Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

An evaluation of PROMIS health domains in adults with haemophilia: A cross-sectional study.

INTRODUCTION: The Patient-Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental and social well-being from the patient perspective. PROMIS measures are used in clinical practice and research across various patient populations but are not yet validated among patients with haemophilia. AIM: Evaluate the sensitivity of PROMIS to indicators of haemophilia clinical severity and compare PROMIS measures to those from other PRO instruments. METHODS: Male adults with haemophilia (n = 115) completed the PROMIS-29 short form which includes 4 questions for each of 7 domains: depression, anxiety, ability to participate in social roles and activities, physical function, pain interference, fatigue and sleep disturbance. Participant responses for each domain were scored on a T-score metric with a mean of 50 and a standard deviation of 10 based on the original PROMIS reference sample of US adults. Participants also completed other generic and haemophilia-specific health-related quality of life questionnaires. RESULTS: Participants who experienced higher pain and depression levels reported significantly worse health in every PROMIS domain compared with their peers. Those who had recently needed to use crutches, visit an emergency department or were currently unemployed or disabled also reported poor PROMIS scores on most domains. Construct validity was supported by correlations between PROMIS domain scores and domain scores reported using the EQ-5D-5L and Haem-A-QoL. CONCLUSION: The PROMIS instrument provides a potentially valuable tool to evaluate the impact of haemophilia and suggests usefulness in research and clinical practice.

Disease-related distress among adults with haemophilia: A qualitative study.

INTRODUCTION: Distress related to disease burden has been defined and described among people with chronic diseases including diabetes and cancer. In these populations, disease-specific distress is associated with health outcomes. Haemophilia-related distress is less understood. AIM: To identify qualitative features of haemophilia-related distress among affected adults to ultimately inform the creation of a measurement tool. METHODS: Adults with haemophilia A or B associated with a large haemophilia treatment centre in the south-eastern U.S. were recruited to participate in this qualitative study. Fifteen participants completed semi-structured telephone interviews. Interviews lasted 1-2 hours and explored experiences of distress related to various aspects of haemophilia. Interviews were audio taped, transcribed and coded using NVIVO, software for organizing, managing and analysing qualitative data. Coding was deductive and inductive, and the analysis was thematic. RESULTS: Haemophilia-related distress was broadly related to feelings of isolation and vulnerability which incorporated health system factors, physical functioning, caretaker roles and psychological considerations. Specific features associated with haemophilia-related distress included lack of trust in the knowledge of haemophilia and care provided by staff in community healthcare settings, concerns about the future such as health insurance access and ageing/disability, long-standing feelings of being different from others and feeling like an outsider, treatment burdens and fear of acute bleeds. Protective factors included supportive relationships with family, friends and haemophilia care teams through which participants received practical and emotional support. CONCLUSION: Features of haemophilia-related distress were identified. Results will facilitate distress measurement and intervention efforts to reduce distress in adults with haemophilia.

Association Analysis: Fetal Alcohol Spectrum Disorder and Hypertension Status in Children and Adolescents.

BACKGROUND: This study examined the relationship between prenatal exposure to alcohol, manifested through fetal alcohol syndrome (FAS) and pFAS, and hypertension in children and adolescents. METHODS: This study was designed to analyze the association between fetal alcohol spectrum disorders (FASD) Status and hypertension status. FAS/pFAS-diagnosed respondents (n = 125) were collected from a FASD Clinical database in Atlanta, Georgia. Non-FAS/pFAS respondents (n = 500) were taken from the National Health and Nutrition Examination Survey (NHANES). Chi-square analyses were used to examine the extent to which FASD status, sex, race/ethnicity, medication use, and obesity status each related to hypertension status. A logistic regression was performed analyzing the relationship between FASD status (y/n: independent) and hypertension status (y/n: dependent) while controlling for age, sex, race/ethnicity, medication use, and obesity status. RESULTS: Univariate relationships between hypertension status and FASD status (OR = 8.46, p < 0.001), medication use (OR = 3.25, p < 0.001), and obesity status (OR = 3.03, p = 0.02) proved to be statistically significant (p < 0.05). FASD status significantly predicted hypertension status (ß = 2.31, OR = 10.06, p < 0.001) after accounting for age, sex, race/ethnicity, medication use, and obesity status. CONCLUSIONS: The major findings of this study suggest a significant relationship between FASD and hypertension in youth. Race/ethnicity and obesity also proved important in predicting hypertensive blood pressure readings independent of FASD diagnosis. Further research is needed to isolate prenatal alcohol exposure (PAE) as a factor promoting increased hypertension and to assess the risk for hypertension in alcohol-affected adults.

A Comparison Among 5 Methods for the Clinical Diagnosis of Fetal Alcohol Spectrum Disorders.

BACKGROUND: Despite the prevalence of fetal alcohol spectrum disorders (FASD) and the importance of accurate identification of patients, clinical diagnosis may not be consistent across sites due to the heterogeneous nature of FASD and the characteristics of different diagnostic systems used. Here, we compare 5 systems designed to operationalize criteria recommended for the diagnosis of effects of prenatal alcohol exposure (PAE). We determined the extent of consistency among them as well as factors that may reduce intersystem reliability. Compared are: Emory Clinic, Seattle 4-Digit System (Diagnostic Guidelines for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code, Seattle, WA, University Publication Services, 2004), Centers for Disease Control and Prevention (Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis, Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA, 2004), Canadian Guidelines (CMAJ, 172, 2005, S1), and the Hoyme Modifications (Pediatrics, 115, 2005, 39). METHODS: Subjects were 1,581 consecutively registered patients applying for evaluation at a university-based clinic treating alcohol and drug-exposed children. Records of the multidisciplinary evaluation (pediatric, social, psychological) were abstracted. Diagnostic criteria for all 5 systems were applied, and patients were diagnosed according to each of the systems. We compared results using Cohen's Kappa to evaluate the extent of agreement. RESULTS: Percent of individuals diagnosed with FASD ranged from 4.74% (CDC) to 59.58% (Hoyme). Examination using Cohen's Kappa found modest agreement among systems, particularly when individual diagnoses, Fetal Alcohol Syndrome (FAS), partial FAS (pFAS), and Alcohol-Related Neurodevelopmental Disorder (ARND) were used. Examination of diagnostic criteria found almost perfect agreement on growth (weight; height), with limited overlap for physical features (palpebral fissures, hypoplastic philtrum, upper vermillion) and for neurobehavioral outcomes. Child's race and age influenced agreement among systems, with African American and older children more frequently diagnosed. CONCLUSIONS: Results suggest problems in convergent validity among these systems, as demonstrated by a lack of reliability in diagnosis. Absence of an external standard makes it impossible to determine whether any system is more accurate, but outcomes do suggest areas for future research that may refine diagnosis.

Examining two different schedules of financial incentives for smoking cessation among pregnant women.

OBJECTIVE: To examine whether an efficacious voucher-based incentives intervention for decreasing smoking during pregnancy and increasing fetal growth could be improved without increasing costs. The strategy was to redistribute the usual incentives so that higher values were available early in the quit attempt. METHOD: 118 pregnant smokers in greater Burlington, Vermont (studied December, 2006-June, 2012) were randomly assigned to the revised contingent voucher (RCV) or usual contingent voucher (CV) schedule of abstinence-contingent vouchers, or to a non-contingent voucher (NCV) control condition wherein vouchers were provided independent of smoking status. Smoking status was biochemically verified; serial sonographic estimates of fetal growth were obtained at gestational weeks 30-34. RESULTS: RCV and CV conditions increased point-prevalence abstinence above NCV levels at early (RCV: 40%, CV: 46%, NCV: 13%, p=.007) and late-pregnancy (RCV: 45%; CV: 36%; NCV, 18%; p=.04) assessments, but abstinence levels did not differ between the RCV and CV conditions. The RCV intervention did not increase fetal growth above control levels while the CV condition did so (p<.05). CONCLUSION: This trial further supports the efficacy of CV for increasing antepartum abstinence and fetal growth, but other strategies (e.g., increasing overall incentive values) will be necessary to improve outcomes further.

Connectomics signatures of prenatal cocaine exposure affected adolescent brains.

Recent in vivo neuroimaging studies revealed that several brain networks are altered in prenatal cocaine exposure (PCE) affected adolescent brains. However, due to a lack of dense and corresponding cortical landmarks across individuals, the systematical alterations of functional connectivities in large-scale brain networks and the alteration of structural brain architecture in PCE affected brain are largely unknown. In this article, we adopted a newly developed data-driven strategy to build a large set of cortical landmarks that are consistent and corresponding across PCE adolescents and their matched controls. Based on these landmarks, we constructed large-scale functional connectomes and applied the well-established approaches of deriving genomics signatures in genome-wide gene expression studies to discover functional connectomics signatures for the characterization of PCE adolescent brains. Results derived from experimental data demonstrated that 10 structurally disrupted landmarks were identified in PCE, and more importantly, the discovered informative functional connectomics signatures among consistent landmarks distinctively differentiate PCE brains from their matched controls.

Cryptic residual GALT activity is a potential modifier of scholastic outcome in school age children with classic galactosemia.

Classic galactosemia is a potentially lethal disorder that results from profound deficiency of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme in the Leloir pathway of galactose metabolism. Although early diagnosis and rigorous dietary restriction of galactose prevent or resolve the potentially lethal acute symptoms, patients are at markedly increased risk of long-term complications including significant cognitive, speech, and behavioral difficulties, among other problems. The mechanisms that underlie these long-term complications remain unclear, as do the factors that modify their severity. Here we explored the scholastic and behavioral outcomes experienced by a cohort of 54 school age children with classic galactosemia. Data collected included survey responses from parents and teachers, school records including standardized test scores, and GALT genotype data used to estimate predicted residual GALT activity based on a yeast expression system. As expected, many but not all of the children in our study demonstrated speech, scholastic, and behavioral difficulties. Perhaps most striking, we found that predicted cryptic residual GALT activity, often below the threshold of detection of clinical assays, appeared to modify scholastic outcome. These data raise the intriguing possibility that cryptic GALT activity might also influence the severity of other long-term complications in classic galactosemia.

Increased "default mode" activity in adolescents prenatally exposed to cocaine.

Prenatal cocaine exposure (PCE) is associated with attention/arousal dysregulation and possible inefficiencies in some cognitive functions. However, the neurobiological bases of these teratogenic effects have not been well characterized. Because activities in the default mode network (DMN) reflect intrinsic brain functions that are closely associated with arousal regulation and cognition, alterations in the DMN could underlie cognitive effects related to PCE. With resting-state and task activation functional magnetic resonance imaging (fMRI), this study investigated the possible PCE related changes in functional brain connectivity and brain activation in the DMN. In the resting state, the PCE group was found to have stronger functional connectivity in the DMN, as compared to the nonexposed controls. During a working memory task with emotional distracters, the PCE group exhibited less deactivation in the DMN and their fMRI signal was more increased by emotional arousal. These data revealed additional neural effects related to PCE, and consistent with previous findings, indicate that PCE may affect behavior and functioning by increasing baseline arousal and altering the excitatory/inhibitory balancing mechanisms involved in cognitive resource allocation.

Smoking in pregnancy and parenting stress: maternal psychological symptoms and socioeconomic status as potential mediating variables.

INTRODUCTION: The purpose of this study was to examine the impact of smoking in pregnancy on parenting stress. Maternal psychological symptoms and socioeconomic status (SES) were evaluated as potential mediating factors between prenatal cigarette use and later parenting stress. METHOD: The sample included 218 mothers who were recruited at the hospital after birth and completed a 6-month visit with their infants at a university laboratory. Based on the mothers' responses to interviews at the hospital on tobacco use during pregnancy, the sample included 77 nonsmokers and 141 smokers. Information on sociodemographic variables, prenatal care, and other substance use during pregnancy was collected at the hospital interview. At the 6-month visit, the mothers completed measures of parenting stress and psychological symptoms. Cotinine levels were assessed at both timepoints. RESULTS: Regression analysis showed that maternal smoking during pregnancy predicted parenting stress in infancy. Maternal symptoms of psychological distress and SES were evaluated simultaneously to determine whether they functioned as mediating variables between smoking in pregnancy and parenting stress. A multiple mediation analysis (Preacher & Hayes, 2008a) showed that maternal psychological symptoms functioned as a mediating variable but that SES did not. CONCLUSIONS: Results suggest that mothers who smoke in pregnancy are likely to experience higher levels of psychological symptoms, which, in turn, predict higher levels of parenting stress. Smoking in pregnancy may be a marker for symptoms of psychological distress in mothers.

Memory and brain volume in adults prenatally exposed to alcohol.

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.

Default mode network dysfunction in adults with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) is known to cause significant cognitive and attentional dysfunction. Given the relationship between default mode network (DMN) activity and task-related attentional modulation, it is possible that PAE affects activity of this network. In the present study, task-related deactivation as well as structural and resting state functional connectivity of the DMN were examined using diffusional tensor imaging and functional magnetic resonance imaging in non-dysmorphic and dysmorphic PAE populations and compared to healthy controls. The dysmorphic PAE group was found to have reduced DMN deactivation as compared to controls, indicating poorer attentional modulation during the cognitive task. Additionally, structural connectivity and baseline functional connectivity were lower in both PAE groups as compared to controls. Primarily the findings suggest that learning problems seen with PAE may be a combination of general attentional and specific cognitive deficits. A secondary implication is that DMN activity is affected to varying extents depending on the degree of PAE.

Verbal and nonverbal memory in adults prenatally exposed to alcohol.

BACKGROUND: Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. METHODS: In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. RESULTS: Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. CONCLUSION: These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

The effect of psychological distress on health outcomes: A systematic review and meta-analysis of prospective studies.

Distress effects are widely examined in cross-sectional studies with less known about effects on future health. This review summarizes distress impacts on health among adults in prospective studies and describes available distress measurement tools. Four inter-disciplinary databases were searched. Effects of distress on mortality and other outcomes were reviewed and estimated in a meta-analysis. A total of 19 studies were assessed which incorporated 10 distress tools. Distress had a detrimental effect on health regardless of the population studied, distress tool used, and health outcome examined. There was an increased mortality risk among those reporting high versus low distress (pooled hazard ratio (95% confidence interval) = 1.29 (1.15-1.46)).

Voxelwise and skeleton-based region of interest analysis of fetal alcohol syndrome and fetal alcohol spectrum disorders in young adults.

Though fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders are among the most common developmental disorders, their understanding is incomplete. Diffusion tensor imaging (DTI), which is sensitive to microstructural organization in white matter, may provide a relevant measure in this population demonstrating incompletely characterized white matter pathology. In this study, tract-based spatial statistics (TBSS) routine and a skeleton-based region of interest analyses were employed to detect differences in DTI-derived metrics between young adults who were alcohol exposed and an unexposed control group. Participants include 28 with dysmorphic features associated with FAS, 29 who were prenatally exposed but do not show physical effects, and 25 with the same low socioeconomic status but unexposed. The TBSS analysis revealed a statistically significant decrease in fractional anisotropy at the isthmus of the corpus callosum and its connected callosal fibers in dysmorphic individuals relative to controls (clusterwise P(FWE) < 0.05). This finding was consistent with that of the follow-up skeleton-based region of interest analysis (F((2,79)) = 3.256, p = 0.044). In addition, the patterns in axial and radial diffusivity changes suggest that demyelination may be associated with the degraded white matter integrity observed in the dysmorphic group.

Effects of prenatal alcohol exposure on brain activation during an arithmetic task: an fMRI study.

BACKGROUND: While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task. METHODS: Participants were young adults from a low socio-economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n = 17) and PAE who were subdivided based on the presence (n = 19) or absence of physical dysmorphic signs (n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter-matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol-exposed population. RESULTS: An exposure-dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task-related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation. CONCLUSIONS: Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.

Longitudinal changes of amygdala functional connectivity in adolescents prenatally exposed to cocaine.

BACKGROUND: Prenatal cocaine exposure (PCE) is associated with arousal dysregulation, but interactions between exposure and age are rarely investigated directly with longitudinal study designs. Our previous study had examined task-elicited emotional arousal and noted persistently high amygdala activations in the development of adolescents with PCE. However, while externally imposed emotional arousal could be considered a "state" effect depending on specific task stimuli, it is still unclear whether similar developmental alterations extend to intrinsic functional connectivity (FC), reflecting more of a "trait" effect. METHODS: We used a longitudinal design and analyzed resting-state functional magnetic resonance imaging data acquired twice from 25 adolescents with PCE and 16 non-exposed controls. Both groups were each scanned first at the mean age of 14.3 and then again at 16.6 years. Seeding in bilateral amygdalae and comparing the 2nd scan with the 1st, we examined the interaction effect between PCE and age on FCs in the emotional network. RESULTS: Compared with the younger age, we observed a generally decreased FC in the emotional network of the control group at the older age, but these FCs were generally increased at the older age in this same network of the PCE group. Additionally, this interaction effect of exposure by age in the right fusiform was positively correlated with the emotional interference imposed by external task stimuli. CONCLUSIONS: These results provided additional data directly characterizing developmental changes in the emotional network of adolescents with PCE, complementing and extending the notion of a PCE-associated long-term teratogenic effect on arousal regulation.

Exploring changes in distress among individuals with bleeding disorders: What is linked to improvements in distress?

Adults with chronic bleeding disorders report high distress, but it is unclear how distress varies over time. Patients rated their distress on a 10-point scale at two clinic visits. Of 83 patients, roughly one-quarter reported consistent no/low distress (29%), one-quarter reported consistent distress (22%), and half (49%) reported a change in distress of at least two points. Overall activity levels, depressive symptoms, and non-White race were significantly associated with worsening and consistent distress in adjusted analyses while improvements in activity levels and depressive symptoms during the study period were associated with distress improvement. Our results suggest that distress is modifiable.