A semiparametric likelihood-based method for regression analysis of mixed panel-count data

Panel-count data arise when each study subject is observed only at discrete time points in a recurrent event study, and only the numbers of the event of interest between observation time points are recorded (Sun and Zhao, 2013). However, sometimes the exact number of events between some observation times is unknown and what we know is only whether the event of interest has occurred. In this article, we will refer this type of data to as mixed panel-count data and propose a likelihood-based semiparametric regression method for their analysis by using the nonhomogeneous Poisson process assumption. However, we establish the asymptotic properties of the resulting estimator by employing the empirical process theory and without using the Poisson assumption. Also, we conduct an extensive simulation study, which suggests that the proposed method works well in practice. Finally, the method is applied to a Childhood Cancer Survivor Study that motivated this study

Stroke impact on mortality and psychologic morbidity within the Childhood Cancer Survivor Study.

BackgroundPoor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).MethodsThe CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.ResultsAmong 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).ConclusionsStroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer

Prospective Safety Surveillance of GH-Deficient Adults: Comparison of GH-Treated vs Untreated Patients.

Context:In clinical practice, the safety profile of GH replacement therapy for GH-deficient adults compared with no replacement therapy is unknown.Objective:The objective of this study was to compare adverse events (AEs) in GH-deficient adults who were GH-treated with those in GH-deficient adults who did not receive GH replacement.Design and Setting:This was a prospective observational study in the setting of US clinical practices.Patients and Outcome Measures:AEs were compared between GH-treated (n = 1988) and untreated (n = 442) GH-deficient adults after adjusting for baseline group differences and controlling the false discovery rate. The standardized mortality ratio was calculated using US mortality rates.Results:After a mean follow-up of 2.3 years, there was no significant difference in rates of death, cancer, intracranial tumor growth or recurrence, diabetes, or cardiovascular events in GH-treated compared with untreated patients. The standardized mortality ratio was not increased in either group. Unexpected AEs (GH-treated vs untreated, P ≤ .05) included insomnia (6.4% vs 2.7%), dyspnea (4.2% vs 2.0%), anxiety (3.4% vs 0.9%), sleep apnea (3.3% vs 0.9%), and decreased libido (2.1% vs 0.2%). Some of these AEs were related to baseline risk factors (including obesity and cardiopulmonary disease), higher GH dose, or concomitant GH side effects.Conclusions:In GH-deficient adults, there was no evidence for a GH treatment effect on death, cancer, intracranial tumor recurrence, diabetes, or cardiovascular events, although the follow-up period was of insufficient duration to be conclusive for these long-term events. The identification of unexpected GH-related AEs reinforces the fact that patient selection and GH dose titration are important to ensure safety of adult GH replacement

Maternal health conditions during pregnancy and acute leukemia in children with Down syndrome: A Children's Oncology Group study

Children with Down syndrome (DS) have about a 20-fold increased risk of developing leukemia. Early childhood infections may protect against acute lymphoid leukemia (ALL) in children with and without DS. We examined whether maternal infections and health conditions during pregnancy were associated with acute leukemia in children with DS

Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort

Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers

Vitamin supplement use among children with Down syndrome and risk of leukemia: A Children’s Oncology Group (COG) Study

Vitamin supplements have been proposed for children with Down syndrome (DS) with claims of improving cognitive abilities, or immune or thyroid function. Several studies have shown decreased levels of zinc in this population. Because children with DS have a 50-fold increased risk of developing acute leukemia during the first 5 years of life, we explored the relation between child vitamin and herbal supplement use and the risk for leukemia in a case-control study. During the period 1997–2002, we enrolled 158 children with DS aged 0–18 years that were diagnosed with acute lymphoblastic leukemia (ALL) (n=97) or acute myeloid leukemia (AML) (n=61) at participating COG institutions. We enrolled 173 DS children without leukemia (controls), selected from the cases’ primary care clinic and frequency matched on age. Data were collected via telephone interviews with mothers of the index child regarding use of multivitamins, zinc, vitamin C, iron, and herbal supplements, including age at first use, frequency and duration. Among controls, 57% reported regular multivitamin use (≥ 3 times/week for ≥ 3 months) compared with 48% of ALL cases and 61% of AML cases. We found no evidence of an association between child’s regular multivitamin use and ALL or AML (adjusted odds ratios (ORs)=0.94 [95% confidence interval 0.52, 1.70] and 1.90 [0.73, 4.91], respectively. There was a suggestion of an increased risk for AML associated with regular multivitamin use during the first year of life or for an extended duration (ORs = 2.38 [0.94, 5.76] and 2.59 [1.02, 6.59], respectively). Despite being the largest study of DS-leukemia, our sample size was small, resulting in imprecise effect estimates. Future research should include larger sample sizes as well as a full assessment of diet including vitamin supplementation to adequately examine the relation between nutritional status and childhood leukemia

Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study

Objective: GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design: Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database. Methods: Evident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries. Results: During the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74-1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73-1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76-1.69). For GH-treated patients from the USA aged < 35 years, the SIR (six cases) was 3.79 (1.39-8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18-5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30-1.08). Conclusions: With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age < 35 years or CO GHD

Auditory complications in childhood cancer survivors: A report from the childhood cancer survivor study

Studies have found associations between cancer therapies and auditory complications, but data are limited on long-term outcomes and risks associated with multiple exposures