Adjusted Hazard Rate Ratio Research Articles

A target trial emulation comparing the antidepressant effectiveness of selective serotonin reuptake inhibitors (SSRIs) highlighting the importance of patent-related confounding by indication.

The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication. We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.

Primary central nervous system tumors survival in children in ten Colombian cities: a VIGICANCER report.

Primary central nervous system (CNS) tumors are the second most common cancer in children and adolescents, leading to premature death and disability. Population-based survival estimates aid decision-making in cancer control, however data on survival for primary CNS tumors in Latin America is lacking. We describe survival rates for children with primary CNS tumors treated in ten Colombian cities. We analyzed data from children and adolescents newly diagnosed with cancer between 2012 and 2021, participating in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) in ten cities in Colombia. VIGICANCER collects information on clinical outcomes from twenty-seven pediatric oncology units and conducts active follow-up every three months. VIGICANCER does not register craniopharyngiomas; we excluded intracranial germ cell tumors for this report. We used the Kaplan-Meier method to estimate the overall survival probability, stratified by sociodemographic variables, topography, WHO grading, receipt of radiation therapy, and type of surgical resection. We analyzed the prognostic capacity of variables using multivariate proportional Cox's regression, stratified by city and year of diagnosis. During the study period, VIGICANCER included 989 primary CNS tumors in 879 children and 110 adolescents. The cohort median age was 9 years; 53% of patients were males, and 8% were Afro-descendants. Most common tumors were supratentorial astrocytomas (47%), astrocytic tumors (35%), medulloblastomas (20%), ependymomas (11%), and mixed and unspecified gliomas (10%). Five-year overall survival of the entire cohort was 54% (95% CI, 51-58); for supratentorial gliomas, WHO grade I was 77%, II was 62%, III-IV was 27%, respectively, and for medulloblastoma was 61%. The adjusted hazard rate ratio for patients with WHO grade III and IV, for those with subtotal resection, for brainstem location, and for those not receiving radiation therapy was 7.4 (95% CI, 4.7-11.8), 6.4 (95% CI, 4.2-9.8), 2.8 (95% 2.1-3.8), 2.0 (95% CI, 1.3-2.8) and 2.3 (95% CI, 1.7-3.0), respectively. We found that half of Colombia's children and adolescents with primary CNS tumors survive five years, compared to 70% to 80% in high-income countries. In addition to tumor biology and location, gross total resection was crucial for improved survival in this cohort. Systematic monitoring of survival and its determinants provides empirical data for guiding cancer control policies.

Outcomes of Kidney Transplants From Toxoplasma-Positive Donors: An Organ Procurement and Transplant Network Database Analysis.

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

The Association Between Heterosexual anal Intercourse and HIV Acquisition in Three Prospective Cohorts of Women.

The extent to which receptive anal intercourse (RAI) increases the HIV acquisition risk of women compared to receptive vaginal intercourse (RVI) is poorly understood. We evaluated RAI practice over time and its association with HIV incidence during three prospective HIV cohorts of women: RV217, MTN-003 (VOICE), and HVTN 907. At baseline, 16% (RV 217), 18% (VOICE) of women reported RAI in the past 3 months and 27% (HVTN 907) in the past 6 months, with RAI declining during follow-up by around 3-fold. HIV incidence in the three cohorts was positively associated with reporting RAI at baseline, albeit not always significantly. The adjusted hazard rate ratios for potential confounders (aHR) were 1.1 (95% Confidence interval: 0.8-1.5) for VOICE and 3.3 (1.6-6.8) for RV 217, whereas the ratio of cumulative HIV incidence by RAI practice was 1.9 (0.6-6.0) for HVTN 907. For VOICE, the estimated magnitude of association increased slightly when using a time-varying RAI exposure definition (aHR = 1.2; 0.9-1.6), and for women reporting RAI at every follow-up survey (aHR = 2.0 (1.3-3.1)), though not for women reporting higher RAI frequency (> 30% acts being RAI vs. no RAI in the past 3 months; aHR = 0.7 (0.4-1.1)). Findings indicated precise estimation of the RAI/HIV association, following multiple RVI/RAI exposures, is sensitive to RAI exposure definition, which remain imperfectly measured. Information on RAI practices, RAI/RVI frequency, and condom use should be more systematically and precisely recorded and reported in studies looking at sexual behaviors and HIV seroconversions; standardized measures would aid comparability across geographies and over time.

Risk Factors and Prognosis of Epilepsy Following Brain Abscess: A Nationwide Population-Based Cohort Study.

Epilepsy in patients with brain abscess is frequent, but risk factors and prognosis remain undetermined. This study examined risk factors of epilepsy among survivors of brain abscess and associated prognosis. Nationwide, population-based healthcare registries were used to compute cumulative incidences and cause-specific adjusted hazard rate ratios (adj. HRRs) with 95% CIs for epilepsy among 30-day survivors of brain abscess from 1982 through 2016. Data were enriched with clinical details by medical record review of patients hospitalized from 2007 through 2016. Adjusted mortality rate ratios (adj. MRRs) were examined using epilepsy as a time-dependent variable. The study included 1,179 30-day survivors of brain abscess among whom 323 (27%) developed new-onset epilepsy after a median of 0.76 years (interquartile range [IQR] 0.24-2.41). At admission for brain abscess, the median age was 46 years (IQR 32-59) in patients with epilepsy compared with 52 years (IQR 33-64) in those without epilepsy. The proportion of female individuals was similar in patients with and without epilepsy (37%). Adj. HRRs for epilepsy were 2.44 (95% CI 1.89-3.15) for aspiration or excision of brain abscess, 2.37 (1.56-3.60) for alcohol abuse, 1.75 (1.27-2.40) for previous neurosurgery or head trauma, 1.62 (1.17-2.25) for stroke, and 1.55 (1.04-2.32) for age group 20-39 years. Cumulative incidences were increased in patients with alcohol abuse (52% vs 31%), aspiration or excision of brain abscess (41% vs 20%), previous neurosurgery or head trauma (41% vs 31%), and stroke (46% vs 31%). Analysis using clinical details from medical record review of patients from 2007 through 2016 demonstrated adj. HRRs of 3.70 (2.24-6.13) for seizures at admission for brain abscess and 1.80 (1.04-3.11) for frontal lobe abscess. By contrast, adj. HRR was 0.42 (0.21-0.86) for occipital lobe abscess. Using the entire registry-based cohort, patients with epilepsy had an adj. MRR of 1.26 (1.01-1.57). Important risk factors of epilepsy were seizures during admission for brain abscess, neurosurgery, alcoholism, frontal lobe abscess, and stroke. Epilepsy was associated with an increased mortality. Antiepileptic treatment may be guided by individual risk profiles, and a specialized follow-up is highlighted by an increased mortality in survivors with epilepsy.

Risk factors for suicide among patients having received treatment with electroconvulsive therapy: A nationwide study of 11,780 patients.

Despite the putative anti-suicidal effect of electroconvulsive therapy (ECT), patients receiving ECT remain at high risk of dying from suicide due to the severity of their underlying mental illness. We aimed to quantify this risk and to identify risk factors for suicide among patients receiving ECT. Using nationwide Danish registers, we identified all patients that initiated ECT between 2006 and 2016. These patients were matched on sex and age to 10 reference individuals from the general Danish population. Firstly, we compared 2-year suicide risk between patients initiating ECT and the matched reference individuals. Secondly, we investigated if any patient characteristics were associated with suicide following ECT via Cox proportional hazards regression. A total of 11,780 patients receiving ECT and 117,800 reference individuals were included in the analyses. Among the patients receiving ECT, 161 (1.4%) died from suicide within two years. Compared to the reference individuals, patients having received ECT had a substantially elevated suicide rate (Hazard rate ratio (HRR)=44.48, 95%CI=31.12-63.59). Among those having received ECT, the following characteristics were associated with suicide: Male sex (adjusted HRR (AHRR)=2.32, 95%CI=1.63-3.30), medium-term higher education (AHRR=2.64, 95%CI=1.57-4.44); long-term higher education (AHRR=3.16, 95%CI=1.68-5.94), history of substance use disorder (AHRR=1.51, 95%CI=1.01-2.26) and history of intentional self-harm/suicide attempt (AHRR=4.18, 95%CI=2.76-6.32). Those who are male, have obtained medium-/long-term higher education, or have a history of substance use disorder or intentional self-harm/suicide attempt, are at particularly elevated risk of suicide following ECT. These findings may guide clinical initiatives to reduce suicides.

Abstract PR05: Utilizing electronic fertility clinic records and registry linkage to establish a retrospective population-based cohort study to evaluate the association between in vitro fertilization (IVF) and subsequent cancer risk in women

Abstract Background: Since the introduction of in vitro fertilization (IVF) in 1978, the use of assisted reproduction technology (ART) has increased annually with an estimated 240,000 ART-conceived children born each year worldwide. Despite its widespread use, the impact on subsequent maternal and child health is not well understood. Specifically, cancer risk in women receiving IVF treatment has not been adequately evaluated, in part due to the complex nature of the research question and the need for large numbers of exposed women with long follow-up to evaluate rare cancer outcomes. Methods: To address this research question, we designed a country-wide retrospective medical record linkage study that utilizes electronic records from all IVF units in operation in Israel between 1997 and 2014. Linkage to cancer registry is facilitated via unique national identification numbers. We selected Israel for this study because it has the highest rate of ART/IVF exposure in the world, with 24 IVF units in the country that perform more than 45,000 ART cycles annually. Fertility treatment is fully covered by national health insurance with no restriction on the number of cycles or type of procedure, thus reducing potential selection issues related to access to care that may exist in other populations. We are currently collecting medically documented and detailed exposure information from the IVF units, including causes of infertility, hormonal treatments, procedures (e.g., IVF), and important covariates (e.g., parity, body mass index, etc.). To date we have collected exposure and covariate information from 18,470 women receiving treatment at 9 IVF clinics and conducted an interim linkage with the cancer registry through December 2014, providing on average 15 years of follow-up. We calculated standardized incidence ratios (SIRs) for all cancers combined and separately for breast cancer and further evaluated breast cancer risk with number of treatment cycles using Cox proportional hazards regression. Results: Based on interim registry linkage we identified 611 invasive cancers including 272 breast cancers among 18,470 women with more than 236,000 woman-years of follow-up. The incidence of cancer [SIR (95% confidence interval (CI)): 0.96 (0.88-1.04)] or breast cancer [0.98 (0.87-1.11)] was not elevated compared to the general population. Further, breast cancer risk was not associated with increased number of IVF treatment cycles [adjusted hazard rate ratio (RR) (95% CI) per IVF cycle: 1.01 (0.96-1.09)]. Conclusions: With this data we have demonstrated the feasibility of linking IVF clinic data with the nationwide cancer registry to evaluate cancer risk. In our preliminary analyses, IVF treatment was not associated with risk of incident invasive cancer or breast cancer. Given that continued linkage with the cancer registry is feasible, we will be able to monitor long-term cancer risks associated with IVF treatment using the enumerated data. This abstract is also being presented as Poster A15. Citation Format: Britton Trabert, Galit Hirsh-Yechezkel, Adel Farhi, Inna Zaslavsky, Shai E. Elizur, Arik Kahana, Raoul Orvieto, Hananel Holzer, Ilan Calderon, Shevach Friedler, Einat Shalom-Paz, Raphael Ron-El, Arie Raziel, Louise A. Brinton, Liat Lerner-Geva. Utilizing electronic fertility clinic records and registry linkage to establish a retrospective population-based cohort study to evaluate the association between in vitro fertilization (IVF) and subsequent cancer risk in women [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr PR05.

Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations in brain abscess patients: a nationwide, population-based matched cohort study

ObjectivesThe extent of hereditary haemorrhagic telangiectasia (HHT) and pulmonary arteriovenous malformations (PAVMs) as a risk factor for brain abscess is unknown. MethodsNationwide and population-based registries were used to identify persons with first-time hospitalization for brain abscess (index date) and population controls matched by age, sex and residence (1:10). Accounting for competing risks, cumulative incidence curves of new diagnosis of HHT/PAVM after brain abscess were constructed. Next, Cox regression was used for computation of cause-specific hazard rate ratios (HRRs) adjusted for severe liver disease and congenital heart disease as potential confounders. ResultsHHT/PAVM was prevalent before the index date in 2/1384 (0.1%; 95% CI 0.02–0.52) brain abscess patients and 6/13 838 (0.04%; 95% CI 0.02–0.09) matched population controls. After the index date, a new diagnosis of hereditary haemorrhagic telangiectasia or pulmonary arteriovenous malformations was made in 15/1384 brain abscess patients (range 0 days to 17 years) compared with 7/13 812 population controls yielding an adjusted hazard rate ratio of 31.4 (95% CI 9.95–98.9). Cumulative incidence was 1.5% for brain abscess patients and 0.1% for population controls. DiscussionHHT/PAVM should be considered in patients with cryptogenic brain abscess, although absolute risk is low.

Influence of Acetylsalicylic Acid Use on Risk and Outcome of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Study.

ObjectiveTo investigate the influence of acetylsalicylic acid (ASA) use on risk and outcome of community-acquired Staphylococcus aureus bacteremia (CA-SAB).MethodWe used population-based medical databases to identify all patients diagnosed in northern Denmark with first-time CA-SAB and matched population controls from 2000–2011. Categories for ASA users included current users (new or long-term users), former users, and nonusers. The analyses were adjusted for comorbidities, comedication use, and socioeconomic indicators.ResultsWe identified 2638 patients with first-time CA-SAB and 26 379 matched population controls. Compared with nonusers, the adjusted odds ratio (aOR) for CA-SAB was 1.00 (95% confidence interval [CI], 0.88–1.13) for current users, 1.00 (95% CI, 0.86–1.16) for former users, 2.04 (95% CI, 1.42–2.94) for new users, and 0.95 (95% CI, 0.84–1.09) for long-term users. Thirty-day cumulative mortality was 28.0% among current users compared with 21.6% among nonusers, yielding an adjusted hazard rate ratio (aHRR) of 1.02 (95% CI, 0.84–1.25). Compared with nonusers, the aHRR was 1.10 (95% CI, 0.87–1.40) for former users, 0.60 (95% CI, 0.29–1.21) for new users, and 1.06 (95% CI, 0.87–1.31) for long-term users. We observed no difference in the risk or outcome of CA-SAB with increasing ASA dose or by presence of diseases commonly treated with ASA.ConclusionsUse of ASA did not seem to influence the risk or outcome of CA-SAB. The apparent increased risk among new users may relate to residual confounding from the circumstances underlying ASA treatment initiation. Our finding of no association remained robust with increasing ASA dose and across multiple patient subsets.

Association between the detection of alcohol, illicit drugs and/or psychotropic medications/opioids in patients admitted due to trauma and trauma recidivism: A cohort study.

ObjectiveTo quantify the association between the presence and type of drug detected and trauma recidivism in a cohort of patients admitted due to trauma.MethodA cohort study was conducted based on data from a project where the presence of alcohol and other drugs (cannabis, cocaine, amphetamines, methamphetamines, tricyclic antidepressants, barbiturates, opiates and benzodiazepines) was analysed in 1,187 patients aged 16 to 70 years admitted due to trauma. The patients were followed for a period of between 10 to 52 months until June 2016. For this study, the recurrence of injuries from a sample of 929 patients from this cohort was analysed according to their consumption profile. Survival curves were estimated and adjusted Hazard Rate Ratios (aHRR) and adjusted incidence rate ratios (aIRR) were calculated.ResultsThe incidence rate of TR was 10.94 cases per 100 patient-years in the group of patients negative for substances and 27.99 per 100 patient-years in positive patients. The survival curves show very significant differences in cumulative recurrence-free survival between the groups (Log Rank: p<0.001). Both the aHRR and the aIRR estimates show an increased risk of re-injury due to alcohol consumption (aIRR: 2.33 (1.72–3.15), p<0.001), cannabis use (aIRR: 1.87 (1.09–3.20), p = 0.022) and polydrug use (aIRR: 2.34 (1.80–3.04), p<0.001).ConclusionsThe presence of alcohol and/or illicit drugs in these patients doubles the risk of trauma recidivism.

Abstract 4727: Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients

Abstract Background: DNA repair genes function in the maintenance of genome integrity and prevent tumorigenesis. On another hand, DNA repair genes modulate cancer cell responses to DNA-damaging therapeutics. We hypothesize that altered expression of DNA repair genes are correlated with therapeutic outcomes of head and neck cancer patients. Patients and methods: Messenger RNA (mRNA) expressions of DDB2 and XPC were examined in specimens of 95 head and neck cancer patients using real-time quantitative RT-PCR. Patients were dichotomized by ROC curve analysis based on their DDB2 and XPC mRNA levels. Overall survival (OS) rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. Results: The levels of DDB2 and XPC mRNA expression in tumor tissues were reduced (tumor/normal &amp;lt; 0.9) in 84 and 80 cases, respectively, when compared with those in adjacent normal parts. Lower DDB2 (tumor/normal &amp;lt; 0.24) and XPC (tumor/normal &amp;lt; 0.36) mRNA expressions were correlated with larger tumor, positive lymph node invasion, advanced stage, and poor 5-yr OS rates (26.7% vs. 54.3%, and 28.1% vs. 53.0%, respectively). Multivariate Cox model showed that, in addition to T and N stages, lower XPC mRNA level (&amp;lt; 0.36) was an independent risk factor for patient's survival (HRR = 2.68, 95% CI 1.12-6.40). Concurrent chemotherapy and radiotherapy (CCRT) did not improve OS of patients with lower XPC mRNA (&amp;lt; 0.36) and showed even worse outcomes within 5 years for patients with lower DDB2 expression (&amp;lt; 0.24). However, patients with higher DDB2 (&amp;gt; 0.24) and XPC (&amp;gt; 0.36) mRNA levels had improved 5-yr OS rates if they received CCRT (64.4% vs. 41.8% and 73.3% vs. 39.2%). Conclusion: mRNA expressions of XPC and DDB2 might be useful biomarkers for prognosis and efficacy of CCRT medication in head and neck cancer patients. Citation Format: Chang-Shen Lin, Ka-Wo Lee, Jau-Ling Huang, Yu-Chu Wang, Yi-Shan Tsai. Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4727. doi:10.1158/1538-7445.AM2014-4727

Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients

BackgroundAtaxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients. Patients and methodsThe ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan–Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. ResultsReduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27–4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16–6.32), and larger tumor (T3/T4, HRR = 2.21; 95% CI 1.10–4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05–20.66) or with lower ATM and T3/T4 tumor (HRR = 5.23; 95% CI 2.04–13.40) exhibited the poorest outcome. ConclusionThe expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker.

Prediagnostic Use of Hormone Therapy and Mortality After Breast Cancer

A few studies have observed reduced breast cancer mortality in women who used hormone therapy before diagnosis. Due to the high prevalence of past and current hormone use, it is important to investigate whether these preparations are related to breast cancer mortality. To evaluate the influence of prediagnostic use of hormone therapy on breast cancer mortality, a prospective cohort of 12,269 women ages 50 years or more diagnosed with incident invasive breast cancer and residents of Wisconsin, Massachusetts, or New Hampshire were enrolled in three phases beginning in 1988. They were followed for death until December 31, 2005, using the National Death Index. Cumulative mortality and multivariable adjusted hazard rate ratios for breast cancer and other mortality causes were calculated for women according to any hormone therapy use, and for exclusive use of estrogen or estrogen-progestin (EP). During an average 10.3 years of follow-up, 1,690 deaths from breast cancer were documented. Cumulative mortality from breast cancer was lower among hormone therapy users, specifically current users at the time of diagnosis, and EP users, compared with nonusers. Adjusted survival varied by type and duration of hormone therapy before diagnosis. A reduced risk of death from breast cancer was associated with EP preparations (hazard rate ratio, 0.73; 0.59-0.91) and with > or =5 years of EP use (0.60; 0.43-0.84). No association was observed for women who were former or current users of E-alone preparations. Although use of combined EP preparations increases breast cancer risk, in this study, use of these hormones before diagnosis was associated with reduced risk of death after a breast cancer diagnosis. The better survival among users, particularly of EP, persisted after adjustment of screening, stage, and measured confounders.

Metabolic Syndrome and Early Death

This editorial appraises an article in the current issue of Hypertension that examines the prospective relationships between features of the metabolic syndrome (MetS) and early death in a population-based cohort form Northern Italy.1 We also discuss, in light of that study’s findings, how relevant conventional definitions of the MetS are for identifying individuals at high risk of early death. The MetS describes a constellation of metabolic and cardiovascular disease risk factors. Although varying definitions of the MetS exist, all of the commonly used definitions include a measure of obesity, hyperglycemia, hypertension, and dyslipidemia.2–4 These definitions are based on “expert” opinion and not on evidence derived from prospective studies, which would be preferable. Thus, it remains uncertain whether the component features of the MetS or the thresholds at which each component is defined as present or absent are informative and optimal for predicting risk of disease or early death. It is also undetermined whether MetS represents a distinct pathophysiological entity. Notwithstanding these issues, the syndrome is extensively used in research studies, and many advocate its use in clinical practice5 to identify people at high risk of cardiovascular disease and early death. The idea that cardiovascular risk factors with a common etiology cluster in certain individuals at high risk of cardiovascular disease was first popularized by Reaven6 in the 1980s, although the origins of the MetS date back much earlier.7 Reaven’s6 emphasis was on elucidating the underlying pathophysiology of cardiovascular disease, for which he postulated that insulin resistance plays a pivotal role, and not on developing a diagnosis of MetS, which could be used in clinical practice. Superficially, at least, MetS relates strongly with cardiovascular morbidity and early death8; this is perhaps unsurprising, because so too do each of the component features of the …

Cancer Mortality Among Textile Workers in Shanghai, China: A Preliminary Study

We assessed the association between cotton textile work and cancer mortality. The cancer mortality experience of 912 (444 cotton, 468 silk) textile workers in Shanghai, China, was compared. Workers were followed from 1981 to 2003. The associations between cotton textile work and death due to all cancers combined (with and without lung cancer) and to gastrointestinal cancers were estimated with Cox models, adjusting for age, work years, and pack-years. There were 69 deaths. The adjusted hazard rate ratio (HR) was 2.10 (95% confidence interval [CI], 0.98-4.47) for all cancers combined and 2.56 (95% CI, 1.14-5.74) after excluding lung cancer. For gastrointestinal cancers, the adjusted HR was 2.09 (95% CI, 0.83-5.27). These preliminary data suggest that, with the exception of lung cancer, cotton workers have significantly higher cancer mortality rates than silk workers.

Gestational Glucose Tolerance and Risk of Type 2 Diabetes in Young Pima Indian Offspring

The in utero environment is a powerful risk factor for type 2 diabetes in offspring, but little is known about the risk conveyed by nondiabetic gestational glucose levels. This issue was explored in 911 nondiabetic Pima Indian mothers and 1,436 of their children. Associations were assessed in multivariate models between maternal third trimester glucose tolerance and indexes of body composition and glycemic control in their children. At parturition, the mothers' ages ranged from 14 to 43 years. Offspring were studied at age 0-39 years. An SD (1.3 mmol/l) of maternal glucose was associated with 56 g higher birth weight (P = 0.0002). This effect persisted when only offspring of normal glucose tolerant mothers were examined (57 g, P < 0.0001). In Cox proportional hazards models, the adjusted hazard rate ratio for offspring risk of diabetes per SD maternal glucose was 1.6 (95% CI 1.3-2.0, P < 0.0001). When only offspring of normal glucose tolerant mothers were examined, the risk was reduced but remained significant (1.3 [1.04-1.71], P = 0.026). In conclusion, maternal glycemia during pregnancy is associated with increased birth weight and risk of diabetes in Pima Indian offspring, even when mothers are normal glucose tolerant during pregnancy. Thus, prevention of offspring type 2 diabetes may require strategies that focus on improving gestational glucose tolerance even within the normal range.

Disparities and survival among breast cancer patients.

Although rates of survival for women with breast cancer have improved, the survival disparity between African American and white women in the United States has increased. To determine whether this survival disparity persists in an insured population with access to medical care. In this retrospective cohort study, we extracted data from the tumor registries of six nonprofit, integrated health care delivery systems affiliated with the Cancer Research Network and assessed the survival of African American (n = 2276) and white (n = 18 879) female enrollees who were diagnosed with invasive breast cancer from January 1, 1993, through December 31, 1998. Cox proportional hazards regression was used to estimate the death rate among African American women relative to that of white women after adjustment for potential explanatory factors including stage at diagnosis, tumor characteristics, and treatment. Five-year survival was lower for African American women (73.8%) than for white women (81.6%). African American women were less likely to have tumor characteristics with good prognosis. Controlling for age at diagnosis, stage, grade, tumor size, and estrogen and progesterone receptor status, the adjusted hazard rate ratio for African American women was 1.34 (95% confidence interval = 1.22 to 1.46). Similar risks were found among women ages 20-49 and 50 and older. Controlling for treatment slightly lowered the hazard rate ratio to 1.31 (95% confidence interval = 1.20 to 1.43). Among women with invasive breast cancer, being insured and having access to medical care does not eliminate the survival disparity for African American women.

Alcohol and risk of atrial fibrillation or flutter: a cohort study.

The evidence for an association between alcohol consumption and risk of atrial fibrillation is conflicting. We prospectively examined the association between alcohol consumption and risk of atrial fibrillation or flutter among 47 949 participants (mean age, 56 years) in the Danish Diet, Cancer, and Health Study. The consumption of alcohol was analyzed as sex-specific quintiles by Cox proportional hazards regression models. The mean +/- SD consumption of alcohol per day was 28.2 +/- 25 g in men and 13.9 +/- 15 g in women. During follow-up (mean, 5.7 years), atrial fibrillation or flutter developed in 556 subjects (374 men and 182 women). After adjusting for established risk factors, there was a modest increase in risk of atrial fibrillation or flutter by increasing alcohol consumption in men. When using the lowest quintile of alcohol consumption in men as a reference, the adjusted hazard rate ratios in men in quintiles 2, 3, 4, and 5 were 1.04, 1.44, 1.25, and 1.46, respectively (P for trend, .04). When using the lowest quintile of alcohol consumption in women as a reference, the adjusted hazard rate ratios in women in quintiles 2, 3, 4, and 5 were 1.09, 1.27, 1.23, and 1.14, respectively (P for trend, .69). Inclusion of information on the frequency of alcohol consumption and the preferred source of alcohol did not change these associations. Consumption of alcohol was associated with an increased risk of atrial fibrillation or flutter in men. In women, moderate consumption of alcohol did not seem to be associated with risk of atrial fibrillation or flutter.

Can the survival difference between breast cancer patients in Denmark and Sweden 1989 and 1994 be explained by patho-anatomical variables?—A population-based study

Analyses of data from cancer registries have shown a 10% unit difference in 5-year relative survival between Danish and Swedish patients with breast cancer. This study investigates the effect of age and patho-anatomic variables on this survival difference. Hospital records were collected for women over 40 years of age diagnosed in 1989 or 1994 in east Denmark and south Sweden; patho-anatomical variables and survival were compared between 2289 Danish and 1715 Swedish women. Tumours were smaller, node-negative axillae more frequent and well-differentiated tumours almost 10% more frequent in Sweden. A superior 5-year relative survival in Sweden was found in the 50- to 79-year age group. The adjusted hazard rate ratio between countries was 1.7 in 1989 and 1.3 in 1994. Conditional survival after surviving the first 5 years was similar for the two countries. Adjusting for patho-anatomical variables reduced but did not eliminate the higher risk of death among the Danish patients. Higher population death rates could explain some but not all of the residual elevated risk for Danish women.

Effect of statin (HMG-Co-A-Reductase Inhibitor) use on 1-year mortality and hospitalization rates in older patients with cardiovascular disease living in nursing homes.

To quantify the effect of statins on 1-year mortality, hospitalizations, and decline in physical function among patients with cardiovascular disease (CVD) aged 65 and older living in nursing homes. Retrospective cohort study. All Medicare/Medicaid certified nursing homes (N = 1,492) in Maine, New York, Mississippi, and South Dakota. We identified 51,559 older patients with CVD from a population database that merged sociodemographic data and functional, clinical, and drug treatments from more than 300,000 newly admitted nursing home residents from 1992 to 1997. Statin users (n = 1,313) were matched with nonusers (n = 1,313) in the same facilities. All-cause mortality, hospitalization, combined endpoint of mortality or hospitalization, and decline in physical function were determined at 1 year, and survival analysis was performed. Prevalence of statin use in this frail older cohort with CVD was 2.6%. Statin use varied by age, gender, comorbid condition, medication use, and cognitive and physical function. One-year mortality was 229/1,000 person-years in the statin group and 404/1,000 person-years in the nonusers, with an adjusted hazard rate ratio (HRR) of 0.69, 95% confidence interval (CI) = 0.58-0.81. The estimated number needed to treat was seven (95% CI = 5-13). This association with improved all-cause mortality was evident for women and men and for age groups 75 to 84, and 85 and older. Statin therapy is associated with improved clinical outcomes, including reduction in 1-year all-cause mortality, and the combined endpoint of death or hospitalization in a frail older population with CVD. Some caution should be taken in interpreting these results because potential bias from residual confounding could affect these results.