Average Hazard Ratio Research Articles

Device-measured stationary behaviour and cardiovascular and orthostatic circulatory disease incidence.

Previous studies have indicated that standing may be beneficially associated with surrogate metabolic markers, whereas more time spent sitting has an adverse association. Studies assessing the dose-response associations of standing, sitting and composite stationary behaviour time with cardiovascular disease (CVD) and orthostatic circulatory disease are scarce and show an unclear picture. To examine associations of daily sitting, standing and stationary time with CVD and orthostatic circulatory disease incidence. We used accelerometer data from 83 013 adults (mean age ± standard deviation = 61.3 ± 7.8; female = 55.6%) from the UK Biobank to assess daily time spent sitting and standing. Major CVD was defined as coronary heart disease, heart failure and stroke. Orthostatic circulatory disease was defined as orthostatic hypotension, varicose vein, chronic venous insufficiency and venous ulcers. To estimate the dose-response hazard ratios (HR) we used Cox proportional hazards regression models and restricted cubic splines. The Fine-Gray subdistribution method was used to account for competing risks. During 6.9 (±0.9) years of follow-up, 6829 CVD and 2042 orthostatic circulatory disease events occurred. When stationary time exceeded 12 h/day, orthostatic circulatory disease risk was higher by an average HR (95% confidence interval) of 0.22 (0.16, 0.29) per hour. Every additional hour above 10 h/day of sitting was associated with a 0.26 (0.18, 0.36) higher risk. Standing more than 2 h/day was associated with an 0.11 (0.05, 0.18) higher risk for every additional 30 min/day. For major CVD, when stationary time exceeded 12 h/day, risk was higher by an average of 0.13 (0.10, 0.16) per hour. Sitting time was associated with a 0.15 (0.11, 0.19) higher risk per extra hour. Time spent standing was not associated with major CVD risk. Time spent standing was not associated with CVD risk but was associated with higher orthostatic circulatory disease risk. Time spent sitting above 10 h/day was associated with both higher orthostatic circulatory disease and major CVD risk. The deleterious associations of overall stationary time were primarily driven by sitting. Collectively, our findings indicate increasing standing time as a prescription may not lower major CVD risk and may lead to higher orthostatic circulatory disease risk.

Risk of cardiovascular events after influenza infection-related hospitalizations in adults with congenital heart disease: A nationwide population based study

BackgroundCardiovascular complications due to viral infection pose a significant risk in vulnerable patients such as those with congenital heart disease (CHD). Limited data exists regarding the incidence of influenza and its impact on cardiovascular outcomes among this specific patient population. MethodsA retrospective cohort study was designed using the Canadian Congenital Heart Disease (CanCHD) database - a pan-Canadian database of CHD patients with up to 35 years of follow-up. CHD patients aged 40 to 65 years with influenza virus-associated hospitalizations between 2010 and 2017 were identified and 1:1 matched with CHD patients with limb fracture hospitalizations on age and calendar time. Our primary endpoint was cardiovascular complications: heart failure, acute myocardial infarction, atrial arrhythmia, ventricular arrhythmia, heart block, myocarditis, and pericarditis. ResultsOf the 303 patients identified with incident influenza virus-associated hospitalizations, 255 were matched to 255 patients with limb fracture hospitalizations. Patients with influenza virus-related hospitalizations showed significantly higher cumulative probability of cardiovascular complications at one year (0.16 vs. 0.03) and five years (0.33 vs. 0.15) compared to patients hospitalized with bone fracture. Time-dependent hazard function modeling demonstrated a significantly higher risk of cardiovascular complications within nine months post-discharge for influenza-related hospitalizations. This association was confirmed by Cox regression model (average hazard ratio throughout follow-up: 2.48; 95% CI: 1.59 – 3.84). ConclusionsThis pan-Canadian cohort study of adults with CHD demonstrated an association between influenza virus-related hospitalization and risk of cardiovascular complications during the nine months post discharge. This data is essential in planning surveillance strategies to mitigate adverse outcomes and provides insights into interpreting complication rates of other emerging pathogens, such as COVID-19.

Survival and complication rates of tooth- and implant-supported restorations after an observation period up to 36 years.

Tooth- and implant-supported fixed dental prostheses are well-documented and aesthetic treatment alternatives, and after a comprehensive periodontal treatment, a protocol with a good long-term prognosis if the maintenance program is strictly followed. To reexamine a pre-existing patient cohort in order to obtain estimated long-term survival and complication outcomes of fixed dental prostheses. For this study, patients treated with fixed dental prostheses between 1978 and 2002 were reexamined between 2019 and 2020. The restorations were divided in single crowns and fixed dental prostheses supported by teeth (TSC, FPTDP) and implants (ISC, FPIDP). Survival and complication rates were obtained. Kaplan-Meier functions were used to model complication probabilities, and average hazard ratios of different strata were compared using weighted Cox regression. The mean observation time of 40 patients and 223 reconstructions was 20.3 (±9.7, 1.2-36.2) years. The estimated survival rates were 84% (CI: 77%-92%) for TSC, 63% (CI: 51%-79%) for FPTDP, 87% (CI: 71%-100%) for ISC, and 64% (CI: 34%-100%) for FPIDP after 25 years. Biological complications included carious lesions (10.6%), periodontitis (7.9%), and peri-implantitis (6.8%). Technical complications included chipping (20.2%) and loss of retention (10.8%). Biological complications lead to abutment loss in more than two-thirds of cases, regardless of the type of abutment (tooth or implant). Technical complications are less associated with abutment loss than biological complications.

Sample Size Calculation Under Nonproportional Hazards Using Average Hazard Ratios.

Many clinical trials assess time-to-event endpoints. To describe the difference between groups in terms of time to event, we often employ hazard ratios. However, the hazard ratio is only informative in the case of proportional hazards (PHs) over time. There exist many other effect measures that do not require PHs. One of them is the average hazard ratio (AHR). Its core idea is to utilize a time-dependent weighting function that accounts for time variation. Though propagated in methodological research papers, the AHR is rarely used in practice. To facilitate its application, we unfold approaches for sample size calculation of an AHR test. We assess the reliability of the sample size calculation by extensive simulation studies covering various survival and censoring distributions with proportional as well as nonproportional hazards (N-PHs). The findings suggest that a simulation-based sample size calculation approach can be useful for designing clinical trials with N-PHs. Using the AHR can result in increased statistical power to detect differences between groups with more efficient samplesizes.

A Systematic Review of Existing Data on Statin Use and New-Onset Type 2 Diabetes: The Need for Clear Answers

Background: The relationship between statins use and the development of new-onset type 2 diabetes mellitus (NOT2DM) has been a subject of ongoing debate and investigation. In February 2012, the Food and Drug Administration (FDA) disclosed that statin use could lead to a modest rise in glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), potentially contributing to the development of diabetes. We systematically reviewed the available evidence and summarized the impact of statin use on NOT2DM. Aim: This systematic review aims to examine and provide a comprehensive overview of existing data relating to statin use and their association with the development of new-onset type 2 diabetes (NOT2DM). The primary objectives were to assess and explore: (1) the potential association between statin use and the development of new-onset diabetes; (2) the magnitude, extent, and incidence of new-onset diabetes due to statin use. The secondary objective was to explore the underlying mechanisms. Data Sources: PubMed, Scopus, Science Direct, Wiley, and Google Scholar and databases between January 2012 and February 2021. Data Extraction: The 2 reviewers Musa Basheer Mansour and Sara Elsheikh Ahmedana [MBM and SEA] independently assessed the qualities of the extracted studies and summarized data of the selected studies in tabulated forms for outcomes of interest and performed methodological and quality assessments based on review questions, citations, country of the study, aim, population characteristics, design, setting, sample size, sample technique, data source, measures, analysis, confounder variable and key observations for systematic review. We applied search keywords such as Statins, New-onset diabetes, Diabetes mellitus, Underlying mechanism, and incidents of diabetes. Results: A total of 66 studies were identified through database searches in the initial search, and 7 studies were included in this review. Of the 2,567,888 adult patients, 861,925 were nondiabetic patients on statin use, and 1,705,963 were diabetic on statin or non-statin users. We considered Hazard Ratios (HR), Odds Ratios (OR), and Confidence Intervals (CI) of each study for further analysis. The mean OR for three studies showed that each statin therapy resulted in a 68% increased risk of NOT2DM (OR, 1.683; 95% CI: 1.273-2.237). The significant relationship between statin use and the rising risk of NOT2DM was also confirmed by an average HR of 1.53 (95% CI: 1.2-1.7) for the remaining four studies. Recent and short-term use of statins, as well as time- and dose-dependent connections, were linked to an increased risk of NOT2DM in statin users compared to non-users. These risks were more prominent among older adults, normotensive males, hypertensive females, and individuals with low physical activity. Although no proven mechanisms were found, the possible processes are discussed. Conclusion: The systematic review found a significant level of risk of NOT2DM associated with statin use. The authors argued that the short-term diabetes risk caused by statin treatment was more prevalent among patients exposed to risk factors for diabetes. Although the precise mechanisms behind this association remain unclear, this research provides clinical practice with evidence-based guidelines. Additionally, conducting future research may be appropriate based on the gaps in knowledge identified from the results of this review.

A Systematic Review of Existing Data on Statin Use and New - Onset Type 2 Diabetes: The Need for Clear Answers

Background: The relationship between statins use and the development of new-onset type 2 diabetes mellitus (NOT2DM) has been a subject of ongoing debate and investigation. In February 2012, the Food and Drug Administration (FDA) disclosed that statin use could lead to a modest rise in glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), potentially contributing to the development of diabetes. We systematically reviewed the available evidence and summarized the impact of statin use on NOT2DM. Aims and Objectives: This systematic review aims to examine and provide a comprehensive overview of existing data relating to statin use and their association with the development of new-onset type 2 diabetes (NOT2DM). The primary objectives were to assess and explore: (1) the potential association between statin use and the development of new-onset diabetes; (2) the magnitude, extent, and incidence of new-onset diabetes due to statin use. The secondary objective was to explore the underlying mechanisms. Data Sources: PubMed, Scopus, Science Direct, Wiley, and Google Scholar and databases between January 2012 and February 2021. Data Extraction: The 2 reviewers Musa Basheer Mansour and Sara Elsheikh Ahmedana [MBM and SEA] independently assessed the qualities of the extracted studies and summarized data of the selected studies in tabulated forms for outcomes of interest and performed methodological and quality assessments based on review questions, citations, country of the study, aim, population characteristics, design, setting, sample size, sample technique, data source, measures, analysis, confounder variable and key observations for systematic review. We applied search keywords such as Statins, New-onset diabetes, Diabetes mellitus, Underlying mechanism, and incidents of diabetes. Results: A total of 66 studies were identified through database searches in the initial search, and 7 studies were included in this review. Of the 2,567,888 adult patients, 861,925 were nondiabetic patients on statin use, and 1,705,963 were diabetic on statin or non-statin users. We considered Hazard Ratios (HR), Odds Ratios (OR), and Confidence Intervals (CI) of each study for further analysis. The mean OR for three studies showed that each statin therapy resulted in a 68% increased risk of NOT2DM (OR, 1.683; 95% CI: 1.273-2.237). The significant relationship between statin use and the rising risk of NOT2DM was also confirmed by an average HR of 1.53 (95% CI: 1.2-1.7) for the remaining four studies. Recent and short-term use of statins, as well as time- and dose-dependent connections, were linked to an increased risk of NOT2DM in statin users compared to non-users. These risks were more prominent among older adults, normotensive males, hypertensive females, and individuals with low physical activity. Although no proven mechanisms were found, the possible processes are discussed. Conclusion: The systematic review found a significant level of risk of NOT2DM associated with statin use. The authors argued that the short-term diabetes risk caused by statin treatment was more prevalent among patients exposed to risk factors for diabetes. Although the precise mechanisms behind this association remain unclear, this research provides clinical practice with evidence-based guidelines. Additionally, conducting future research may be appropriate based on the gaps in knowledge identified from the results of this review.

Long-term follow-up results of multiparametric prostate MRI and the prognostic value of PI-RADS: a single-center retrospective cohort study

We aim to examine the long-term outcomes of patients who underwent multiparametric prostate magnetic resonance imaging (mp-MRI) for suspected prostate cancer (PCa), specifically based on their initial Prostate Imaging Reporting and Data System (PI-RADS) categories and various clinical factors. Our secondary aim is to evaluate the prognostic value of the PI-RADS through the National Comprehensive Cancer Network (NCCN) risk group distribution. This research was conducted as a single-center retrospective cohort study in a tertiary care hospital. A total of 1,359 cases having at least one histopathological examination after the initial mp-MRI and/or adequate clinical/radiological follow-up data were included in the clinically significant PCa (cs-PCa) diagnosis-free survival analysis. Initial mp-MRI dates were accepted as the start of follow-up for the time-to-event analysis. The event was defined as cs-PCa diagnosis (International Society of Urological Pathology ≥2). Patients who were not diagnosed with cs-PCa during follow-up were censored according to predefined literature-based criteria at the end of the maximum follow-up duration with no reasonable suspicion of PCa and no biopsy indication. The impact of various factors on survival was assessed using a log-rank test and multivariable Cox regression. Subsequently, 394 cases diagnosed with PCa during follow-up were evaluated, based on initial PI-RADS categories and NCCN risk groups. Three main risk factors for cs-PCa diagnosis during follow-up were an initial PI-RADS 5 category, initial PI-RADS 4 category, and high MRI-defined PSA density (mPSAD), with average hazard ratios of 29.52, 14.46, and 3.12, respectively. The PI-RADS 3 category, advanced age group, and biopsy-naïve status were identified as additional risk factors (hazard ratios: 2.03, 1.54-1.98, and 1.79, respectively). In the PI-RADS 1-2 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 99.1%, 96.5%, and 93.8%, respectively. For the PI-RADS 3 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 94.9%, 90.9%, and 89.1%, respectively. For the PI-RADS 4 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 56.6%, 55.1%, and 55.1%, respectively. These rates were found to all be 24.2% in the PI-RADS 5 cohort. Considering the 394 cases diagnosed with PCa during follow-up, PI-RADS ≥4 cases were more likely to harbor unfavorable PCa compared to PI-RADS ≤3 cases (P < 0.001). In the PI-RADS 3 subgroup analysis, a low mPSAD (<0.15 ng/mL2) was found to be a protective prognostic factor against unfavorable PCa (P = 0.005). The PI-RADS category has a significant impact on patient management and provides important diagnostic and prognostic information. Higher initial PI-RADS categories are associated with decreased follow-up losses, a shorter time to PCa diagnosis, increased biopsy rates, a higher likelihood of developing cs-PCa during follow-up, and a worse PCa prognosis. Combining mPSAD with PI-RADS categories could enhance diagnostic stratification in the identification of cs-PCa.

Simultaneous inference procedures for the comparison of multiple characteristics of two survival functions.

Survival time is the primary endpoint of many randomized controlled trials, and a treatment effect is typically quantified by the hazard ratio under the assumption of proportional hazards. Awareness is increasing that in many settings this assumption is a priori violated, for example, due to delayed onset of drug effect. In these cases, interpretation of the hazard ratio estimate is ambiguous and statistical inference for alternative parameters to quantify a treatment effect is warranted. We consider differences or ratios of milestone survival probabilities or quantiles, differences in restricted mean survival times, and an average hazard ratio to be of interest. Typically, more than one such parameter needs to be reported to assess possible treatment benefits, and in confirmatory trials, the according inferential procedures need to be adjusted for multiplicity. A simple Bonferroni adjustment may be too conservative because the different parameters of interest typically show considerable correlation. Hence simultaneous inference procedures that take into account the correlation are warranted. By using the counting process representation of the mentioned parameters, we show that their estimates are asymptotically multivariate normal and we provide an estimate for their covariance matrix. We propose according to the parametric multiple testing procedures and simultaneous confidence intervals. Also, the logrank test may be included in the framework. Finite sample type I error rate and power are studied by simulation. The methods are illustrated with an example from oncology. A software implementation is provided in the R package nph.

Potential Mediators for Treatment Effects of Novel Diabetes Medications on Cardiovascular and Renal Outcomes: AMeta-Regression Analysis.

Prior research suggests clinical effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are mediated by changes in glycated hemoglobin, body weight, systolic blood pressure, hematocrit, and urine albumin-creatinine ratio. We aimed to confirm these findings using a meta-analytic approach. We updated a systematic review of 9 GLP-1RA and 13 SGLT2i trials and summarized longitudinal mediator data. We obtained hazard ratios (HRs) for cardiovascular, renal, and mortality outcomes. We performed linear mixed-effects modeling of LogHRs versus changes in potential mediators and investigated differences in meta-regression associations among drug classes using interaction terms. HRs generally became more protective with greater glycated hemoglobin reduction among GLP-1RA trials, with average HR improvements of 20% to 30%, reaching statistical significance for major adverse cardiovascular events (ΔHR, 23%; P=0.02). Among SGLT2i trials, associations with HRs were not significant and differed from GLP1-RA trials for major adverse cardiovascular events (Pinteraction=0.04). HRs for major adverse cardiovascular events, myocardial infarction, and stroke became less efficacious (ΔHR, -15% to -34%), with more weight loss for SGLT2i but not for GLP-1RA trials (ΔHR, 4%-7%; Pinteraction<0.05). Among 5 SGLT2i trials with available data, HRs for stroke became less efficacious with larger increases in hematocrit (ΔHR, 123%; P=0.09). No changes in HRs by systolic blood pressure (ΔHR, -11% to 9%) and urine albumin-creatinine ratio (ΔHR, -1% to 4%) were found for any outcome. We confirmed increased efficacy findings for major adverse cardiovascular events with reduction in glycated hemoglobin for GLP1-RAs. Further research is needed on the potential loss of cardiovascular benefits with increased weight loss and hematocrit for SGLT2i.

Toxicity-benefit analysis of advanced prostate cancer trials using weighted toxicity scoring.

110 Background: The weighted toxicity score (WTS) is a metric suitable for comparing the toxicity burden in experimental versus control arms of randomized controlled trials (RCTs). When compared against clinical endpoints, the WTS can be used to evaluate the cost versus benefit of anti-cancer agents. This study sought to apply the WTS to prostate cancer (PC) clinical trials. Methods: Select phase 3 PC RCTs with reported adverse event (AE) data were compiled. The WTS was computed for each trial arm and compared to reported hazard ratios (HRs) of primary and/or secondary endpoints (i.e., overall survival (OS) and progression-free survival (PFS)). Average WTSs for the experimental versus control arms were used to calculate the toxicity differential between treatment arms. Average HRs for OS and PFS were used to compare efficacy. Results: Sixteen RCTs were analyzed (investigational agents: androgen-receptor signaling inhibitors (ARSi) [n = 4], poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy [n = 3], ARSi + PARPi as well as ARSi + ARSi combination therapies [n = 3 each], and triple therapy [n=3]). The median number of distinct reported AEs across all studies was 18 (range, 9-61). Overall, toxicity and efficacy were greater among experimental than control arms (6.62 versus 4.00 median WTS; median HR for OS 0.71, median HR for PFS 0.61). The triple therapy studies observed the lowest increase in toxicity by adding an ARSi to control therapy (10.4%), associated with 52% lower risk of progression, and 29% lower risk of death. Comparably, the ARSi + PARPi trials noted the highest increase in toxicity (79.7%), with 32% lower risk of progression and 12% lower risk of death. The PARPi monotherapy, ARSi monotherapy, and ARSi + ARSi combination therapy studies reported increased toxicity due to experimental therapy in descending order (Table). Conclusions: The WTS enables toxicity versus benefit assessment for anti-cancer regimens. Clinical application of this metric may facilitate individualized treatment planning in advanced PC management. [Table: see text]

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

AST to ALT ratio as a prospective risk predictor for liver cirrhosis in patients with chronic HBV infection.

Serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR) is one of the most frequent indicators to discriminate fibrosis and cirrhosis. However, the results remained controversial. The aim of this study was to evaluate the predictive effect of AAR on hepatitis B virus (HBV)-related cirrhosis development. A retrospective cohort study was conducted based on 1754 chronic HBV-infected patients. Clinical variables at their initial visit and follow-up data were collected. Cox proportional hazards model was constructed to evaluate the predictive value of AAR on cirrhosis risk, and its discrimination accuracy was determined by receiver operating characteristic (ROC). The time-dependent effect was assessed by a Fine and Gray competing risk model. Compared to patients with lower AAR, those with elevated AAR level had higher risk of cirrhosis development by adjusting for host characteristics (dichotomized analyses: hazard ratio = 2.77, P = 8.25 × 10 -4 ; tertile analyses: hazard ratio = 2.95, P = 1.61 × 10 -3 ), with an increasing risk trend ( Ptrend = 4.56 × 10 -4 ). The effect remained prominent when ALT or AST was abnormal, while no significant risk was observed when AST and ALT were simultaneously normal. Time-dependent effect analysis demonstrated a persistently higher risk, with the average hazard ratio equivalent to 1.92. AAR level could improve the discrimination efficacy of host variables with area under the curve increased from 0.684 to 0.711 ( P = 0.039 ). Higher AAR was significantly associated with increased risk of HBV-related cirrhosis, and might be a potential predictor of cirrhosis development.

Sample size calculation for mixture model based on geometric average hazard ratio and its applications to nonproportional hazard.

With the advent of cancer immunotherapy, some special features including delayed treatment effect, cure rate, diminishing treatment effect and crossing survival are often observed in survival analysis. They violate the proportional hazard model assumption and pose a unique challenge for the conventional trial design and analysis strategies. Many methods like cure rate model have been developed based on mixture model to incorporate some of these features. In this work, we extend the mixture model to deal with multiple non-proportional patterns and develop its geometric average hazard ratio (gAHR) to quantify the treatment effect. We further derive a sample size and power formula based on the non-centrality parameter of the log-rank test and conduct a thorough analysis of the impact of each parameter on performance. Simulation studies showed a clear advantage of our new method over the proportional hazard based calculation across different non-proportional hazard scenarios. Moreover, the mixture modeling of two real trials demonstrates how to use the prior information on the survival distribution among patients with different biomarker and early efficacy results in practice. By comparison with a simulation-based design, the new method provided a more efficient way to compute the power and sample size with high accuracy of estimation. Overall, both theoretical derivation and empirical studies demonstrate the promise of the proposed method in powering future innovative trial designs.

Risk of Postoperative Ischemic Stroke and Myocardial Infarction in Patients Operated for Cancer.

Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery. We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge. The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke. We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.

Association of the age of onset of metabolic syndrome with the risk of all cancer types

BackgroundThe association between the age at onset of metabolic syndrome and cancer risk remains unknown. This study explored the association between age at metabolic syndrome onset and the risk of overall and site-specific cancer incidence. MethodsThis study included 31,688 participants with new-onset metabolic syndrome and 31,688 participants matched according to sex, age (±1 y), and examination year among the 179,328 participants who underwent Kailuan health examinations from 2006 to 2017 in Tangshan, China. Weighted Cox regression was used to calculate the hazard ratios and 95% confidence intervals of new-onset metabolic syndrome for overall and site-specific cancer incidence across age groups. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating the risk factors from the population. ResultsDuring an average follow-up period of 10.22 y, we identified 2,710 cases of cancer and 4,218 deaths that occurred before the diagnosis of cancer. With an increase in metabolic syndrome onset age, the hazards of overall cancer incidence were gradually attenuated. The average hazard ratios (95% confidence intervals) of overall cancer were 1.94 (1.25–2.99) for metabolic syndrome onset age <45 year old, 1.41 (1.15–1.71) for age 45–54 years old, 1.38 (1.11–1.73) for age 55–64 years old, and 1.07 (0.89–1.28) for age ≥65 years old, respectively (p for interaction = 0.005). Similar results were obtained for colorectal, liver, and breast cancers in the site-specific analysis. ConclusionsNew-onset metabolic syndrome was associated with a higher risk of overall cancer and incidence of several types of cancer, and the associations were stronger with a younger age of onset. Trial registrationKailuan Study, ChiCTR2000029767 (Registered February 12, 2020, https://www.chictr.org.cn/showprojEN.html?proj=48316).

New-Onset Age of Nonalcoholic Fatty Liver Disease and Cancer Risk

The onset age of nonalcoholic fatty liver disease (NAFLD) is decreasing, and whether earlier ages of NAFLD onset are associated with increased cancer risk is currently unclear. To explore the association between NAFLD new-onset age and cancer risk. This cohort study was conducted among 179 328 participants included in the Kailuan Cohort Study between 2006 and 2021. In total, 46 100 incident NAFLD cases were identified. For each case, a participant matched by age (older or younger by 1 year) and sex was randomly selected to create a new matched study cohort. Data were analyzed from December 2022 through April 2023. Onset of NAFLD. The association between the onset age of NAFLD and the risk of different cancer types was evaluated using weighted Cox regression models. Population-attributable fractions (PAFs) were used to quantify the association of NAFLD with cancer risk at different ages. Among 63 696 participants (mean [SD] age, 51.37 [12.43] years; ‭10 932 females [17.2%] and ‭52 764 males [82.8%]), 31 848 individuals had NAFLD and 31 848 individuals were in the control group. During a median (IQR) follow-up of 10.16 (7.89-11.67) years, 2415 patients were diagnosed with cancer. Compared with the matched group, patients aged less than 45 years at NAFLD onset exhibited a higher risk of cancer (average hazard ratio [AHR], 1.52; 95% CI, 1.09-2.12), and as the onset age of NAFLD increased, the cancer risk decreased (ages 45-54 years: AHR, 1.50; 95% CI, 1.15-1.97; ages 55-64 years: AHR, 1.13; 95% CI, 0.97-1.33; ages >65 years: AHR, 0.75; 95% CI, 0.45-1.27; P for interaction < .001). Among patients aged less than 45 years at NAFLD onset, cancers were mainly digestive system and lung cancers, with AHR values of 2.00 (95% CI, 1.08-3.47) and 2.14 (95% CI, 1.05-4.36), respectively. PAFs also showed that in patients aged less than 45 years at NAFLD onset, 17.83% (95% CI, 4.92%-29.86%) of cancer risk was attributable to NAFLD.‬‬‬‬. This study found that NAFLD was associated with increased cancer risk and there was an interaction with onset age, such that the younger the onset age of NAFLD, the greater the cancer risk.

DNA repair genes, air pollution, and breast cancer risk

PurposeWe investigated if selected polymorphisms in DNA repair genes modify the association between air pollution and breast cancer (BCa) risk. MethodsWe included 150,929 postmenopausal women (5969 with BCa) from UK Biobank, a population-based prospective cohort. Information on BCa risk factors was collected at baseline. Cox proportional hazards regression was used to examine interactions of exposure for which we previously found associations with BCa in this cohort (2007 PM10 and cumulative average PM10) with 15 SNPs, adjusting for BCa risk factors. The associations between PM10 and BCa risk were stratified by genotype level. ResultsThe positive associations of 2007 PM10 and cumulative average PM10 with BCa risk were stronger in women with one or two copies of XRCC2 rs3218536C allele versus none (2007 PM10 Hazard Ratio (HR) per 1 µg/m3 = 1.04, 95% Confidence Interval (CI) 1.02–1.07, HR = 1.01, 95% CI 1.00–1.02, respectively, versus HR = 0.94, 95% CI 0.83–1.06, p-interaction = 0.02; cumulative average PM10 HR per 1 µg/m3 = 1.11, 95% CI 1.07–1.15, HR = 1.07, 95% CI 1.05–1.08 versus HR = 0.92, 95% CI 0.78–1.09, p-interaction = 0.05). The association of cumulative average PM10 with BCa was stronger in women with two copies of XRCC1 rs25489 T allele versus one or none (HR = 3.04, 95% CI 1.54–5.96 vs. HR = 1.06, 95% CI 1.02–1.11 and HR = 1.07, 95% CI 1.06–1.09; p-interaction = 0.06). ConclusionsOur results suggest stronger associations of 2007 PM10 and cumulative average PM10 with postmenopausal BCa risk in carriers of XRCC2 rs3218536C allele and stronger associations of cumulative average PM10 in those with two copies of XRCC1 rs25489 T allele.

POINT: Should New Drug Development in Heart Failure Focus on Patients Discharged From an Acute Heart Failure Admission? Lessons From Recent Studies

POINT: Should New Drug Development in Heart Failure Focus on Patients Discharged From an Acute Heart Failure Admission? Lessons From Recent Studies

Parental death and initiation of antidepressant treatment in surviving children and youth: a national register-based matched cohort study.

Population-based longitudinal studies on bereaved children and youth's mental health care use are scarce and few have assessed the role of surviving parents' mental health status. Using register data of individuals born in Sweden in 1992-1999, we performed a matched cohort study (n=117,518) on the association between parental death and subsequent initiation of antidepressant treatment among individuals bereaved at ages 7-24 years. We used flexible parametric survival models to estimate the hazard ratios (HRs) over time after bereavement, adjusting for individual and parental factors. We further examined if the association varied by age at loss, sex, parental sociodemographic factors, cause of death, and the surviving parents' psychiatric care. The bereaved were more likely to initiate antidepressants treatment than the nonbereaved matched individuals during follow-up (incidence rate per 1000 person years 27.5 [26.5-28.5] vs. 18.2 [17.9-18.6]). The HRs peaked in the first year after bereavement and remained higher than the nonbereaved individuals until the end of the follow-up. The average HR over the 12 years of follow-up was 1.48 (95% confidence interval [1.39-1.58]) for father's death and 1.33 [1.22-1.46] for mother's death. The HRs were particularly high when the surviving parents received psychiatric care before bereavement (2.11 [1.89-2.56] for father's death; 2.14 [1.79-2.56] for mother's death) or treated for anxiety or depression after bereavement (1.80 [1.67-1.94]; 1.82 [1.59-2.07]). The risk of initiating antidepressant treatment was the highest in the first year after parental death and remained elevated over the next decade. The risk was particularly high among individuals with surviving parents affected by psychiatric morbidity. The Swedish Research Council.

Does substance use disorder treatment completion reduce the risk of treatment readmission in Chile?

BackgroundRecovery from substance use disorders (SUD) often entails multiple treatment episodes, which clashes with a context of a treatment system with limited resources and long waiting. Treatment retention and completion have been pointed out as key elements for sustainable achievement; however, most of the evidence generated focuses on opioids and injected substances, which is hardly transferable to the Latin American context. ObjectivesThis study aims to estimate the effect of SUD treatment completion on the risk of being readmitted to a SUD treatment in Chile. MethodsWe conducted a retrospective analysis on a database of 107,559 treatment episodes from 85,048 adult patients admitted to SUD treatment during 2010–2019 in Chile. We adjusted two separate Prentice Williams and Petersen Gap Time models, to explore the association between treatment completion (vs. non-completion) and up to the third treatment readmission among residential and ambulatory modalities while controlling for time-varying covariates. To examine whether the effect of treatment completion differs between events, we included an interaction term with the stratification variable. ResultsWe found that completing the treatment cuts readmission risk for the first event by 17% (Average Hazard Ratio [95% CI] = 0.83 [0.78, 0.88]) and by 14% for the second entry (Average Hazard Ratio [95% CI] = 0.86 [0.78, 0.94]) in ambulatory treatments. We did not find evidence that completing a treatment reduces the readmission risk for residential treatments or third attempts in ambulatory ones. ConclusionTreatment completion was associated with benefits in cutting readmission risk for the first and second episodes in ambulatory treatments among Chilean adults. It is important to explore different mechanisms than treatment retention for residential treatments.