Long term morbidity and mortality among survivors of infant neuroblastoma: A report from the Childhood Cancer Survivor Study (CCSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10051-10051
Author(s):  
Danielle Novetsky Friedman ◽  
Pamela J Goodman ◽  
Wendy Leisenring ◽  
Lisa Diller ◽  
Susan Lerner Cohn ◽  
...  

10051 Background: Infants with neuroblastoma typically have low-risk disease with excellent survival. Therapy has been de-intensified over time to minimize late effects, however the impact on survivors’ risk of late mortality, subsequent malignant neoplasms (SMN), and chronic health conditions (CHC) is unclear. Methods: We evaluated late mortality, SMNs and CHCs (graded according to CTCAE v4.03), overall and by diagnosis era, among 990 5-year neuroblastoma survivors diagnosed at < 1 year of age between 1970-1999. Cumulative mortality, standardized mortality ratios (SMR), and standardized incidence ratios (SIR) of SMNs were estimated using the National Death Index and SEER rates, respectively. Cox proportional hazards estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC, compared to 5,051 CCSS siblings. Results: Among survivors (48% female; median attained age: 24 years, range 6-46), there was increased treatment with surgery alone across the 1970s, 1980s and 1990s (21.5%, 35.3%, 41.1%, respectively), but decreased treatment with combination surgery + radiation (22.5%, 5.3%, 0.3%, respectively) and surgery + radiation + chemotherapy (28.7%, 14.7%, 9.3%, respectively). The 20-year cumulative mortality was 2.3% (95% CI, 1.4-3.8), primarily due to SMNs (SMRSMN= 10.0, 95% CI, 4.5-22.3). The 20-year cumulative incidence of SMN was 1.2% (95% CI, 0.3-3.2), 2.5% (95% CI, 1.3-4.4), and zero for those diagnosed in the 1970s, 1980s, and 1990s, respectively. SIR was highest for renal SMNs (SIR 12.5, 95% CI, 1.7-89.4). Compared to siblings, survivors were at increased risk for grade 1-5 CHC (HR 2.1, 95% CI, 1.9-2.3) with similar HR across eras (HR1970s= 1.9, 95% CI, 1.6-2.2; HR1980s= 2.2, 95% CI, 1.9-2.6; HR1990s= 2.0, 95% CI, 1.7-2.4). The HR of severe, disabling, life-threatening and fatal CHC (grades 3-5) decreased in more recent eras (HR1970s= 4.7, 95% CI, 3.4-6.6; HR1980s= 4.4, 95% CI, 3.2-6.2; HR1990s= 2.9, 95% CI, 2.0-4.3). Conclusions: Survivors of infant neuroblastoma remain at increased risk for late mortality, SMN, and CHCs many years after diagnosis. However, the risk of grade 3-5 CHCs has declined in more recent eras, likely reflecting de-intensification of therapy.

2020 ◽  
Author(s):  
Hayley Martin ◽  
Kelly Thevenet-Morrison ◽  
Ann Dozier

Abstract Background: It is well established that mothers with above-normal pre-pregnancy BMI are at increased risk of breastfeeding cessation; however, the impact of pregnancy weight-gain (PWG) is less well-defined. Excess PWG may alter the hormonal preparation of breast tissue for lactation, increase the risk of complications that negatively impact breastfeeding (e.g. Cesarean-section, gestational diabetes), and may make effective latch more difficult to achieve. Methods: Our objective was to determine the impact of PWG and pre-pregnancy BMI on the risk of breastfeeding cessation utilizing the Institute of Medicine’s 2009 recommendations. Cox proportional hazards models were utilized to estimate the risk of cessation of exclusive breastfeeding, and cessation of any breastfeeding among women who initiated exclusive and any breastfeeding, respectively, in a cross sectional sample of survey respondents from a New York county (N=1207). PWG category was interacted with pre-pregnancy BMI (3 levels of pre-pregnancy BMI, 3 levels of PWG). Confounders of the relationship of interest were evaluated using directed acyclic graphs and bivariate analyses; variables not on the proposed causal pathway and associated with the exposure and outcome were included in multivariate models. Results: After adjustment, women of normal and obese pre-pregnancy BMI with greater-than-recommended PWG had 1.39 (1.03-1.86) and 1.48 (1.06-2.07) times the risk of any breastfeeding cessation within the first 3 months postpartum compared to women with normal pre-pregnancy BMI who gained within PWG recommendations. Overweight women with greater-than-recommended PWG were at increased risk of cessation, although not significantly (aHR[95% CI]: 1.29 [0.95 – 1.75]). No significant relationship was observed for exclusive breastfeeding cessation. Conclusions: Pre-pregnancy BMI and PWG may be modifiable risk factors for early breastfeeding cessation. Understanding the mechanism behind this risk should be ascertained by additional studies aimed at understanding the physiological, social, logistical (positioning) and other issues that may lead to early breastfeeding cessation.


2020 ◽  
Author(s):  
Hayley Martin ◽  
Kelly Thevenet-Morrison ◽  
Ann Dozier

Abstract Background: It is well established that mothers with above-normal pre-pregnancy BMI are at increased risk of breastfeeding cessation; however, the impact of pregnancy weight-gain (PWG) is less well-defined. Excess PWG may alter the hormonal preparation of breast tissue for lactation, increase the risk of complications that negatively impact breastfeeding (e.g. Cesarean-section, gestational diabetes), and may make effective latch more difficult to achieve. Methods: Our objective was to determine the impact of PWG and pre-pregnancy BMI on the risk of breastfeeding cessation utilizing the Institute of Medicine’s 2009 recommendations. Cox proportional hazards models were utilized to estimate the risk of cessation of exclusive breastfeeding, and cessation of any breastfeeding among women who initiated exclusive and any breastfeeding, respectively, in a cross sectional sample of survey respondents from a New York county (N=1207). PWG category was interacted with pre-pregnancy BMI (3 levels of pre-pregnancy BMI, 3 levels of PWG). Confounders of the relationship of interest were evaluated using directed acyclic graphs and bivariate analyses; variables not on the proposed causal pathway and associated with the exposure and outcome were included in multivariate models. Results: After adjustment, women of normal and obese pre-pregnancy BMI with greater-than-recommended PWG had 1.39 (1.03-1.86) and 1.48 (1.06-2.07) times the risk of any breastfeeding cessation within the first 3 months postpartum compared to women with normal pre-pregnancy BMI who gained within PWG recommendations. Overweight women with greater-than-recommended PWG were at increased risk of cessation, although not significantly (aHR[95% CI]: 1.29 [0.95 – 1.75]). No significant relationship was observed for exclusive breastfeeding cessation. Conclusions: Pre-pregnancy BMI and PWG may be modifiable risk factors for early breastfeeding cessation. Understanding the mechanism behind this risk should be ascertained by additional studies aimed at understanding the physiological, social, logistical (positioning) and other issues that may lead to early breastfeeding cessation.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Yang ◽  
Zhaohui Du ◽  
Yafei Liu ◽  
Jiahui Lao ◽  
Xiaoru Sun ◽  
...  

Abstract Background Assessment the impact of disability on mortality among the elderly is vital to healthy ageing. The present study aimed to assess the long-term influence of disability on death in the elderly based on a longitudinal study. Method This study used the Chinese Longitudinal Healthy Longevity Study (CLHLS) data from 2002 to 2014, including 13,666 participants aged 65 years and older in analyses. The Katz ADL index was used to assess disability status and levels. Cumulative mortality rates were estimated by the Kaplan-Meier method. Cox proportional hazards models were conducted to estimate associations between disability and all-cause mortality for overall participants, two age groups as well as specific chronic disease groups. All reported results were adjusted by survey weights to account for the complex survey design. Results During the 12-year follow-up, the death density was 6.01 per 100 person-years. The 3-years’ cumulative mortality rate of nondisabled elderly was 11.9% (95%CI: 10.9, 12.9%). As the level of disability increased, the cumulative mortality rate was from 28.1% (95%CI: 23.0, 33.1%) to 77.6% (95%CI: 63.8, 91.4%). Compared with non-disabled elderly, the multiple-adjusted hazard ratio of death due to disability was 1.68 (95% CI: 1.48, 1.90). The hazard ratios varied from 1.44 (95%CI: 1.23, 1.67) to 4.45 (95%CI: 2.69, 7.38) after classifying the disability levels. The hazard ratios of death in the young-old group (65–79 years) were higher than the old-old group (80 years and over) in both level B (HR = 1.58, 95%CI: 1.25, 2.00 vs. HR = 1.22, 95%CI: 1.06, 1.39, P = 0.029) and level G (HR = 24.09, 95%CI: 10.83, 53.60 vs. HR = 2.56, 95%CI: 1.75, 3.74, P < 0.001). For patients with hypertension, diabetes, heart disease, cerebrovascular disease as well as dementia, disability increases their relative risk of mortality by 1.64 (95%CI: 1.40, 1.93), 2.85 (95%CI: 1.46, 5.58), 1.45 (95%CI: 1.02, 2.05), 2.13 (95%CI: 1.54, 2.93) and 3.56 (95%CI: 1.22, 10.38) times, respectively. Conclusions Disability increases the risk of all-cause death in the elderly, especially those with chronic diseases and the young-old group. Further studies are needed to better understand how to effectively prevent disability in the older population.


Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000816 ◽  
Author(s):  
Kashish Goel ◽  
Vuyisile T Nkomo ◽  
Joshua P Slusser ◽  
Ryan Lennon ◽  
Robert D Brown ◽  
...  

ObjectivesThe objective was to assess the impact of procedural characteristics on risk of stroke or transient ischaemic attack (TIA) after transcatheter aortic valve replacement (TAVR).MethodsWe included 370 consecutive patients who underwent balloon-expandable TAVR from 1 November 2008 to 30 June 2014. Procedural characteristics that may be associated with stroke/TIA were assessed. The primary outcome was stroke/TIA at 30 days. A propensity score was constructed using a logistic regression model with 29 parameters. Cox proportional hazards models were used with a propensity score covariate.ResultsMean age was 80.9±7.9 years and mean Society of Thoracic Surgeons score was 8.3±5.0. The total number of balloon dilations ranged from 2 to 7. Out of 370 patients, 13 patients (3.5%) suffered stroke/TIA in the first 30 days after TAVR. In univariate analysis, postdeployment balloon dilation (PD) (HR 3.8, 95% CI 1.24 to 11.61; p=0.02) and emergent cardiopulmonary bypass (CPB) (HR 9.66, 95% CI 2.66 to 35.15; p<0.001) were significantly associated with 30-day stroke/TIA. In the multivariable Cox-proportional hazards model, PD (HR 4.95, 95% CI 1.02 to 24.03; p=0.04) and emergent CPB (HR 7.15, 95% CI 1.39 to 36.89; p=0.02) were independently associated with increased risk of 30-day stroke/TIA after adjusting for propensity score, total number of balloon dilations and periprosthetic regurgitation.ConclusionPostdilation as compared with total number of dilations, and emergent CPB were independently associated with increased risk of clinical neurological events in the first 30 days after TAVR. Reduction in balloon postdilation with appropriate valve sizing may reduce the risk of stroke or TIA after TAVR.


2019 ◽  
Vol 188 (8) ◽  
pp. 1484-1492 ◽  
Author(s):  
Stella Koutros ◽  
Jay H Lubin ◽  
Barry I Graubard ◽  
Aaron Blair ◽  
Patricia A Stewart ◽  
...  

Abstract We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.


2021 ◽  
pp. 089686082110189
Author(s):  
Mu-Chi Chung ◽  
Tung-Min Yu ◽  
Ming-Ju Wu ◽  
Ya-Wen Chuang ◽  
Chih-Hsin Muo ◽  
...  

Background: The impact of peritoneal dialysis-associated peritonitis (PD peritonitis) on long-term outcomes is uncertain. This nationwide retrospective study was conducted in Taiwan to understand the incidence, risk factors and long-term outcomes of PD peritonitis. Methods: A total of 11,202 incident adult peritoneal dialysis (PD) patients from 2000 to 2010 were collected from a Longitudinal Health Insurance Database and followed up until the end of 2011. Definition of peritonitis, the primary outcome, simultaneously met the diagnosis of peritonitis (International Classification of Diseases, Ninth Revision, Clinical Modification 567) and antibiotic use. Secondary outcomes included the impact of peritonitis on PD discontinuation and survival. Cox proportional hazards models with and without time-dependent variables were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: There were 7634 peritonitis episodes in 4245 patients during the follow-up period. The overall incidence of peritonitis was 0.18 episodes per patient-year. Peritonitis-associated risk factors included older age, female gender, chronic heart failure, cerebrovascular disease, liver cirrhosis and lower monthly income. In an adjusted Cox hazard proportional regression with the time-dependent model, peritonitis patients had a higher risk of PD discontinuation (HR 2.71, 95% CI 2.52–2.92) and mortality (HR 1.68, 95% CI 1.57–1.81) compared to patients without peritonitis. The adjusted HRs for mortality increased with each prior episode: one episode, two episodes and more than two episodes (all p < 0.05). The adjusted HRs for PD discontinuation also increased with the frequency of peritonitis. These negative effects were greatest during the first year and persisted significantly after 5 years. In a sensitivity analysis in which peritonitis within 30 days of death or PD discontinuation was excluded, peritonitis patients still had significantly increased risk of PD discontinuation and mortality compared to patients without peritonitis. Conclusions: Although peritonitis incidence was low, our findings reveal that peritonitis carried acute and long-term sequelae of higher PD discontinuation and lower patient survival.


2020 ◽  
Author(s):  
Hayley Martin ◽  
Kelly Thevenet-Morrison ◽  
Ann Dozier

Abstract Background: It is well established that mothers with above-normal pre-pregnancy BMI are at increased risk of breastfeeding cessation; however, the impact of pregnancy weight-gain (PWG) is less well-defined. Excess PWG may alter the hormonal preparation of breast tissue for lactation, increase the risk of complications that negatively impact breastfeeding (e.g. Cesarean-section, gestational diabetes), and may make effective latch more difficult to achieve. Methods: Our objective was to determine the impact of PWG and pre-pregnancy BMI on the risk of breastfeeding cessation utilizing the Institute of Medicine’s 2009 recommendations. Cox proportional hazards models were utilized to estimate the risk of cessation of exclusive breastfeeding, and cessation of any breastfeeding among women who initiated exclusive and any breastfeeding, respectively, in a cross sectional sample of survey respondents from a New York county (N=1207). PWG category was interacted with pre-pregnancy BMI (3 levels of pre-pregnancy BMI, 3 levels of PWG). Confounders of the relationship of interest were evaluated using directed acyclic graphs and bivariate analyses; variables not on the proposed causal pathway and associated with the exposure and outcome were included in multivariate models. Results: After adjustment, women of normal and obese pre-pregnancy BMI with greater-than-recommended PWG had 1.39 (1.03-1.86) and 1.48 (1.06-2.07) times the risk of any breastfeeding cessation within the first 3 months postpartum compared to women with normal pre-pregnancy BMI who gained within PWG recommendations. Overweight women with greater-than-recommended PWG were at increased risk of cessation, although not significantly (aHR[95% CI]: 1.29 [0.95 – 1.75]). No significant relationship was observed for exclusive breastfeeding cessation. Conclusions: Pre-pregnancy BMI and PWG may be modifiable risk factors for early breastfeeding cessation. Understanding the mechanism behind this risk should be ascertained by additional studies aimed at understanding the physiological, social, logistical (positioning) and other issues that may lead to early breastfeeding cessation.


Author(s):  
Atieh Amouzegar ◽  
Samaneh Asgari ◽  
Fereidoun Azizi ◽  
Amir Abbas Momenan ◽  
Mohammadreza Bozorgmanesh ◽  
...  

Abstract Context The relationship between metabolic syndrome (MetS) and the risk of fracture is a matter of debate. Objective This work aimed to determine the impact of MetS and its components on the risk of hospitalized fractures, during a median follow-up of 15.9 years. Methods A total of 7,520 participants (4,068 women) 30 years or older entered the study. Multivariable Cox proportional hazards regression were applied for data analysis. Results The prevalence of MetS was 40.0% and 40.4% in men and women, respectively. During the follow-up, hospitalized fracture was observed in 305 cases (men = 152). The multivariable hazard ratio (HR) and 95% confidence interval (CI) of MetS for incident fracture for men and women was 0.72 (0.49-1.05, P = .08) and 1.38 (0.96-1.98, P = .08), respectively. In the fully adjusted model, high fasting plasma glucose (FPG) among men tended to be associated with a lower risk of fracture [0.67 (0.44-1.02, P = .06)]; among women, high waist circumference (WC) was associated with a greater risk [2.40 (1.55-3.73)]. Among the population 50 years and older in the pooled sample, MetS was not accompanied by the risk of fracture, but high WC was associated with a higher risk [1.58 (1.07-2.33)]. For incident hip/pelvic fracture, abdominal obesity—but not MetS per se—was also a strong and independent risk factor. Conclusion A significant sex difference in the association between MetS and its components with incident fracture was observed. Women with central adiposity were at increased risk of hospitalized fracture, whereas men with high FPG were at decreased risk.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1773
Author(s):  
Milo van Hoefen Wijsard ◽  
Sara J. Schonfeld ◽  
Flora E. van Leeuwen ◽  
Annette C. Moll ◽  
Armida W. Fabius ◽  
...  

Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.e., bilateral retinoblastoma or unilateral with family history, mutation testing was not available) and 924 nonhereditary retinoblastoma survivors diagnosed during 1914–2006 at two US medical centers with follow-up through 2016. Using Cox proportional hazards regression, we compared benign tumor risk by hereditary status and evaluated the association between benign tumors and SMNs. There were 100 benign tumors among 73 hereditary survivors (cumulative incidence = 17.6%; 95% confidence interval [CI] = 12.9–22.8%) and 22 benign tumors among 16 nonhereditary survivors (cumulative incidence = 3.9%; 95%CI = 2.2–6.4%), corresponding to 4.9-fold (95%CI = 2.8–8.4) increased risk for hereditary survivors. The cumulative incidence after hereditary retinoblastoma was highest for lipoma among males (14.0%; 95%CI = 7.7–22.1%) and leiomyoma among females (8.9%; 95%CI = 5.2–13.8%). Among hereditary survivors, having a prior SMN was associated with 3.5-fold (95%CI = 2.0–6.1) increased risk of developing a benign tumor; the reciprocal risk for developing an SMN after a benign tumor was 1.8 (95%CI = 1.1–2.9). These large-scale, long-term data demonstrate an increased risk for benign tumors after hereditary versus nonhereditary retinoblastoma. If confirmed, the association between benign tumors and SMNs among hereditary patients may have implications for long-term surveillance.


2017 ◽  
Vol 45 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Øystein Karlstad ◽  
Kari Furu ◽  
Camilla Stoltenberg ◽  
Siri E. Håberg ◽  
Inger Johanne Bakken

Background: Studies from several countries have reported that children youngest in grade are at higher risk of attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment. Norwegian children start school the year they turn six, making children born in December youngest in their grade. We used data on medication, specialist healthcare diagnoses, and primary healthcare diagnoses from national registers to investigate associations between birth month and ADHD. Methods: All children born in Norway between 1998 and 2006 ( N=509,827) were followed from age six until 31 December 2014. We estimated hazard ratios for ADHD medication and diagnoses by birth month in Cox proportional-hazards models. We compared risk among siblings to control for potentially confounding socioeconomic factors, and assessed risk of receiving ADHD medication by birth month while attending different grades in cross-sectional time-series analyses. Results: At end of follow-up, 5.3% of boys born in October–December had received ADHD medication, compared with 3.7% of boys born in January–March. Corresponding numbers for girls were 2.2% and 1.3%, respectively. The adjusted hazard ratio for ADHD medication for children born in October–December (reference: January–March) was 1.4 (95% confidence interval: 1.4–1.5) for boys and 1.8 (1.7–2.0) for girls. Analyses with diagnoses as outcome showed consistent results, and analyses restricted to siblings within the study population also supported the findings. Analysis by grade revealed an increased risk for children born late in the year from grade 3 onwards, with most marked differences in higher grades. Conclusions: Children youngest in grade had the highest risk of receiving ADHD treatment. Differences were most marked among older children.


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