Demographic and Clinical Factors Associated With Health-Related Quality-of-Life Profiles Among Prostate Cancer Survivors.

PURPOSE: Our purpose was to describe the prevalence and predictors of symptom and function clusters related to physical, emotional, and social components of general health-related quality of life (HRQOL) in a population-based sample of prostate cancer (PCa) survivors. METHODS: Participants (N = 1,162) completed a baseline survey at a median of 9 months after diagnosis to ascertain the co-occurrence of eight symptom and functional domains that are common across all cancers and not treatment-specific. We used latent profile analysis (LPA) to identify subgroup profiles of survivors with low, moderate, or high HRQOL levels. Multinomial logistic regression models were used to identify clinical and sociodemographic factors associated with survivors' membership in the low versus moderate or high HRQOL profile. RESULTS: The LPA identified 16% of survivors who were categorized in the low HRQOL profile at baseline, indicative of the highest symptom burden and lowest functioning. Factors related to survivors' membership in the low versus higher HRQOL profile groups included less than age 65 years at diagnosis, identifying as non-Hispanic Black race, not working, being a former versus never smoker, systemic therapy, less companionship, more comorbidities, lower health care financial well-being, or less spirituality. Several factors remained associated with remaining in the low versus higher HRQOL profiles on the follow-up survey (n = 699), including younger age, Black race, comorbidity, and lower financial and spiritual well-being. CONCLUSION: About one of six PCa survivors experienced elevated physical and psychosocial symptoms that were independent of local curative therapy, but with younger age, race, comorbidity, and lower financial and spiritual well-being as stable risk factors for poor HRQOL over time.

Hormonal treatment for newly diagnosed metastatic prostate cancer: a population-based study from the California cancer registry.

INTRODUCTION: To evaluate how often men with metastatic prostate cancer (mPC) receive standard of care treatment with androgen deprivation therapy (ADT). METHODS: Men aged ≥20 years with newly diagnosed mPC (stage IV) between 2010 and 2018 were identified using California Cancer Registry data. Receipt of hormonal therapy as initial cancer treatment was examined by patient/tumor characteristics at time of diagnosis. Chi-square tests and logistic regression, adjusted for covariates, were performed to assess association between receipt of hormonal therapy and patient/tumor characteristics. RESULTS: We identified 13,680 men with newly diagnosed mPC, of which 3637 had local metastasis (N1) only while 9596 had distant metastasis (M1) with or without N1 disease. 21.8 % (n = 2980) of men did not receive ADT. The highest rate of receiving ADT was among men between ages 75-84 (81.6%) and the lowest rate was in men over 85 (76.0%). Asian men had the largest proportion receiving ADT (n = 962, 81.5%) with remaining subgroups having similar proportion of men receiving ADT (76.8% to 77.2%). Once adjusted for covariates, regression results showed men with a higher Gleason score (8-10) were more likely to receive ADT (OR 2.04, 1.82-2.27, p = < 0.001) as well as men with distant sites of metastatic disease (OR 4.02, 3.62-4.46, p = < 0.001). Men residing in neighborhoods with the lowest socioeconomic status were least likely to receive ADT (OR 0.79, 0.68-0.93, p = 0.0032). No differences in receipt of ADT were observed by race/ethnicity. DISCUSSION: Despite significant advancements in the treatment of mPC in recent years, over one-fifth of patients did not receive ADT, which is the backbone for all new systemic therapies. This dataset might help address some of the prostate cancer care disparities in California.

Underutilization of intravesical chemotherapy and immunotherapy for high grade non-muscle invasive bladder cancer in California between 2006-2018: Effect of race, age and socioeconomic status on treatment disparities.

OBJECTIVE: Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), those with high risk disease have the greatest risk of recurrence and disease progression. The underutilization of intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) has been a longstanding concern in clinical practice. This study aimed to determine the disparities present in receipt of adjuvant intravesical chemotherapy and immunotherapy in treatment of patients with high grade NMIBC following initial transurethral resection of a bladder tumor (TURBT). METHODS: The California Cancer Registry data was used to identify 19,237 patients diagnosed with high grade NMIBC who underwent TURBT. Treatment variables include re-TURBT, re-TURBT and intravesical chemotherapy (IVC) and/or BCG. Independent variables include age, sex, race/ethnicity, neighborhood socioeconomic status (nSES), primary insurance payer and marital status at diagnosis. Multiple logistic regression and multinomial regression models were used to examine variation in the treatments received following TURBT. RESULTS: The proportion of patients receiving TURBT followed by BCG was similar across all racial and ethnic groups (28%-32%). BCG therapy was higher in patients belonging to the highest nSES quintile (37% for highest vs. 23%-26% for the 2 lowest quintiles). In multiple variable analyses, receipt of any intravesical therapy (IVT) was influenced by nSES, age, marital status, race/ethnicity, and insurance type. Patients in the lowest nSES quintile had a 45% less likelihood of receiving IVT compared to the highest nSES group (OR [95%CI]: 0.55[0.49, 0.61]). Race/ethnicity differences in receipt of any adjuvant therapy were noted in the middle to lowest nSES quintile for Hispanic and Asian/Pacific Islander patients when compared to non-Hispanic White patients. When comparing variation in treatment by insurance type at diagnosis, those with Medicare or other insurance were 24% and 30% less likely to receive BCG after TURBT compared to those with private insurance, (OR [95%CI]: 0.76 [0.70, 0.82] and 0.70[0.62, 0.79]) respectively. CONCLUSION: In patients with a diagnosis of high risk NMIBC, disparities in utilization of BCG are seen based on SES, age, and insurance type.

Association of Sociodemographic Characteristics With Survival Among Patients With Urachal Cancer in California From 1988 to 2019.

This cohort study evaluates the sociodemographic characteristics of patients with urachal cancer, cancer treatments, and the association of patient characteristics with overall survival.

Physical activity and bleeding outcomes among people with severe hemophilia on extended half-life or conventional recombinant factors.

BACKGROUND: Few have assessed physical activity (PA) and annual bleed rates (ABRs) among people with hemophilia on extended half-life (EHL) factors (recombinant factor VIII Fc [rFVIIIFc]/recombinant factor IX Fc [rFIXFc]) and conventional factors (recombinant factor VIII [rFVIII]/recombinant factor IX [rFIX]). OBJECTIVE: To assess changes in PA and ABR at consecutive annual visits in individuals with severe hemophilia A and B (HA/HB) on prophylactic treatment with rFVIIIFc/rFIXFc versus rFVIII/rFIX. PATIENTS/METHODS: We conducted a retrospective chart review of 344 people with severe HA/HB (ages 6-35) receiving prophylaxis with rFVIIIFc/rFIXFc (EHL factors) or rFVIII/rFIX (conventional factors) for ≥6 months in 2014-2015. Differences in changes in outcomes from 2014 to 2015 were compared across the treatment groups. RESULTS: Baseline characteristics and adherence to the prophylactic regimen were similar across the treatment groups. Greater increase in weekly PA frequency and duration were observed among all EHL groups, except for children treated with rFIXFc. The increase in PA frequency was greater among the children on rFVIIIFc group, adults on rFVIIIFc group, and adults on rFIXFc group by 1.2, 1.2, and 1.4 events/week, respectively, compared to their rFVIII/rFIX counterparts. The increases in PA duration were 44, 60, and 80 min/wk greater among the children on rFVIIIFc, adults on rFVIIIFc, and adults on rFIXFc groups, respectively. Larger reductions in total ABR were observed in children and adults treated with rFVIIIFc compared to rFVIII (0.4 and 0.7 fewer bleeds). Larger reductions were also observed in spontaneous ABR in adult rFVIIIFc and rFIXFc groups (0.8 and 0.3 fewer bleeds, respectively). CONCLUSIONS: This study suggests that rFVIIIFc/FIXFc agents can positively impact PA while maintaining low ABRs.

Are We Undercounting MDS? An Analysis of Incidence Patterns of Myelodysplastic Syndromes in SEER 21 Regions: 2001-2016.

Background: Myelodysplastic syndromes (MDSs), a group of reportable malignancies in the Surveillance, Epidemiology, and End Results (SEER) Program since 2001, are poorly understood neoplasms. There have been several updates since they became reportable, with several changes introduced to cases diagnosed in 2010 and onwards. None have examined changes in patterns of MDS incidence over the long term, accounting for such changes. Objective: The objective of this analysis was to assess changes in incidence of MDS from 2001 to 2016 by demographic characteristics and histology, applying coding changes implemented in 2010. Methods: Incidence-SEER 21 region data for the 2001-2016 period were used to estimate incidence rates using SEER*Stat version 8.3.6. Cases were included that were diagnosed as MDS during this period having the following International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) histology codes: 9980, 9982-9986, 9989, and 9991-9992. Annual incidence rates for the total population, as well as by demographic characteristics and histology, were estimated. All incidence rates were age adjusted using the 2000 US standard population (19 age groups; census P25-1130). Results: A total of 86,146 MDS cases were diagnosed during the 2001-2016 period, with an age-adjusted incidence rate of 4.7 cases per 100,000 population. The majority (~61%) were classified as MDS, unclassifiable (MDS-U, ICD-O-3: 9989). Annual rates steadily increased from 3.7 per 100,000 in 2001 to 5.6 per 100,000 in 2010, then declined to 3.8 per 100,000 in 2016, making an inverted V-shaped pattern. This pattern was observed for both sexes and all assessed racial and ethnic groups, as well as among the ≥65-year age groups. When the rates were assessed by histology, this pattern was observed for MDS-U, but not for other subtypes. Conclusion: MDS-U subtype dominates the observed trend in incident rates. The decline in rates since 2010 is most likely due to changes in coding and diagnostic criteria introduced in 2010. Further analysis is warranted to conclusively determine all factors leading to the changes observed.

Incremental Health Care Burden of Treatment-Resistant Depression Among Commercial, Medicaid, and Medicare Payers.

OBJECTIVE: This study compared health care use and costs among patients with treatment-resistant versus treatment-responsive depression across Medicaid, Medicare, and commercial payers. METHODS: A retrospective cohort study was conducted by using Truven Health Analytics' commercial (2006-2017; N=111,544), Medicaid (2007-2017; N=24,036), and Medicare supplemental (2006-2017; N=8,889) claims databases. Participants were adults with major depressive disorder who had received one or more antidepressant treatments. Treatment resistance was defined as failure of two or more antidepressant treatments of adequate dose and duration. Annual use (hospitalizations and outpatient and emergency department [ED] visits) and costs were compared across patients by treatment-resistant status in each payer population. Incremental burden of treatment-resistant depression was estimated with regression analyses. Monthly changes in costs during 1-year follow-up were assessed to understand differential cost trends by treatment-resistant status. RESULTS: In the three payer populations, patients with treatment-resistant depression incurred higher health care utilization than those with treatment-responsive depression (hospitalization, odds ratios [ORs]=1.32-1.76; ED visits, ORs=1.38-1.45; outpatient visits, incident rate ratio=1.29-1.54; p<0.001 for all). Compared with those with treatment-responsive depression, those with treatment resistance incurred higher annual costs (from $4,093 to $8,054 higher; p<0.001). Patients with treatment-resistant depression had higher costs at baseline compared with patients with treatment-responsive depression and incurred higher costs each month throughout follow-up. CONCLUSIONS: Treatment-resistant depression imposes a significant health care burden on insurers. Treatment-resistant depression may exist and affect health care burden before a patient is identified as having treatment-resistant depression. Findings underscore the need for effective and timely treatment of treatment-resistant depression.

An empirical investigation of time-varying cost-effectiveness across the product life cycle.

Cost-effectiveness is traditionally treated as a static estimate driven by clinical trial efficacy and drug price at launch. Prior studies suggest that cost-effectiveness varies over the drug's lifetime. We examined the impact of "learning by doing," one of the least studied drivers of changes in cost-effectiveness across the product life cycle. We combined time-series trends in effectiveness over time by cancer regimen using the Surveillance, Epidemiology, and End Results-Medicare database. We estimated the time-varying effects of treatments in colorectal and pancreatic cancer over their life cycle, including FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) and gemcitabine, on survival of patients. Mean prices over time by strength and dosage form were calculated using historical wholesale acquisition costs. We found consistent downward trends in the mortality hazard ratios, which suggest that effectiveness improves over time. In the case of first-line FOLFOX for colorectal cancer, the implied incremental cost-effectiveness ratio based on the observational data fell from $610,000 per life year gained in 2004 to $27,000 per life year gained in 2011. Cost-effectiveness estimated at launch is unlikely to be representative of cost-effectiveness over the drug's lifetime. In the drugs studied, the impact of time-varying clinical effectiveness dominated the impact of changing prices overtime.

Access to credible information on schizophrenia patients' medication adherence by prescribers can change their treatment strategies: evidence from an online survey of providers.

OBJECTIVE: Overestimating patients' medication adherence diminishes the ability of psychiatric care providers to prescribe the most effective treatment and to identify the root causes of treatment resistance in schizophrenia. This study was conducted to determine how credible patient drug adherence information (PDAI) might change prescribers' treatment decisions. METHODS: In an online survey containing 8 clinical case vignettes describing patients with schizophrenia, health care practitioners who prescribe antipsychotics to patients with schizophrenia were instructed to choose a preferred treatment recommendation from a set of predefined pharmacologic and non-pharmacologic options. The prescribers were randomly assigned to an experimental or a control group, with only the experimental group receiving PDAI. The primary outcome was the prescribers' treatment choice for each case. Between-group differences were analyzed using multinomial logistic regression. RESULTS: A convenience sample (n=219) of prescribers completed the survey. For 3 nonadherent patient vignettes, respondents in the experimental group were more likely to choose a long-acting injectable antipsychotic compared with those in the control group (77.7% experimental vs 25.8% control; P<0.001). For 2 adherent but poorly controlled patient vignettes, prescribers who received PDAI were more likely to increase the antipsychotic dose compared with the control group (49.1% vs 39.1%; P<0.001). For the adherent and well-controlled patient vignette, respondents in both groups made similar treatment recommendations across all choices (P=0.099), but respondents in the experimental arm were more likely to recommend monitoring clinical stability (87.2% experimental vs 75.5% control, reference group). CONCLUSION: The results illustrate how credible PDAI can facilitate more appropriate clinical decisions for patients with schizophrenia.

Evaluating Matching-Adjusted Indirect Comparisons in Practice: A Case Study of Patients with Attention-Deficit/Hyperactivity Disorder.

Differences in patient characteristics across trials may bias efficacy estimates from indirect treatment comparisons. To address this issue, matching-adjusted indirect comparison (MAIC) measures treatment efficacy after weighting individual patient data to match patient characteristics across trials. To date, however, there is no consensus on how best to implement MAIC. To address this issue, we applied MAIC to measure how two attention-deficit/hyperactivity disorder (ADHD) treatments (guanfacine extended release and atomoxetine hydrochloride) affect patients' ADHD symptoms, as measured by the ADHD Rating Scale IV score. We tested MAIC sensitivity to: matched patient characteristics, matched statistical moments, weighting matrix, and placebo-arm matching (i.e., matching on outcomes in the placebo arm). After applying MAIC, guanfacine and atomoxetine had similar reductions in ADHD symptoms (Δ: 0.4, p < 0.737). The results were similar for three of four sensitivity analyses. When we applied MAIC with placebo-arm matching, however, guanfacine reduced symptoms more than atomoxetine (Δ: -3.9, p < 0.004). We discuss the implication of this finding and advise MAIC practitioners to carefully consider the use of placebo-arm matching, depending on the presence of residual confounding across trials. Copyright © 2016 John Wiley & Sons, Ltd.

Undertreatment of osteoporosis and the role of gastrointestinal events among elderly osteoporotic women with Medicare Part D drug coverage.

OBJECTIVES: To examine the rate of osteoporosis (OP) undertreatment and the association between gastrointestinal (GI) events and OP treatment initiation among elderly osteoporotic women with Medicare Part D drug coverage. METHODS: This retrospective cohort study utilized a 20% random sample of Medicare beneficiaries. Included were women ≥66 years old with Medicare Part D drug coverage, newly diagnosed with OP in 2007-2008 (first diagnosis date as the index date), and with no prior OP treatment. GI event was defined as a diagnosis or procedure for a GI condition between OP diagnosis and treatment initiation or at the end of a 12-month follow-up, whichever occurred first. OP treatment initiation was defined as the use of any bisphosphonate (BIS) or non-BIS within 1 year postindex. Logistic regression, adjusted for patient characteristics, was used to model the association between 1) GI events and OP treatment initiation (treated versus nontreated); and 2) GI events and type of initial therapy (BIS versus non-BIS) among treated patients only. RESULTS: A total of 126,188 women met the inclusion criteria: 72.1% did not receive OP medication within 1 year of diagnosis and 27.9% had GI events. Patients with a GI event were 75.7% less likely to start OP treatment (odds ratio [OR]=0.243; P<0.001); among treated patients, patients with a GI event had 11.3% lower odds of starting with BIS versus non-BIS (OR=0.887; P<0.001). CONCLUSION: Among elderly women newly diagnosed with OP, only 28% initiated OP treatment. GI events were associated with a higher likelihood of not being treated and, among treated patients, a lower likelihood of being treated with BIS versus non-BIS.

Evaluating the economic burden of psoriasis in the United States.

BACKGROUND: Psoriasis has significant economic impact on patients. However, its total economic burden has not been fully quantified. OBJECTIVES: To assess the annual economic burden of psoriasis in the United States. METHODS: A systematic literature review was conducted to obtain estimates of the components of the economic burden of psoriasis. Prevalence estimates were used to estimate the 2013 psoriasis population. Incremental medical costs were calculated based on studies that compared psoriasis patients and controls. Productivity loss was estimated using measures of presenteeism, absenteeism, and unemployment. Reductions in health-related quality of life (HRQOL) were calculated from survey responses. RESULTS: The prevalence of psoriasis in the US was estimated to be 7.4 million in 2013. Comparatively, psoriasis patients incurred incremental medical costs of $2284, experienced a $2203 reduction in HRQOL, and a $1935 reduction in productivity. The total burden of psoriasis was estimated as $35.2 billion, with $12.2 billion in incremental medical costs (35%), $11.8 billion from reduced HRQOL (34%), and $11.2 billion from productivity losses (32%). LIMITATIONS: This study is constrained by the scope and populations of the existing literature. CONCLUSIONS: The economic burden of psoriasis in the US is significant, with a majority of it coming from indirect costs.

Prenatal exposure to air toxics and risk of Wilms' tumor in 0- to 5-year-old children.

OBJECTIVE: To study prenatal air toxic exposure and Wilms' tumor in children. METHODS: We identified 337 Wilms' tumor cases among children younger than 6 years (1988 to 2008) from the California Cancer Registry, randomly selected 96,514 controls from California birth rolls in 20:1 ratio matched to all cancer cases, then linked birth addresses to air monitors within 15 miles to assess exposures. Multiple logistic regressions were applied to estimate effects. RESULTS: Children prenatally exposed to formaldehyde, polycyclic aromatic hydrocarbons, perchloroethylene, or acetaldehyde in the third trimester had an increased odds of Wilms' tumor per interquartile increase in concentration (odds ratio [95% confidence interval]: 1.28 [1.12 to 1.45], 1.10 [0.99 to 1.22], 1.09 [1.00 to 1.18], 1.25 [1.07 to 1.45], respectively). CONCLUSIONS: We found positive associations for four air toxics. This is the first study of this kind. Future studies are needed to confirm our findings.

Patient Outcomes and Cost Effects of Medicaid Formulary Restrictions on Antidepressants.

Many state Medicaid programs have implemented policies designed to reduce spending on prescription drugs by restricting access to branded products. For patients with major depressive disorder, formulary restrictions could severely limit access to antidepressant therapies and disrupt care. We linked data on patient outcomes and spending from 24 state Medicaid programs to information on formulary restrictions from 2001 to 2008. Outcomes included frequency of MDD-related hospitalizations and ER visits per patient and total healthcare spending. We estimated the effect of the policies on patient outcomes and spending using a difference-and-difference approach. We found that restricting access to antidepressants increased the probability of an MDD-related hospitalization by 1.7 percentage points (16.6%). Furthermore, we found no evidence that these restrictions resulted in any net savings for Medicaid.

Early life factors and risk of childhood rhabdomyosarcoma.

Although little is known about etiology of childhood rhabdomyosarcoma (RMS), early life factors are suspected in the etiology. We explored this hypothesis using linked data from the California Cancer Registry and the California birth rolls. Incident cases were 359 children <6-year-old (218 embryonal, 81 alveolar, 60 others) diagnosed in 1988-2008. Controls (205, 173), frequency matched on birth year (1986-2007), were randomly selected from the birth rolls. We examined association of birth characteristics such as birth weight, size for gestational age, and timing of prenatal care with all-type RMS, embryonal, and alveolar subtypes. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. In contrast to a previous study, we observed statistically non-significant association for embryonal subtype among high birth weight (4000-5250 g) children for term births [OR (95% CI): 1.28 (0.85, 1.92)] and all births adjusted for gestational age [OR (95% CI): 1.21 (0.81, 1.81)]. On the other hand, statistically significant 1.7-fold increased risk of alveolar subtype (95% CI: 1.02, 2.87) was observed among children with late or no prenatal care and a 1.3-fold increased risk of all RMS subtypes among children of fathers ≥35 years old at child birth (95% CI: 1.00, 1.75), independent of all covariates. Our finding of positive association on male sex for all RMS types is consistent with previous studies. While we did not find a convincingly positive association between high birth weight and RMS, our findings on prenatal care supports the hypothesis that prenatal environment modifies risk for childhood RMS.

Obesity and age at menarche.

A cohort study of 3,169 girls born in April 1984-April 1987 in Odense and Aalborg, Denmark, was performed to examine whether maternal prepregnancy body mass index (BMI) accounted for daughter's age of menarche (AOM) and, if so, whether it accounted for part or all of the association between daughter's BMI and AOM. Multiple regression analyses adjusted for covariates indicated a weak inverse association between maternal BMI and AOM and a much stronger inverse association between offspring BMI and AOM independent of maternal BMI.

Smoking and alcohol use during pregnancy and age of menarche in daughters.

BACKGROUND: We assessed whether exposure to prenatal smoking or alcohol accelerates age of menarche (AOM) in offspring. METHODS: We studied a Danish cohort of 3169 singleton females born in April 1984-April 1987. Linear regressions were conducted to examine associations between prenatal smoking or alcohol exposure and offspring's AOM on: (i) the daughters who provided data on both month and the year of menarche (n= 1634) and (ii) the entire sample that provided at least the year of menarche (n= 3169). We also examined associations between only pre-pregnancy smoking or childhood exposure to smoking and AOM. The full model was adjusted for maternal pre-pregnancy body mass index, maternal age at childbirth, parental socio-economic status, parity, consumption of milk products during pregnancy and marital status. RESULTS: Among those who provided both year and month, AOM was accelerated by 2.8 months (95% CI in months: -5.3, -0.4) among those exposed to 10+ cigarettes/day throughout pregnancy and by 4.1 months (95% CI in months: -7.7, -0.5) among those with mothers who quit smoking sometime during pregnancy, compared with the unexposed group after adjustment for covariates. Similar, but much weaker, associations were observed among girls whose mothers smoked 1-9 cigarettes/day throughout pregnancy or whose fathers smoked compared with their unexposed counterparts after adjustment for covariates [-0.8 months (95% CI: -2.6, 1.0)]. No associations were observed between AOM and only pre-pregnancy smoking or only childhood exposure or prenatal alcohol exposure. CONCLUSIONS: Our study indicates that heavy smoking throughout the pregnancy may be important in prenatal programming of AOM.

Familial clustering and DRD4 effects on electroencephalogram measures in multiplex families with attention deficit/hyperactivity disorder.

OBJECTIVE: The current study tests electroencephalogram (EEG) measures as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD) by examining sibling and parent-offspring similarity, familial clustering with the disorder, and association with the dopamine receptor D4 (DRD4) candidate gene. METHOD: The sample consists of 531 participants (191 parents and 340 children) from 132 multiplex families with ADHD who participated in a larger genetics study. All members of the families underwent extensive assessment including semi-structured diagnostic interviews and EEG recording. RESULTS: Strong sibling similarity and parent-offspring correlations in EEG power emerged, suggesting high trait heritability. Increased theta power was observed among children with ADHD when compared with unaffected children, and there were no differences according to ADHD subtype. Within the parent sample, ADHD diagnostic status and ADHD subtype group differences emerged in the theta, alpha, and beta frequency bands. DRD4 effects for both parents and children were apparent in the beta frequency band and for children only in the theta frequency band. CONCLUSIONS: This study suggests that EEG measures are a promising avenue of study in the search for putative endophenotypes for ADHD, and that variability at the DRD4 gene may contribute to this endophenotype.

Parental age at childbirth and age of menarche in the offspring.

BACKGROUND: Early age of menarche (AOM) is associated with serious health problems including breast cancer and heart disease. Rising parental age at childbirth is associated with some adverse health outcomes in the offspring, but whether early menarche is one of them is not known. METHODS: We studied a Danish cohort of singleton females (n = 3168) born in 1984-1987. Prenatal data were collected from mothers around 36th week of pregnancy (self-administered questionnaire), although the menarcheal age was collected from daughters aged 17-21 years in 2005 (Web-based questionnaire). We assessed each parental age association in separate linear regression models adjusted for covariates (socioeconomic status, parity, maternal pre-pregnancy BMI, marital status, maternal smoking and daughter's self-reported BMI), then included both ages in a third model. RESULTS: Each year increase in maternal age showed a 9 day earlier onset of menarche in daughters [95% confidence interval (CI): -15.98, -2.90] and a 5 day earlier onset for each year increase in paternal age [95% CI: -10.85, 0.00], after adjusting for covariates. However, these associations attenuated when adjusted for the other parent [change in AOM in days: (i) maternal: -8.49 (95% CI: -17.09, 0.12), (ii) paternal: -1.14 (95% CI: -8.13, 5.84)]. CONCLUSIONS: We found no significant association between parental age and AOM, but the small sample of advance aged parents (over 30 years) limits the information we have. Future studies with a larger sample or a sample with over-representation of older parents will be of value.