Cardiac biomarkers and association with subsequent cardiomyopathy and mortality among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

BACKGROUND: Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest-directed radiation therapy (RT). NT-proBNP values above age- and sex-specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross-sectional associations between abnormal NT-proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death. RESULTS: At a median age of 35.5 years (interquartile range, 29.8-42.5 years), NT-proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose-dependent increased risk for abnormal NT-proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events-graded cardiomyopathy and with normal systolic function, survivors with abnormal NT-proBNP had higher rates per 1000 person-years of cardiac mortality (2.93 vs 0.96; P < .0001) and future cardiomyopathy (32.10 vs 15.98; P < .0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28-4.08) according to a multivariable assessment. CONCLUSIONS: Abnormal NT-proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding.

Exercise right heart catheterization for pulmonary hypertension identified on screening echocardiography in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

Pulmonary hypertension, determined noninvasively by tricuspid regurgitant jet velocity on Doppler echocardiography, was previously identified in 25% of long-term survivors who received chest-directed radiotherapy. To validate noninvasively defined pulmonary hypertension, survivors (mean age 48 years), exposed to chest radiotherapy, underwent right heart catheterization with planned cardiopulmonary exercise testing during catheterization. Eight participants had an elevated mean pulmonary artery pressure at rest (≥25 mm Hg) or with subsequent exercise (>30 mm Hg), evidence of hemodynamically confirmed pulmonary hypertension by right heart catheterization. Cardiopulmonary exercise testing further defined the magnitude and etiology of cardiopulmonary limitations in this life-threatening late effect.

Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy: A Cross-sectional Study.

BACKGROUND: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data. OBJECTIVE: To systematically assess cardiac outcomes among survivors of childhood cancer. DESIGN: Cross-sectional study. SETTING: St. Jude Children's Research Hospital. PATIENTS: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier. MEASUREMENTS: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test. RESULTS: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 [95% CI, 1.1 to 6.9]) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 [CI, 1.1 to 3.7]) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. LIMITATIONS: Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available. CONCLUSION: Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer. PRIMARY FUNDING SOURCE: National Cancer Institute, American Lebanese Syrian Associated Charities.

Long-term decline in intelligence among adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation.

Survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy (CRT) are at risk for cognitive impairment, although whether impairment progresses with age into adulthood is unknown. We report change in intelligence for 102 adult survivors of childhood ALL (age range, 26.6-54.7 years) during a median interval of 28.5 years. Survivors demonstrated lower Performance intelligence (mean, 95.3; standard deviation, 16.5; P = .005) but not Verbal IQ (mean, 97.4; standard deviation, 15.44; P = .09) at initial testing. Verbal intelligence declined an average of 10.3 points (P < .0001) during the follow-up interval with no decline in Performance intelligence. Decline was associated with current attention problems (P = .002) but not gender, CRT dose, age at CRT exposure, or years between testing. Results suggest long-term survivors of childhood ALL treated with CRT are at risk for progressive decline in verbal intellect, which may be driven by attention deficits. This trial was registered at clinicaltrials.gov as no. NCT00760656.

Using an mHealth approach to collect patient-generated health data for predicting adverse health outcomes among adult survivors of childhood cancer.

Introduction: Cancer therapies predispose childhood cancer survivors to various treatment-related late effects, which contribute to a higher symptom burden, chronic health conditions (CHCs), and premature mortality. Regular monitoring of symptoms between clinic visits is useful for timely medical consultation and interventions that can improve quality of life (QOL). The Health Share Study aims to utilize mHealth to collect patient-generated health data (PGHD; daily symptoms, momentary physical health status) and develop survivor-specific risk prediction scores for mitigating adverse health outcomes including poor QOL and emergency room admissions. These personalized risk scores will be integrated into the hospital-based electronic health record (EHR) system to facilitate clinician communications with survivors for timely management of late effects. Methods: This prospective study will recruit 600 adult survivors of childhood cancer from the St. Jude Lifetime Cohort study. Data collection include 20 daily symptoms via a smartphone, objective physical health data (physical activity intensity, sleep performance, and biometric data including resting heart rate, heart rate variability, oxygen saturation, and physical stress) via a wearable activity monitor, patient-reported outcomes (poor QOL, unplanned healthcare utilization) via a smartphone, and clinically ascertained outcomes (physical performance deficits, onset of/worsening CHCs) assessed in the survivorship clinic. Participants will complete health surveys and physical/functional assessments in the clinic at baseline, 2) report daily symptoms, wear an activity monitor, measure blood pressure at home over 4 months, and 3) complete health surveys and physical/functional assessments in the clinic 1 and 2 years from the baseline. Socio-demographic and clinical data abstracted from the EHR will be included in the analysis. We will invite 20 cancer survivors to investigate suitable formats to display predicted risk information on a dashboard and 10 clinicians to suggest evidence-based risk management strategies for adverse health outcomes. Analysis: Machine and statistical learning will be used in prediction modeling. Both approaches can handle a large number of predictors, including longitudinal patterns of daily symptoms/other PGHD, along with cancer treatments and socio-demographics. Conclusion: The individualized risk prediction scores and added communications between providers and survivors have the potential to improve survivorship care and outcomes by identifying early clinical presentations of adverse events.

Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.

BACKGROUND: Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors. METHODS: Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors. RESULTS: Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)]. CONCLUSIONS: Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies. IMPACT: These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.

Women's perspectives on counseling about risks for medication-induced birth defects.

PURPOSE: This qualitative study explored women's experiences with counseling about medication-induced birth defects, as well as how and when they would like to receive information on medication-induced birth defects from their health care providers (HCPs). METHODS: We conducted four focus groups with 36 women of reproductive age (18-45 years old) in Pittsburgh, Pennsylvania. Twenty-one women were using medications to treat a chronic health condition, and two were pregnant. Content analysis was performed by three independent coders using a grounded theory approach. Discrepancies were resolved by consensus. RESULTS: Women reported depending on their HCPs for information about the risks of teratogenic effects of medications on a pregnancy, but felt the information they had been provided was not always comprehensive. Women want HCPs to initiate discussions about potentially teratogenic medications at the time the medications are prescribed, regardless of whether the woman is sexually active or planning a pregnancy. Women want clear information about all potential outcomes for a fetus. Factors women reported as being critical to effective teratogenic risk counseling included privacy, sufficient time to discuss the topic, and a trusting relationship with their HCP. CONCLUSIONS: Women of reproductive age think that providing information about the possible teratogenic effects of medications could be improved by routine discussions of teratogenic risks at the time medications are prescribed.

Exercise Intolerance, Mortality, and Organ System Impairment in Adult Survivors of Childhood Cancer.

PURPOSE: Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality. METHODS: Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality. RESULTS: Survivors (mean age ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min; P for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance. CONCLUSION: Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.

Association of Exercise Intolerance With Emotional Distress, Attainment of Social Roles, and Health-Related Quality of Life Among Adult Survivors of Childhood Cancer.

Importance: Exercise intolerance is associated with increased risk for morbidity and mortality in childhood cancer survivors. However, an association between exercise intolerance and psychosocial outcomes has not been fully explored. Objective: To examine the associations between exercise intolerance and emotional distress, attainment of social roles, and health-related quality of life in childhood cancer survivors. Design, Setting, and Participants: A cross-sectional study including 1041 adult survivors of childhood cancer and 286 community controls in the St Jude Lifetime Cohort was conducted at St Jude Children's Research Hospital. The study was performed from April 1, 2012, to March 15, 2020. Exposures: Exercise intolerance was defined as relative peak oxygen uptake less than 85% of age- and sex-estimated levels from maximal cardiopulmonary exercise testing. Main Outcomes and Measures: Emotional distress was measured with the 18-item Brief Symptom Inventory-18, which includes overall Global Severity Index and depression, anxiety, and somatization subscales. Participants with T scores greater than or equal to 63 were classified as having elevated levels of distress. Social attainment was evaluated using patient-reported educational, employment, and marital status. Health-related quality of life was examined with the Medical Outcomes Survey Short Form-36. Participants with T scores less than or equal to 40 were classified as reporting poor health-related quality of life. Results: Of the 1041 participants, 528 were women (50.7%). The prevalence of exercise intolerance among survivors (mean [SD] age, 35.5 [9.2] years) was higher than that among controls (age, 34.5 [10.0] years) (survivors: 634 [60.9%] vs controls: 75 [26.2%], P < .001). After adjusting for age at diagnosis and cardiopulmonary exercise testing, sex, race/ethnicity, smoking, physical activity, and exercise intolerance were associated with an increased risk for anxiety (prevalence rate ratio [PRR], 1.95; 95% CI, 1.20-3.16), somatization (PRR, 1.86; 95% CI, 1.23-2.80), and unemployment (PRR, 1.76; 95% CI, 1.23-2.52); an inverse association was noted with having a college degree (PRR, 0.67; 95% CI, 0.50-0.88). Exercise intolerance was associated with an increased the risk for scoring less than or equal to 40 on the physical component summary of the Medical Outcomes Survey Short Form-36 (PRR, 3.69; 95% CI, 2.34-5.84). These associations persisted when either cancer treatment exposures or chronic health conditions were added to the model. Conclusions and Relevance: The findings of this study suggest that exercise intolerance is independently associated with emotional distress, attainment of social roles, and health-related quality of life of long-term survivors of childhood cancer. The results also suggest that improving physiologic capacity may benefit general health and wellness, as well as emotional health, ability to participate in social roles, and health-related quality of life.

Perspectives of primary care clinicians on teratogenic risk counseling.

BACKGROUND: Women of childbearing age are commonly prescribed medications by primary care providers (PCPs) that may cause birth defects if used during pregnancy. METHODS: To identify what PCPs perceive as barriers to and potential facilitators of providing counseling to women of childbearing age when teratogenic medications are prescribed, we conducted eight focus groups with 48 PCPs recruited from four clinical settings in Pittsburgh, Pennsylvania. We explored PCPs' experiences counseling women about teratogenic medications. Each focus group was audio-recorded, transcribed, and coded using a grounded theory approach by three independent coders. RESULTS: PCPs feel responsible for counseling women when they prescribe medications that may cause birth defects, but note difficulties identifying clinically relevant sources of information on teratogenicity. Other barriers to providing counseling include limited visit times and lack of reimbursement for preconception or teratogenic risk counseling. PCPs find it challenging to identify patients who may become pregnant and who therefore need contraceptive and/or teratogenic risk counseling. PCPs expressed a desire for online resources that could be used when explaining medication risks to patients. PCPs feel that the development of patient information materials, electronic decision support tools, clinical care systems that routinely assess patients' pregnancy risk, and changes in the reimbursement structure may facilitate counseling patients about teratogenic risks. CONCLUSIONS: PCPs perceive themselves as playing an important role in providing their patients information on risk of medication-induced birth defects. To ensure safe prescription of teratogenic medications, PCPs suggest interventions at both the clinic and healthcare system levels.

Patient difficulty using tablet computers to screen in primary care.

BACKGROUND: Patient-administered computerized questionnaires represent a novel tool to assist primary care physicians in the delivery of preventive health care. OBJECTIVE: The aim of this study was to assess patient-reported ease of use with a self-administered tablet computer-based questionnaire in routine clinical care. DESIGN: All patients seen in a university-based primary care practice were asked to provide routine screening information using a touch-screen tablet computer-based questionnaire. Patients reported difficulty using the tablet computer after completion of their first questionnaire. PATIENTS: Ten thousand nine hundred ninety-nine patients completed the questionnaire between January 2004 and January 2006. MEASUREMENTS: We calculated rates of reporting difficulty (no difficulty, some difficulty, or a lot of difficulty) using the tablet computers based on patient age, sex, race, educational attainment, marital status, and number of comorbid medical conditions. We constructed multivariable ordered logistic models to identify predictors of increased self-reported difficulty using the computer. RESULTS: The majority of patients (84%) reported no difficulty using the tablet computers to complete the questionnaire, with only 3% reporting a lot of difficulty. Significant predictors of reporting more difficulty included increasing age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.05-1.05)]; Asian race (OR 2.3, 95% CI 1.8-2.9); African American race (OR 1.4, 95% CI 1.2-1.6); less than a high school education (OR 3.0, 95% CI 2.6-3.4); and the presence of comorbid medical conditions (1-2: OR 1.3, 95% CI 1.2-1.5; > or =3: OR 1.7 95% CI 1.5-2.1). CONCLUSIONS: The majority of primary care patients reported no difficulty using a self-administered tablet computer-based questionnaire. While computerized questionnaires present opportunities to collect routine screening information from patients, attention must be paid to vulnerable groups.

Vagal tone and temperament as predictors of emotion regulation strategies in young children.

We examined indices of vagal tone and two dimensions of temperament as predictors of emotion regulation (ER) strategies among children (n = 54, ages 4-7) of mothers with a history of depression and control mothers. Children's (adaptive and maladaptive) ER strategies were observed during a delay of gratification (frustration) task in one protocol. In a separate and independent protocol, vagal tone was assessed during rest (baseline), during emotional challenge (reactivity) and post-challenge (recovery) and mothers rated their children's temperament (effortful control, negative affectivity). Lower vagal recovery and higher negative affectivity were associated with maladaptive ER responses to frustration. However, vagal tone and temperament were not associated with adaptive ER responses and maternal depression status did not affect the results. Overall, the findings are consistent with models of vagal tone and temperament as markers of individual differences in ER.

One-Year Developmental Outcomes for Infants of Mothers With Bipolar Disorder.

OBJECTIVE: Few data about the development of infants born to women with bipolar disorder have been published. We hypothesized that infants of women with bipolar disorder (by DSM-IV criteria) treated with psychotropics (BD+) or untreated with psychotropics (BD-) would demonstrate poorer cognitive and behavioral development than infants of controls. On the basis of previous studies, we expected that psychotropic-exposed infants of women in the BD+ group would have poorer neuromotor performance during infancy. METHODS: This longitudinal study included 197 mother-infant dyads recruited to participate between July 2006 and March 2011: 81 with prenatal maternal bipolar disorder without psychotropic treatment (BD-, n = 27) or bipolar disorder with psychotropic exposure (BD+, n = 54) and 116 in which infants were exposed to neither bipolar disorder nor psychotropics. Maternal psychopathology and pharmacotherapy exposure assessments were completed at 20, 30, and 36 prenatal weeks and 12, 26, and 52 weeks postpartum. Infants were evaluated with the Bayley Scales of Infant Development, Second Edition, which included the psychomotor (Psychomotor Development Index [PDI]), cognitive (Mental Development Index [MDI]), and behavioral (Behavioral Rating Scale [BRS]) components. RESULTS: Neither prenatal exposure to BD- or BD+ significantly impacted overall PDI (P = .2449), MDI (P = .7886), or BRS (P = .6072) scores. However, we observed a significant effect of BD+ exposure-by-time interaction for the BRS Motor Quality index (F245 = 3.16, P = .0441), with BD+ exposed infants less likely to be above the 75th percentile at the 52-week assessment (mean = 11.5%) compared with BD- (mean = 40.0%) and nonexposed infants (mean = 48.4%). CONCLUSIONS: We found no significant impact of prenatal BD- or BD+ exposure on infant PDI, MDI, or overall BRS scores at 12, 26, or 52 weeks of age, with most scores remaining within normal limits. Consistent with previous studies, we found a specific effect of prenatal BD+ exposure on quality of motor functioning at 1 year. However, the majority of infants were within normal limits on this developmental outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00585702.

Increasing Cardiomyopathy Screening in Childhood Cancer Survivors: A Cost Analysis of Advanced Practice Nurse Phone Counseling.

PURPOSE/OBJECTIVES: To document the per survivor and per additional survivor screening costs of a mailed survivorship care plan (SCP) with advanced practice nurse (APN) telephone counseling (SCP+C) or without APN telephone counseling (SCP).
. DESIGN: Randomized, longitudinal clinical trial.
. SETTING: St. Jude Children's Research Hospital in Memphis, Tennessee.
. SAMPLE: 411 at-risk pediatric cancer survivors (aged 26-59 years), stratified by age (younger than 30 years versus 30 years or older), recommended screening frequency (every one, two, or five years), gender, and cancer diagnosis (hematologic versus solid tumor).
. METHODS: Clinical and resource data costs were derived from trial data and external estimates.
. MAIN RESEARCH VARIABLES: The cost-effectiveness of left ventricular systolic function screening per survivor and per each additional survivor screened.
. FINDINGS: The per-survivor costs of SCP (n = 206) and SCP+C (n = 205) were $74.91 and $224.69, respectively. The estimated costs of SCP and SCP+C per additional survivor screened for two years disseminated in a medium-sized clinic (n = 101 survivors annually) were $345.41 and $293.85, respectively.
. CONCLUSIONS: Adding APN counseling to a printed SCP may help preserve cardiac health at little or no cost per additional survivor screened.
. IMPLICATIONS FOR NURSING: APN counseling is cost-effective and superior to the standard of care in supporting at-risk survivors' cardiac screening participation.

Idiodynamic profiles of cardiovascular activity: a P-technique approach.

A study was conducted to expand the conventional view of cardiovascular (CV) reactivity by using the idiodynamic paradigm for investigation of individuals. Patterns of autonomic CV regulation were assessed in six subjects across diverse laboratory tasks on three separate occasions. Individual CV profiles were derived from these data with P-technique factor analysis, and then group aggregated with chain P-technique. The composite pattern suggested a three-component solution consisting of cardiac rate, cardiac contractility, and peripheral resistance factors. Individual profiles were compared to the composite pattern; these profiles differed in the number of components derived, percentage variance explained by these components, and relative dominance of specific CV components. A hypothesis that emerged is that the subjects differed in the complexity of CV control. It appears that the idiodynamic framework, combined with novel research designs and statistical methods, may help expand the view of CV reactivity beyond the traditional unitary view as response magnitude.

Impact of prenatal exposure to serotonin reuptake inhibitors or maternal major depressive disorder on infant developmental outcomes.

OBJECTIVE: To examine the impact of prenatal exposure to both serotonin reuptake inhibitors (SRIs; during any trimester) and maternal major depressive disorder (MDD; by DSM-IV criteria) on infant functioning. We hypothesized that infants with prenatal exposure to SRIs or MDD would have lower psychomotor, mental, and behavioral scores compared with nonexposed infants. METHOD: This longitudinal study included 166 mother-infant dyads: 68 with prenatal MDD/SRI (n = 41) or MDD/no SRI exposure (n = 27) and 98 nonexposed controls. Maternal depression and SRI exposure assessments were completed at or as near to 20, 30, and 36 prenatal weeks and 12, 26, 52, and 78 weeks postpartum as feasible. Infants were evaluated with the Bayley Scales of Infant Development, Second Edition, including the psychomotor (Psychomotor Development Index; PDI), cognitive (Mental Development Index; MDI), and behavioral (Behavioral Rating Scale; BRS) components. Study assessments occurred between 2003 and 2009. RESULTS: Neither prenatal exposure to MDD/SRI nor MDD/no SRI significantly impacted overall PDI, MDI, or BRS scores. However, we observed a significant SRI exposure by time interaction for the PDI (P = .038). MDD/SRI exposure was associated with lower PDI scores at 26 (mean = 97.0) and 52 weeks (mean = 92.9) compared with nonexposed infants (mean = 101.4 and 100.5). This difference was no longer significant at the 78-week assessment. CONCLUSIONS: Consistent with previous studies, we found no impact of prenatal MDD/SRI exposure on MDI scores. Less favorable PDI scores were observed in the first year; notably, these scores remained well within the normative range. The effects of prenatal MDD/SRI exposure on motor functioning may be transitory. A longitudinal pattern of poor developmental outcomes has not been established. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00279370.

Incidental detection of late subsequent intracranial neoplasms with magnetic resonance imaging among adult survivors of childhood cancer.

PURPOSE: Survivors of childhood cancer are at an increased risk of developing subsequent neoplasms. In long-term survivors of childhood malignancies treated with and without cranial radiation therapy (CRT), undergoing unenhanced magnetic resonance imaging (MRI) of the brain, we estimated detection of intracranial neoplasms. METHODS: To investigate neurocognitive outcomes, 219 survivors of childhood cancer underwent unenhanced screening MRI of the brain. Of the survivors, 164 had been treated for acute lymphoblastic leukemia (ALL) (125 received CRT) and 55 for Hodgkin lymphoma (HL) (none received CRT). MRI examinations were reviewed and systematically coded by a single neuroradiologist. Demographic and treatment characteristics were compared for survivors with and without subsequent neoplasms. RESULTS: Nineteen of the 219 survivors (8.7 %) had a total of 31 subsequent intracranial neoplasms identified by neuroimaging at a median time of 25 years (range 12-46 years) from diagnosis. All neoplasms occurred after CRT, except for a single vestibular schwannoma within the cervical radiation field in a HL survivor. The prevalence of subsequent neoplasms after CRT exposure was 14.4 % (18 of 125). By noncontrast MRI, intracranial neoplasms were most suggestive of meningiomas. Most patients presented with no specific, localizing neurological complaints. In addition to the schwannoma, six tumors were resected based on results of MRI screening, all of which were meningiomas on histologic review. CONCLUSION: Unenhanced brain MRI of long-term survivors of childhood cancer detected a substantial number of intracranial neoplasms. Screening for early detection of intracranial neoplasms among aging survivors of childhood cancer who received CRT should be evaluated. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of incidentally detected subsequent intracranial neoplasms after CRT in long-term survivors of childhood cancer and the minimal symptoms reported by those with intracranial tumors in our study indicate that brain MRI screening of long-term survivors who received CRT may be warranted. Prospective studies of such screening are needed.

Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy.

BACKGROUND: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. METHODS: We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. RESULTS: Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose-response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT). CONCLUSIONS: Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.

Providers' perspectives on challenges to contraceptive counseling in primary care settings.

BACKGROUND: Although three quarters of reproductive-age women see a health provider annually, less than half receive recommended contraceptive counseling services. We sought to explore providers' perspectives on the challenges to contraceptive counseling in primary care clinics to develop strategies to improve counseling services. METHODS: A qualitative, focus group (n = 8) study was conducted in November and December 2007; 48 of 90 providers practicing in four primary care clinics at the University of Pittsburgh Medical Center participated. Providers included physicians, nurses, and pharmacists working in these clinics' multidisciplinary teams. Discussions explored perceived barriers to the provision of counseling services. All groups were audiorecorded, transcribed, and entered into Atlas.Ti, a qualitative data management software. The data were analyzed using a grounded theory approach to content analysis. RESULTS: Perceived patient, provider, and health system barriers to contraceptive counseling were identified. Perceived patient barriers included infrequent sexual activity, familiarity with a limited number of methods, desire for pregnancy despite medical contraindications, and religious beliefs. Provider barriers included lack of knowledge, training, and comfort; assumptions about patient pregnancy risk; negative beliefs about contraceptive methods; reliance on patients to initiate discussions; and limited communication between primary care providers (PCPs) and subspecialists. Health system barriers included limited time and competing medical priorities. CONCLUSIONS: PCPs vary widely in their knowledge, perceived competence, and comfort in providing contraceptive counseling. General efforts to improve integration of contraceptive counseling into primary care services in addition to electronic reminders and efficient delivery of contraceptive information are needed.