Time-dependent Cox Proportional Hazards Models Research Articles

Fine particulate matter measured by satellites predicts the risk of age-related macular degeneration in a longitudinal cohort study.

Although studies have revealed that ambient particulate matter (PM) has detrimental effects on the ocular surface, there have been limited reports detailing the effect of ambient PM on the posterior segment of the eye. A large-scale longitudinal cohort study evaluating the association between fine PM, especially PM2.5, and the retina could elucidate the risk of ambient pollutants for retinal diseases. We investigated the association between PM2.5 and the development of age-related macular degeneration (AMD). We conducted a population-based cohort study of 4,284,128 participants in Taiwan between 2001 and 2011. PM2.5 was continuously measured by satellites and subsequently assigned to each geographic district along with its postcode. A time-dependent Cox proportional-hazard model was used to assess the overall effects of average PM2.5. We used distributed lag non-linear models to evaluate the dose-response relationship between PM2.5 and AMD development. The annual mean of PM2.5 exposure was 34.23 ± 7.17μg/m3. The PM2.5 concentrations were highest in spring, followed by those in winter, autumn, and summer. Twelve thousand ninety-five new AMD cases were reported during the study period. After adjusting for covariates, the AMD risk increased by 19% (95% confidence interval 1.13-1.25) for a 10μg/m3 PM2.5 increase. The present study demonstrated that chronic exposure to PM2.5 increases the risk of AMD. Almost half of the Taiwanese live in a polluted area where the PM2.5 levels are higher than the World Health Organization recommended air quality guideline of 10μg/m3 had a 1.4-fold risk, which significantly increases concern about their visual health and social burden.

Impact of Latent Tuberculosis on Diabetes.

While an increased risk of active and latent tuberculosis infection (LTBI) in people with type-2 diabetes (DM) has been demonstrated, it is less well characterized whether LTBI is associated with an increased risk of developing DM. We investigated the link between LTBI and DM in people living with HIV in the Swiss HIV Cohort Study via time-dependent Cox proportional hazards models. We found that LTBI significantly increased the risk of developing DM (HR = 1.47), which was robust across different adjustment and censoring techniques. Our results thus suggest that LTBI may be associated with an increased risk of developing DM.

Abstract P1-15-01: Effect of concomitant statin treatment in postmenopausal patients with hormone-receptor positive early-stage breast cancer receiving adjuvant denosumab or placebo: A post-hoc analysis of ABCSG-18

Abstract Background Statins are a common class of cholesterol-lowering drugs prescribed for the prevention and treatment of cardiovascular disease. Moreover, it was suggested that statins may possess anti-cancer properties and interact with RANK ligand expression. Therefore, we aimed at evaluating a hypothetical synergistic effect of statins with denosumab in early-stage breast cancer (BC) patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 18. Methods ABCSG-18 (NCT00556374) is a prospective, randomized, double-blind, phase III study; postmenopausal patients with hormone receptor (HR) positive BC receiving a non-steroidal aromatase inhibitor were randomly assigned to denosumab or placebo. In this post-hoc analysis, we investigated the potential effects of concomitant statin therapy on recurrence risk of BC, fracture risk and bone mineral density (BMD) using time-dependent Cox proportional hazards models. Sensitivity analyses accounting for immortal time and confounding bias were performed. Results In the analysis of the study population (n=3,420), statin therapy (n=824) was associated with worse disease-free survival (DFS) (HR 1.35, 95%; CI 1.04-1.75; p=0.023). Sensitivity analysis relativized these results (HR 1.22, 95% CI 0.94 - 1.59; p=0.14). While there was no significant effect of lipophilic statins (n=710) on recurrence risk (HR 1.30, 95% CI 0.99 - 1.72; p=0.062), patients on hydrophilic statins (n=87) had worse DFS compared with patients not receiving any statins (HR 2.00, 95% CI 1.09-3.66; p=0.026). This finding was mainly driven by the effect of hydrophilic statins on DFS in the denosumab arm (HR 2.63, 95% CI 1.21 - 5.68; p=0.014). No association between statin use and fracture risk or osteoporosis was observed. Conclusion In this population of early-stage breast cancer patients from a prospective randomized study, an association of hydrophilic statins with increased recurrence risk was observed. According to this retrospective analysis hydrophilic statins may increase recurrence risk especially in patients treated with denosumab. Still, our data need to be interpreted with caution due to their retrospective nature and the low number of patients receiving hydrophilic statins. Therefore, no final conclusion is possible. This hypothesis generating result warrants further exploration. Citation Format: Christoph Minichsdorfer, Thorsten Fuereder, Michael Leutner, Christian F. Singer, Stephanie Kacerovsky-Strobl, Daniel Egle, Richard Greil, Marija Balic, Florian Fitzal, Georg Pfeiler, Sophie Frantal, Rupert A. Bartsch, Michael Gnant. Effect of concomitant statin treatment in postmenopausal patients with hormone-receptor positive early-stage breast cancer receiving adjuvant denosumab or placebo: A post-hoc analysis of ABCSG-18 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-15-01.

Association of Occupational Noise Exposure and Incidence of Metabolic Syndrome in a Retrospective Cohort Study.

Metabolic syndrome is one of the common causes of cardiovascular diseases and cancers. Although noise is an environmental factor to which people can be commonly exposed at work and in daily life, there are currently insufficient studies on the relationship between noise and metabolic syndrome. Therefore, the purpose of this study is to investigate the relationship between noise and metabolic syndrome. Using a multivariate time-dependent Cox proportional hazard model, the impacts of occupational noise exposure on metabolic syndrome and its components were analyzed in a retrospective cohort of 60,727 participants from 2014 to 2017. The noise exposure group showed a significantly higher incidence of metabolic syndrome and was associated with elevated triglycerides, blood sugar, and blood pressure, but decreased high-density lipoprotein, among subgroups. There was no statistically significant association with abdominal obesity. Occupational noise exposure significantly contributed to the incidence of metabolic syndrome and changes in its components. This study could be a basis for establishing policies and guidelines to reduce noise exposure that might improve workers’ health.

Influenza vaccine in chronic obstructive pulmonary disease among elderly male veterans.

BackgroundPrior studies have established those elderly patients with chronic obstructive pulmonary disease (COPD) are at elevated risk for developing influenza-associated complications such as hospitalization, intensive-care admission, and death. This study sought to determine whether influenza vaccination could improve survival among elderly patients with COPD.Materials/MethodsThis study included Veterans (age ≥ 65 years) diagnosed with COPD that received care at the United States Veterans Health Administration (VHA) during four influenza seasons, from 2012–2013 to 2015–2016. We linked VHA electronic medical records and Medicare administrative files to Centers for Disease Control and Prevention National Death Index cause of death records as well as influenza surveillance data. A multivariable time-dependent Cox proportional hazards model was used to compare rates of mortality of recipients of influenza vaccination to those who did not have records of influenza vaccination. We estimated hazard ratios (HRs) adjusted for age, gender, race, socioeconomic status, comorbidities, and healthcare utilization.ResultsOver a span of four influenza seasons, we included 1,856,970 person-seasons of observation where 1,199,275 (65%) had a record of influenza vaccination and 657,695 (35%) did not have a record of influenza vaccination. After adjusting for comorbidities, demographic and socioeconomic characteristics, influenza vaccination was associated with reduced risk of death during the most severe periods of influenza seasons: 75% all-cause (HR = 0.25; 95% CI: 0.24–0.26), 76% respiratory causes (HR = 0.24; 95% CI: 0.21–0.26), and 82% pneumonia/influenza cause (HR = 0.18; 95% CI: 0.13–0.26). A significant part of the effect could be attributed to “healthy vaccinee” bias as reduced risk of mortality was also found during the periods when there was no influenza activity and before patients received vaccination: 30% all-cause (HR = 0.70; 95% CI: 0.65–0.75), 32% respiratory causes (HR = 0.68; 95% CI: 0.60–0.78), and 51% pneumonia/influenza cause (HR = 0.49; 95% CI: 0.31–0.78). However, as a falsification study, we found that influenza vaccination had no impact on hospitalization due to urinary tract infection (HR = 0.97; 95% CI: 0.80–1.18).ConclusionsAmong elderly patients with COPD, influenza vaccination was associated with reduced risk for all-cause and cause-specific mortality.

External Validation of LCR1-LCR2, a Multivariable Hepatocellular Carcinoma Risk Calculator, in a Multiethnic Cohort of Patients With Chronic Hepatitis B

<h3>Background and Aims</h3> The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in hepatitis B. <h3>Methods</h3> Preincluded patients were from the Hepather cohort, a multicenter, multiethnic prospective study in 6071 patients. The coprimary study outcome was the negative predictive value of LCR1-LCR2 at 5 years for the occurrence of HCC and survival without HCC according to the predetermined LCR1-LCR2 cutoffs, adjusted for risk covariables and for chronic hepatitis B treatment and quantified using time-dependent Cox proportional hazards models. A post hoc analysis compared the number of patients needed to screen one cancer by LCR1-LCR2 and PAGE-B. <h3>Results</h3> A total of 3520 patients, 191 (5.4%) with cirrhosis, with at least 1 year of follow-up were included. A total of 76 HCCs occurred over a median (interquartile range) of 6.0 years (4.8–7.3) of follow-up. Among the 3367 patients with low-risk LCR1-LCR2, the 5-year negative predictive value was 99.3% (95% confidence interval = 99.0–99.6), with a significant Cox hazard ratio (6.4, 3.1–13.0; <i>P</i> < .001) obtained after adjustment for exposure to antivirals, age, gender, geographical origin, HBe-Ag status, alcohol consumption, and type-2 diabetes. LCR1-LCR2 outperformed PAGE-B for number of patients needed to screen mean (95% CI), 8.5 (3.2–8.1) vs 26.3 (17.5–38.5; <i>P</i> < .0001), respectively. <h3>Conclusion</h3> The performance of LCR1-LCR2 to identify patients with chronic hepatitis B at very low risk of HCC at 5 years was externally validated. ClinicalTrials.gov: NCT01953458.

A Longitudinal Study on the Association of Interrelated Factors Among Frailty Dimensions, Cognitive Domains, Cognitive Frailty, and All-Cause Mortality.

Cognitive frailty integrating impaired cognitive domains and frailty dimensions has not been explored. This study aimed to explore 1) associations among frailty dimensions and cognitive domains over time and 2) the extended definitions of cognitive frailty for predicting all-cause mortality. This four-year cohort study recruited 521 older adults at baseline (2011-2013). We utilized 1) generalized linear mixed models exploring associations of frailty dimensions (physical dimension: modified from Fried et al.; psychosocial dimension: integrating self-rated health, mood, and social relationship and support; global frailty: combining physical and psychosocial frailty) with cognition (global and domain-specific) over time and 2) time-dependent Cox proportional hazard models assessing associations between extended definitions of cognitive frailty (cognitive domains-frailty dimensions) and all-cause mortality. At baseline, the prevalence was 3.0% for physical frailty and 37.6% for psychosocial frailty. Greater physical frailty was associated with poor global cognition (adjusted odds ratio = 1.43-3.29, β: -1.07), logical memory (β: -0.14 to -0.10), and executive function (β: -0.51 to -0.12). Greater psychosocial frailty was associated with poor global cognition (β: -0.44) and attention (β: -0.15 to -0.13). Three newly proposed definitions of cognitive frailty, "mild cognitive impairment (MCI)-psychosocial frailty," "MCI-global frailty," and "impaired verbal fluency-global frailty," outperformed traditional cognitive frailty for predicting all-cause mortality (adjusted hazard ratio = 3.49, 6.83, 3.29 versus 4.87; AIC = 224.3, 221.8, 226.1 versus 228.1). Notably, extended definitions of cognitive frailty proposed by this study better predict all-cause mortality in older adults than the traditional definition of cognitive frailty, highlighting the importance of psychosocial frailty to reduce mortality in older adults.

Abstract 11147: Associations of Physical and Mental-Health Related Quality of Life and Sleep Disturbance with Cardiovascular Disease Risk in Post-Menopausal Breast Cancer Survivors

Introduction: Lower health-related quality of life (HRQoL) and greater sleep disturbance (SD) are associated with an increased risk of cardiovascular disease (CVD) in the general population. However, these associations may differ in breast cancer (BC) survivors who experience competing risks from cancer and its associated treatment. We examined whether physical or mental HRQoL (including individual subscales) or SD were associated with CVD risk in BC survivors. Methods: We conducted a longitudinal analysis in the Women’s Health Initiative (WHI) of post-menopausal women free of prevalent CVD at baseline and diagnosed with invasive BC during study follow-up from 1993 - 2010. CVD was defined as physician-adjudicated coronary heart disease or stroke. Physical and mental HRQoL, measured by the SF-36 Physical and Mental Component Scores (PCS and MCS, respectively), and SD, measured by the WHI Insomnia Rating Scale (IRS), were recorded post-BC diagnosis. Higher PCS and MCS scores indicate better HRQoL while higher IRS scores indicate worse SD. Time-dependent Cox proportional hazards models were used starting at BC diagnosis until 2010 or censoring adjusted for relevant confounders most proximal to or at BC diagnosis. Results: In 2,884 BC survivors, 157 developed CVD during a median follow-up of 9.5 years. After adjustment, higher PCS scores were significantly associated with a lower risk of CVD (Table). For a 5-unit difference, the risk of CVD was 9% lower for those with higher PCS scores (95% CI: 0.83, 0.99). Of the SF-36 sub-scales, higher scores on vitality, physical functioning, and general health were significantly associated with a lower risk of CVD (Table). Conclusions: In BC survivors, we found that better physical HRQoL was associated with lower CVD risk. While further research is needed to replicate these findings, our results support existing recommendations that women with breast cancer adopt health behaviors that promote physical health.

Comparison of biochemical response during antiviral treatment in patients with chronic hepatitis B infection.

This multicenter cohort study aimed to compare the real-world biochemical response rates during tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) treatment in chronic hepatitis B virus (HBV) infection patients. Overall, 1282 treatment-naïve patients with CHB who commenced TAF (n=270), TDF (n=617), or ETV (n=395) were analysed for biochemical response rates during the antiviral treatment using a time-dependent Cox proportional hazard model after the inverse probability of treatment weighting (IPTW). Patients treated with ETV were older (55.1±11.5years) than TAF or TDF (P<.0001). ETV was more frequently prescribed to patients with diabetes mellitus (DM, P=.003), hypertension (P<.0001), chronic kidney disease (P<.0001), and negative e-antigen (P<.0001). Cumulative biochemical response rate was independently lower in patients with radiologic fatty liver (HR, 0.75; 95% CI, 0.61-0.94) and obese patients without DM (HR, 0.85; 95% CI, 0.68-0.98) according to multivariable Cox analyses based on time-dependent variables after IPTW for age, sex, liver cirrhosis, baseline e-antigen, ALT, and HBV DNA levels. ETV treated patients (HR, 1.38; 95% CI, 1.13-1.68) showed higher biochemical response rates compared with TAF- or TDF-treated patients after adjusting for similar parameters. In real-world practice, ETV was preferable for older, hepatitis B e-antigen negative patients with underlying comorbidities. Biochemical responses in patients treated with ETV, TAF, and TDF were significantly affected by metabolic factors such as fatty liver, obesity, and DM. However, the mechanism behind the higher biochemical response rate in patients treated with ETV should be investigated further.

European Leukemianet (ELN) Response Predicts Disease Progression but Not Thrombosis or Death in Polycythemia Vera (PV): An Analysis of a Multicenter Database

European Leukemianet (ELN) Response Predicts Disease Progression but Not Thrombosis or Death in Polycythemia Vera (PV): An Analysis of a Multicenter Database

A Real-World Evaluation of the Association between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera (Analysis of Data from the REVEAL Study)

A Real-World Evaluation of the Association between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera (Analysis of Data from the REVEAL Study)

Prevention paradox between stroke and multiple potential risk factors using data from a population-based cohort study

Previous studies have found the prevention paradox in the association between stroke events and a single specific risk factor, indicating that a population-based strategy may be more effective than a high-risk-based strategy for prevention. We tested the hypothesis that the prevention paradox does not apply when focusing on multiple potential risk factors simultaneously. The study cohort included 9051 individuals from Japan aged 40–89 years. The time-dependent Cox proportional-hazards models were used to identify the primary risk factor associated with stroke onset. We classified participants based on risk factors in two distinct ways: 1) classifying the high-risk group participants according to a single specific risk factor that had a large association with stroke in both sexes and all ages and 2) classifying the high-risk group participants according to 1–3 risk factor(s) including hypertension, hyperglycemia, and/or dyslipidemia. Then, we compared the proportions of the total number of participants who developed stroke in both groups to assess the prevention paradox. We found that hypertension was a primary risk factor for stroke incidence, regardless of sex and age. The percentage of patients with a single specific risk of and developed stroke was 46%–63%, while the percentage of patients with 1–3 risk factor(s) was 71–83%. This finding leads to the conclusion that the prevention paradox does not hold when multiple stroke risk factors were associated, suggesting that a high-risk-based strategy that focuses on patients with multiple risk factors may be more effective in preventing strokes.

Occupational Noise Exposure and Incidence of High Fasting Blood Glucose: A 3-Year, Multicenter, Retrospective Study.

The role of hazardous occupational noise exposure on the development of prediabetes is not well researched. We aimed to elucidate exposure to hazardous occupational noise as an independent risk factor for high fasting blood glucose (FBG). Participants exposed/non-exposed to occupational noise were recruited from the Common Data Model cohorts of 2013/2014 from two centers and were followed-up for 3 years. Multivariate time-dependent Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and were adjusted for various covariates. Pooled HRs were calculated. Among the 43,858 participants of this retrospective cohort study, 37.64% developed high FBG. The mean (standard deviation) age in the cohort was 40.91 (9.71) years. In the fully adjusted models, the HRs of high FBG in the two centers were 1.35 (95% CI: 1.24–1.48) and 1.22 (95% CI: 1.17–1.28), and the pooled HR was 1.28 (95% CI: 1.16–1.41). A Kaplan–Meier plot of high FBG incidence by occupational noise exposure showed significant results (p < 0.001). We found that occupational noise exposure is significantly associated with high FBG. Preventing exposure to hazardous noise in the work environment may help reduce the risk for prediabetes among workers.

Mortality Risk of Specific Caners and Long-term Exposure to Particulate Matter in the South Korean National Sample Cohort

BACKGROUND AND AIM: Cancer is a major burden of disease worldwide. International Agency for Research on Cancer classified particulate matter (PM) as carcinogenic to human. Long-term exposure to PM has been associated with cancer mortality mainly from lung cancer. Although a few U.S studies demonstrated the association with mortality of various cancer types, evidence for non-lung cancer is limited. The aim of this study is to compare PM associations with cancer mortality across different types of cancer in the Seoul Metropolitan Areas, South Korea using a population-based nationwide cohort. METHODS: Using the National Health Insurance Services-National Sample cohort, we selected the subjects who received national screening during 2005-2007, aged over 30, were non-severely disabled, and had full address information. We defined mortality of seventeen specific cancers based on the International Classification of Disease, 10th reversion. Individual-level long-term PM concentrations were estimated for the previous 5 years of 2002-2015 from a previously developed prediction model. We performed time-dependent Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals per 10ug/m3 increase in PM2.5 and PM10 adjusting for sociodemographic characteristics, family history of cancer, health behaviors, and area-level characteristics. RESULTS:Of 206,717 included subjects, 4,122 subjects were died with cancer for 2007-2015 and lung cancer was accounted the most (24.81%). Although none of estimates were statistically significant possibly because of small sample size, HRs of PM2.5 were greater than 1 for lung, stomach, esophagus, non-Hodgikins, oral and pharynx, and brain cancer mortality (HR range: 1.44-7.14). These results were similar for PM10 but with reduced effect estimates. CONCLUSIONS:Although we found no evidence of the association, our findings of positive risk estimates for PM2.5 in lung, oral and pharynx, and brain cancer mortality were consistent with those in U.S. studies. Future studies should re-examine the association in expanded cohorts. KEYWORDS: Ambient air pollution, Particulate matter, Cancer mortality, National sample cohort

Simple sugar intake and cancer incidence, cancer mortality and all-cause mortality: A cohort study from the PREDIMED trial

To examine associations between intake of simple sugars and cancer incidence, cancer mortality, and total mortality in a prospective cohort study based on the PREDIMED trial conducted from 2003 to 2010. Participants were older individuals at high cardiovascular risk. Exposures were total sugar, glucose and fructose from solid or liquid sources, and fructose from fruit and 100% fruit juice. Cancer incidence was the primary outcome; cancer mortality and all-cause mortality were secondary outcomes. Multivariable-adjusted, time-dependent Cox proportional hazard models were used. Of 7447 individuals enrolled, 7056 (94.7%) were included (57.6% women, aged 67.0±6.2 years). 534 incident cancers with 152 cancer deaths and 409 all-cause deaths were recorded after a median follow-up of 6 years. Intake of simple sugars in solid form was unrelated to outcomes. Higher cancer incidence was found per 5g/day increase in intake of liquid sugars, with multivariable-adjusted HR of 1.08 (95% CI, 1.03-1.13) for total liquid sugar, 1.19 (95% CI, 1.07-1.31) for liquid glucose, 1.14 (95% CI, 1.05-1.23) for liquid fructose, and 1.39 (95% CI, 1.10-1.74) for fructose from fruit juice. Cancer and all-cause mortality increased to a similar extent with intake of all sugars in liquid form. In categorical models, cancer risk was dose-related for all liquid sugars. Simple sugar intake in drinks and fruit juice was associated with an increased risk of overall cancer incidence and mortality and all-cause mortality. This suggests that sugary beverages are a modifiable risk factor for cancer and all-cause mortality.

Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.

Simple SummaryThis study is the first to estimate the impact of smoking-related chronic obstructive pulmonary disease (COPD) on invasive ductal carcinoma (IDC) patients receiving standard treatments. Smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I–III IDC receiving standard treatments. The frequency of hospitalization for COPD with at least one acute exacerbation within one year before breast surgery was highly associated with high mortality for women with IDC receiving standard treatments.Purpose: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments. Methods: we recruited women with clinical stage I–III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group). Results: PSM yielded 2319 patients with stage I–III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83–1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18–2.36) compared with no COPDAE. Conclusion: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I–III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.

Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with rheumatoid arthritis: a cohort study using the Clinical Practice Research Datalink.

ObjectivesClinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.MethodsThis was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7–12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.ResultsAmong 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.ConclusionClinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.

Prediction of Postictal Delirium Following Status Epilepticus in the ICU: First Insights of an Observational Cohort Study.

To identify early predictors of postictal delirium in adult patients after termination of status epilepticus. Retrospective study. ICUs at a Swiss tertiary academic medical center. Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018. None. Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation). Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1-3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53-7.33). Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2-3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.

Metformin and the Incidence of Lymphoid Malignancies in Patients with Type 2 Diabetes

Purpose: Metformin, a first-line antidiabetic drug in type 2 diabetes, is being evaluated for prevention and treatment of various solid tumors. Metformin has also been shown to act against lymphoid malignancies (LM) in preclinical models, although population-based data are lacking. Thus, we examined whether metformin use is associated with reduced risk of LM in patients with type 2 diabetes.Patients and Methods: This was a population-based cohort study using data from the United Kingdom Clinical Practice Research Datalink. We included patients > 18 years of age newly-treated with non-insulin antidiabetic drugs between 1998 and 2014. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of LM (inpatient diagnoses of non-Hodgkin and Hodgkin lymphoma, chronic and acute lymphocytic leukemia, and multiple myeloma) comparing the use of metformin with the use of other antidiabetic drugs, and lagged by one year for cancer latency. Secondary analyses included stratifications of metformin use by cumulative duration and dose, as well as of LM by disease type. All estimates were adjusted to ethnicity, socioeconomic status, time-updated use of other antidiabetic drugs, known risk factors (autoimmune diseases and solid organ transplant), and important comorbidities.Results: The cohort included a total of 100,091 patients, which generated 502 LM events during 500,774 person-years of follow-up (rate, 1/1000 person-years). Overall, metformin use was not associated with the incidence of LM (adjusted HR, 0.86; 95% CI, 0.63-1.16). Furthermore, there was no significant trend for duration (P=0.46) or cumulative dose (P= 0.60) of metformin use with LM incidence, with the highest categories being > 5 years and > 2,492 grams (Table 1). When stratified by disease type, metformin use was not associated with the incidence of multiple myeloma, chronic lymphocytic leukemia acute, and non-Hodgkin lymphoma (Table 2). Similar findings were seen for acute lymphoblastic leukemia (adjusted HR, 0.36; 95% CI, 0.04-3.41), and Hodgkin lymphoma (adjusted HR, 0.94; 95% CI, 0.23-3.91).Conclusions To our knowledge, this is the first population-based study to examine the association between metformin use and LM incidence. We observed no duration- or dose-response of metformin with LM incidence, which are paramount in the concept of chemoprevention. There were no important differences between LM types, although precision for acute lymphoblastic leukemia and Hodgkin lymphoma was limited due to sample size. While our findings are observational and apply to the diabetic population, our findings provide no rationale for the prospective investigation of metformin to prevent LM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis