Siamese Survival Analysis with Competing Risks

Survival analysis in the presence of multiple possible adverse events, i.e., competing risks, is a pervasive problem in many industries (healthcare, finance, etc.). Since only one event is typically observed, the incidence of an event of interest is often obscured by other related competing events. This nonidentifiability, or inability to estimate true cause-specific survival curves from empirical data, further complicates competing risk survival analysis. We introduce Siamese Survival Prognosis Network (SSPN), a novel deep learning architecture for estimating personalized risk scores in the presence of competing risks. SSPN circumvents the nonidentifiability problem by avoiding the estimation of cause-specific survival curves and instead determines pairwise concordant time-dependent risks, where longer event times are assigned lower risks. Furthermore, SSPN is able to directly optimize an approximation to the C-discrimination index, rather than relying on well-known metrics which are unable to capture the unique requirements of survival analysis with competing risks

Using observational data to estimate an upper bound on the reduction in cancer mortality due to periodic screening

BACKGROUND: Because randomized cancer screening trials are very expensive, observational cancer screening studies can play an important role in the early phases of screening evaluation. Periodic screening evaluation (PSE) is a methodology for estimating the reduction in population cancer mortality from data on subjects who receive regularly scheduled screens. Although PSE does not require assumptions about natural history of cancer it requires other assumptions, particularly progressive detection – the assumption that once a cancer is detected by a screening test, it will always be detected by the screening test. METHODS: We formulate a simple version of PSE and show that it leads to an upper bound on screening efficacy if the progressive detection assumption does not hold (and any effect of birth cohort is minimal) To determine if the upper bound is reasonable, for three randomized screening trials, we compared PSE estimates based only on screened subjects with PSE estimates based on all subjects. RESULTS: In the three randomized screening trials, PSE estimates based on screened subjects gave fairly close results to PSE estimates based on all subjects. CONCLUSION: PSE has promise for obtaining an upper bound on the reduction in population cancer mortality rates based on observational screening data. If the upper bound estimate is found to be small and any birth cohort effects are likely minimal, then a definitive randomized trial would not be warranted

Competing risks survival analysis applied to data from the Australian Orthopaedic Association National Joint Replacement Registry

BACKGROUND AND PURPOSE: The Kaplan-Meier (KM) method is often used in the analysis of arthroplasty registry data to estimate the probability of revision after a primary procedure. In the presence of a competing risk such as death, KM is known to overestimate the probability of revision. We investigated the degree to which the risk of revision is overestimated in registry data. PATIENTS AND METHODS: We compared KM estimates of risk of revision with the cumulative incidence function (CIF), which takes account of death as a competing risk. We considered revision by (1) prosthesis type in subjects aged 75–84 years with fractured neck of femur (FNOF), (2) cement use in monoblock prostheses for FNOF, and (3) age group in patients undergoing total hip arthroplasty (THA) for osteoarthritis (OA). RESULTS: In 5,802 subjects aged 75–84 years with a monoblock prosthesis for FNOF, the estimated risk of revision at 5 years was 6.3% by KM and 4.3% by CIF, a relative difference (RD) of 46%. In 9,821 subjects of all ages receiving an Austin Moore (non-cemented) prosthesis for FNOF, the RD at 5 years was 52% and for 3,116 subjects with a Thompson (cemented) prosthesis, the RD was 79%. In 44,365 subjects with a THA for OA who were less than 70 years old, the RD was just 1.4%; for 47,430 subjects > 70 years of age, the RD was 4.6% at 5 years. INTERPRETATION: The Kaplan-Meier method substantially overestimated the risk of revision compared to estimates using competing risk methods when the risk of death was high. The bias increased with time as the incidence of the competing risk of death increased. Registries should adopt methods of analysis appropriate to the nature of their data.Marianne H. Gillam, Philip Ryan, Stephen E. Graves, Lisa N. Miller, Richard N. de Steiger and Amy Salte

Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan

<p>Abstract</p> <p>Background</p> <p>We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases.</p> <p>Methods</p> <p>Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records.</p> <p>Results</p> <p>Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, <it>p </it>= 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, <it>p </it>= 0.02), women (HR = 1.81, CI: 1.11-2.94, <it>p </it>= 0.02), and age (HR = 0.98, CI: 0.97-1.00, <it>p </it>= 0.02).</p> <p>Conclusions</p> <p>Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing.</p

Influence of oral beclomethasone dipropionate on early non-infectious pulmonary outcomes after allogeneic hematopoietic cell transplantation: results from two randomized trials.

Early non-infectious pulmonary complications represent a significant cause of mortality after hematopoietic cell transplantation (HCT). We tested the hypothesis that oral beclomethasone dipropionate (BDP) is effective for preventing early non-infectious pulmonary complications after allogeneic HCT. We retrospectively reviewed the medical records of 120 patients, 60 in each treatment arm, to identify non-infectious and infectious pulmonary events and pulmonary function test results from all patients who participated in two randomized trials of oral BDP for treatment of acute gastrointestinal GVHD. 17-Beclomethasone monopropionate (17-BMP), the active metabolite of BDP, was evaluated in blood from the right atrium in four patients. Thirty-three of 42 (79%) placebo-treated patients experienced a decrease of the DL(CO) from pretransplant to day 80 after transplant, compared with 27 of 49 (55%) BDP-treated patients (P=0.02). In the first 200 days after randomization, there were no cases of non-infectious pulmonary complications in BDP-treated patients, vs four cases among placebo-treated patients (P=0.04). Levels of 17-BMP were detected in atrial blood at steady state. Delivery of a potent glucocorticoid such as 17-BMP to the pulmonary artery after oral dosing of BDP may be useful in modulating pulmonary inflammation and preventing the development of non-infectious pulmonary complications after allogeneic HCT.Bone Marrow Transplantation advance online publication, 29 June 2009; doi:10.1038/bmt.2009.129

Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence

Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55-5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed

Competing risk and heterogeneity of treatment effect in clinical trials

It has been demonstrated that patients enrolled in clinical trials frequently have a large degree of variation in their baseline risk for the outcome of interest. Thus, some have suggested that clinical trial results should routinely be stratified by outcome risk using risk models, since the summary results may otherwise be misleading. However, variation in competing risk is another dimension of risk heterogeneity that may also underlie treatment effect heterogeneity. Understanding the effects of competing risk heterogeneity may be especially important for pragmatic comparative effectiveness trials, which seek to include traditionally excluded patients, such as the elderly or complex patients with multiple comorbidities. Indeed, the observed effect of an intervention is dependent on the ratio of outcome risk to competing risk, and these risks – which may or may not be correlated – may vary considerably in patients enrolled in a trial. Further, the effects of competing risk on treatment effect heterogeneity can be amplified by even a small degree of treatment related harm. Stratification of trial results along both the competing and the outcome risk dimensions may be necessary if pragmatic comparative effectiveness trials are to provide the clinically useful information their advocates intend

Cumulative exposure to air pollution and long term outcomes after first acute myocardial infarction: A population-based cohort study. Objectives and methodology

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease is a leading cause of morbidity and mortality worldwide and epidemiological studies have consistently shown an increased risk for cardiovascular events in relation to exposure to air pollution. The Israel Study of First Acute Myocardial Infarction was designed to longitudinally assess clinical outcomes, psychosocial adjustment and quality of life in patients hospitalized with myocardial infarction. The current study, by introducing retrospective air pollution data, will examine the association between exposure to air pollution and outcome in myocardial infarction survivors. This report will describe the methods implemented and measures employed. The study specifically aims to examine the relationship between residential exposure to air pollution and long-term risk of recurrent coronary event, heart failure, stroke, cardiac and all-cause death in a geographically defined cohort of patients with myocardial infarction.</p> <p>Methods/Design</p> <p>All 1521 patients aged ≤65 years, admitted with first myocardial infarction between February 1992 and February 1993 to the 8 hospitals serving the population of central Israel, were followed for a median of 13 years. Data were collected on sociodemographic, clinical and environmental factors. Data from air quality monitoring stations will be incorporated retrospectively. Daily measures of air pollution will be summarised, allowing detailed maps to be developed in order to reflect chronic exposure for each participant.</p> <p>Discussion</p> <p>This study addresses some of the gaps in understanding of the prognostic importance of air pollution exposure after myocardial infarction, by allowing a sufficient follow-up period, using a well-defined community cohort, adequately controlling for multiple and multilevel confounding factors and providing extensive data on various outcomes.</p

Risks of second primary cancer among patients with major histological types of lung cancers in both men and women

10.1038/sj.bjc.6605616British Journal of Cancer10271190-1195BJCA