BackgroundThere currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.Patients and methodsPatients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician’s choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.ResultsA total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9–1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4–2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.ConclusionsTreatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.Trial registrationClinicalTrials.gov: NCT02625623.

The death of a child is a traumatic event that can have long-term effects on the lives of parents. This study examined bereaved parents of deceased children (infancy to age 34) and comparison parents with similar backgrounds (n = 428 per group) identified in the Wisconsin Longitudinal Study. An average of 18.05 years following the death, when parents were age 53, bereaved parents reported more depressive symptoms, poorer well-being, and more health problems and were more likely to have experienced a depressive episode and marital disruption than were comparison parents. Recovery from grief was associated with having a sense of life purpose and having additional children but was unrelated to the cause of death or the amount of time since the death. The results point to the need for detection and intervention to help those parents who are experiencing lasting grief. Keywords bereavement; nonnormative parenting; death of child; parental grief; midlife Each year, over 50,000 U.S. children die (U.S. National Center for Health Statistics, 2000). The death of a child is one of the most painful events that an adult can experience and is linked to complicated/traumatic grief reactions (Prigerson et al., 1999). For parents, the dissolution of the attachment relationship with the child elicits severe anxiety and other negative emotions associated with loss (Bowlby, 1980). Parents might also experience guilt about having been unable to protect the child (Gilbert, 1997). Furthermore, because the death of a child defies the expected order of life events, many parents experience the event as a challenge to basic existential assumptions (Wheeler, 2001).In light of the significance of child death as a traumatic experience for parents, research on parental bereavement is more limited than might be expected. Most studies have been clinical NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript descriptions of participants in grief support groups (e.g., Compassionate Friends), so the findings likely have been influenced both by the self-selection factors that led individuals to seek this type of help and by the participants' experiences in the support groups. As a result, the findings cannot be generalized to the broader population of bereaved parents. Furthermore, drawing from traditional models of grief resolution that emphasize relatively short-term adaptations, researchers have usually assessed functioning for only a brief period during the acute phase of bereavement. Few studies have examined longer term outcomes, and most that have done so have used retrospective reports, which are subject to distortion when individuals recall their functioning many years earlier (e.g., Nelson & Frantz, 1996;Stehbens & Lascari, 1974).The purpose of the present study was to examine the life course impacts of parental bereavement in an unselected sample of adults who were studied prospectively from early adulthood, prior to the birth of the child, to middle age, usually many years after the death of the child. We ide...

In the present study, 96 co-residing mothers of adolescents and adults with an autism spectrum disorder (ASD) participated in an 8-day diary study and reported on their daily experiences. In comparison with a nationally representative sample of mothers of children without disabilities, mothers of adolescent and adult children with ASD spent significantly more time providing childcare and doing chores, and less time in leisure activities. Fatigue, arguments, avoided arguments, and stressful events were also more common among mothers of individuals with ASD. However, mothers of individuals with ASD reported similar levels of positive interactions and volunteerism as the comparison group. Daily experiences were subsequently related to well-being in both groups. These findings highlight the need for family support services.

Expressed emotion measures the emotional climate of the family and is predictive of symptom levels in a range of medical and psychiatric conditions. This study extends the investigation of the effects of expressed emotion to families of individuals with autism. A sample of 149 mothers co-residing with their adolescent or adult child with autism over an 18-month period was drawn from a large multiwave longitudinal study. High expressed emotion was related to increased levels of maladaptive behavior and more severe symptoms of autism over time. Also, characteristics of the son or daughter influenced levels of maternal expressed emotion over time. Although autism is a complex genetic disorder, the effect of the family environment in shaping the behavioral phenotype should not be underestimated.

Using daily diary methods, mothers of adolescents and adults with ASD (n = 86) were contrasted with a nationally representative comparison group of mothers of similarly-aged unaffected children (n = 171) with respect to the diurnal rhythm of cortisol. Mothers of adolescents and adults with ASD were found to have significantly lower levels of cortisol throughout the day. Within the ASD sample, the son or daughter's history of behavior problems interacted with daily behavior problems to predict the morning rise of the mother's cortisol. A history of elevated behavior problems moderated the effect of behavior problems the day before on maternal cortisol level. Implications for interventions for both the mother and the individual with ASD are suggested. Keywordsstress; cortisol; parenting; behavior problems; adolescents; adults Parents of children with autism spectrum disorders (ASD) often report higher levels of stress and poorer psychological well-being than parents of children with other types of developmental disabilities (Abbeduto et al., 2004;Blacher & McIntyre, 2006;Eisenhower, Baker, & Blacher, 2005). Past research has examined various child-related factors that might explain this elevated level of psychological distress among parents of children with ASD, with findings consistently indicating that child behavior problems are significant sources of stress (Hastings et al., 2005;Herring et al., 2006;Lounds, Seltzer, Greenberg, & Shattuck, 2007). It is not known, however, whether this level of stress disturbs the physiology and health of these parents, highlighting a need for research on the biological markers of stress in families of individuals with ASD. The present study sought to address this gap by examining the associations between behavior problems in adolescents or adults with ASD and maternal salivary cortisol, a hormone secreted from the adrenal gland, in a sample of mothers and their adolescent or adult children with ASD.Correspondence concerning this article should be addressed to: Marsha Mailick Seltzer, Waisman Center, University of WisconsinMadison, 1500 Highland Ave., Madison, WI 53705. Phone: (608) Fax: (608) Biological Markers of StressCortisol is a hormonal marker of stress which has received considerable attention in studies of psychological and physical health. During exposure to an acute stressful event, the hypothalamic-pituitary-adrenal (HPA) axis is activated and releases cortisol from the adrenal cortex into the bloodstream. Cortisol, in turn, acts on a variety of adaptive responses including protein synthesis and glucose regulation, immune function, and mental activity (Flinn, 2006). In the short term, these changes enable the body to respond to the immediate challenge (i.e., extending the "fight or flight" response induced by adrenaline); however, chronic stress and persistent activation of the HPA axis can have detrimental impacts on health and well-being, such as a suppression of bone growth and certain immune responses, as well as poorer cognitive performance (McEwe...

The primary goal of this study was to calculate the prevalence of the premutation of the FMR1 gene and of the “gray zone” using a population-based sample of older adults in Wisconsin (n=6,747 samples screened). Compared with past research, prevalence was relatively high (1 in 151 females and 1 in 468 males for the premutation and 1 in 35 females and 1 in 42 males for the gray zone as defined by 45–54 CGG repeats). A secondary study goal was to describe characteristics of individuals found to have the premutation (n = 30, 7 males and 23 females). We found that premutation carriers had a significantly higher rate of divorce than controls, as well as higher rates of symptoms that might be indicative of fragile X-associated tremor ataxia syndrome (FXTAS; numbness, dizziness/faintness) and fragile X primary ovarian insufficiency (FXPOI; age at last menstrual period). Although not statistically significant, premutation carriers were twice as likely to have a child with disability.

We examined factors related to subjective quality of life (QoL) of adults with Autism Spectrum Disorder (ASD) aged 25 to 55 (n = 60), using the World Health Organization Quality of Life measure (WHOQOL-BREF). We used three different assessment methods: adult self-report, maternal proxy-report, and maternal report. Reliability analysis showed that adults with ASD rated their own QoL reliably. QoL scores derived from adult self-reports were more closely related to those from maternal proxy-report than from maternal report. Subjective factors such as perceived stress and having been bullied frequently were associated with QoL based on adult self-reports. In contrast, level of independence in daily activities and physical health were significant predictors of maternal reports of their son or daughter’s QoL.

Using data from the Study of Midlife in the United States (MIDUS), this article examines: (1) the effect of having children with developmental or mental health problems on parents’mental and physical health, (2) the extent to which this effect varies by parental age and gender, and (3) the effects of disability-related factors on the well-being of parents of children with disabilities. Compared to parents of non-disabled children, parents of disabled children experienced significantly higher levels of negative affect, marginally poorer psychological well-being, and significantly more somatic symptoms, controlling for sociodemographic variables. Mothers did not differ from fathers in their well-being. Older parents were significantly less likely to experience the negative effect of having a disabled child than younger parents, suggesting an age-related attenuation of the stress of non-normative parenting.