Search

STUDY QUESTION What is the clinical validity and utility of preconception Expanded Carrier Screening (ECS) application on the management of prospective parents? SUMMARY ANSWER The high detection rate of at-risk couples (ARCs) and the high proportion opting for IVF/preimplantation genetic testing (PGT) treatment demonstrate the clinical utility of ECS in the preconception space in IVF and general population. WHAT IS KNOWN ALREADY About 2–4% of couples are at risk of conceiving a child with an autosomal recessive or X-linked genetic disorder. In recent years, the increasing cost-effectiveness of genetic diagnostic techniques has allowed the creation of ECS panels for the simultaneous detection of multiple recessive disorders. Comprehensive preconception genetic screening holds the potential to significantly improve couple’s genetic risk assessment and reproductive planning to avoid detectable inheritable genetic offspring. STUDY DESIGN, SIZE, DURATION A total of 3877 individuals without a family history of genetic conditions were analyzed between January 2017 and January 2020. Of the enrolled individuals, 1212 were gamete donors and 2665 were patients planning on conceiving from both the IVF and the natural conception group. From the non-donor cohort, 1133 were analyzed as individual patients, while the remaining ones were analyzed as couples, for a total of 766 couples. PARTICIPANTS/MATERIALS, SETTING, METHODS A focused ECS panel was developed following American College of Obstetrics and Gynecology ACOG-recommended criteria (prevalence, carrier rate, severity), including highly penetrant severe childhood conditions. Couples were defined at-risk when both partners carried an autosomal recessive pathogenic/likely pathogenic variant (PLP) on the same gene or when the woman was a carrier of an X-linked PLP variant. ARC detection rate defined the clinical validity of the ECS approach. Clinical utility was evaluated by monitoring ARCs reproductive decision making. MAIN RESULTS AND THE ROLE OF CHANCE A total of 402 individuals (10.4%) showed PLP for at least one of the genes tested. Among the 766 couples tested, 173 showed one carrier partner (22.6%), whereas 20 couples (2.6%) were found to be at increased risk. Interestingly, one ARC was identified as a result of cascade testing in the extended family of an individual carrying a pathogenic variant on the Survival Of Motor Neuron 1SMN1 gene. Of the identified ARCs, 5 (0.7%) were at risk for cystic fibrosis, 5 (0.7%) for fragile X syndrome, 4 (0.5%) for spinal muscular atrophy, 4 (0.5%) for Beta-Thalassemia/Sickle Cell Anemia, 1 (0.1%) for Smith-Lemli-Opitz Syndrome and 1 (0.1%) for Duchenne/Becker Dystrophy. Fifteen ARCs were successfully followed up from both the IVF and the natural conception groups. All of these (15/15) modified their reproductive planning by undergoing ART with Preimplantation Genetic Testing for Monogenic disease and Aneuploidies (PGT-M and PGT-A). To date, 6/15 (40%) couples completed their PGT cycle with euploid/unaffected embryos achieving a pregnancy after embryo transfer and three of them have already had an unaffected baby. LIMITATIONS, REASONS FOR CAUTION The use of a limited panel of core gene-disease pairs represents a limitation on the research perspective as it can underestimate the rate of detectable carriers and ARCs in this cohort of prospective parents. Expanding the scope of ECS to a larger panel of conditions is becoming increasingly feasible, thanks to a persistent technological evolution and progressive cataloging of gene–disease associations. WIDER IMPLICATIONS OF THE FINDINGS These results highlight the potential clinical validity and utility of ECS in reducing the risk of a pregnancy affected by a detectable inheritable genetic condition. The steady reduction in the costs of genetic analyses enables the expansion of monogenic testing/screening applications at the preimplantation stage, thus, providing valid decisional support and reproductive autonomy to patients, particularly in the context of IVF. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. A.C., M.F., S.C., M.P., L.G., and C.P. are employees of Igenomix Italy. C.S. is the head of the scientific board of Igenomix. TRIAL REGISTRATION NUMBER N/A.

The Trail Making Test (TMT), a widely used neuropsychological test, is highly effective in detecting brain damage. A shortcoming of the test is that it requires drawing lines and thus is impractical for use with persons suffering manual impairment. The 3 studies described herein were designed to describe and evaluate a nonmanual Trail Making Test (NMTMT) that would be suitable for use with manually impaired individuals. The NMTMT utilizes color to permit oral reporting of the stimuli constituting a series of numbers (Part A) or alternating series of numbers and letters (Part B). The studies, which involved a total of 200 university students, indicate that the standard TMT and the NMTMT are moderately related to each other and have similar patterns of association and nonassociation with other neuropsychological measures. Participants with scores falling near the bottom of the NMTMT distribution have a high probability of scoring at least 1 standard deviation below the mean of the TMT distribution for Part B. The clinically important relationship of Part A to Part B seems to be retained in the NMTMT. It is concluded that the NMTMT shows promise as a substitute for the TMT when the TMT cannot be used.

Objective To conduct a systematic review of the prognostic value of self-reported traits/problems/strengths and environmental barriers/facilitators for participation outcomes in persons with traumatic brain injury (TBI). Data Sources Articles published through August 15, 2013, obtained by conducting electronic searches of PubMed, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature databases and a review of reference lists of reviewed articles. Study Selection Reviewed articles were written in English and presented findings on adult humans with TBI, participation outcomes, and ≥1 self-reported trait/problem/strength (eg, depression, pain, coping style) and/or ≥1 environment barrier/facilitator (eg, social support, family functioning, access to services). Data Extraction Each of the 996 abstracts was examined by 2 reviewers, and those failing to meet all inclusion criteria were excluded. Data were extracted from the 63 retained articles by 2 independent reviewers, who met to resolve any differences in study quality rating or evidence recorded. Study quality was determined using American Academy of Neurology (AAN) criteria. Data Synthesis Conclusions regarding prognostic importance of self-report and environmental barrier/facilitator variables were made using AAN criteria. Conclusions regarding barrier/facilitator variables indicated that access to transportation, access to services, and participation in social interaction were possibly predictive of employment outcome, whereas living arrangements and social support were possibly not predictive of employment outcome. Conclusions regarding self-report variables indicated that the number of postconcussive symptoms, fatigue, and physical competence were probably predictive of employment and need for supervision, whereas self-efficacy was probably not predictive of employment. Subjective well-being, pain, and social interaction were possibly predictive of employment, whereas coping style was possibly not predictive. Conclusions Although additional investigation is needed, self-report variables are likely to make important contributions to predicting participation outcomes. Future research should be guided by coherent conceptual models and use a consistent set of assessment instruments to facilitate comparisons between studies.

PURPOSE/OBJECTIVE: Performance validity is often conceptualized as a dichotomous process. Effort likely lies on a continuum, however, and psychologists' tendency to rely on pass/fail descriptors of one's effort may not be the only approach. The current study aims to show that when performance validity is considered on a continuum, it may provide clinical information related to cognitive functioning. RESEARCH METHOD/DESIGN: Forty-four patients with moderate or severe traumatic brain injury were evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status upon their emergence from posttraumatic amnesia. From this data, previously developed effort index scores and "other cognitive functions" index scores were calculated. RESULTS: Performance on the effort index significantly accounted for the patients' performance on a cognitive composite score after considering education and severity of injury. CONCLUSIONS/IMPLICATIONS: Findings suggest that more in-depth analysis of validity test performance is beneficial to gauge a patient's level of effort and is important to consider when interpreting results and in treatment planning. (PsycINFO Database Record (c) 2014 APA, all rights reserved). Language: en

Introduction The Forced-choice Graphics Memory Test (FGMT) is a newly developed measure to assess feigned cognitive impairment. This study investigated the ability and reliability of FGMT for identification of malingering in patients with traumatic brain injury (TBI). Methods The FGMT was administered to 40 healthy volunteers instructed to respond validly (Healthy Control, H-C), 40 healthy volunteers instructed to feign cognitive impairment (Healthy Malingering, H-M), 40 severe TBI patients who responded validly (TBI control, TBI-C), and 30 severe TBI patients who evidenced invalid performance (TBI malingering, TBI-M). Results Both malingering groups (H-M and TBI-M) performed much more poorly than the nonmalingering groups (H-C and TBI-C). The FGMT overall total score, score on easy items, and score on hard items differed significantly across the four groups. The total score showed the highest classification accuracy in differentiating malingering from nonmalingering. A cutoff of less than 18 (total items) successfully identified 95% of TBI-C and 93.3% of TBI-M participants. The FGMT also demonstrated high test–retest reliability and internal consistency. FGMT scores were not affected by TBI patients' education, gender, age, or intelligence. Conclusion Our results suggest that the FGMT can be used as a fast and reliable tool for identification of feigned cognitive impairment in patients with TBI.

The Wisconsin Card Sorting Test (WCST) has been demonstrated to have a relatively stable factor structure in traumatic brain injury (TBI) samples. What is less clear is whether the scores derived from WCST factors are related to functional outcomes. The purpose of the current study was to replicate the WCST factor structure in a sample with severe TBI, and to evaluate the relationship between the factor scores and outcome.Retrospective correlational study.Participants (n=143) who had suffered severe TBI were administered a battery of neuropsychological tests including the WCST within one month of admission to a brain injury rehabilitation program. In addition, participants were administered supervision (Supervision Rating Scale; SRS) and productivity measures (Community Integration Questionnaire- Productivity subscale; CIQ-P) at admission and following discharge.None.For individuals who were more than one year post injury, more failure to maintain set errors were associated with better occupational outcomes, while more nonperseverative errors were associated with increased supervision needs.The WCST factor scales are related to functional outcomes in severe TBI. Specifically, the inability to establish a series of correct responses is associated with poorer outcome.

Lateralized interference between concurrent cognitive and manual activities is used to infer cerebral hemisphere specialization for the cognitive activity. However, some evidence indicates that lateralized interference depends largely on manual asymmetry in the single-task (baseline) condition. To test the competing explanations, we asked 40 right-handed (RH) and 40 left-handed (LH) adults to key press and calculate concurrently. Baseline manual asymmetries were manipulated by increasing the complexity of the task performed by the dominant hand. Nevertheless, in the dual-task conditions, RHs showed more overall interference when performing with the right hand and LHs showed a nonsignificant tendency in the opposite direction. The results indicate that differential interference patterns, similar to those previously reported for right- and left-handers, may be obtained even when the usual baseline manual asymmetries are reversed.

Primary objective : To investigate the relationship of family functioning to patients' progress in a post-acute TBI rehabilitation programme. Research design : Cohort study investigating predictors of change from admission to follow-up. Methods and procedures : Caregivers of 37 persons with severe TBI consecutively admitted to a residential post-acute rehabilitation facility completed the Family Assessment Device (FAD) within a few weeks of admission. The Disability Rating Scale (DRS) was completed upon admission and ~1 month after discharge. FAD scores were used to predict DRS change scores after controlling for injury severity, admit FAD scores, and time from admission to follow-up. Main outcomes and results : Persons with unhealthy family functioning showed less improvement on DRS total, level of functioning (LOF), and employability (EMP) scores. Conclusions : The results emphasize that family functioning is an important variable to include in future models predicting rehabilitation outcome, and the im...

Although paced serial addition (PSA) tasks are considered to be tests of general information-processing capacity, recent work suggests that performance on such tasks is influenced by arithmetic-specific variables. We designed two visual PSA experiments to determine whether the performance of normal adults would support predictions derived from the cognitive psychology of calculation. Experiment 1 showed that mixing familiar (Arabic numeral) and less familiar (Roman numeral) stimulus formats reduced scores below the averaged scores for pure Arabic and Roman lists. The Roman-Arabic order of addends was more difficult than the Arabic-Roman order. Experiment 2, which involved only Arabic numerals as addends, showed that performance could be impaired by constraining the trial-to-trial variability of sums. The results of both experiments confirm the importance of arithmetic-specific variables in PSA and provide support for an associative network model of calculation. In addition, the findings implicate interference from extraneous addends and responses as the performance-limiting factor.

Within the context of a post-acute rehabilitation setting, association and agreement between results from the Neurobehavioural Cognitive Status Examination (NCSE) and from the neuropsychological (NP) evaluation are examined. All participants (n = 48) had sustained a severe traumatic brain injury and NCSE testing preceded NP testing by an average of 1 month. A significant relationship and fair classification agreement (i.e. presence or absence of cognitive impairment) was found between the overall results from NCSE and NP evaluation. Significant relationships were also observed between most NCSE subtests and paired NP tests thought to be assessing the same cognitive domains. However, the classification agreement (i.e. the presence or absence of deficient performance) between most NCSE subtests and paired NP tests was poor. The findings are discussed from the standpoint of individual treatment planning.

Assessment of current level of functioning among clients with traumatic brain injury (TBI) often guides the establishment of realistic outcome goals for post-acute rehabilitation. Further, data generated from neuropsychological testing provide a clinician with a better understanding of a client's pattern of cognitive strengths and weaknesses. The Disability Rating Scale (DRS) is commonly used by TBI rehabilitation facilities to assess a client's general level of functioning in terms of impairment, disability, and handicap. Previous studies have used clients' neuropsychological test results to predict future level of functioning. These studies have shown mixed results regarding the predictive validity of the test findings; however, they usually employ only a limited number of tests for prediction representing a limited number of cognitive domains. Using a concurrent validity design, the present study investigated the bivariate associations between various neuropsychological testing domains (i.e. intellectual, academic, language, visuoperceptual, memory, and executive functioning) and level of functioning as indexed by the DRS. Participants were administered the DRS and the neuropsychological evaluation during the initial part of post-acute rehabilitation. Composite scores were derived for each of the neuropsychological domains. Most participants were categorized as sustaining a severe TBI. The mean age and education of this predominately male sample was 28.84 years (SD = 9.13) and 11.83 years (SD = 1.7), respectively. Results revealed a significant positive relationship between performances in intellectual, executive, academic, and visuoperceptual domains and level of functioning.

Although the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been shown to be a useful tool in evaluating the cognitive status of patients with dementia, stroke, schizophrenia and post-acute traumatic brain injury (TBI), no studies have examined its utility in an acute TBI setting. The current study investigates the RBANS' sensitivity to acute TBI, hypothesizing that the presence and severity of injury is predictive of worse RBANS performance.Neuropsychological testing was conducted an average of 6.1 days after emergence from post-traumatic amnesia (PTA). RBANS results were evaluated based on a normative basis, pre-injury estimates, and brain injury severity.In this sample of acute TBI patients (n = 51), the mean index scores on the RBANS ranged from 1.59-2.36 SD below the mean of the standardization sample. Each WRAT-4 Reading sub-test score was above the corresponding RBANS Total Scale Index score (t(31) = 10.32, p 0.001). Regression analyses revealed that Delayed Memory (β = - 0.365, p 0.007) and Total Score (β = -0.297, p 0.023) indices were significantly predicted by PTA length after controlling for age and education.The RBANS appears to be a useful tool in assessing the presence and severity of acute TBI.

Objective To describe the development and implementation of a social peer-mentoring program for persons with traumatic brain injury (TBI) and to explore whether this program yielded increased social functioning outcomes compared with wait-list (WL)controls. Design Pilot randomized controlled study. Participants Community-dwelling individuals with TBI(12 matched with social peer mentors and 18 completing the WL condition). Intervention Trained social peer mentors (SPMs)were matched to partners with TBI (peer partners (PP)) to foster skill-building in planning of social activities and improving social communication abilities through phone contacts and joint participation in social events within the community over a 3-month period. Measures Social Activity Interview, Center for Epidemiological Studies Depression Scale, UCLA Loneliness Scale, Satisfaction with Life Scale, 6-Item Interpersonal Support Evaluation List (baseline and postmentoring); weekly social activity data(1-month baseline, continuously collected during 3-month mentoring or WL period); satisfaction survey. Results Both SPM and PP participants reported high satisfaction with the mentoring program. Statistically significant improvements in perceived social support after mentoring were observed for the mentored group than for WL participants; however, an increase in depressive symptoms was also observed. While significant improvements in social activity level and social network size were not found, a trend toward increased satisfaction with social life was present for mentored participants. Conclusions Satisfaction ratings for the SPM program were uniformly high and selected positive findings encourage further investigation of social mentoring as an intervention to effect improvements in social integration. Small sample size and reduced "dosage" of mentor interactions were limitations of this pilot study. Benefits of and challenges to implementation of an SPM program are outlined.

Supervision needs typically increase following moderate-to-severe traumatic brain injury (TBI). Research assessing the impact of TBI residential rehabilitation programmes on supervision needs is limited.Prospective cross-sectional study.Ninety-four participants with moderate-to-severe TBI admitted to a post-acute brain injury rehabilitation programme (PABIR) were administered the supervision rating scale (SRS) at admission and at 1 month post-discharge. To account for spontaneous neurological recovery, patients were separated into those who were less than 1 year (L1Y, n = 55) or greater than 1 year (G1Y, n = 39) post-injury.None.A mixed factorial design yielded a significant interaction (F(1, 92) = 18.2; p0.0001) with post-hoc results revealing that the L1Y group improved more dramatically in terms of supervision needs than the G1Y group. Using reliable change methodologies, 52.7% of the L1Y demonstrated decreasing scores on the SRS vs 20.5% of the G1Y group.Decreases in supervision needs following PABIR can be found, even after accounting for the impact of spontaneous neurological recovery both at the group and individual level.

In previous demonstrations of differences between left- and right-handers in dual-task performance, participants' hand preference has been confounded with asymmetry of manual skill. The present study was designed to disentangle those two factors as sources of lateralized interference in the concurrent-task paradigm. Forty-eight normal adults (24 females and 24 males) counted backward by ones or by twos while typing an easy or difficult sequence of letters with either hand. When participants were grouped according to self-reported hand preference, both groups showed bilaterally symmetric slowing, relative to single-task conditions. However, when the same participants were grouped according to manual asymmetry in the baseline condition, the cognitive task interfered significantly more with the faster hand than with the slower hand. Baseline typing rate, averaged across hands, did not influence dual-task interference. Both self-reported left-hand preference and left-hand superiority in baseline typing were associated with reduced interference on the cognitive task, and the reduced interference in those groups seemed to reflect relatively loose coupling between manual and cognitive tasks. The results support and extend Caroselli et al.'s (1997) findings regarding the effect of baseline manual asymmetry on the pattern of dual-task interference. Irrespective of the participant's hand preference, the presence or absence of baseline asymmetry may be sufficient to determine whether dual-task interference is lateralized.

To investigate through pilot exploration the relationships between depression, self-concept and perceived quality of life (QoL) in post-acute patients with acquired brain injury (ABI).Nineteen patients with ABI were administered the Beck Depression Inventory-II and the Quality of Life Inventory, along with the Tennessee Self-Concept Scale-2 and the Head Injury Semantic Differential Scale, measures of self-concept. The relationships between these measures were explored using correlational analyses.Ratings of self-concept were correlated with perceived QoL, suggesting that poorer view of self was associated with lower subjective QoL. Additionally, depressive symptoms were associated with lower QoL ratings, consistent with previous research.These results suggest that intra-personal variables, such as self-concept and depression, impact the perceived QoL of the ABI survivor. Future research exploring the mediating effects of these variables on QoL may clarify this relationship and may aid in developing more effective interventions for these individuals.

Objective : Evaluate changes in community integration for survivors of traumatic brain injury (TBI) who participated in a post-acute rehabilitation programme. Design : Cohort, prospective study investigating change from admission to post-discharge. Participants : Individuals, the majority of whom were diagnosed with severe TBI, were placed into one of two groups as follows: (1) admitted for treatment less than 1 year post-injury (L1Y) or (2) admitted for treatment between 1-5 years post-injury (G1Y). Measure : The Community Integration Questionnaire (CIQ). Results : Both groups showed significant improvements from admission to follow-up; however, some CIQ findings were more pronounced for the L1Y group. Reliable change (RC) methodology was used to assess individual change. Results of this approach were consistent with group results, but tempered the perception of degree of change. Conclusions : Findings cannot simply be attributed to neurological recovery and individual factors are important to examine wh...

Objective To investigate the factor structure and concurrent validity of the Caregiver Appraisal Scale (CAS) in a sample of caregivers of adults with traumatic brain injury (TBI). Design Prospective cohort study. Setting Two sites: (1) Outpatient clinics associated with a comprehensive inpatient brain injury rehabilitation program and (2) a comprehensive residential postacute rehabilitation program in the Southern United States. Participants One hundred forty-nine caregivers of adults with TBI enrolled in the TBI Model Systems Project and 92 caregivers of adults with TBI admitted to a residential postacute rehabilitation program. Most caregivers were women and either parents or spouses of the injured person. Main outcome measures Caregiver Appraisal Scale (CAS); Subjective Burden Scale (SBS); Objective Burden Scale (OBS); General Health Questionnaire (GHQ). Results Principal components analysis with varimax rotation yielded four factors: perceived burden (PB), caregiver relationship satisfaction (CRS), caregiving ideology (CI), and caregiving mastery (CM), which were found to be fairly stable across treatment settings. Adequate concurrent validity was demonstrated for the perceived burden factor, and adequate internal consistency was found for three of four scales. Conclusions Preliminary support for the use of the CAS in caregivers of adults with TBI was obtained. However, further scale development, particularly for the CM factor, will likely improve the stability and usefulness of this instrument.

Interhemispheric transfer was examined in 13 normal controls and in 13 children with hydrocephalus and partial agenesis of the corpus callosum involving a missing splenium associated with spina bifida meningomyelocele and aqueductal stenosis. Children with hydrocephalus demonstrated greater left visual-field superiority for forms indicative of difficulty in interhemispheric transfer of visual information. Interhemispheric transfer time (ITT) was somewhat longer in the children with hydrocephalus, but neither the ITT task nor the dichotic listening and tactile naming tasks provided clear evidence of difficulties in callosal transfer. Sensory and perceptual control tasks revealed similar visual acuity and monotic word perception but larger 2-point discrimination thresholds and poorer tactile matching.

Tests of paced serial addition are used to detect diminished information-processing capacity. Nonetheless, performance might be influenced by modality-specific interference or by variables that specifically affect numerical processing. In a series of three experiments with normal adults, we manipulated, respectively, the modality in which addends were presented, the modality in which responses were produced, and the format in which visual addends were displayed. Performance was enhanced when stimuli were presented visually and when responses were made manually. When visual addends were used, Arabic numerals were processed more effectively than number words. Thus, performance was influenced by modality-specific interference and by presentation format. We conclude that paced serial addition tasks may not provide a pure measure of general information-processing capacity.

According to Kinsbourne's functional cerebral distance model, asymmetric interference between concurrent cognitive and manual tasks reflects the functional specialization of the cerebral hemispheres. However, alternative explanations include initial-values artifact (statistical bias model), motor asymmetry (manual dominance model), and a combination of functional cerebral distance and manual dominance (two-factor model). We evaluated the competing models in four experiments with right- and left-handed university students for whom manual dominance was in effect reversed by requiring the dominant hand to perform the more difficult manual task. The cognitive load of the nonmanual task was varied within each experiment. The results did not support any of the models but, instead, reflected only tradeoffs between manual and nonmanual performance. The primary implications for future research are that performance on both tasks must be measured, and each task must be sensitive to interference from the other task, if observed asymmetries are to be interpretable. Copyright©1997 Elsevier Science Ltd.

Webster (1988) described a means of using scattergrams to represent the manual and nonmanual data from dual-task laterality experiments in a composite analysis. We used Webster's method and the conventional approach (i.e., separate analyses) to analyze the results of an experiment in which 40 right-handed adults performed a verbal and a manual task concurrently. Whereas separate analyses yielded dissimilar outcomes for the two tasks, the scattergram analysis showed that overall interference was greater when the right hand performed the manual task than when the left hand performed the manual task. Advantages of the scattergram method for analyzing dual-task data are discussed.