MACEs and all-cause death among patients with moderate to severe obstructive sleep apnea and concomitant coronary artery disease. CPAP use exceeding 4 hours/night may add more benefits on MACEs, repeat revascularization, and blood pressure. Registry: PROSPERO database; Name: Effects of Continuous Positive Airway Pressure on Cardiovascular Events and Metabolic Components in Patients with Obstructive Sleep Apnea and Coronary Artery Disease; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID= CRD42020213546; Identifier: CRD42020213546. Yang D, Li L, Dong J, Yang W, Liu Z. Effects of continuous positive airway pressure on cardiac events and metabolic components in patients with moderate to severe obstructive sleep apnea and coronary artery disease: a meta-analysis. J Clin Sleep Med. 2023;19(12):2015-2025.

Abstract 13262: Phytosterol Intake and Risk of Coronary Heart Disease in U.S. Men and Women

Introduction: Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol. Evidence regarding dietary phytosterols in relation to coronary heart disease (CHD) risk remains limited. We aimed to prospectively assess the associations between total and individual phytosterol intake and CHD risk in U.S. men and women. Methods: A total of 214,108 men and women from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study without cardiovascular disease or cancer at baseline were included in the analyses. Diet was assessed using a validated food frequency questionnaire every 2-4 years since baseline. Cox proportional hazards regression models were used to evaluate associations between phytosterol intake and CHD risk. Results: During 5,516,455 person-years of follow-up, 10,152 CHD cases were documented. Comparing extreme quintiles, pooled hazard ratios (HRs) (95% CIs) of CHD were 0.91 (0.85-0.98; P -trend=0.08) for total phytosterols, 0.88 (0.82-0.95; P -trend=0.02) for campesterol, 0.96 (0.90-1.02; P -trend=0.22) for stigmasterol, and 0.91 (0.84-0.98; P -trend=0.03) for beta-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and beta-sitosterol: the risk reduction plateaued at intakes above ~180 mg/day, 30 mg/day, and 130 mg/day, respectively ( P -nonlinearity&lt;0.001). Among 23,543 participants with existing CHD risk markers, phytosterol intake was inversely associated with plasma levels of total cholesterol, triglycerides, C-reactive protein, and interleukin-6, and was positively associated with adiponectin. Phytosterol intake was not associated with LDL or HDL cholesterol levels. Conclusions: Higher long-term intake of total and major subtypes of phytosterols was associated with modest CHD risk reduction, which may plateau at moderate intake levels. The role of phytosterols in preventing CHD needs further investigation.

Outcomes of alpha-blockers as medical expulsive therapy following shockwave lithotripsy: a systematic review and meta-analysis.

To determine stone-free rate following shockwave lithotripsy (SWL) with/without alpha-blockers as well as complication rates (individual and classified using the Clavien-Dindo system). We performed a systematic review of all randomized controlled trials that included more than 20 patients (age > 18 years) and examined the use of alpha-blockers after SWL. Meta-analysis was performed using 'metafor' in R. We report risk ratios (RRs) with 95% confidence intervals (95% CIs). The PROSPERO ID for the trial was: CRD42021248108. We assessed 158 full-text articles and included a total of 21 studies in our review. There were 1445 patients receiving alpha-blockers and 1478 control patients. Those receiving alpha-blockers were significantly more likely to be stone-free (RR 1.12, 95% CI 1.07-1.16; P < 0.001). This effect was robust to 'trim-and-fill' adjustment. In those taking alpha-blockers there was a significant reduction in Clavien III-V complications and, on trim-and-fill adjustment, a significant reduction in Clavien I-II complications. There were also significant reduction in rates of steinstrasse, pain and requirement for auxiliary procedures. There was no significant difference in retreatment rates. These effects were robust to trim-and-fill adjustment. There is a modest increase in stone-free rates in those receiving alpha-blockers following SWL, with a reciprocal modest risk reduction for steinstrasse, pain and auxiliary procedures. However, alpha-blockers do not reduce the risk of requiring retreatment.

Physical activity and the risk of non-Hodgkin lymphoma subtypes: A pooled analysis.

Non-Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case-control studies to examine the association between moderate-to-vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T-cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study-specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio=0.87, 95% CI=0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case-control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.

OBJECTIVESThe objective was to compare COVID‐19 outcomes in the Omicron‐driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained.METHODSIn this cohort study, we included public sector patients aged ≥20 years with a laboratory‐confirmed COVID‐19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection.RESULTSWe included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta‐driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58).CONCLUSIONSIn the Omicron‐driven wave, severe COVID‐19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta‐driven wave.

Clinical Ambiguity and Conflicts of Interest in Interventional Cardiology Decision Making

Problem definition: Among the most vexing issues in the U.S. healthcare ecosystem is inappropriate use of percutaneous coronary intervention (PCI) procedures, also known as overstenting. A key driver of overstenting is physician subjectivity in eyeballing a coronary angiogram. Advanced tests such as fractional flow reserve (FFR) provide more precise and objective measures of PCI appropriateness, yet the decision to perform these tests is endogenous and not immune to clinical ambiguity associated with eyeballing. Additionally, conflicts of interest, arising from revenue-generating incentives, play a role in overstenting. Academic/practical relevance: Conventional wisdom suggests more precise diagnostic testing will help reduce overtreatment. However, the literature rarely recognizes that the testing decision is itself endogenous. Our research highlights the role of endogeneity surrounding interventional cardiology decision making. Methodology: This study uses stochastic modeling and simulation. Results: Under a low conflict-of-interest level, the physician performs the advanced test for intermediate lesions. Under a high conflict-of-interest level, however, the physician would perform the advanced test only for high-grade lesions, because of a financial disincentive: Performing the advanced test may lower PCI revenue if the test results argue against the procedure. Surprisingly, despite this disincentive, a more revenue-driven physician can be more inclined to perform the advanced test. Managerial implications: Our model leads to implications for various efforts aimed at tackling overstenting: (1) Attention should be paid not only to the sheer quantity of FFR procedures but to which patients receive FFR procedures; (2) reducing the risk of the advanced test has a behavior-inducing effect, yet a modest risk reduction may lower patient welfare; and (3) offering a bonus to the physician for performing FFR procedures equal to a third of its reimbursement rate will cause only a 5% increase in average physician payment while inducing a 26% decline in overstenting. In addition, we show implementing a bundled payment scheme may discourage the use of FFR procedures and lead to more salient overstenting.

Renin-angiotensin aldosterone inhibitor use at hospital discharge among patients with moderate to severe acute kidney injury and its association with recurrent acute kidney injury and mortality

Recurrent episodes of acute kidney injury (AKI) are common among AKI survivors. Renin-angiotensin aldosterone inhibitors (RAASi) are often indicated for these patients but may increase the risk for recurrent AKI. Here, we examined whether RAASi associates with a higher risk for recurrent AKI and mortality among survivors of moderate to severe AKI in a retrospective cohort of Veterans who survived Stage II or III AKI. The primary exposure was RAASi at hospital discharge and the primary endpoint was recurrent AKI within 12 months. Cox proportional hazards models were fit on a propensity score-weighted cohort to compare time to recurrent AKI and mortality by RAASi exposure. Among 96,983 patients, 40% were on RAASi at discharge. Compared to patients who continued RAASi use, those discontinuing use experienced no difference in risk for recurrent AKI but had a significantly higher risk of mortality [hazard ratio 1.33 (95% confidence interval1.26-1.41)]. No differences in recurrent AKI risk was observed for non-users started or not on RAASi compared to prevalent users who continued RAASi. Subgroup analyses among those with diabetes, chronic kidney disease, heart failure, and malignancy were similar with exception of a modest reduction in recurrent AKI risk among RAASi discontinuers with chronic kidney disease. Thus, RAASi use among survivors of moderate to severe AKI was associated with little to no difference in risk for recurrent AKI but was associated with improved survival. Reinitiating or starting RAASi among patients with strong indications is warranted but should be balanced with individual overall risk for recurrent AKI and with adequate monitoring.

Abstract 4667: Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts

Abstract Purpose: Daily low-dose aspirin is recommended for certain individuals for prevention of cardiovascular disease and colorectal cancer. However, there are known risks associated with aspirin use. Identifying subgroups of individuals most likely to benefit from aspirin for cancer prevention would help to tailor risk-benefit calculations to maximize benefits and minimize risks. We investigated whether associations between daily aspirin use and risk of several cancers vary by other cancer risk factors, including age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer. Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011), a population-based cohort study, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009), a multicenter randomized controlled trial. Daily aspirin use was self-reported at baseline and defined as use ≥5 days/week. Our main outcome measures were incident colorectal, ovarian, breast, endometrial, and aggressive prostate cancers. We used multivariable Cox proportional hazards regression to examine associations between daily aspirin use and risk of each cancer, overall and across strata of risk factors. Results: Compared with non-use and non-daily use, daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.80-0.89). Risk reductions were generally consistent across strata of other risk factors but attenuated with increasing BMI (p-interaction=0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI: 0.80-1.08) but a reduced risk among obese women (HR: 0.73, 95% CI: 0.52-0.98, p-interaction=0.12). We observed suggestive modest risk reductions for breast (HR: 0.96, 95% CI: 0.91-1.00) and aggressive prostate (HR: 0.95, 95% CI: 0.90-1.00) cancer and a null association for endometrial cancer (HR: 0.96, 95% CI: 0.86-1.07), with no strong effect modification observed. Conclusions: Daily aspirin use was associated with reduced colorectal cancer risk across strata of cancer risk factors. The magnitude of the benefit varied by BMI for colorectal cancer and was restricted to obese women for ovarian cancer. The potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use. Citation Format: Lauren M. Hurwitz, Kara A. Michels, Michael B. Cook, Ruth M. Pfeiffer, Britton Trabert. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4667.

Clinical Ambiguity and Conflicts of Interest in Interventional Cardiology Decision-Making

Problem Definition: Among the most vexing issues in the U.S. healthcare ecosystem is inappropriate usage of percutaneous coronary intervention (PCI) procedures, also known as “overstenting.” A key driver of overstenting is physician subjectivity in “eyeballing” a coronary angiogram. Advanced tests such as fractional flow reserve (FFR) provide more precise and objective measures of PCI appropriateness, yet the decision to perform these tests is endogenous and not immune to clinical ambiguity associated with “eyeballing.” Additionally, conflicts of interest, arising from revenue-generating incentives, play a role in overstenting. Academic/Practical Relevance: Conventional wisdom suggests more-precise diagnostic testing will help reduce overtreatment. However, the literature rarely recognizes that the testing decision is itself endogenous. Our research highlights the role of endogeneity surrounding interventional cardiology decision-making. Methodology: Stochastic modeling and simulation. Results: Under a low conflict-of-interest level, the physician performs the advanced test for intermediate lesions. Under a high conflict-of-interest level, however, the physician would perform the advanced test only for high-grade lesions, because of a financial disincentive: Performing the advanced test may lower PCI revenue if the test results argue against the procedure. Surprisingly, despite this disincentive, a more revenue-driven physician can be more inclined to perform the advanced test. Managerial Implications: Our model leads to implications for various efforts aimed at tackling overstenting: (1) Attention should be paid not only to the sheer quantity of FFR procedures, but to which patients receive FFR procedures; (2) reducing the risk of the advanced test has a behavior-inducing effect, yet a modest risk reduction may lower patient welfare; and (3) offering a bonus to the physician for performing FFR procedures equal to a third of its reimbursement rate will cause only a 5% increase in average physician payment while inducing a 26% decline in overstenting. In addition, we show implementing a bundled-payment scheme may discourage the use of FFR procedures and lead to more salient overstenting.

Mother-Infant Co-Sleeping and Maternally Reported Infant Breathing Distress in the UK Millennium Cohort.

Mother–infant co-sleeping or bed sharing is discouraged by health organisations due to evidence that it is associated with unexplained sudden infant death. On the other hand, there is evidence that it should theoretically be beneficial for infants. One line of this evidence concerns breathing regulation, which at night is influenced by the rocking movement of the mother’s chest as she breathes. Here, the hypothesis that mother–infant co-sleeping will be associated with a lower probability of infant breathing distress is tested in the UK Millennium Cohort Study (n = 18,552 infants). Maternal, infant, family, and socio-economic covariates were included in logistic regression analysis, and in a machine learning algorithm (Random Forest) to make full use of the number of variables available in the birth cohort study data. Results from logistic regression analysis showed that co-sleeping was associated with a reduced risk of breathing difficulties (OR = 0.69, p = 0.027). The Random Forest algorithm placed high importance on socio-economic aspects of infant environment, and indicated that a number of maternal, child, and environmental variables predicted breathing distress. Co-sleeping by itself was not high in the Random Forest variable importance ranking. Together, the results suggest that co-sleeping may be associated with a modest reduction in risk of infant breathing difficulties.