| 1. |
- Bellavia, Andrea, et al.
(author)
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Using Laplace Regression to Model and Predict Percentiles of Age at Death When Age Is the Primary Time Scale
- 2015
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In: American Journal of Epidemiology. - : OXFORD UNIV PRESS INC. - 0002-9262 .- 1476-6256. ; 182:3, s. 271-277
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Journal article (peer-reviewed)abstract
- Increasingly often in epidemiologic research, associations between survival time and predictors of interest are measured by differences between distribution functions rather than hazard functions. For example, differences in percentiles of survival time, expressed in absolute time units (e.g., weeks), may complement the popular risk ratios, which are unitless measures. When analyzing time to an event of interest (e.g., death) in prospective cohort studies, the time scale can be set to start at birth or at study entry. The advantages of one time origin over the other have been thoroughly explored for the estimation of risks but not for the estimation of survival percentiles. In this paper, we analyze the use of different time scales in the estimation of survival percentiles with Laplace regression. Using this regression method, investigators can estimate percentiles of survival time over levels of an exposure of interest while adjusting for potential confounders. Our findings may help to improve modeling strategies and ease interpretation in the estimation of survival percentiles in prospective cohort studies.
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| 2. |
- Akesson, Agneta, et al.
(author)
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Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men A Population-Based Prospective Cohort Study
- 2014
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In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 64:13, s. 1299-1306
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Journal article (peer-reviewed)abstract
- BACKGROUND Adherence to a combination of healthy dietary and lifestyle practices may have an impressive impact on the primary prevention of myocardial infarction (MI). OBJECTIVES The aim of this study was to examine the benefit of combined low-risk diet and healthy lifestyle practices on the incidence of MI in men. METHODS The population-based, prospective cohort of Swedish men comprised 45-to 79-year-old men who completed a detailed questionnaire on diet and lifestyle at baseline in 1997. In total, 20,721 men with no history of cancer, cardiovascular disease, diabetes, hypertension, or high cholesterol levels were followed through 2009. Low-risk behavior included 5 factors: a healthy diet (top quintile of Recommended Food Score), moderate alcohol consumption (10 to 30 g/day), no smoking, being physically active (walking/bicycling >= 40 min/day and exercising >= 1 h/week), and having no abdominal adiposity (waist circumference <95 cm). RESULTS During 11 years of follow-up, we ascertained 1,361 incident cases of MI. The low-risk dietary choice together with moderate alcohol consumption was associated with a relative risk of 0.65 (95% confidence interval [CI]: 0.48 to 0.87) compared with men having 0 of 5 low-risk factors. Men having all 5 low-risk factors compared with those with 0 low-risk factors had a relative risk of 0.14 (95% CI: 0.04 to 0.43). This combination of healthy behaviors, present in 1% of the men, could prevent 79% (95% CI: 34% to 93%) of the MI events on the basis of the study population. CONCLUSIONS Almost 4 of 5 MIs in men may be preventable with a combined low-risk behavior. (C) 2014 by the American College of Cardiology Foundation.
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| 3. |
- Berg, Lena M, et al.
(author)
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Associations between crowding and ten-day mortality among patients allocated lower triage acuity levels without need of acute hospital care on departure from the emergency department
- 2019
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In: Annals of Emergency Medicine. - : Elsevier BV. - 0196-0644 .- 1097-6760. ; 74:3, s. 345-356
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVE: We describe the association between emergency department (ED) crowding and 10-day mortality for patients triaged to lower acuity levels at ED arrival and without need of acute hospital care on ED departure.METHODS: This was a registry study based on ED visits with all patients aged 18 years or older, with triage acuity levels 3 to 5, and without need of acute hospital care on ED departure during 2009 to 2016 (n=705,699). The sample was divided into patients surviving (n=705,076) or dying (n=623) within 10 days. Variables concerning patient characteristics and measures of ED crowding (mean length of stay and ED occupancy ratio) were extracted from the hospital's electronic health records. ED length of stay per ED visit was estimated by the average length of stay for all patients who presented to the ED during the same day and shift and with the same acuity level. The 10-day mortality after ED discharge was used as the outcome measure. Multivariable logistic regression analyses were conducted.RESULTS: The 10-day mortality rate was 0.09% (n=623). The event group had larger proportions of patients aged 80 years or older (51.4% versus 7.7%) and triaged with acuity level 3 (63.3% versus 35.6%), and greater comorbidity (age-combined Charlson comorbidity index median interquartile range 6 versus 0). We observed an increased 10-day mortality for patients with a mean ED length of stay greater than or equal to 8 hours versus less than 2 hours (adjusted odds ratio 5.86; 95% confidence interval [CI] 2.15 to 15.94) and for elevated ED occupancy ratio. Adjusted odds ratios for ED occupancy ratio quartiles 2, 3, and 4 versus quartile 1 were 1.48 (95% CI 1.14 to 1.92), 1.63 (95% CI 1.24 to 2.14), and 1.53 (95% CI 1.15 to 2.03), respectively.CONCLUSION: Patients assigned to lower triage acuity levels when arriving to the ED and without need of acute hospital care on departure from the ED had higher 10-day mortality when the mean ED length of stay exceeded 8 hours and when ED occupancy ratio increased.
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| 4. |
- Crippa, Alessio, et al.
(author)
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Coffee Consumption and Mortality From All Causes, Cardiovascular Disease, and Cancer : A Dose-Response Meta-Analysis
- 2014
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In: American Journal of Epidemiology. - : OXFORD UNIV PRESS INC. - 0002-9262 .- 1476-6256. ; 180:8, s. 763-775
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Research review (peer-reviewed)abstract
- Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity < 0.001). The largest risk reductions were observed for 4 cups/day for all-cause mortality (16%, 95% confidence interval: 13, 18) and 3 cups/day for CVD mortality (21%, 95% confidence interval: 16, 26). Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality.
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| 5. |
- Crippa, Alessio, et al.
(author)
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Red and processed meat consumption and risk of bladder cancer : a dose-response meta-analysis of epidemiological studies.
- 2018
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In: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 57:2, s. 689-701
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Journal article (peer-reviewed)abstract
- BACKGROUND/OBJECTIVES: Several epidemiological studies have analyzed the associations between red and processed meat and bladder cancer risk but the shape and strength of the associations are still unclear. Therefore, we conducted a dose-response meta-analysis to quantify the potential association between red and processed meat and bladder cancer risk.METHODS: Relevant studies were identified by searching the PubMed database through January 2016 and reviewing the reference lists of the retrieved articles. Results were combined using random-effects models.RESULTS: Five cohort studies with 3262 cases and 1,038,787 participants and 8 cases-control studies with 7009 cases and 27,240 participants met the inclusion criteria. Red meat was linearly associated with bladder cancer risk in case-control studies, with a pooled RR of 1.51 (95% confidence interval (CI) 1.13, 2.02) for every 100 g increase per day, while no association was observed among cohort studies (P heterogeneity across study design = 0.02). Based on both case-control and cohort studies, the pooled relative risk (RR) for every 50 g increase of processed meat per day was 1.20 (95% CI 1.06, 1.37) (P heterogeneity across study design = 0.22).CONCLUSIONS: This meta-analysis suggests that processed meat may be positively associated with bladder cancer risk. A positive association between red meat and risk of bladder cancer was observed only in case-control studies, while no association was observe in prospective studies.
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| 6. |
- Crippa, Alessio, et al.
(author)
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The ProBio trial : molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer
- 2020
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In: Trials. - : BioMed Central. - 1745-6215. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis.Methods: The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC.Discussion: Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study.Conclusions: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.
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| 7. |
- Di Giuseppe, Daniela, et al.
(author)
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Cigarette smoking and risk of rheumatoid arthritis : a dose-response meta-analysis
- 2014
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In: Arthritis Research & Therapy. - : BMC. - 1478-6362 .- 1478-6354. ; 16:2
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Journal article (peer-reviewed)abstract
- Introduction: Although previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA. Methods: Relevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis. Results: We included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (P-heterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies. Conclusions: Lifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years.
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| 8. |
- Discacciati, Andrea, et al.
(author)
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Lifestyle and dietary factors in prostate cancer prevention
- 2014
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In: Recent Results in Cancer Research. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0080-0015 .- 2197-6767. ; 202, s. 27-37
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Journal article (peer-reviewed)abstract
- The etiology of prostate cancer (PCa) is still largely unknown and the only well-established risk factors are those that are non-modifiable (age, race, and family history). Therefore, the identification of lifestyle and dietary factors which might prevent PCa development and progression is of paramount importance from a public health point of view. Accumulating evidence indicates that obesity may have a dual effect on PCa: an increased risk of aggressive PCa and a decreased risk of localized PCa. Both occupational and leisure time physical activity have been observed to be associated with a reduced PCa risk. Different dietary factors including coffee have been examined in several epidemiological studies, but results have been mostly inconsistent. However, these inconsistencies can be, at least partly, explained by the fact that the majority of those studies examined total PCa risk only and, in addition, they did not take into account the different genetic characteristics within the study populations. Therefore, the future epidemiological studies should focus on the analysis of PCa subtypes separately in order to examine possible etiological heterogeneity of PCa in relation to some exposures. In addition, differences in the genetic characteristics of the study participants should be taken into account to explore the possibility of gene-environment interactions.
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| 9. |
- Discacciati, Andrea
(author)
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Risk factors for prostate cancer : analysis of primary data, pooling, and related methodological aspects
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Prostate cancer is the second most common cancer among men worldwide, yet its etiology remains poorly understood. Obesity, on the other hand, is a prevalent but preventable medical condition that is associated with hormonal and metabolic changes. Since prostate cancer is a hormone-related cancer, the hypothesis of a link between body fatness and prostate cancer risk has been formulated. Furthermore, the considerable biologic heterogeneity of prostate cancer warrants analyses to be carried out separately by aggressiveness of the disease, differentiating indolent from potentially lethal tumors. This thesis has two aims. First, to elucidate the association between obesity, as measured by body mass index (BMI), and the risk of localized, advanced, and fatal prostate cancer. This is done using both primary data (Paper I) and aggregated data extracted from published epidemiological studies (Paper IV). Second, to deal with some methodological aspects related to the analysis of primary and aggregated data (Paper II; Paper III; Paper V). In Paper I, we used primary data from the Cohort of Swedish Men to examine the association of BMI during early adulthood (30 years of age) and middle-late adulthood (45–79 years of age) with the incidence of localized and advanced prostate cancer and with prostate cancer mortality. BMI during middle-late adulthood was observed to be inversely associated with the incidence of localized prostate cancer, while it was directly associated with the incidence of advanced prostate cancer and with prostate cancer mortality. At the same time, we observed limited evidence of an inverse association between BMI during early-adulthood and the risk of advanced and fatal prostate cancer. In Paper II, we extended the use of quantile regression for censored data to those situations where the time scale of interest is attained age at the event instead of follow-up time. In particular, we described how to use Laplace regression to model percentiles of age at the event in the presence of delayed entries, by conditioning on age at entry. In Paper III, we identified three major misinterpretations of risk and rate advancement periods (RAP): first, equating RAP with the difference in mean survival times; second, interpreting RAP as the time by which the survival curve for the exposed individuals is shifted compared with that for the unexposed; third, equating the RAP to a simple ratio of two log–relative risks. Furthermore, we showed how RAP estimation is sensitive to the specification of the age-disease association. In Paper IV, we carried out a dose–response meta-analysis to summarize the available evidence on the association between BMI during middle-late adulthood and the incidence of localized and advanced prostate cancer. Based on aggregated data extracted from 13 prospective studies, we observed that BMI was inversely associated with the incidence of localized prostate cancer, while it was directly associated with the incidence of advanced prostate cancer. In Paper V, we stressed the importance of assessing the goodness of fit of dose–response metaanalysis models. We presented and discussed three tools (deviance, coefficient of determination, and decorrelated-residuals–versus–exposure plot) that are useful to test, quantify, and visually display the fit of dose–response meta-analysis models, while taking into account the correlation structure of the study-specific log–relative risks. In conclusion, Paper I and Paper IV supported the hypothesis of etiological heterogeneity of prostate cancer in relation to obesity during middle-late adulthood. In particular, BMI was observed to be directly associated with advanced prostate cancer and with prostate cancer mortality. Paper II extended the use of quantile regression for censored data to those situations where attained age is the time scale of interest, Paper III clarified the appropriate use and interpretation of RAP, and Paper V proposed useful and relevant methods for assessing the goodness of fit of dose–response models in research synthesis.
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| 10. |
- Eriksson, Mikael, et al.
(author)
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Low-Dose Tamoxifen for Mammographic Density Reduction : A Randomized Controlled Trial
- 2021
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In: Journal of Clinical Oncology. - 0732-183X. ; 39:17, s. 1899-
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Journal article (peer-reviewed)abstract
- PURPOSE: Tamoxifen prevents breast cancer in high-risk women and reduces mortality in the adjuvant setting. Mammographic density change is a proxy for tamoxifen therapy response. We tested whether lower doses of tamoxifen were noninferior to reduce mammographic density and associated with fewer symptoms.PATIENTS AND METHODS: Women, 40-74 years of age, participating in the Swedish mammography screening program were invited to the 6-month double-blind six-arm randomized placebo-controlled noninferiority dose-determination KARISMA phase II trial stratified by menopausal status (EudraCT 2016-000882-22). In all, 1,439 women were accrued with 1,230 participants accessible for intention-to-treat analysis. The primary outcome was proportion of women treated with placebo, 1, 2.5, 5, and 10 mg whose mammographic density decreased at least as much as the median reduction in the 20 mg arm. The noninferior margin was 17%. Secondary outcome was reduction of symptoms. Post hoc analyses were performed by menopausal status. Per-protocol population and full population were analyzed in sensitivity analysis.RESULTS: The 1,439 participants, 566 and 873 pre- and postmenopausal women, respectively, were recruited between October 1, 2016, and September 30, 2019. The participants had noninferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group, a reduction confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group.CONCLUSION: Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen, but fewer side effects compared with the standard dose of 20 mg. Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer.
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