An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.
We conducted a cohort study of the risk of acute non-fatal myocardial ...infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation.
In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥ 75 years (p trend = 0.03), while no trend was seen for PDE5I (p trend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11).
In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.
To determine whether recommended amounts of leisure-time physical activity (ie, 7.5-15 metabolic equivalent task MET hours/week) are associated with lower cancer risk, describe the shape of the ...dose-response relationship, and explore associations with moderate- and vigorous-intensity physical activity.
Data from 9 prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence were pooled. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% CIs of the relationships between physical activity with incidence of 15 types of cancer. Dose-response relationships were modeled with restricted cubic spline functions that compared 7.5, 15.0, 22.5, and 30.0 MET hours/week to no leisure-time physical activity, and statistically significant associations were determined using tests for trend (
< .05) and 95% CIs (< 1.0).
A total of 755,459 participants (median age, 62 years range, 32-91 years; 53% female) were followed for 10.1 years, and 50,620 incident cancers accrued. Engagement in recommended amounts of activity (7.5-15 MET hours/week) was associated with a statistically significant lower risk of 7 of the 15 cancer types studied, including colon (8%-14% lower risk in men), breast (6%-10% lower risk), endometrial (10%-18% lower risk), kidney (11%-17% lower risk), myeloma (14%-19% lower risk), liver (18%-27% lower risk), and non-Hodgkin lymphoma (11%-18% lower risk in women). The dose response was linear in shape for half of the associations and nonlinear for the others. Results for moderate- and vigorous-intensity leisure-time physical activity were mixed. Adjustment for body mass index eliminated the association with endometrial cancer but had limited effect on other cancer types.
Health care providers, fitness professionals, and public health practitioners should encourage adults to adopt and maintain physical activity at recommended levels to lower risks of multiple cancers.
Prostate cancer is a significant public health burden and a major cause of morbidity and mortality among men worldwide. Analyzing geographic patterns and temporal trends may help identify high‐risk ...populations, suggest the degree of PSA testing, and provide clues to etiology. We used incidence data available from the International Agency for Research on Cancer (IARC) and certain cancer registries for 43 populations across five continents during a median period of 24 years. Trends in overall prostate cancer rates showed five distinct patterns ranging from generally monotonic increases to peaking of rates followed by declines, which coincide somewhat with changes in the prevalence of PSA testing. Trends in age‐specific rates generally mirrored those in the overall rates, with several notable exceptions. For populations where overall rates increased rapidly and then peaked, exemplified in North America and Oceania, the highest incidence tended to be most pronounced and occurred during earlier calendar years among older men compared with younger ones. For populations with almost continual increases in overall rates, exemplified in Eastern Europe and Asia, peaks were evident among men aged ≥75 years in many instances. Rates for ages 45–54 years did not clearly stabilize or decline in the majority of studied populations. Global geographic variation remained substantial for both overall and age‐specific incidence rates regardless of levels of PSA testing, with the lowest rates consistently in Asia. Explanations for the persistent geographic differences and the continuing increases of especially early‐onset prostate cancer remain unclear.
Whats' new?
Prostate cancer is one of the most commonly occurring malignancies among men worldwide, second only to lung cancer. Nonetheless, geographic and temporal trends in prostate cancer incidence remain understudied. Here, extensive analyses of data from population‐based cancer registries reveal five distinct temporal patterns in global prostate cancer incidence overall. Age‐specific trends were also identified. Notably, rates peaked among men aged ≥75 years in most of the high‐income populations reflecting declining PSA screening at older ages and diagnosis at younger ages. In contrast, rates for men aged 45–54 years did not clearly stabilize or decline in most populations, and PSA testing is not likely to fully explain the rapidly rising rates of early‐onset prostate cancer.
ObjectivesLatent class trajectory modelling (LCTM) is a relatively new methodology in epidemiology to describe life-course exposures, which simplifies heterogeneous populations into homogeneous ...patterns or classes. However, for a given dataset, it is possible to derive scores of different models based on number of classes, model structure and trajectory property. Here, we rationalise a systematic framework to derive a ‘core’ favoured model.MethodsWe developed an eight-step framework: step 1: a scoping model; step 2: refining the number of classes; step 3: refining model structure (from fixed-effects through to a flexible random-effect specification); step 4: model adequacy assessment; step 5: graphical presentations; step 6: use of additional discrimination tools (‘degree of separation’; Elsensohn’s envelope of residual plots); step 7: clinical characterisation and plausibility; and step 8: sensitivity analysis. We illustrated these steps using data from the NIH-AARP cohort of repeated determinations of body mass index (BMI) at baseline (mean age: 62.5 years), and BMI derived by weight recall at ages 18, 35 and 50 years.ResultsFrom 288 993 participants, we derived a five-class model for each gender (men: 177 455; women: 111 538). From seven model structures, the favoured model was a proportional random quadratic structure (model F). Favourable properties were also noted for the unrestricted random quadratic structure (model G). However, class proportions varied considerably by model structure—concordance between models F and G were moderate (Cohen κ: men, 0.57; women, 0.65) but poor with other models. Model adequacy assessments, evaluations using discrimination tools, clinical plausibility and sensitivity analyses supported our model selection.ConclusionWe propose a framework to construct and select a ‘core’ LCTM, which will facilitate generalisability of results in future studies.
Sex disparities in cancer mortality and survival Cook, Michael B; McGlynn, Katherine A; Devesa, Susan S ...
Cancer epidemiology, biomarkers & prevention,
08/2011, Letnik:
20, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.
We extracted U.S. ...vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.
For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83).
Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.
Future analytic studies should attempt to understand causes of observed sex disparities in cancer.
Abstract
Dendritic cells (DC) in the lung that induce Th17 differentiation remain incompletely understood, in part because conventional CD11b
+
DCs (cDC2) are heterogeneous. Here, we report a ...population of cDCs that rapidly accumulates in lungs of mice following house dust extract inhalation. These cells are Ly-6C
+
, are developmentally and phenotypically similar to cDC2, and strongly promote Th17 differentiation ex vivo. Single cell RNA-sequencing (scRNA-Seq) of lung cDC2 indicates 5 distinct clusters. Pseudotime analysis of scRNA-Seq data and adoptive transfer experiments with purified cDC2 subpopulations suggest stepwise developmental progression of immature Ly-6C
+
Ly-6A/E
+
cDC2 to mature Ly-6C
–
CD301b
+
lung resident cDC2 lacking
Ccr7
expression, which then further mature into CD200
+
migratory cDC2 expressing
Ccr7
. Partially mature Ly-6C
+
Ly-6A/E
–
CD301b
–
cDC2, which express
Il1b
, promote Th17 differentiation. By contrast, CD200
+
mature cDC2 strongly induce Th2, but not Th17, differentiation. Thus, Th17 and Th2 differentiation are promoted by lung cDC2 at distinct stages of maturation.
Global international trends in female breast cancer incidence have been described previously but no comparable analysis of male breast cancer incidence rates has been conducted. We obtained male and ...female case and population data using Cancer Incidence in Five Continents (CI5). We calculated age‐adjusted, sex‐specific incidence rates and female‐to‐male incidence rate ratios (FMIRRs) and compared trends of such for the period 1988–2002. This analysis included 8,681 male breast cancer cases and 1.14 million female breast cancer cases. The highest male incidence rate was observed in Israel at 1.24 per 100,000 man‐years, and the highest female incidence rate was observed in the United States at 90.7 per 100,000 woman‐years. The lowest incidence rates for males (0.16) and females (18.0) were observed in Thailand. In general, male breast cancer incidence trends were variable; a minority of countries displayed evidence for an increase. In contrast, female incidence rates have been increasing in a majority of countries. The Pearson correlation coefficient (r) for male and female breast cancer incidence rates by country during 1988–2002 was 0.69. Male breast cancer rates were generally less than 1 per 100,000 man‐years, in contrast to the much higher rates of female breast cancer, providing for an overall FMIRR of 122. The differences in both incidence rates and time trends between males and females may reflect sex differences in underlying risk factors, pathogenesis, and/or overdiagnosis. Conversely, the high correlation between male and female breast cancer incidences may indicate that both sexes share some common risk factors for breast cancer.
What's new?
Are the causes of breast cancer in men similar to those in women? Is male breast cancer a different disease entity, or is it the same in men and women? In this study, the authors have compiled the first epidemiologic analysis comparing international trends for male and female breast‐cancer incidence. They conclude that, while incidence patterns are similar, there may also be sex‐specific processes that play a role in the pathogenesis of this disease.
Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has ...examined this potential association.
Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA.
Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered.
This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.
There are many barriers to using science to inform conservation policy and practice. Conservation scientists wishing to produce management-relevant science must balance this goal with the imperative ...of demonstrating novelty and rigor in their science. Decision makers seeking to make evidence-based decisions must balance a desire for knowledge with the need to act despite uncertainty. Generating science that will effectively inform management decisions requires that the production of information (the components of knowledge) be salient (relevant and timely), credible (authoritative, believable, and trusted), and legitimate (developed via a process that considers the values and perspectives of all relevant actors) in the eyes of both researchers and decision makers. We perceive 3 key challenges for those hoping to generate conservation science that achieves all 3 of these information characteristics. First, scientific and management audiences can have contrasting perceptions about the salience of research. Second, the pursuit of scientific credibility can come at the cost of salience and legitimacy in the eyes of decision makers, and, third, different actors can have conflicting views about what constitutes legitimate information. We highlight 4 institutional frameworks that can facilitate science that will inform management: boundary organizations (environmental organizations that span the boundary between science and management), research scientists embedded in resource management agencies, formal links between decision makers and scientists at research-focused institutions, and training programs for conservation professionals. Although these are not the only approaches to generating boundary-spanning science, nor are they mutually exclusive, they provide mechanisms for promoting communication, translation, and mediation across the knowledge-action boundary. We believe that despite the challenges, conservation science should strive to be a boundary science, which both advances scientific understanding and contributes to decision making. Hay muchas barreras para utilizar ciencia para informar a la política y práctica de la conservación. Los científicos de la conservación que desean producir ciencia relevante para el manejo deben equilibrar esta meta con el imperativo de demostrar novedad y rigor en su ciencia. Los tomadores de decisiones que buscan que sus decisiones se basen en evidencias deben equilibrar el deseo de conocimientos con la necesidad de actuar a pesar de la incertidumbre. La generación de ciencia que informe efectivamente a las decisiones de manejo requiere que la producción de información (los componentes del conocimiento) sea sobresaliente (relevante y oportuna), creíble (autoritativa, verosímil y confiable) y legítima (desarrollada mediante un proceso que considera los valores y perspectivas de todos los actores relevantes) a la vista tanto de investigadores como de tomadores de decisiones. Percibimos tres retos clave para quienes desean generar ciencia de la conservación que logre estas tres características de la información. Primero, las audiencias científicas y de manejo pueden tener percepciones contrastantes sobre la relevancia de la investigación. Segundo, la credibilidad se puede lograr a costa de la relevancia y legitimidad a la vista de los tomadores de decisiones y tercero, los diferentes actores pueden tener percepciones conflictivas sobre los que constituye información legítima. Resaltamos cuatro marcos institucionales que pueden facilitar que la ciencia informe al manejo: organizaciones de frontera (organizaciones ambientales que trasponen la frontera entre la ciencia y el manejo), investigadores científicos insertados en agencias de manejo de recursos, vínculos formales entre tomadores de decisiones y científicos en instituciones enfocadas a la investigación, y programas de capacitación para profesionales de la conservación. Aunque estos no son los únicos métodos para generar ciencia que traspone fronteras, ni son mutuamente excluyentes, proporcionan mecanismos que promueven la comunicación, traslación y mediación para trasponer la frontera conocimiento-acción. Consideramos que no obstante los retos, la ciencia de la conservación debería pugnar por ser una ciencia de frontera, que incrementa el entendimiento científico y contribuye a la toma de decisiones.
Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body ...mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues.
Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted.
Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index.
This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
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