The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study.

Epigenetic clocks have been widely used to predict disease risk in multiple tissues or cells. Their success as a measure of biological ageing has prompted research on the connection between epigenetic pathways of ageing and the socioeconomic gradient in health and mortality. However, studies examining social correlates of epigenetic ageing have yielded inconsistent results. We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighbourhood environment, and childhood SES) and eight epigenetic clocks in two well-powered US ageing studies: The Multi-Ethnic Study of Atherosclerosis (MESA) (n = 1,211) and the Health and Retirement Study (HRS) (n = 4,018). In both studies, we found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm clocks (Bonferroni-corrected p-value < 0.01). In the HRS, significant associations with the Levine and Yang clocks were also evident. These associations were only partially mediated by smoking, alcohol consumption, and obesity, which suggests that differences in health behaviours alone cannot explain the SES gradient in epigenetic ageing in older adults. Further analyses revealed concurrent associations between polygenic risk for accelerated intrinsic epigenetic ageing, SES, and the Levine clock, indicating that genetic risk and social disadvantage may contribute additively to faster biological aging.

The impact of late-career job loss and genetic risk on body mass index: Evidence from variance polygenic scores.

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G × E) interplay, we interacted layoffs from business closures-a plausibly exogenous environmental exposure-with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.

Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study.

BACKGROUND: Clostridium difficile infection (CDI) is the most common hospital-acquired infection. Unfortunately, genes that identify CDI-susceptible patients have not been well described. We performed a genome-wide association study (GWAS) to determine genetic variants associated with the development of CDI. METHODS: A cohort study of Caucasian patients undergoing autologous stem cell transplantation for multiple myeloma was performed. Patients were genotyped using Illumina® Whole Genome Genotyping Infinium chemistry. We then compared CDI-positive to CDI-negative patients using logistic regression for baseline clinical factors and false discovery rate (FDR) for genetic factors [single nucleotide polymorphisms (SNPs)]. SNPs associated with CDI at FDR of p < 0.01 were then incorporated into a logistic regression model combining clinical and genetic factors. RESULTS: Of the 646 patients analyzed (59.7% male), 57 patients were tested CDI positive (cases) and were compared to 589 patients who were tested negative (controls). Hemoglobin, albumin, and hematocrit were lower for cases (p < 0.05). Eight SNPs on five genes (FLJ16171, GORASP2, RLBP1L1, ASPH, ATP7B) were associated with CDI at FDR p < 0.01. In the combined clinical and genetic model, low albumin and three genes RLBP1L1, ASPH, and ATP7B were associated with CDI. CONCLUSION: Low serum albumin and genes RLBP1L1 and ASPH located on chromosome 8 and ATP7B on chromosome 13 were associated with CDI. Of particular interest is ATP7B given its copper modulatory role and the sporicidal properties of copper against Clostridium difficile.

Motor delays in MDMA (ecstasy) exposed infants persist to 2 years.

BACKGROUND: Recreational use of 3,4 methylenedioxymethamphetamine (ecstasy, MDMA) is increasing worldwide. Its use by pregnant women causes concern due to potentially harmful effects on the developing fetus. MDMA, an indirect monoaminergic agonist and reuptake inhibitor, affects the serotonin and dopamine systems. Preclinical studies of fetal exposure demonstrate effects on learning, motor behavior, and memory. In the first human studies, we found prenatal MDMA exposure related to poorer motor development in the first year of life. In the present study we assessed the effects of prenatal exposure to MDMA on the trajectory of child development through 2 years of age. We hypothesized that exposure would be associated with poorer mental and motor outcomes. MATERIALS AND METHODS: The DAISY (Drugs and Infancy Study, 2003-2008) employed a prospective longitudinal cohort design to assess recreational drug use during pregnancy and child outcomes in the United Kingdom. Examiners masked to drug exposures followed infants from birth to 4, 12, 18, and 24 months of age. MDMA, cocaine, alcohol, tobacco, cannabis, and other drugs were quantified through a standardized clinical interview. The Bayley Scales (III) of Mental (MDI) and Motor (PDI) Development and the Behavior Rating Scales (BRS) were primary outcome measures. Statistical analyses included a repeated measures mixed model approach controlling for multiple confounders. RESULTS: Participants were pregnant women volunteers, primarily white, of middle class socioeconomic status, average IQ, with some college education, in stable partner relationships. Of 96 women enrolled, children of 93 had at least one follow-up assessment and 81 (87%) had ≥ two assessments. Heavier MDMA exposure (M=1.3±1.4 tablets per week) predicted lower PDI (p<.002), and poorer BRS motor quality from 4 to 24 months of age, but did not affect MDI, orientation, or emotional regulation. Children with heavier exposure were twice as likely to demonstrate poorer motor quality as lighter and non-exposed children (O.R.=2.2, 95%, CI=1.02-4.70, p<.05). DISCUSSION: Infants whose mothers reported heavier MDMA use during pregnancy had motor delays from 4 months to two years of age that were not attributable to other drug or lifestyle factors. Women of child bearing age should be cautioned about the use of MDMA and MDMA-exposed infants should be screened for motor delays and possible intervention.

Developmental outcomes of 3,4-methylenedioxymethamphetamine (ecstasy)-exposed infants in the UK.

OBJECTIVE: This paper aims to review findings from a longitudinal study of prenatal methylenedioxymethamphetamine (MDMA, "ecstasy") on infant development. METHODS: In a prospective, longitudinal cohort design, we followed 28 MDMA-exposed and 68 non-MDMA-exposed infants from birth to 2 years of age. Women recruited voluntarily into a study of recreational drug use during pregnancy were interviewed to obtain type, frequency, and amount of recreational drug use. Their children were followed for a 2-year period after birth. A large number of drug and environmental covariates were controlled. Infants were seen at 1, 4, 12, 18, and 24 months using standardized normative tests of mental and motor development. RESULTS: There were no differences between MDMA-exposed and non-MDMA-exposed infants at birth except that MDMA-exposed infants were more likely to be male. Motor delays were evident in MDMA infants at each age and amount of MDMA exposure predicted motor deficits at 12 months in a dose-dependent fashion. CONCLUSIONS: Prenatal MDMA exposure is related to fine and gross motor delays in the first 2 years of life. Follow-up studies are needed to determine long-term effects.

GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis.

PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, cancer treatment may have to be interrupted or delayed. In this study, we looked beyond OM's known risk factors of renal function and melphalan dose with a genome-wide association study (GWAS) to evaluate whether genetic variants in conjunction with clinical risk factors influence predisposition for OM. METHODS: Genotyping was performed using Illumina HumanOmni1-Quad v1.0 BeadChip and further assessed for data quality. We tested 892,589 germline single-nucleotide polymorphisms (SNPs) for association with OM among 972 Caucasian patients treated with high-dose melphalan and ASCT in Total Therapy clinical trials (TT2, TT3, TT4) for newly diagnosed MM. Statistical analyses included t tests, stepwise regression modeling, and logistic regression modeling to find baseline clinical factors and genotypes associated with OM. RESULTS: We found that 353 (36.3 %) patients had grades 2-4 OM. Type of treatment protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were associated with grades 2-4 OM. The addition of these SNPs increased sensitivity in detecting grades 2-4 OM cases to 52 %. CONCLUSIONS: These SNPs may be important for their roles in inflammatory pathways, epithelial healing, and chemotherapy detoxification.

Effects of hypothermia for perinatal asphyxia on childhood outcomes.

BACKGROUND: In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits. METHODS: We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher. RESULTS: A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children's health status and in results on 10 of 11 psychometric tests. CONCLUSIONS: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

MDMA and heightened cortisol: a neurohormonal perspective on the pregnancy outcomes of mothers used 'Ecstasy' during pregnancy.

OBJECTIVE: The illicit recreational drug 3,4-methylenedioxymethamphetamine (MDMA) or Ecstasy has strong neurohormonal effects. When taken by recreational users at dance clubs and raves, it can generate an 800% increase in the stress hormone cortisol, whereas drug-free users show chronically raised levels of cortisol. The aim here is to critically debate this neurohormonal influence for the children of pregnant MDMA-using mothers. METHODS: High levels of cortisol are known to be damaging for neuropsychobiological well-being in adult humans. MDMA can damage foetal development in laboratory animals, and the prospective Drugs and Infancy Study was established to monitor the effects of MDMA taken recreationally by pregnant women. RESULTS: The Drugs and Infancy Study revealed that young mothers, who took MDMA during the first trimester of pregnancy, gave birth to babies with significant gross psychomotor retardation. These mothers would have experienced high levels of cortisol due to Ecstasy/MDMA use, and since cortisol can cross the placenta, this is likely to have also occurred in the foetus. CONCLUSIONS: In terms of causation, the developmental problems may reflect a combination of neurotransmitter and neurohormonal effects on the hypothalamic-pituitary-adrenal axis, with serotonergic activity being influenced by the high levels of cortisol.

Psychiatric profiles of mothers who take Ecstasy/MDMA during pregnancy: reduced depression 1 year after giving birth and quitting Ecstasy.

BACKGROUND: The recreational drug MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is associated with heightened psychiatric distress and feelings of depression. The Drugs and Infancy Study (DAISY) monitored the psychiatric symptom profiles of mothers who used Ecstasy/MDMA while pregnant, and followed them over the first year post-partum. METHODS: We compared 28 young women whom took MDMA during their pregnancy with a polydrug control group of 68 women who took other psychoactive drugs while pregnant. The Brief Symptom Inventory (BSI) was completed for several periods: The first trimester of pregnancy; and 1, 4 and 12 months after childbirth. Recreational drug use was monitored at each time point. RESULTS: During the first trimester of pregnancy, MDMA-using mothers reported higher depression scores than the polydrug controls. At 1 year after childbirth, their BSI depression scores were significantly lower, now closer to the control group values. At the same time point, their self-reported use of MDMA became nearly zero, in contrast to their continued use of Cannabis/marijuana, nicotine and alcohol. We found significant symptom reductions in those with BSI obsessive-compulsive and interpersonal sensitivity, following Ecstasy/MDMA cessation. CONCLUSIONS: The findings from this unique prospective study of young recreational drug-using mothers are consistent with previous reports of improved psychiatric health after quitting MDMA.

Patient reasoning in palliative surgical oncology.

BACKGROUND: The purpose of this study was to determine the patient reasoning behind treatment choice after palliative surgical consultation. METHODS: Patients undergoing palliative surgical consultation were prospectively enrolled in this observational cohort study (11/2009-5/2011) and administered an open-ended questionnaire asking for their reasoning in choosing their treatment strategy. RESULTS: Of 98 patients enrolled, 54 were treated non-operatively and 44 with surgery. Patient responses indicating their reason for treatment selection were categorized into (1) quality of life or symptom relief, (2) unclear or response not related to treatment strategy, (3) increase length of life, (4) treat the cancer, (5) concerns over surgical complications, (6) doctor's recommendation, (7) religious reasons for treatment choice, and (8) for family. The most frequently cited reason for treatment selection was symptom relief or quality of life improvement in 46 patients. Thirty-eight patients cited their doctor's recommendation while 20 patients selected their treatment to increase length of life or treat their cancer. Only 2 patients cited concerns over surgical complications as their reason for choosing their treatment strategy. CONCLUSIONS: The most common reasons for treatment selection in palliative surgical consultation include symptom relief or improvement in quality of life and the doctor's recommendation with few patients listing concerns over surgical morbidity.

Nurse executives' perceptions of end-of-life care provided in hospitals.

CONTEXT: With the aging of our population, almost one in five adults, or 19% of the population, will be older than 65 years by 2030. Many persons have expressed concern about the inadequate preparation of hospitals to provide high-value end-of-life care for the current and anticipated population of older adults. OBJECTIVES: The purpose of this study was to explore the perceptions of nurse executives about the provision of end-of-life care in the hospital setting. METHODS: We conducted a pilot, descriptive, naturalistic, qualitative study using in-person interviews to capture nurse executives' understandings, beliefs, and perceptions of end-of-life care in their facilities. RESULTS: Data were collected from 10 nurse executives. We identified five major factors, three barriers and two facilitators, in their descriptions of provision of end-of-life care provided in the hospital: 1) communication inadequacies, 2) education inadequacies, 3) hospital system constraints, 4) hospice services availability, and 5) nurse executive advocacy. CONCLUSION: These findings highlight the need for interventions that focus on improving communication at the bedside and in transitions of care, enhancing educational interventions, and developing patient-centered care systems, which translate into a higher quality end-of-life experience for patients and their family members. Nurse executives are currently an underused resource in end-of-life care but are poised to be able to champion innovative models and a culture of change that integrates high-value care for patients with serious and chronic illnesses.

Personal financial effects of multiple myeloma and its treatment.

BACKGROUND: Improvements in some treatment programs for multiple myeloma (MM) are increasing survival. As patients live longer with MM as a chronic disease, the personal financial effects of MM treatment become a serious concern. OBJECTIVE: The objective of this study was to identify the personal financial effects of MM and its treatment in 5 areas: employment, disability, health/medical and life insurance, retirement, and out-of-pocket expenses. METHODS: We mailed a questionnaire about financial issues to 1015 patients who had received intensive treatment for MM at the study site. Data analysis included descriptive statistics and comparisons using independent t tests. RESULTS: Our sample (n = 762; mean age, 61 [SD, 9.26] years) experienced issues with employment (66% employed at diagnosis and treatment; 33% employed at questionnaire time), disability (35% applied), health/medical and life insurance (29% lost coverage and 8% changed coverage), retirement (13% retired during treatment), and out-of-pocket expenses (36% of income in first treatment year and 28% of income during most recent 12 months). CONCLUSIONS: Issues of employment, disability, health insurance, retirement, and out-of-pocket costs for treatment are major challenges for patients. IMPLICATIONS FOR PRACTICE: In the midst of assessing physical needs during clinical trials for chemotherapy and stem cell transplants, healthcare providers must keep sight of patients' personal financial needs so that we can intervene promptly with referrals to social work, rehabilitation therapy, and other healthcare professions to help patients decrease the personal financial effects of MM and its treatment.

Sleep measured by polysomnography in patients receiving high-dose chemotherapy for multiple myeloma prior to stem cell transplantation.

PURPOSE/OBJECTIVES: To describe the objective sleep of patients receiving chemotherapy for multiple myeloma (MM) prior to stem cell transplantation. DESIGN: A descriptive study with repeated measures. SETTING: An international referral center in an urban area of the southern United States. SAMPLE: A convenience sample of a subset of 12 patients with MM, recruited from a randomized, controlled trial. METHODS: Objective sleep was assessed using two nights of polysomnography, one obtained before and one after a second cycle of high-dose chemotherapy prior to stem cell transplantation. Demographic and clinical data were obtained through a retrospective chart review. MAIN RESEARCH VARIABLES: Objective sleep including sleep characteristics, sleep-related respiratory events, and periodic limb movements (PLMs) of sleep. FINDINGS: Sleep was characterized by a relatively short sleep time, excessive time spent awake after the onset of sleep, and poor sleep efficiency (objective sleep quality). Patients spent more than the expected percent of time in non-rapid eye movement sleep and less in rapid eye movement sleep. Arterial oxyhemoglobin saturation nadirs reflected episodes of low arterial oxygen saturation. PLMs during sleep were in the mildly elevated range. CONCLUSIONS: Findings suggest that patients had poor sleep efficiency (objective sleep quality) and were slightly better sleepers after receiving a second cycle of high-dose chemotherapy. A number of patients also demonstrated obstructive sleep apnea and frequent PLMs. IMPLICATIONS FOR NURSING: Findings support the need for additional investigation of sleep in patients with MM, particularly poor sleep efficiency and PLMs. Improving sleep may improve quality of life by decreasing associated symptoms such as pain, fatigue, and depression. KNOWLEDGE TRANSLATION: Oncology nurses should consider assessing patients with MM for insomnia symptoms, excessive daytime sleepiness, obstructive sleep apnea, and a history of jerking or kicking their legs when asleep. Those symptoms may suggest the need for additional investigation of a possible sleep disorder, which may negatively influence mood and function.

Effects of exercise on fatigue, sleep, and performance: a randomized trial.

PURPOSE/OBJECTIVES: To compare usual care with a home-based individualized exercise program (HBIEP) in patients receiving intensive treatment for multiple myeloma (MM)and epoetin alfa therapy. DESIGN: Randomized trial with repeated measures of two groups (one experimental and one control) and an approximate 15-week experimental period. SETTING: Outpatient setting of the Myeloma Institute for Research and Therapy at the Rockfellow Cancer Center at the University of Arkansas for Medical Sciences. SAMPLE: 187 patients with newly diagnosed MM enrolled in a separate study evaluating effectiveness of the Total Therapy regimen, with or without thalidomide. METHODS: Measurements included the Profile of Mood States fatigue scale, Functional Assessment of Cancer Therapy-Fatigue, ActiGraph® recordings, 6-Minute Walk Test, and hemoglobin levels at baseline and before and after stem cell collection. Descriptive statistics were used to compare demographics and treatment effects, and repeated measures analysis of variance was used to determine effects of HBIEP. MAIN RESEARCH VARIABLES: Fatigue, nighttime sleep, performance (aerobic capacity) as dependent or outcome measures, and HBIEP combining strength building and aerobic exercise as the independent variable. FINDINGS: Both groups were equivalent for age, gender, race, receipt of thalidomide, hemoglobin levels, and type of treatment regimen for MM. No statistically significant differences existed among the experimental and control groups for fatigue, sleep, or performance (aerobic capacity). Statistically significant differences (p < 0.05) were found in each of the study outcomes for all patients as treatment progressed and patients experienced more fatigue and poorer nighttime sleep and performance (aerobic capacity). CONCLUSIONS: The effect of exercise seemed to be minimal on decreasing fatigue, improving sleep, and improving performance (aerobic capacity). IMPLICATIONS FOR NURSING: Exercise is safe and has physiologic benefits for patients undergoing MM treatment; exercise combined with epoetin alfa helped alleviate anemia.

One-year outcomes of prenatal exposure to MDMA and other recreational drugs.

OBJECTIVE: A widely used illicit recreational drug among young adults, 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy, is an indirect monoaminergic agonist/reuptake inhibitor affecting the serotonin system. Preclinical studies found prenatal exposure related to long-term learning and memory impairments. There are no studies of sequelae of prenatal MDMA exposure in humans, despite potential harmful effects to the fetus. METHODS: A total of 96 women in the United Kingdom (28 MDMA users; 68 non-MDMA) were interviewed about recreational drug use during pregnancy. Their infants were seen at 12 months using standardized assessments of cognitive, language, and motor development (Preschool Language Scale, Bayley Mental and Motor Development and Behavior Rating Scales [Mental Development Index, Psychomotor Development Index, Behavioral Rating Scale]). Mothers completed the Child Domain Scale of the Parenting Stress Index, The Home Observation of the Environment Scale (in interview), the Brief Symptom Inventory, and the Drug Abuse Screening Test. Women were primarily middle class with some university education, in stable partner relationships, and polydrug users. MDMA and other drug effects were assessed through multiple regression analyses controlling for confounding variables, and analysis of covariance comparing heavier versus lighter and nonexposed groups. RESULTS: Amount of prenatal MDMA exposure predicted poorer infant mental and motor development at 12 months in a dose-dependent manner. Heavily exposed infants were delayed in motor development. Lighter-exposed infants were comparable to nonexposed infants. There were no effects on language, emotional regulation, or parenting stress. CONCLUSIONS: Findings document persistent neurotoxic effects of heavier prenatal MDMA exposure on motor development through the first year of life.

Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other recreational drugs during pregnancy.

3,4-methylenedioxymethamphetamine (MDMA) or "Ecstasy" is one of the most widely used illicit recreational drugs among young adults. MDMA is an indirect monoaminergic agonist and reuptake inhibitor that primarily affects the serotonin system. Preclinical studies in animals have found prenatal exposure related to neonatal tremors and long-term learning and memory impairments. To date, there are no prospective studies of the sequelae of prenatal exposure to MDMA in humans, despite concerns about its potential for harmful effects to the fetus. The present study is the first to prospectively identify MDMA-using women during pregnancy and to document patterns and correlates of use with neonatal and early infancy outcomes of offspring. All mothers and infants were prospectively recruited through the Case Western Reserve University (CWRU) and University of East London (UEL) Drugs and Infancy Study (DAISY) that focused on recreational drug use in pregnant women. Women were interviewed about substance use prior to and during pregnancy and infants were seen at 1 and 4 months using standardized, normative assessments of neonatal behavior, and cognitive and motor development, including the NICU Network Neurobehavioral Scale (NNNS), the Bayley Mental and Motor Development Scales (MDI, PDI), and the Alberta Infant Motor Scales (AIMS). The sample was primarily middle class with some university education and in stable partner relationships. The majority of women recruited had taken a number of illicit drugs prior to or during pregnancy. Group differences between those polydrug using women who had specifically used MDMA during pregnancy (n=28) and those who had not (n=68) were assessed using chi-square and t-tests. MDMA and other drug effects were assessed through multiple regression analyses controlling for confounding variables. Women who used MDMA during pregnancy had fewer prior births and more negative sequelae associated with their drug use, including more health, work, and social problems. MDMA exposed infants differed in sex ratio (more male births) and had poorer motor quality and lower milestone attainment at 4 months, with a dose-response relationship to amount of MDMA exposure. These findings suggest risk to the developing infant related to MDMA exposure and warrant continued follow-up to determine whether early motor delays persist or resolve.

Maternal cognitions and mother-infant interaction in postnatal depression and generalized anxiety disorder.

Postnatal depression and anxiety have been shown to increase the risk of disturbances in mother-child interaction and child development. Research into mechanisms has focused on genetics and maternal behavior; maternal cognitions have received little attention. Our aim was to experimentally determine if worry and rumination in mothers with generalized anxiety disorder (GAD) and major depressive disorder (MDD), diagnosed in the postnatal 6 months, interfered with maternal responsiveness to their 10-month old infants. Mothers (N = 253: GAD n = 90; MDD n = 57; control n = 106) and their infants were randomized to either a worry/rumination prime (WRP) or a neutral prime (NP); mother-infant interactions were assessed before and after priming. Type of priming was a significant predictor of maternal cognitions, with WRP resulting in more negative thoughts, higher thought recurrence and more self-focus relative to NP across the entire sample. Interaction effects between group and priming were significant for two parenting variables: Compared with controls, WRP had a more negative impact on maternal responsiveness to infant vocalization for GAD, and to a lesser extent for MDD; WRP led to decreased maternal vocalization for GAD. Also, mothers with GAD used stronger control after the NP than WRP, as well as compared with other groups, and overall post-priming, their children exhibited lower emotional tone and more withdrawal. Across the entire sample, WRP was associated with increased child vocalization relative to NP. This study demonstrated that disturbances in maternal cognitions, in the context of postnatal anxiety and to a lesser degree depression, play a significant role in mother-child interaction.

Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis.

BACKGROUND: Venous thromboembolism (VTE) is a significant but poorly understood complication in patients with newly diagnosed multiple myeloma (NDMM). As a result, most patients receive thromboprophylaxis with low molecular weight heparin (LMWH). The purpose of this retrospective study was to identify risk factors for VTE in NDMM and evaluate the effectiveness of LMWH. METHODS: A total of 604 patients with newly diagnosed myeloma completed 3 induction cycles with multiagent chemotherapy with up-front randomization to thalidomide between 1998 and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part of an exercise trial. The primary study endpoint was grades 3-4 VTE. RESULTS: A total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with a higher incidence among EPO recipients (P = .001), although only significant for upper extremity DVT (P = .0002). The EPO-treated patients had higher hemoglobin (Hb) levels throughout the study (P < .0005), although no relationship between higher Hb levels and increasing incidence of VTE could be shown. A history of VTE was a strong predictor of VTE on univariate analysis (P < .000005). Enoxaparin did not reduce the rate of VTE (P = .158). Logistic regression analysis identified thalidomide therapy (P = .001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418-4.159) and prophylactic EPO (P = .002; OR, 2.488; 95% CI, 1.432-4.324) as risk factors for VTE. Myeloma response and survival were not negatively affected by prophylactic EPO or VTE. CONCLUSIONS: Prophylactic EPO, thalidomide therapy, and VTE history, but not higher Hb levels, were found to increase the risk of VTE among NDMM patients receiving multiagent chemotherapy. This risk was not found to be reduced in this population by LMWH thromboprophylaxis.