Papers by Nina Kadan-lottick
This thesis details two studies using novel approaches to understand kidney transplant outcomes: ... more This thesis details two studies using novel approaches to understand kidney transplant outcomes: instrumental variables and social network analysis. Together, these studies demonstrate the value of interdisciplinary approaches to advance the field of kidney trans-plantation. While some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long‐term outcomes, a causal relationship remains controversial. In our first study, we investigate this relationship using an instrumental variables model (IVM), a quasi‐randomization technique for drawing causal inferences. We identified 73,714 adult, deceased‐donor, kidney‐only transplant recipients from the Scientific Registry of Transplant Recipients (SRTR) between 1997 and 2010. We used cold is-chemia time (CIT) as an instrument to test the hypothesis that DGF causes death‐censored graft loss and mortality at 1 and 5 years post‐transplant, controlling for an array of characteristics know...
Journal of Pediatric and Adolescent Gynecology, 2021
Background Adolescent and young adult (AYA) women undergoing cancer treatment face unique reprodu... more Background Adolescent and young adult (AYA) women undergoing cancer treatment face unique reproductive health risks. This study sought to determine sexual health practices and communication with oncology providers among female AYA cancer patients. Methods After IRB approval, actively treated cancer patients were offered participation if they were female, age 15-39 years, and English-speaking. Excluded were pregnant patients and those with a history of hysterectomy or removal of both ovaries and/or fallopian tubes. Participants completed an online survey regarding demographics, cancer history, sexual history, and communication with their oncologists. The main outcome measures assessed included rates of contraception, condom use, and sexual activity. Communications about sexual health with oncologists was also assessed. Results The 8 participants were a median of 24 years (range 16-37) with a history of breast cancer (50%), hematologic malignancies (25%), and other malignancies (25%)....
Energy Research & Social Science
Oil and gas development has led to environmental hazards and community concerns, particularly in ... more Oil and gas development has led to environmental hazards and community concerns, particularly in relation to water supply issues. Filing complaints with state agencies enables citizens to register concerns and seek investigations. We evaluated associations between county-level socio-economic and demographic factors, oil and gas drilling, and three outcomes in Pennsylvania between 2004-2016: number of oil and gas complaints filed, and both the number and proportion of state investigations of water supply complaints yielding a confirmed water supply impairment (i.e., "positive determination"). We used hierarchical Bayesian Poisson and binomial regression analyses. From 2004-2016, 9,404 oil and gas-related complaints were filed, of which 4,099 were water supply complaints. Of those, 3,906 received investigations, and 215 yielded positive determinations. We observed a 47% increase in complaints filed per $10,000 increase in annual median household income (MHI) (Rate Ratio [RR]: 1.47, 95% credible interval [CI]: 1.09-1.96) and an 18% increase per 1% increase in educational attainment (RR: 1.18, 95% CI: 1.11-1.26). While the number of complaints filed did not vary by race/ethnicity, the odds of a complaint yielding a positive determination were 0.81 times lower in counties with a higher proportion of marginalized populations (Odds Ratio [OR]: 0.81 per 1% increase in percent Black, Asian, and Native American populations combined, 95% CI: 0.64-0.99). The odds of positive determinations were also lower in areas with higher income (OR per $10,000 increase in MHI: 0.35, 95% CI: 0.09-0.96). Our results suggest these relationships are complex and may indicate potential environmental and procedural inequities, warranting further investigation.
Pediatric patients who undergo hematopoietic cell transplant (HCT) are at risk for neurocognitive... more Pediatric patients who undergo hematopoietic cell transplant (HCT) are at risk for neurocognitive impairments, which can impact quality of life. Given limited long-term studies, we aimed to characterize the late neurocognitive outcomes in a cohort of pediatric HCT survivors. Eligible survivors (HCT at age < 21 year and ≥ 1 year post-HCT) completed a 60-question survey of neurocognitive function and quality of life, which included the Childhood Cancer Survivor Study Neurocognitive Questionnaire (CCSS-NCQ) and the Neuro-Quality of Life Cognitive Function Short Form (Neuro-QoL). Analyses of risk factors included univariate comparisons and multivariable logistic regression. Participants (n = 199, 50.3% female, 53.3% acute leukemia, 87.9% allogeneic transplants) were surveyed at median age of 37.8 years (interquartile range [IQR] 28.5–48.8) at survey and median 27.6 years (IQR 17.0–34.0) from transplant. On the CCSS-NCQ, 18.9–32.5% of survivors reported impairments (Z score > 1.28) in task efficiency, memory, emotional regulation, or organization, compared with expected 10% in the general population (all p < 0.01). In contrast, survivors reported average Neuro-QoL (T score 49.6±0.7) compared with population normative value of 50 (p = 0.52). In multivariable regression, impaired Neuro-QoL (T score < 40) was independently associated with hearing issues (OR 4.97, 95% CI 1.96-12.6), history of stroke or seizure (OR 4.46, 95% CI 1.44-13.8), and sleep disturbances (OR 6.95, 95% CI 2.53–19.1). Although long-term survivors of pediatric HCT reported higher rates of impairment in specific neurocognitive domains, cognitive quality of life was perceived as similar to the general population. Subsets of survivors with certain co-morbidities had substantially worse neurocognitive outcomes. While the long-term impact of pediatric HCT can include neurocognitive deficits, survivors report average cognitive quality of life.
Journal of Clinical Oncology
10035 Background: Although long-term adverse consequences of childhood cancer treatment may be mi... more 10035 Background: Although long-term adverse consequences of childhood cancer treatment may be mitigated by screening, prevention, and interventions, many survivors do not take advantage of survivorship care. We hypothesized that patients who are at risk for poor compliance with long-term follow-up are identifiable at diagnosis. Methods: To identify factors associated with poor follow-up compliance, 7 CONNECCS institutions evaluated a childhood acute lymphoblastic leukemia (ALL) survivor cohort diagnosed 1996-99. Data collected included: diagnosis year, age, race, ethnicity, gender, insurance, distance from center, CNS disease, and risk classification. Primary endpoints were compliance with 5 and 10-year follow-up. Differences in compliance were tested using chi-squared or t-tests. Logistic regression (including institution as a clustering variable) was used to calculate adjusted odds ratios (OR). Results: At diagnosis, the 358 ALL patients were: female (47%), age= 6.5 + 4.6 years, ...
Journal of Clinical Oncology
9584 Background: Childhood ALL survivors are at increased risk of impaired EF. Both parent rating... more 9584 Background: Childhood ALL survivors are at increased risk of impaired EF. Both parent ratings and performance-based measures are used to identify vulnerable patients. We seek to assess the association between these modalities to 1) each other, and 2) need for special education and stimulants. Methods: This 22-site cross-sectional study included 256 children in remission for standard-risk precursor-B ALL previously enrolled on legacy Children's Oncology Protocols from 1993 - 2000. Patients had no history of CNS leukemia, cranial radiation, or pre-existing neurodevelopmental disorders; were ≥1 year off-therapy; and were 6-16 years at evaluation. Patients were administered performance-based measures of working memory, Digit Span (DS) and Letter-Number Sequencing (LNS) comprising the Working Memory Index (WMI) from the Wechsler Intelligence Scales for Children - Fourth Edition. Patients completed the Controlled Oral Word Association Test (COWAT). Parents completed demographic s...
Journal of Clinical Oncology
9546 Background: Obesity is a potential complication in children treated for ALL. Limited data ex... more 9546 Background: Obesity is a potential complication in children treated for ALL. Limited data exist regarding timing of BMI changes and risk in long-term survivors of ALL treated without cranial radiation (CRT). This study describes temporal trends in BMI during and after therapy for SR-ALL and identifies associated factors. Methods: We conducted a retrospective cohort study of children with SR-ALL enrolled on two sequential clinical trials between 1993 and 2000 and on the COG ALTE02C2 follow-up study. Therapy included prednisone or dexamethasone during induction, the same steroid in maintenance phases, and no CRT. Standing height and weight was ascertained at diagnosis (dx), start of consolidation, start of maintenance, start of the last cycle of maintenance, and at least one year off therapy. Age and gender-specific BMI percentiles (BMI%) were calculated using 2000 CDC growth charts for patients 2-20 years. Results: The 269 subjects were a median of 3.5 years at dx, 46.7% female,...
Journal of Clinical Oncology
10063 Background: Little is known regarding the health practices and behaviors of childhood cance... more 10063 Background: Little is known regarding the health practices and behaviors of childhood cancer patients who have not received recommended survivorship care, a group that represents the majority of survivors. Methods: Using the Yale Tumor Registry, consisting of patients from Southern Connecticut, we identified patients who were diagnosed from 2000-2011 with an invasive cancer at age ≤18 years, are currently alive and cancer-free at least one year after therapy, live within 100 miles of Yale HEROS Childhood Cancer Survivor Clinic, never previously attended a survivor clinic, and consented to a research study to investigate survivor care. Participants completed postal or on-line surveys regarding health communication preferences, utilization of services, and behaviors. Results: The 68 participants had a mean age of 16.8 (range 6-27) years at evaluation and 6.7 years since diagnosis with 53% female and 50% currently >18 years. Overall, 100% had seen a primary care physician and ...
Journal of Adolescent Health
PURPOSE The patient-provider relationship has been understudied in adolescents with cancer. The c... more PURPOSE The patient-provider relationship has been understudied in adolescents with cancer. The currentstudy describes an exploratory factor analysis of a patient-provider relationship self-report measure developed for use in adolescent oncology. METHODS A self-report measure was included in an iPad/tablet survey delivered to 102 adolescent cancer patients (diagnosed between the ages of 10 and 20). Principal factor analysis with promax rotation and a three-factor structure was specified. RESULTS The final solution identified three underlying dimensions of the patient-provider relationship-SupportingIndependence (69.7% variance explained; Cronbach's α = .89), Family-Centered Communication (50.0% variance explained; Cronbach's α = .73), and Respectful Relationships (40.1% variance; Cronbach's α = .66). DISCUSSION The current measure highlights the unique developmental place of adolescent cancer patients in their preference for aspects of both patient-centered and family-centered care. The current analysis begins to fill the need for adolescent-tailored measurement to assess the patient-provider relationship in this population.
Journal of Clinical Oncology
PURPOSE Children’s Oncology Group (COG) AALL0331 tested whether intensified postinduction therapy... more PURPOSE Children’s Oncology Group (COG) AALL0331 tested whether intensified postinduction therapy that improves survival in children with high-risk B-cell acute lymphoblastic leukemia (ALL) would also improve outcomes for those with standard-risk (SR) ALL. PATIENTS AND METHODS AALL0331 enrolled 5,377 patients between 2005 and 2010. All patients received a 3-drug induction with dexamethasone, vincristine, and pegaspargase (PEG) and were then classified as SR low, SR average, or SR high. Patients with SR-average disease were randomly assigned to receive either standard 4-week consolidation (SC) or 8-week intensified augmented Berlin-Frankfurt-Münster (BFM) consolidation (IC). Those with SR-high disease were nonrandomly assigned to the full COG-augmented BFM regimen, including 2 interim maintenance and delayed intensification phases. RESULTS The 6-year event-free survival (EFS) rate for all patients enrolled in AALL0331 was 88.96% ± 0.46%, and overall survival (OS) was 95.54% ± 0.31%. ...
Pediatric Blood & Cancer
Background: Survival for SR (age 1-9.99 yrs. and initial white blood cell count <50,000/microlite... more Background: Survival for SR (age 1-9.99 yrs. and initial white blood cell count <50,000/microliter) BALL patients with DS has improved over time through enrollment on therapeutic trials and enhanced supportive care. Objectives: To assess contemporary outcomes for DS patients with SR-ALL. Design/Method: COG AALL0331 utilized a 3-drug induction (IND), with post-induction assignment into refined risk groups (SR-Low, SR-Average (Av), SR-High) based on leukemia genetics and early response. DS patients received risk-stratified therapy with additional supportive care guidelines, including leucovorin rescue after intrathecal methotrexate until maintenance, and highly encouraged hospitalizations during high-risk blocks until neutrophil recovery. SR-Av patients underwent a 2 × 2 randomization at end-IND to standard (SC) vs. intensified consolidation (IC) and standard interim maintenance (IM)/delayed intensification (DI) vs. intensified IM/DI. The IM/DI randomization was closed in 2008 due to superior results of escalating IV methotrexate (MTX) during IM for SR ALL patients treated on CCG 1991; all patients enrolled in AALL0331 subsequently received escalating IV MTX during IM. SR-high DS patients nonrandomly received IC and a single intensified IM/DI vs double IM/DI given to non-DS patients. SR-Low DS and non-DS patients participated in a randomization to additional pegaspargase doses during consolidation and IM. Results: AALL0331 enrolled 5311 SR BALL patients (4/2005-5/2010), 141 (2.7%) had DS. 129 DS patients were CNS1 (91.5%), 11 CNS2 (7.7%) and 1 was CNS3. 138 patients were M1 at end induction, 3 did not have available results. There was no difference in the proportion of patients with a rapid early response or slow early response between DS and non-DS patients (p = 0.578). Risk distribution was significantly different (p<0.0001) for DS vs non-DS patients: SR-Low (15% vs. 47.3%), SR-Av (66.7% vs. 36.9%), and SR-High (18% vs. 15.8%). The 5-year EFS for all SR BALL patients with DS vs non-DS was 86%±3.1% vs 89%±0.45% (p = 0.025), and OS for DS vs non-DS patients was 90%±2.7% vs 96%±0.28% (p<0.0001). IND mortality for DS patients was initially excessive (11.5%), but after additional treatment modifications were made, decreased to 1.7%, 5-year EFS by risk groups for DS vs. non-DS patients was: SR-Low 100.00%±0.00% vs 95.35%±0.51%; SR-Av 88.07%±4.35% vs 89.63%±0.84%, and SR-High 82.35%±9.25% vs 86.18%±1.44%. DS was not prognostic in multivariate analyses that accounted for risk group. Conclusion: With treatment modifications and additional supportive care, SR-ALL DS patients had excellent EFS and OS, similar to patients without DS in equivalent risk groups.
Pediatric Blood & Cancer
Parents’ perception of their children's vulnerability to illness following cancer treatment i... more Parents’ perception of their children's vulnerability to illness following cancer treatment is largely unknown, but is important to understand given known challenges of transitioning survivors to postcancer care. We investigated the frequency of and factors associated with perceived vulnerability by parents of childhood cancer survivors attending a regional survivorship clinic.
Blood
The EFS/OS for SR (age 1-9.99 yrs and initial white blood cell count <50,000/microliter) B-cel... more The EFS/OS for SR (age 1-9.99 yrs and initial white blood cell count <50,000/microliter) B-cell precursor (B-ALL) patients (pts) has steadily improved over time. The COG AALL0331 SR ALL trial utilized a 3 drug induction without anthracylines, with post-induction assignment into refined risk groups (SR-Low, SR-Average (Av), SR-High) based on leukemia genetics and early response. COG studies have shown that intensified post-induction therapy improved EFS/OS in NCI high risk ALL patients <10 yrs of age; however, the relative value of individual components is uncertain. AALL0331 included a 2 X 2 randomization at end-induction to standard (SC) vs. intensified consolidation (IC) and standard interim maintenance (IM) / delayed intensification (DI) vs. intensified IM/DI for SR-Av (not Low or High) pts, defined as those whose leukemic blasts did not show triple trisomies (TT) of chromosomes 4+10+17, ETV6-RUNX1, or very high risk features and had an excellent early response based on day...
Blood
Introduction: Over the past 30 years, survival rates for childhood ALL have improved and neurotox... more Introduction: Over the past 30 years, survival rates for childhood ALL have improved and neurotoxicity has been reduced by largely replacing cranial radiation therapy (CRT) with additional systemic and intrathecal therapy. However, survivors treated without CRT may still be at risk for long-term neurocognitive deficits and reduced quality of life. Neurobehavioral problems during adolescence are particularly problematic as increased environmental demands for self-direction and higher order cognition are expected. As existing studies of cognition and behavior in adolescent survivors are limited by small samples, single-site data collection, and short follow-up intervals, we examined the prevalence of and risk factors for cognitive, behavior, and academic problems in adolescent survivors of childhood ALL using the Childhood Cancer Survivors Study (CCSS) cohort. Methods: Caregiver report data were analyzed for 1426 5+ year survivors of childhood ALL who were diagnosed between 1970 and 1...
Blood
Introduction: Overall, children with new-onset SR (age 1-9 years (yr), WBC <50,000/microliter)... more Introduction: Overall, children with new-onset SR (age 1-9 years (yr), WBC <50,000/microliter) B-ALL enrolled on COG AALL0331 achieved excellent 5-yr event free (EFS) (89%) and overall survival (OS) (96%) (Maloney, ASH 2013). AALL0331 utilized a common 3-drug induction (IND), with post-IND assignment into refined risk groups per clinical, cytogenetic, and early response criteria. The SR-Low group was defined by favorable cytogenetics (triple trisomies of chromosomes 4+10+17 or ETV6-RUNX1), no central nervous system or testicular leukemia, and rapid marrow response (<5% blasts by day (d) 15 and end-IND minimal residual disease (MRD)…
Cancer
BACKGROUND: Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone miner... more BACKGROUND: Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone mineral density (BMD). The authors sought to determine the frequency of reduced BMD detected by off-therapy surveillance, factors associated with reduced BMD, and the association of reduced BMD with fractures. METHODS: This cross-sectional study included childhood leukemia/lymphoma survivors attending 2 survivorship clinics who received guideline-recommended BMD surveillance ≥2 years post-therapy with dual-energy x-ray absorptiometry (from January 1, 2004 to August 31, 2016). Lumbar spine BMD z-scores were height-forage adjusted. Low and very low BMD were >1 SD and >2 SDs below norms, respectively. Treatment, chronic conditions, and fractures were abstracted from medical records. Logistic regression was used to examine the association of low BMD with patient/treatment factors and fractures. RESULTS: In total, 542 patients (51.5% female) with a mean age of 15.5 years (range, 4.4-52.2 years) who were 6 years post-therapy (range, 2.0-35.1 years) were evaluated, including 116 who reported post-therapy fractures. Lumbar spine low BMD was identified in 17.2% of survivors, and very low BMD was identified in 3.5% of survivors, but frequencies varied considerably between subgroups; 10.8% of survivors aged 15 to 19 years at diagnosis had very low BMD. In multivariable analyses, older age at diagnosis, white race, and being underweight were significantly associated with low BMD. Survivors with low BMD had greater odds of nondigit fractures (odds ratio, 2.2; 95% CI, 1.3-3.7) and specifically long-bone fractures (odds ratio, 2.7; 95% CI, 1.5-4.7). CONCLUSIONS: In this study of childhood leukemia/lymphoma survivors undergoing guideline-recommended dual-energy x-ray absorptiometry surveillance, patients who were older at diagnosis, white, and underweight were at the highest risk for lumbar spine low BMD. Low BMD was associated with a greater risk of fractures, emphasizing the clinical importance of surveillance.
JNCI: Journal of the National Cancer Institute
Background A survivorship care plan (SCP), that is, individualized treatment summary and schedule... more Background A survivorship care plan (SCP), that is, individualized treatment summary and schedule of off-therapy surveillance, will be mandated by January 2019. It is unclear whether SCPs improve adherence to recommended follow-up care in the community. In this trial, we evaluated the impact of randomly assigning childhood cancer survivors to 1) SCPs to be taken to their primary care physician (PCP) to implement or 2) survivorship clinic (SC) on health care quality measures. Methods Eligibility included cancer diagnosis younger than age 18 years (2000-2012), cancer free, one or more years off therapy, and no prior survivorship clinic attendance. At 12 months, the random assignment groups were compared (SCP+PCP vs SC) by intent-to-treat analysis with two-sided statistical tests in terms of patient adherence to guideline-recommended surveillance tests (eg, echocardiogram) and number of newly identified late complications of therapy. Results From 2011 to 2013, 96 participants (46.9% female, mean age = 15.9 ± 6.1 years) were randomly assigned. Adherence to 14 evaluated guideline-recommended surveillance tests ranged from 0% to 46.9% in the SCP+PCP group (n = 47) and from 50.0% to 86.4% in the SC group (n = 47). Adherence to 10 tests was statistically significantly different between the groups (all P < .05). One mild new late complication was identified in the SCP+PCP group compared with 21 late complications, ranging from mild to severe, identified in 11 patients in the SC group (2.1% vs 23.4% of patients, respectively, P = .003). Conclusions Our randomized trial suggests that empowering childhood cancer survivors with SCPs to be implemented by their PCPs is not sufficient to meet consensus follow-up recommendations.
The Lancet. Child & adolescent health, 2018
Peripheral neuropathy is a well recognised treatment-related toxicity in children with cancer, as... more Peripheral neuropathy is a well recognised treatment-related toxicity in children with cancer, associated with exposure to neurotoxic chemotherapy agents. Acute damage can occur in sensory, motor, or autonomic neurons, with symptoms that are rarely life threatening, but often severe enough to interfere with function during therapy and after treatment ends. The type of neuropathy and specific symptoms are associated with multiple factors including age at time of therapy, genetic predisposition, chemotherapy type and cumulative dose, and exposure to other agents during therapy. In this Review, we describe the peripheral neuropathy phenotype in children during cancer therapy and among survivors who have completed therapy, to summarise genetic and treatment-related risk factors for neuropathy, and to outline strategies to monitor and detect neuropathy during and after therapy. Additionally, we outline strategies for medical management of neuropathy during treatment and potential rehabil...
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018
Childhood cancer patients report low physical activity levels despite the risk for long-term comp... more Childhood cancer patients report low physical activity levels despite the risk for long-term complications that may benefit from exercise. Research is lacking regarding exercise barriers, preferences, and beliefs among patients (1) on- and off-therapy and (2) across the age spectrum. Cross-sectional study in the Yale Pediatric Hematology-Oncology Clinic (October 2013-October 2014). Participants were ≥ 4 years old, > 1 month after cancer diagnosis at < 20 years, not acutely ill, expected to live > 6 months, and received chemotherapy and/or radiation. Participants (or parents if < 13 years) completed a survey. The 162 patients (99% participated) were 34% children (4.0-12.9 years), 31% adolescents (13.0-17.9 years), and 35% adults (≥ 18 years). Most had leukemia/lymphoma (66%); 32% were on-therapy. On-therapy patients were more likely than off-therapy patients (73 vs. 48%; p = 0.003) to report ≥ 1 barrier related to physical complaints, such as "just too tired" (4...
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Papers by Nina Kadan-lottick