Parents of newborns in the NICU enrolled in genome sequencing research: hopeful,but not naïve

PurposeIn 2014, our institution launched a randomized controlled trial (RCT) comparing rapid genome sequencing (GS) to standard clinical evaluations of infants with suspected genetic disorders. This study aimed to understand parental response to the use of GS for their newborn babies.MethodsTwenty-three of 128 parents whose infant had enrolled in the RCT completed a retrospective survey and interview addressing attitudes about GS and responses to receiving diagnostic information. We also collected information about participants’ genetic literacy, genetic knowledge, numeracy, and symptoms of anxiety and depression.ResultsThe majority reported positive (13; 56.5%) or neutral 4 (4; 17.4%) feelings when approached about GS for their infant and 100% felt that GS was generally beneficial. The 12 participants who had received a unifying diagnosis for their child’s symptoms described personal utility of the information. Some reported the diagnosis led to changes in medical care. Participants showed understanding of some of the psychological risks of GS. For example, 21 (91.3%) agreed or strongly agreed that genetic testing could reveal disturbing results.ConclusionsParents who enrolled their newborn in a RCT of GS demonstrated awareness of a psychological risk, but generally held positive beliefs about GS and perceived the benefits outweighed the risk.     

A mixed methods exploration of families' experiences of the diagnosis of childhood spinal muscular atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with a carrier frequency of 1 in 41 in Australia. Childhood SMA is classified into three types based on the age at which children present with symptoms and the clinical severity. Families'' experiences leading up to the diagnosis have not been described, but are important when considering the potential for a diagnostic odyssey. Using a mixed methods approach, data were collected from interviews and a national survey of families of children with SMA to explore their experiences of this journey. The combined findings (n=28) revealed that the journey to receiving a diagnosis was protracted. The time from first noticing symptoms to finally receiving a diagnosis was emotional and frustrating. Once parents or other family members became aware of symptoms, almost all had consulted with multiple different health professionals before the diagnosis was ultimately made. Not surprisingly, receiving the diagnosis was devastating to the families. The nature of the information and the way it was given to them was not always optimal, particularly because of the difficulties predicting clinical severity. Most felt that their child could have been diagnosed earlier and, although there were mixed views around the benefit of this for their child, they felt it may have reduced the emotional impact on families. Overall, families were more in favour of population carrier screening for SMA when compared with newborn screening of the population. Despite an increasing awareness of SMA, the diagnostic delay continues to have negative impacts on families.     

Parental experiences of ultrarapid genomic testing for their critically unwell infants and children

PurposeTo explore parental experiences of ultrarapid genomic testing for their critically unwell infants and children.MethodsParents of critically unwell children who participated in a national ultrarapid genomic diagnosis program were surveyed >12 weeks after genomic results return. Surveys consisted of custom questions and validated scales, including the Decision Regret Scale and Genomics Outcome Scale.ResultsWith 96 survey invitations sent, the response rate was 57% (n = 55). Most parents reported receiving enough information during pretest (n = 50, 94%) and post-test (n = 44, 83%) counseling. Perceptions varied regarding benefits of testing, however most parents reported no or mild decision regret (n = 45, 82%). The majority of parents (31/52, 60%) were extremely concerned about the condition recurring in future children, regardless of actual or perceived recurrence risk. Parents whose child received a diagnostic result reported higher empowerment.ConclusionThis study provides valuable insight into parental experiences of ultrarapid genomic testing in critically unwell children, including decision regret, empowerment, and post-test reproductive planning, to inform design and delivery of rapid diagnosis programs. The findings suggest considerations for pre- and post-test counseling that may influence parental experiences during the testing process and beyond, such as the importance of realistically conveying the likelihood for clinical and/or personal utility.     

Diagnostic exome sequencing in children: A survey of parental understanding,experience and psychological impact

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English‐speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.     

Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort

Despite clear technical superiority of genome sequencing (GS) over other diagnostic methods such as exome sequencing (ES), few studies are available regarding the advantages of its clinical application. We analyzed 1007 consecutive index cases for whom GS was performed in a diagnostic setting over a 2-year period. We reported pathogenic and likely pathogenic (P/LP) variants that explain the patients’ phenotype in 212 of the 1007 cases (21.1%). In 245 additional cases (24.3%), a variant of unknown significance (VUS) related to the phenotype was reported. We especially investigated patients which had had ES with no genetic diagnosis (n = 358). For this group, GS diagnostic yield was 14.5% (52 patients with P/LP out of 358). GS should be especially indicated for ES-negative cases since up to 29.6% of them  could benefit from GS testing (14.5% with P/LP, n = 52 and 15.1% with VUS, n = 54). Genetic diagnoses in most of the ES-negative/GS-positive cases were determined by technical superiority of GS, i.e., access to noncoding regions and more uniform coverage. Importantly, we reported 79 noncoding variants, of which, 41 variants were classified as P/LP. Interpretation of noncoding variants remains challenging, and in many cases, complementary methods based on direct enzyme assessment, biomarker testing and RNA analysis are needed for variant classification and diagnosis. We present the largest cohort of patients with GS performed in a clinical setting to date. The results of this study should direct the decision for GS as standard second-line, or even first-line stand-alone test.Subject terms: Genetics research, Genomics     

Emotional suppression and psychological responses to a diagnosis of breast cancer

This study examined the relationship between emotional suppression and psychological distress in response to a diagnosis related to breast cancer. After their first visit, 31 patients with breast cancer and 90 with benign breast conditions completed the courtauld emotional control scale (CECS) and the profile of mood states (POMS) and were interviewed about their concerns after being diagnosed. Breast cancer and benign breast condition patients were divided into separate emotional suppression groups or emotional expression groups based on their median CECS score. The POMS scores of breast cancer patients were higher than those of benign breast condition patients; scores in the emotional suppression groups were higher than in the emotional expression groups. Breast cancer patients in the emotional suppression group expressed more negative emotions and fewer positive emotions than benign breast condition patients. Our results suggest that patients who suppressed their emotions experienced and reported more psychological distress when diagnosed with breast cancer.     

Precocious Sexual Development in Girls: The Emotional Impact on the Child and Her Parents

The emotional impact of isolated early development of breasts(thelarche) or pubic hair (adrenarche) has not previously beenreported. The psychological assessment of 16 girls with theendocrine diagnosis of precocious thelarche, adrenarche, orpuberty consisted of a parent interview and a clinical psychologicalassessment of the child in a playroom setting which includedpsychological testing. It is suggested that all three conditionsmay represent potential developmental interferences for thegirl, both directly through bodily changes and indirectly throughparental reactions. Strikingly, girls with precocious pubertyas a group appeared to have coped more successfully, acceptedtheir bodies more, and had a better self-image than those withthelarche or adrenarche. Similarly, parents seemed to have moredifficulty dealing with precocious thelarche and adrenarchethan with precocious puberty. Therefore, it appears that medicallybenign conditions may at times have greater psychological impactthan those which need ongoing medical attention. The importanceof the child's age at the time of onset and of the medical/genitalexaminations, as well as of the assessment of the premorbidpsychological development of the child and the nature of theparent-child relationship is discussed.     

Applying the Clinician-reported Genetic testing Utility InDEx (C-GUIDE) to genome sequencing: further evidence of validity

Genome sequencing (GS) outperforms other rare disease diagnostics, but standardized approaches to assessing its clinical utility are limited. This study assessed the validity of the Clinician-reported Genetic testing Utility InDEx (C-GUIDE), a novel tool for assessing the utility of genetic testing from a clinician’s perspective, for GS. C-GUIDE ratings were completed for patients who received GS results. For each patient, total C-GUIDE and single item global scores were calculated. Construct validity was assessed using linear regression to determine the association between C-GUIDE total and global item scores and measure the effects of potential explanatory variables. Ratings were completed for 67 pediatric and 36 adult patients. GS indications were neurological for 70.9% and results were diagnostic for 28.2%. When the C-GUIDE assessed primary (PV), secondary (SV), and pharmacogenomic (PGx) variants, on average, a one unit increase in the global item score was associated with an increase of 7.3 in the C-GUIDE score (p < 0.05). Diagnostic results were associated with an increase in C-GUIDE score of 5.0 compared to non-diagnostic results (p < 0.05) and an increase of one SV was associated with an increase of 2.5 (p < 0.05). For children, decreased age of one year was associated with an increase in C-GUIDE score of 0.3 (p < 0.05). Findings provide evidence that C-GUIDE measures the construct of clinical utility in pediatric and adult rare disease populations and is sensitive to changes in utility related to variant type. Quantifying the clinical utility of GS using C-GUIDE can inform efforts to optimize its use in patient care.Subject terms: Genetic testing, Outcomes research, Genetic testing     

Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders: Comparing questionnaire results with in-depth interviews

In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression (Hospital Anxiety and Depression Scale), feelings of hopelessness (Beck Hopelessness Scale), and psychological complaints (Symptom Checklist) were assessed to determine their psychological well-being. The manner of discussing the genetic disorder, the test, and its implications during a semistructured interview (reflecting on one's emotions without getting carried away or dismissing or minimizing the subject) was judged in terms of coherence. Participants at risk for neurodegenerative disorders had higher anxiety and depression scores and more psychological complaints than did those at risk for cancer syndromes. Those reporting high intrusion/high avoidance had higher anxiety and depression scores and more psychological complaints than did those reporting low intrusion/low avoidance. However, the scoring of the interview showed that participants reporting high intrusion/high avoidance were more reflective about their emotions without getting carried away or dismissing the subject (e.g., more coherent) than those reporting low intrusion/low avoidance. This result suggests that participants with higher stress scores may be actively dealing with the emotional implications of the test, whereas those with low stress scores may (as yet) be unable to face these implications. It is important to identify the strategy of coping with threat to provide suitable counseling and necessary guidance. However, long-term follow-up is needed to learn the consequences of a denial coping strategy for those participating in a genetic testing program. Am. J. Med. Genet. 75:62–74, 1998. © 1998 Wiley-Liss, Inc.     

维吾尔族、汉族高年级小学生父母教养方式的比较

目的:探讨阿克苏市维吾尔族、汉族高年级小学生父母教养方式的差异及特点。方法:采用中文版Steinberg父母教养方式问卷,对阿克苏市2所小学的976名4~6年级小学生进行问卷调查,其中维族504名、汉族472名。结果:1总体来看,在参与因子上维族父母得分高于汉族(t=2.001,P0.05),心理自主、严格/监督因子得分维族父母均低于汉族(t=14.012,23.230;P0.001);2汉族母亲、父亲文化程度总体来说高于维族父母(χ~2=43.89,46.92;P0.01);3汉族父母对不同性别学生的教养方式,在3个因子上分别比较,差异均无统计学意义(P均0.05);维族父母对女生在参与因子、严格/监督因子得分高于男生(P均0.05);4对独生子女的教养方式,在心理自主、严格/监督因子得分维族父母均低于汉族(t=7.141,10.867;P0.001);对非独生子女,参与因子得分维族父母高于汉族(t=-2.496,P0.05),心理自主、严格/监督因子得分维族父母均低于汉族(t=12.322,19.286;P0.001)。结论:维族父母给予孩子更多的保护、温情,而汉族父母给予孩子更多的心理自主,对子女进行监督的意愿以及实际监督情况更严格;维族家庭教育可能更重视性别教育。     

Disappointment and regret enhance corrugator reactivity in a gambling task

This study investigated how the corrugator and zygomaticus respond to decision outcomes (i.e., gains and losses). We used a gambling task in which participants were presented with obtained followed by non‐obtained outcomes. Activity at the corrugator site was sensitive to decision outcomes, such that higher obtained losses (disappointment) and higher non‐obtained gains (regret) both heightened corrugator reactivity. Activity at the zygomaticus site was not responsive to obtained or non‐obtained outcomes, but did show sensitivity to emotional images in the same participants, in the form of a positive linear relationship with self‐reported emotional valence. Corrugator activity was negatively related to emotional valence. The findings indicate the sensitivity of corrugator to objective decision outcomes and also counterfactual comparisons, highlighting the utility of facial electromyography in research on decision making and gambling behavior.     

烧伤患儿父母心理健康状况调查及心理干预

目的探讨烧伤患儿父母的心理健康状况及心理干预效果。方法采用症状自评量表(SCL-90)对78名烧伤患儿父母在干预前、干预后1周进行调查并作统计分析比较。结果烧伤患儿父母干预前躯体化、强迫、人际关系、抑郁、焦虑、敌对因子分均显著高于国内常模,差异有统计学意义(t分别为17.11,3.39,5.13,8.31,43.5,5.32;P<0.05)。干预后与干预前比较,患儿父母躯体化、强迫、人际关系、抑郁、焦虑、敌对因子分低于干预前,差异有统计学意义(t分别为3.41,2.21,3.52,3.08,3.96,3.56;P<0.05)。结论烧伤患儿父母存在不同程度的心理问题,心理干预能改善患儿父母的心理健康水平。     

Psychological impact of comprehensive tumor genomic profiling results for advanced cancer patients

ObjectiveComprehensive tumor genomic profiling (CTGP) is increasingly used to personalize treatments, providing hope, but potentially disappointment, for patients. We explored psychological outcomes in patients with advanced, incurable cancer, after receiving CTGP results.MethodsParticipants with advanced, incurable cancer (n = 560, mean age 56, 43% university educated) in this longitudinal substudy of the Molecular Screening and Therapeutics Program (MoST), completed questionnaires before and after receiving CGP results. MoST participants, recruited from Australian oncology clinics, undergo CTGP, and if there are actionable findings, are offered treatment in a related therapeutic trial if available.ResultsPatients who received actionable results, (n = 356, 64%) had lower gene-related distress (MICRA) (p < 0.001) and Impact of Events scores (p = 0.039) than patients with non-actionable results. Those with actionable results offered ensured access to tailored treatment (n = 151) reported lower anxiety (p = 0.002) and depressive symptoms (p = 0.01) and greater hope (p = 0.002) than those not offered. Positive attitudes towards uncertainty and higher self-efficacy for coping with results were associated with lower psychological distress and uncertainty, and higher hope and satisfaction with the decision to have CTGP (ps=0.001–0.047). Those with higher knowledge reported greater anxiety (p = 0.034).ConclusionReceiving a non-actionable CTGP result, or an actionable result without ensured access to treatment, may cause increased distress in advanced cancer patients. Coping style was also associated with distress.Practice implicationsPre-testing assessment and counseling addressing attitudes toward uncertainty and self-efficacy, and post-CTGP result support for patients receiving a non-actionable result or who receive an actionable results without ensured access to treatment, may benefit patients.     

Patients' reasons for not presenting emotional problems in general practice consultations.

BACKGROUND: Patients commonly do not mention emotional problems in consultations, and this is a factor in general practitioners' (GPs') difficulty in identifying psychological morbidity. AIM: To investigate patients' self-reported reasons for not disclosing psychological problems in consultations with GPs. METHOD: From nine general practices, a sample of patients with high General Health Questionnaire scores, who planned to present only somatic symptoms to the GP, were interviewed after their consultation with the GP. The interview covered their reasons for not mentioning emotional problems. A patient satisfaction questionnaire was administered. RESULTS: A total of 83 patients were interviewed. Sixty-four patients confirmed that they had not mentioned emotional problems in the consultation; 23 (36%) of these gave primarily realistic reasons for not presenting emotional problems (e.g. able to cope with distress), 29 (45%) gave reasons related to psychological embarrassment or hesitation to trouble the GP, and 12 (19%) were mainly deterred by the doctors' interview behaviours. The latter group had significantly lower satisfaction scores than patients in the other two groups. In addition, patients in all groups commonly reported perceptions of lack of time (48%) and that there is nothing doctors can do to help (39%) as barriers to mentioning emotional problems. CONCLUSION: An understanding of patients' reasons for not disclosing emotional problems can assist in identifying subgroups of patients with different management needs.     

Relationships between emotional control, adjustment to cancer and depression and anxiety in breast cancer patients

The possible relationship between psychological responses among breast cancer patients and disease outcome continues to be an area of controversy and debate. Two parallel findings are reported separately in the literature: first, that emotional control is more common among women with breast cancer than in women with benign breast disease or in healthy controls and second, that a helpless attitude towards the disease is related to a poor prognosis. These previously unrelated psychological responses are examined here in a group of women (N = 359) with early stage breast cancer, who were seen one to three months after diagnosis. The relationships between emotional control, adjustment to cancer and psychological morbidity were examined. Prevalence levels of 16 and 6% were observed for anxiety and depression respectively, which are lower than reported more generally in the literature. The results indicated a highly significant association between scores for the tendency to control emotional reactions and a fatalistic attitude toward cancer. A significant association was observed between anger control and a helpless attitude. Psychological morbidity was also linked to type of adjustment to cancer. The data are interpreted in terms of a process model of psychological responses which suggests that emotional control (an important component of the Type C behaviour pattern) fatalism, helplessness and psychological morbidity are linked.     

Relationship of medical students' admission interview scores to their dean's letter ratings.

The authors examined the relationship between the admission interview scores for 62 students in the 1986 entering class at Dartmouth Medical School and the students' dean's letter ratings given four years later; they found the relationship to be significant (V = .372, p = .014) and the interview scores to be better independent predictors of the ratings than were total Medical College Admission Test scores or science grade-point averages. Among the 17 students receiving "strong" admission interview scores, 53% received dean's letter ratings in the top one-third and 47% received ratings in the lower two-thirds. Of those 34 who received "medium" interview scores, 68% received ratings in the lower two-thirds; all 11 students who received "weak" interview scores received ratings in the lower two-thirds. The authors suggest (1) that admission interview scores help schools to identify more clearly those applicants most likely to become strong, competitive performers in residency and (2) that the significant relationship between interview scores and dean's letter ratings indicates a need to discover what qualities the interview actually measures and to consider the methods by which interviewers are trained, rather than to forsake the interview.     

Breaking bad news--parents' experience of learning that their child has leukaemia

This study aimed to seek parents' experiences of how they learned their child had leukaemia and therefore identify ways of improving this process. To achieve this task a questionnaire was designed to ask parents about specific elements of the initial interview and give them opportunity to add their thoughts and feelings on the subject. All children with a diagnosis of leukaemia over an eighteen-year period were identified and parents of those children still alive were invited to partake in the study. 49 out of 50 families agreed to participate of which 35 (72%) returned completed questionnaires. The majority 29 (83%) expressed overall satisfaction. Their replies confirmed some findings of previous studies, and also offered some new insights. Examples of new findings or expansion on previous findings include observations on the presence of young children at the initial interview; the importance of the language used in conveying the diagnosis and prognostic information, and a preference for actuarial terms when discussing prognosis. Telling parents their child has leukaemia is a challenging and important task. The experience of parents gives us valuable insights into our own communication skills and highlights areas of possible improvement in this difficult area.     

Personal responsibility,regret, and medical stigma among individuals living with lung cancer

Understanding the degree to which adults with lung cancer perceive personal responsibility for their disease, personal regret for actions that may have contributed to lung cancer, and potential stigmatization from others is important, because these perceptions and experiences may be linked with treatment nonadherence, feelings of isolation, avoidance of healthcare providers, and poor quality of life. The purpose of this study was to evaluate rates and intensity of these types of experiences and to characterize the extent to which they are linked with smoking status and psychological adjustment in those living with lung cancer. Adults with lung cancer (N = 213) were recruited from two major cancer centers to complete a mail survey. Perceived responsibility was frequent in those who had ever smoked (74–80 %), whereas regret and feelings of stigmatization were less frequent. When present, however, personal regret and stigmatization were associated with adverse psychological outcomes, particularly for never smokers. These results are consistent with the theory of stereotype threat and have clinical implications for management of people with lung cancer.     

农村中学生心理健康状况与父母教养方式的相关研究

目的了解农村初中生心理健康状况与父母教养方式的关系,为农村初中生心理健康教育提供参考依据。方法采用分层整群抽样对263名中学生进行中学生心理健康量表、父母教养方式量表问卷调查。结果1农村中学生心理健康问题检出率为20.15%;2不同性别中学生强迫因子、人际关系紧张、抑郁因子得分差异有统计学意义（P〈0.05）;不同年级农村初中生学习压力、情绪不平衡、心理不平衡得分差异有统计学意义（P〈0.05）,高年级组明显高于低年级组;3除父母情感温暖、父母偏爱外,父母教养方式各个纬度均与心理健康各因子呈显著正相关（P〈0.05）。结论父母教养方式对初中学生的心理健康水平有影响。