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Families with rare diseases, such as telomere biology disorders (TBDs), may have extensive unmet needs given the heterogeneity, chronicity, and potential severity of illness. TBDs are rare inherited syndromes associated with high risk of bone marrow failure, cancer, pulmonary fibrosis, and other severe, chronic complications. To identify gaps in clinical care, we aimed to ascertain the perceived unmet needs of adults and family caregivers, current or bereaved, of individuals with TBDs. Participants were aged ≥18 years with a self-reported TBD diagnosis and/or ever caregivers to one or more family members with a TBD. Participants completed an online survey (N = 35) and/or an audio-recorded telephone interview (N = 32). We calculated descriptive statistics in SPSS and thematically analyzed interview transcripts. Quantitative and qualitative data were analyzed concurrently. Most participants were aged ≥35 years, female, highly educated, and medically insured. Survey respondents reported numerous unmet needs in psychosocial, medical, financial, and daily activity domains. In interviews, participant descriptions validated and contextualized the salience of these unmet needs. Both qualitative and quantitative data identified critical shortfalls in addressing chronic family distress and specialty care coordination. Adults and caregivers of individuals with TBDs have a high risk of adverse psychosocial sequelae given extensive unmet needs. These findings provide a foundation for understanding the range and extent of gaps in care for families with rare diseases, especially TBDs but that are likely applicable to others. Tailored multi-disciplinary interventions involving patients, families, clinicians, researchers, and patient advocacy communities are required to appropriately address care needs for all rare diseases., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Understanding and remembering the complex experiences of everyday life relies critically on prior schematic knowledge about how events in our world unfold over time. How does the brain construct event representations from a library of schematic scripts, and how does activating a specific script impact the way that events are segmented in time? We developed a novel set of 16 audio narratives, each of which combines one of four location-relevant event scripts (restaurant, airport, grocery store, and lecture hall) with one of four socially relevant event scripts (breakup, proposal, business deal, and meet cute), and presented them to participants in an fMRI study and a separate online study. Responses in the angular gyrus, parahippocampal gyrus, and subregions of the medial prefrontal cortex (mPFC) were driven by scripts related to both location and social information, showing that these regions can track schematic sequences from multiple domains. For some stories, participants were primed to attend to one of the two scripts by training them to listen for and remember specific script-relevant episodic details. Activating a location-related event script shifted the timing of subjective event boundaries to align with script-relevant changes in the narratives, and this behavioral shift was mirrored in the timing of neural responses, with mPFC event boundaries (identified using a hidden Markov model) aligning to location-relevant rather than socially relevant boundaries when participants were location primed. Our findings demonstrate that neural event dynamics are actively modulated by top-down goals and provide new insight into how narrative event representations are constructed through the activation of temporally structured prior knowledge., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Adolescents and young adults (AYAs) with cancer predisposition syndromes often experience significant physical and psychosocial burdens. These burdens include cancer worry and potentially distressing bodily changes due to risk-reducing procedures (e.g., mastectomy) or cancer treatments. This qualitative-descriptive study explored how AYAs with Li-Fraumeni syndrome (LFS) relate and adjust to their bodies under the chronic threat of cancer. Methods: Participants were enrolled in the National Cancer Institute's LFS study. This analysis included 42 AYAs with LFS aged 15-39 years at enrollment who completed one or two telephone interviews that explored LFS-related bodily experiences and challenges. Transcripts were thematically analyzed. Results: The majority of participants ( n = 26/42, 62%) had ≥1 primary cancer. The mean age at first cancer diagnosis was 21 years (range = 0.5-35 years). Participants described challenges relating to the body due to frequent self-monitoring, whole-body magnetic resonance imaging scans, risk-reducing surgeries, and/or cancer treatments. Heightened body awareness and vigilance not only prompted self-protective behaviors but also triggered worry and distress. AYAs coped with bodily changes and concerns by seeking doctors' reassurance, engaging in health-protective behaviors, and reframing perceptions of their altered bodies. Conclusion: Findings suggest AYAs with cancer predisposition syndromes such as LFS experience difficulties relating and adjusting to the body that may compromise psychosocial health. Our results demonstrate that these difficulties may arise across the time course of genetic disease, including before a cancer diagnosis. Clinicians might support AYAs by conducting routine psychosocial risk assessments, providing anticipatory guidance regarding body-related challenges, sharing peer support resources, and referring to mental health providers, as needed.

Objective: Donation after circulatory death heart transplantation potentially increases donor allografts, especially for patients with lower listing status. We assessed the outcomes of donation after circulatory death heart transplantation in patients bridged with durable left ventricular assist devices., Methods: The United Network for Organ Sharing database was queried for adult heart transplants using donation after circulatory death donors from 2019 to 2022. Patients were stratified between those with durable left ventricular assist devices and those with intra-aortic balloon pump, inotropic, or no bridging support (control group). Primary outcome was 1-year mortality. Secondary end points were hospital length of stay, stroke, pacemaker implantation, dialysis, and acute rejection before discharge., Results: A total of 160 left ventricular assist device recipients and 311 control recipients met study inclusion criteria. Recipients bridged with left ventricular assist devices were younger (55 vs 58 years, P < .001) with lower body mass index (28.3 vs 30.3, P < .001), longer waitlist times (112 vs 34 days, P < .001), longer out of body times (5.7 vs 4.6 hours, P < .001), and less frequent normothermic regional perfusion (31% vs 40%, P = .049). Patients with left ventricular assist devices commonly underwent transplantation at United Network for Organ Sharing status 3 and 4 (92%), whereas control patients underwent transplantation at status 2 (27%), status 3 (10%), status 4 (30%), or status 6 (30%). Kaplan-Meier analysis showed no difference in 1-year mortality between groups (P = .34). However, acute rejection was higher in the unadjusted left ventricular assist device cohort (26% vs 13%, P < .001). On multivariable logistic regression, left ventricular assist device was an independent predictor of acute rejection (odds ratio, 2.21, 95% CI, 1.32-3.69, P = .002)., Conclusions: Durable left ventricular assist devices may be associated with a higher risk of developing an early inflammatory response in donation after circulatory death heart transplantation; however, 1-year survival was similar between groups., Competing Interests: Conflict of Interest Statement G.T.S. receives consulting fees from Abbott and Medtronic. N.U. receives grant support from and serves as a consultant for Abbott and Medtronic. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Individuals with inherited cancer syndromes, such as Li-Fraumeni syndrome (LFS), may be motivated to adopt health-protective behaviors, such as eating more fruits and vegetables and increasing physical activity. Examining these health behaviors among young people with high lifetime genetic cancer risk may provide important insights to guide future behavioral interventions that aim to improve health-related quality of life (HRQOL). We used a self-regulatory framework to investigate relationships among diet and physical activity behaviors and psychosocial constructs (e.g., illness perceptions, coping, HRQOL) in adolescents and young adults (AYAs; aged 15-39 years) with LFS. This longitudinal mixed-methods study included 57 AYAs aged 16-39 years at enrollment), 32 (56%) of whom had a history of one or more cancers. Participants completed one or two telephone interviews and/or an online survey. We thematically analyzed interview data and conducted regression analyses to evaluate relationships among variables. AYAs described adopting healthy diet and physical activity behaviors to assert some control over health and to protect HRQOL. More frequent use of active coping strategies was associated with greater reported daily fruit and vegetable intake. Greater reported physical activity was associated with better quality of psychological health. Healthy diet and physical activity behaviors may function as LFS coping strategies that confer mental health benefits. Clinicians might emphasize these potential benefits and support AYAs in adopting health behaviors that protect multiple domains of health. Future research could use these findings to develop behavioral interventions tailored to AYAs with high genetic cancer risk., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Providers and patients have expressed concern that care provided through telehealth results in poorer outcomes than traditional in-person care. On the contrary, we hypothesized that patients with cirrhosis engaging in video/phone-based outpatient gastroenterology/hepatology tele-visits do not differ in mortality from those receiving in-person outpatient clinic visits., Methods: This was a retrospective, case-control study using Veterans Health Administration administrative data of veterans with a cirrhosis diagnosis. Cases were patients who died between April 2021 and July 2022 and had a cirrhosis diagnosis for ≥1 year before death. For each case, a control was randomly selected from the pool of patients alive on the date of death of the case (index date) and matched on age, average Model for End-Stage Liver Disease, and number of gastroenterology/hepatology clinic visits in the prior year. Primary exposure variable was % tele-visits (video/phone) out of total visits in the year before the index date, scaled in 10% increments. Conditional logistic regression was used to assess the association between mortality and % tele-visits. A secondary analysis matched on electronic Child-Turcotte-Pugh score rather than Model for End-Stage Liver Disease., Results: Two thousand nine hundred thirty-three cases were identified and matched with 2,933 controls. After adjusting for covariates, tele-visit-based outpatient care was associated with a small reduction in mortality (odds ratio TH = 0.95, 95% confidence interval = 0.94-0.97). Matching on electronic Child-Turcotte-Pugh score did not change the results., Discussion: Our findings suggest that outpatient cirrhosis care by tele-visit is associated with outcomes no worse than traditional in-person visits. This should reassure providers who hesitate to provide virtual care to patients with cirrhosis due to concerns for poorer outcomes., (Copyright © 2024 by The American College of Gastroenterology.)

Objective(s): To assess the likelihood of ADHD diagnosis in children of non-US-born caregivers relative to children of US-born caregivers., Method: Cross-sectional analysis of a combined 2016 to 2019 National Survey of Children's Health dataset ( n  = 109,881) was performed to identify associations between caregiver's birth outside the U.S. and child's ADHD diagnosis. Logistic regression models adjusted for potential sociodemographic confounders., Results: Children with one or two non-US-born caregivers were less likely to be diagnosed with ADHD (aOR = 0.58, p  < .001; aOR = 0.59, p  < .001, respectively). Likelihood of a diagnosis increased as non-US-born caregivers spent more time in the US. After a diagnosis, children of two non-US-born caregivers were less likely to be treated with medication., Conclusion: The lower likelihood of ADHD diagnosis in children with non-US-born caregivers may reflect an increasing need for public health education to raise awareness about ADHD among this population and the development of culturally sensitive ADHD identification methodologies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Adolescents and young adult (AYA) cancer survivors face unique medical and psychosocial sequalae, including chronic health conditions, late effects of treatment and fear of recurrence. The meaning of cancer survivorship may be further complicated for AYAs with hereditary cancer predisposition syndromes. This study used a patient-centered framework to investigate how AYAs with Li-Fraumeni syndrome (LFS) consider cancer survivorship., Methods: An interprofessional team conducted 30 semi-structured interviews with AYAs (aged 18-41, mean 31 years) enrolled in the National Cancer Institute's LFS Study (NCT01443468). Twenty had experienced at least one cancer diagnosis. Interview data were thematically analyzed by an inter-professional team using interpretive description and grounded theory methods., Findings: Participants viewed "survivorship" as a period marked by no evidence of formerly diagnosed disease. By contrast, participants felt the label "survivor" was tenuous since LFS is characterized by multiple primary malignancies and uncertainty about intervals between one diagnosis and the next. Many AYAs viewed survivorship as requiring a high degree of suffering. Though many personally rejected "survivor" identities, almost all articulated its various functions including positive, negative, and more complicated connotations. Instead, they chose language to represent a range of beliefs about survival, longevity, prognosis, and activism., Conclusions: AYAs with LFS struggle with the term "survivor" due to their multi-organ cancer risk, short intervals between malignancies, and evolving identities. Loved ones' cancer-related suffering informed perspectives on survivorship. Survivorship care for AYAs with cancer risk syndromes requires interprofessional interventions that address their unique biomedical and psychosocial needs., (© 2022 John Wiley & Sons Ltd.)

Objectives: This qualitative-descriptive study explored adolescent and young adult (AYA) perspectives, experiences, and challenges with openness and closedness in family communication about Li-Fraumeni syndrome (LFS)., Methods: We conducted interviews with AYAs (aged 15-39 years) with LFS enrolled in the National Cancer Institute's LFS study (NCT01443468). An interprofessional clinician-researcher team analyzed transcribed data using the constant comparative method and interpretive description., Results: AYAs (N = 38; 26 females, 12 males, mean age=29 years) reported navigating openness and closedness about LFS in their families, which varied by LFS topic, relationship, disease trajectory, and developmental phase. AYAs described communication challenges, including broaching difficult topics (e.g., reproductive decision-making, end-of-life), balancing information-sharing with emotionally protecting family and self, and struggling with interactions that cause relational tensions., Conclusions: AYAs reported experiencing LFS family communication challenges that disrupted their psychosocial well-being. LFS-related stressors and life transitions complicated and were complicated by these challenging family interactions., Practice Implications: Clinicians may support AYAs with LFS by inquiring about family communication, responding empathically to communication concerns, providing resources to support difficult conversations, and engaging mental health providers as needed. Researchers could partner with AYAs to develop tailored communication skills training and social support tools., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Published by Elsevier B.V.)

Little is known about how nursing care at the end of a child's life impacts long-term parental bereavement. We aimed to explain, contextualize, and examine comparisons between quantitative trends in children's end-of-life care and parents' qualitative perceptions. We used a mixed methods design, combining quantitative data from the RESTORE clinical trial with qualitative interviews with bereaved parents. Patients who died during RESTORE were included in quantitative analyses. A subset of their parents was interviewed 7 to 11 years later. The quantitative analyses included 104 children. Eight parents were interviewed; 4 had a child die after cancer, and 4 had a child die after a complex chronic illness. Quantitatively, patients' pain and sedation scores were generally comfortable. Children died with multiple invasive devices in place. Parents' descriptions of their child's comfort and critical care requirements differed by illness trajectory (cancer, complex chronic illness). Parents' memories of their child's suffering aligned with peaks in clinical scores, rather than averages. Invasive devices and equipment altered parents' ability to make meaningful final memories with the dying child. Pediatric intensive care clinicians may need to broaden how they attend to dying children's pain and corresponding parental distress, as parents' memories of their dying child's suffering persist for years., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 by The Hospice and Palliative Nurses Association. All rights reserved.)

Purpose of Review: In recent years, an increasing number of states have legalized marijuana, also known as cannabis, for recreational use. As marijuana becomes more accessible, adolescent use and accidental pediatric exposures are likely to become broad public health concerns. Edible marijuana products, which are consumable foods or beverages that contain cannabis extract, are particularly enticing to youth, as they come in appealing forms such as candies, cookies, and drinks. The purpose of this review is to provide pediatricians with an overview of the different types and potential dangers associated with edible marijuana products., Recent Findings: Edible marijuana products are often indistinguishable in appearance from normal food items and lack the smell and visible smoke associated with inhaled marijuana. Because they are inconspicuous, palatable, and easily accessible, they are increasingly popular among adolescents. Additionally, the packaging of edible baked goods, candies, and drinks is often purposefully very similar to that of mainstream foods, increasing the risk of accidental ingestion by children. An edible marijuana product must be digested before Δ9-tetrahydrocannabinol can enter the bloodstream, so there is a delayed onset of effects when consuming edibles compared with inhaling marijuana. This also predisposes users to accidental overconsumption., Summary: Greater knowledge of edible marijuana product consumption by pediatric populations will allow pediatricians to more effectively help patients and advise caregivers in cases of overconsumption, dependence, or accidental ingestion. It is important for parents, guardians, and educators to be able to successfully identify edible marijuana products and recognize signs of cannabis use., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To examine parents' perceptions of nursing care needs; including specific concerns, preferences and supportive actions for themselves and their dying child during and following the withdrawal of life support in the paediatric intensive care unit., Research Design: Qualitative description with content analysis., Setting: Interviews with eight parents of eight children who died in the paediatric intensive care unit 7-11 years prior., Main Outcome Measures: Descriptive categories of parents' perceptions of end-of-life needs., Findings: Parents identified four shifting and intersecting categories of needs: To be together, To make sense of the child's evolving clinical care, To manage institutional, situational, and structural factors, and To navigate an array of emotions in a sterile context. Being closely connected with the child was highly important, but often intersected with other domains, requiring nurses' support. Parents' memories demonstrated persistent uncertainty about their child's end-of-life care that influenced their long-term grief., Conclusions: Intersections between parent-identified care needs suggest potential mechanisms to strengthen nurses' care for dying children. Equipped with the knowledge that the parent-child bond often shapes parents' priorities; nurses should aim to facilitate connections amidst paediatric intensive care unit processes. Ongoing uncertainty in parents' adaptation to loss suggests that attention to instances when needs intersect can have a lasting impact on parents' grief., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Experiences of illness change the physical body and embodiments, or the ways in which the world and the self are known through the body. When illness is anticipated, such as with inherited cancer predisposition syndromes, risk becomes embodied and shared in family groups. Embodied risk is experienced whether or not symptoms have manifested. To examine how individuals and families with genetic risk experience the world and understand their disease through their bodies, we employ Li-Fraumeni syndrome (LFS) as an exemplar. LFS is a rare, genetic, cancer predisposition syndrome with nearly 100% lifetime cancer risk starting from birth, limited opportunities for prevention, rigorous screening protocols, and early mortality., Methods: Forty-five families, including 117 individuals aged 13-81 years, enrolled in the National Cancer Insitute's LFS study (NCT01443468) completed 66 open-ended interviews regarding LFS experiences. An interdisciplinary team used modified grounded theory to explore physical aspects of living with LFS in psychosocial contexts., Findings: The physicality of living with LFS included constant monitoring of LFS bodies across the family to identify physical change that might indicate carcinogenesis. Cancer screening, risk reduction, and treatment acted as dually protective and invasive, and as an unavoidable features of LFS. Connections between family members with similar embodiments normalized aesthetic changes and supported coping with visible markers of difference. In some circumstances, participants objectified the body to preserve the self and important relationships. In others, intense pain or loss created thresholds beyond which the self could no longer be separated from the body to support coping., Discussion: This paper focuses on Li-Fraumeni syndrome, a familial condition with a well-established genetic identity in which the body-self is experienced in relation to important others, to medical imaging, and to historical experiences with cancer. We expand on theories of embodied risk and inter-embodiment to describe experiences across disease trajectories, with attention to division and union between body, self, and other., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Parents' perceptions of critical care during the final days of their child's life shape their grief for decades. Little is known about nursing care needs of children actively dying in the pediatric intensive care unit (PICU)., Objectives: To examine associations between patient characteristics, circumstances of death, and nursing care requirements for children who died in the PICU., Methods: A secondary analysis of the data set from the Randomized Evaluation of Sedation Titration for Respiratory Failure trial was conducted., Results: This analysis included 104 children; 67 died after withdrawal of life-sustaining treatments; 21, after failed resuscitation; and 16, after brain death. Patients had a median age of 7.5 years, were cognitively appropriate, and were intubated for acute respiratory failure. Daily pain and sedation scores indicated patients' comfort was well managed (mean pain scores: modal, 0; peak, 2; mean sedation scores: modal, -2; peak, -1). Patients with longer PICU stays more often experienced pain and agitation on the day of death. Illness trajectory (acute, complex chronic condition, or cancer) was associated with pain scores (P = .04). Specifically, children with cancer had higher pain scores than children with acute illness trajectories (P = .01). Many patients (62%) had no change in critical care devices in their last days of life (median, 5 devices). Patterns of pain, sedation, comfort medications, and nursing care requirements did not differ by circumstances of death., Conclusion: Children with cancer and longer PICU stays may need comprehensive comfort management. Invasive devices left in place during withdrawal of life support may have inhibited parents' ability to connect with their child. Future research should incorporate parents' perspectives., (©2022 American Association of Critical-Care Nurses.)

The reproductive decision-making of young people (aged 15-39 years) with Li-Fraumeni syndrome (LFS), an early onset inherited cancer syndrome, has not been studied in depth. Using interpretive description methodology, we conducted semi-structured interviews with 30 young Australians (mean age 25.5 years) diagnosed with LFS or at 50% genetic risk. With reflexive thematic analysis, we show how young people's reproductive decision-making and ideals for family formation were shaped by a sense of genetic responsibility to ensure the health of future biological kin. Reproductive technology provided choices for family formation in the context of LFS and also complicated reproductive decisions, as these choices were difficult to understand, make, or carry out. We uphold that reproductive decision-making when living with LFS is a profoundly moral practice that may pose significant challenges for young people navigating their formative years. We offer genetic counseling practice recommendations to support individuals with LFS when making reproductive decisions.

Purpose: Oncology social workers are increasingly finding themselves diagnosed with or caring for a loved one with cancer. Self-disclosure may be useful for building a therapeutic alliance. Yet, practice-informed guidelines for psychosocial oncology providers do not exist., Research Approach: Twenty-three psychosocial oncology providers diagnosed with and/or providing care to someone with cancer completed semi-structured interviews eliciting attitudes and utilization regarding self-disclosure., Methodological Approach: Interviews were digitally recorded and transcribed verbatim. Using grounded theory's constant comparative method, researchers conducted open and theoretical coding., Findings: Participants expressed consensus in defining, and reported a range of evolving practices regarding, self-disclosure. Recommendations for responsible self-disclosure included self-awareness, ongoing assessment, supervision, and enhanced educational programming., Interpretation and Implication: Therapeutic tools must evolve as core features of psychosocial oncology care. A flexible and context-specific framework for clinician self-disclosure related to personal experiences with cancer can guide oncology social work practice.

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome in which individuals have a significantly increased risk of developing multiple cancers throughout the life span. An LFS diagnosis may shift the individual's sense of self and tolerance of cancer risk as they engage in cancer screening and cancer prevention activities. This study examined the impact of family identity on health decision making, communication, and role function. Forty-five families completed one or more interviews during an annual, protocol-specific cancer screening study. An interdisciplinary team analyzed 66 interviews using interpretive description and modified grounding theory. Thematically, identity emerged as an evolving construct regarding self and/or family, embedded in historical and ongoing experiences with LFS. Notions of individual and shared family identities guided decision making related to healthcare and influenced interpersonal communication and role function between supportive networks and families. Alignment between individual, family, and generational identities may shape engagement in genetic testing, risk management, and family life. Medical teams that are unequipped to address the psychosocial challenges that LFS populations face may include mental health professionals on interprofessional care teams to navigate risk management and consequential familial conflict., (© Crown copyright 2021.)

Background and Objectives: Discussing population-based cancer risk and screening is common in general practice. Patients with an inherited cancer syndrome, however, may need more nuanced discussions. Li-Fraumeni syndrome (LFS) is a rare, inherited cancer syndrome that affects many organ systems from birth and requires intensive, whole-body cancer risk management. The aim of this study was to explore the risk management experiences of young people (aged 15-39 years) with, or at risk of, LFS., Method: Using an interpretive description design, semi-structured interviews were conducted with young people diagnosed with, or at risk of, LFS from across Australia. Interview transcripts were analysed with team-based, codebook thematic analysis., Results: Thirty young people (mean age 25.5 years) participated. Participants described intensive screening and risk-reducing mastectomy (for women) as their 'best shot' to control their cancer risks with LFS. Engaging in these options as a young person came with a slew of psychosocial implications., Discussion: General practitioners may help to improve care for young people with inherited cancer syndromes by acknowledging the benefits and complex burdens of their risk management.

Purpose: This study explored the genetic testing experiences of adolescents and young adults (AYAs; aged 15-39 years) with, or at 50% risk of, an early onset cancer predisposition syndrome: Li-Fraumeni syndrome (LFS)., Design: We used interpretive description and conducted semi-structured interviews with 30 AYAs (mean age 25.5 years): 26 with LFS and four at 50% risk. Findings were developed using team-based, inductive thematic analysis., Findings: Participants reported genetic testing uptake to reduce uncertainty about their gene status and to access cancer risk management. Learning their gene status, however, introduced a new uncertainty about living with high multi-organ cancer risk. Participants preoccupied with surviving cancer during diagnostic testing underestimated the implications of LFS. Reliance on family at this life stage complicated decision-making for genetic testing, especially among adolescents., Conclusion: AYAs undergoing genetic testing for LFS have unique support needs based on their life stage and require developmentally appropriate psychosocial care.

Li-Fraumeni Syndrome (LFS) is a hereditary disorder that confers an approximately 90% lifetime risk of cancer and requires comprehensive lifetime cancer screening. We explored healthcare roles for managing LFS-related cancer risks and treatments that were assumed by parents, adolescents, and adult children. Semi-structured interviews were conducted with 23 families. Family groupings were comprised of 2-5 members, with the younger generation in each family ranging in age from 7 to 40 years. Using grounded theory methods, we conducted open and focused coding of interview transcript content. Family members described how the role of health leader was implemented in their family, as well as factors such as maturation of a child or death of a member that determined who assumed particular roles and how these roles shifted over time. They often expressed collective responsibility for helping relatives understand LFS and implement appropriate cancer risk management. Members demonstrated their health role by attending others' medical appointments for support or information gathering. The health leader role was intergenerational and provided the family necessary support in navigating complicated healthcare decisions. Our findings provide insight into healthcare providers regarding how LFS patients and their relatives develop unique medical decision-making and caring roles influenced by the hereditary nature of LFS, and how these roles change over time. Providers who are attuned to family role dynamics may be better able to meet relatives' psychosocial and medical needs by understanding how living with LFS influences the family system's functioning and facilitating members' support for each other., (© 2019 Family Process Institute.)

Li-Fraumeni syndrome (LFS), a rare cancer syndrome caused by pathogenic germline variants in TP53, has serious implications for adolescents and young adults (AYAs; aged 15-39 years). The early-onset and multi-organ cancer risk associated with LFS means health professionals must concurrently contend with the developmental needs of individuals who are diagnosed from a young age, and recent changes in practice due to advances in whole-body cancer surveillance. To help understand how current practice meets the developmental needs of AYAs with, or at risk of, LFS, we conducted a national online survey to explore the experiences of health professionals who care for this population in Australia and New Zealand. Forty-three respondents completed the survey (56% genetic counselors), one-third of whom had facilitated predictive TP53 testing for minors (n = 14/43, 33%). In hypothetical scenarios describing 15-year-olds eligible for predictive TP53 testing, respondents were more supportive of testing for emotionally mature compared to immature minors (p = .009); and more supportive of adolescent wishes compared to parental wishes for testing (p = .020) when families held discordant views on testing. Genetic health professionals were more likely than oncology health professionals to address psychological (p = .017) and information needs about reproductive options for LFS during consultations than to refer them on (p = .004). All respondents supported comprehensive risk management for LFS, but noted important medical, logistical, and psychosocial limitations for AYAs. This study offers valuable insight into developmentally appropriate practices of Australasian health professionals who care for AYAs with, or at risk of, LFS. These findings suggest they may foster the autonomy of minors undergoing predictive TP53 genetic testing and be supportive of new whole-body risk management guidelines., (© 2019 National Society of Genetic Counselors.)

Li-Fraumeni Syndrome (LFS) is characterized by risk of multiple primary malignancies in diverse sites, pediatric onset, near complete penetrance by age 70 years, limited options for prevention, and substantial uncertainty regarding disease manifestation and prognosis. Forty-five families, including 117 individuals aged 13-81 years, enrolled in the US National Cancer Institute's Li-Fraumeni Syndrome Study completed 66 interviews regarding their LFS experiences. An interdisciplinary team used modified grounded theory to examine family distress regarding expectations of loss and change due to likely cancer diagnoses, and the consequences of this likelihood across physical, social, and emotional domains. Disease-free periods were characterized by fearful anticipation of diagnosis or recurrence, uncertainty regarding post-treatment quality of life, and planning for shifts in family dynamics to enable caregiving. The chronicity of waiting for these changes incited dread and inhibited effective coping with the pragmatic, emotional, and existential challenges of the syndrome. Consequently, families reported high burden on roles and resources and limited guidance to prepare for, or achieve resolution with, grief. Anticipatory loss, the experience of bereavement prior to an expected change, distinguishes hereditary cancer risk from a sporadic diagnosis. Such grief is often incomplete in impact or meaning, subjected to rapid or profound change as conditions worsen, and poorly understood. In this study, losses were compounded by profound uncertainty, a chronic feature of LFS, which compromised mourning. Long-term engagement of mental health providers with bereavement training, in partnership with genetics providers, can provide invaluable educational and psychological support to families as they navigate these implacable challenges.

The development of genomic technologies has seemed almost magical. Excitement about it, both in medicine and among the public, stems from the belief that genomic techniques will illuminate the causes of health and disease, will lead to effective interventions for both rare and common genetic conditions, and will inform reproductive decision-making. Novel diagnostic tools, however, are often deployed before targeted therapies are developed, tested, or available and before their psychosocial implications are explored. Newer technologies such as prenatal whole exome screening are seen as offering "decisional autonomy" to expectant parents, although such technologies identify information about genetic sequencing that may not have clear meaning. The "therapeutic gap" between the ability to conduct genetic sequencing and the ability to fully understand what the test results mean, much less what treatments to offer, leaves families with complex and unclear information they cannot act upon with confidence during pregnancy. In this essay, we will consider the psychosocial and ethical implications of such assumptions-and of the uncertain information produced by these technologies-for individuals and families and for societal aspects such as medical service usage and demographic inequities., (© 2019 The Hastings Center.)

Purpose: Li-Fraumeni Syndrome (LFS) is an inherited tumor predisposition syndrome with lifetime cancer risks approaching 100% and evolving risk-management strategies. This study evaluated couples' coping with LFS-related burdens., Research Approach: Constructivist grounded theory and anticipatory loss frameworks guided design and analysis., Sample and Methods: Twenty-six individuals enrolled in the NCI LFS Family Study completed semi-structured interviews with their partner during annual screening visits. An interdisciplinary team completed open and focused coding to identify patterns of coping and adaptation., Findings: Couples described living with ambiguous danger, a state of chronic apprehension resulting from LFS-associated uncertainties. Most couples communicated openly and alternated shouldering the burden, while others engaged in protective buffering to shield each other from distress and sustain the appearance of normalcy., Interpretation: Optimally, coping reduces shared psychosocial distress, yet some strategies may inadvertently increase disconnection., Implications: Mental health support is critical for both partners coping with LFS, together and separately.

In families with hereditary breast/ovarian cancer, complex disease histories challenge established patterns of family communication and influence decision-making for clinical surveillance, genetic testing, and risk management. An interdisciplinary team examined longitudinal interview data from women with identified BRCA1/2 mutations to assess interactions within family and social networks about risk information communication and management. We used interpretive description to identify motivation, content, and derived benefit of these interactions. Participants discussed risk information and management strategies with biological and nonbiological network members for multiple purposes: discharging responsibility for risk information dissemination, protecting important relationships, and navigating decision trajectories. Evolving interactions with loved ones balanced long-standing family communication patterns with differing personal preferences for privacy or open sharing, whereas interactions with nonbiological network members expanded participants' range of choices for sources of risk management information. Ongoing assessment of social networks may help support engagement with risk management by aligning with patient social needs.

The original article [1] was initially published with the following list of authors: Allison Werner-Lin, Shana L. Merrill, and Amanda C. Brandt. This author list is now corrected as follows: Allison Werner-Lin, Shana L. Merrill, Amanda C. Brandt, Rachel E. Barnett, & Ellen T. Matloff.

Purpose: Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition caused by germline TP53 mutations, confers significant cancer risks for young people (15-39 years). Yet evidence of how individuals experience this condition and the psychosocial implications are lacking. Therefore, this systematic review assessed the psychosocial implications of living with, or at risk of, an autosomal dominant condition as a young person, to draw evidence that may be analogous for young people with LFS., Methods: We conducted a systematic search for studies published in peer-reviewed journals using Medline, CINAHL, PsycINFO, and Embase databases. Findings were synthesized and are reported thematically., Results: We screened 352 articles and identified 39 studies, representing the perspectives of 765 young people. Most studies addressed hereditary breast and ovarian cancer (n = 22) and used qualitative methodologies (n = 35). Only one LFS study was identified, highlighting the distinct lack of psychosocial research describing experiences of young people with LFS. Translatable evidence showed that familial factors strongly influenced young people's experiences of genetic testing and their mutation status. Major adverse reactions to genetic test results were rare, although young people with a gene mutation experienced various psychosocial concerns at key developmental milestones, including family planning, developing romantic relationships, and making risk management decisions., Conclusion: Young people undergoing genetic testing for inherited disease require individualized support and recognition of previous lived experiences. We recommend that longitudinal care be made available to young people with inherited disease as they reach developmental milestones that intersect with risk management, risk perception, and family formation.

Deleterious mutations in BRCA1 or BRCA2 genes increase a woman's lifetime risk of breast and ovarian cancer. Risk management guidelines endorse early detection and prevention behaviors. Despite expressed intent, uptake of these measures remains low. This longitudinal, qualitative study integrated retrospective and prospective data to distinguish factors shaping intent to act from those that are catalysts to taking action to reduce cancer risk. Twelve BRCA1/2 mutation-positive women participating in the National Cancer Institute's Breast Imaging Study aged 18-35 completed two semi-structured interviews three years apart. Researchers completed focused coding to identify points of behavioral intent and action and contextual factors acting as catalysts upon participant narratives. All women shared only two action steps: seeking information about cancer risk and completing genetic testing. The constellation of action steps created a unique action trajectory that was defined, with precise ideas about risk perception and clear behavioral response, or iterative, in which unanticipated life events shifted the speed, accessibility, or order in which risk management and family planning goals were prioritized, planned, or executed. Factors shifting action steps included salient, unanticipated life events, such as infertility, insurance/financial constraints, birth of the last child, or a relative's cancer diagnosis. Focus on cancer morbidity may obfuscate how women prioritize actions, and ignore varied pragmatic, relational, and social factors affecting how intended actions are completed, particularly during the reproductive years. We recommend providers update patients' risk management plans at each visit to assess readiness for next steps and reduce reluctance to discuss, or guilt associated with, change.

Families often express difficulty to their providers and request guidance regarding the task of communicating with children about potential adult-onset inherited cancer risks. This disclosure is often complicated by the parent's ongoing adjustment to their mutation status, guilt at potential transmission of the mutation to the child, concern over inciting distress in children, and the varied capacities of children in the home to understand genetic information. Providers often do not have adequate resources to support or facilitate disclosure of genetic test results to children. Optimally, communication about inherited cancer risk is an open, ongoing process within the family. We recommend that parents tailor conversations to the child's developmental, cognitive, emotional, and behavioral abilities to support comprehension. Based on well-established theories of child development, empirical research on family communication of hereditary cancer risk, and clinical counseling experience, we offer recommendations for parental disclosure of genetic risk to children, case examples with critical discussion of relevant topics, common child questions with sample scripted responses, and additional printed and online resources.

Clinical genome and exome sequencing (CGES) may identify variants leading to targeted management of existing conditions. Yet, CGES often fails to identify pathogenic diagnostic variants and introduces uncertainties by detecting variants of uncertain significance (VUS) and secondary findings. This study investigated how families understand findings and adjust their perspectives on CGES. As part of NIH's Clinical Sequencing Exploratory Research Consortium, children were recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and offered exome sequencing. Primary pathogenic and possibly pathogenic, and some secondary findings were returned. Investigators digitally recorded results disclosure sessions and conducted 3-month follow up interviews with 10 adolescents and a parent. An interdisciplinary team coded all transcripts. Participants were initially disappointed with findings, yet reactions evolved within disclosure sessions and at 3-month interviews toward acceptance and satisfaction. Families erroneously expected, and prepared extensively, to learn about risk for common conditions. During disclosure sessions, parents and adolescents varied in how they monitored and responded to each others reactions. Several misinterpreted, or overestimated, the utility of findings to attribute meaning and achieve closure for the CGES experience. Participants perceived testing as an opportunity to improve disease management despite results that did not introduce new treatments or diagnoses. Future research may examine whether families experience cognitive dissonance regarding discrepancies between expectations and findings, and how protective buffering minimizes the burden of disappointment on loved ones. As CGES is increasingly integrated into clinical care providers must contend with tempering family expectations and interpretations of findings while managing complex medical care., (© 2018 Wiley Periodicals, Inc.)

Aim: This study provides preliminary data on the process and content of returning results from exome sequencing offered to children through one of the Clinical Sequencing Exploratory Research (CSER) projects., Materials & Methods: We recorded 25 sessions where providers returned diagnostic and secondary sequencing results to families. Data interpretation utilized inductive thematic analysis., Results: Typically, providers followed a results report and discussed diagnostic findings using technical genomic and sequencing concepts. We identified four provider processes for returning results: teaching genetic concepts; assessing family response; personalizing findings; and strengthening patient-provider relationships., Conclusion: Sessions should reflect family interest in medical management and next steps, and minimize detailed genomic concepts. As the scope and complexity of sequencing increase, the traditional information-laden counseling model requires revision., Competing Interests: Competing interests disclosure The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Young women with BRCA1/2 mutations face difficult health-care decisions regarding family formation, fertility, breastfeeding, and whether/when to undergo cancer risk-reducing surgery. This longitudinal qualitative study investigated these life choices during the reproductive years. We conducted two semistructured interviews over three years with 12 reproductive-age BRCA1/2-positive women. Researchers coded transcripts to examine the evolution of risk perceptions, risk management, and family planning decisions. To cope with the conflict between cancer risk reduction versus plans for pregnancy, breastfeeding, and child rearing, participants deliberately prioritized either risk reducing surgery or family formation goals. Implications for mutation carriers and health-care providers are outlined.

Chromosome microarray (CMA) testing is used widely in prenatal settings. Some copy number variants (CNVs) detected using CMA are associated with variable or uncertain phenotype and/or possible neurocognitive involvement. Little is known about parenting an infant following such findings. Researchers conducted interviews with 23 mothers of infants diagnosed prenatally with a potentially pathogenic CNV to elicit perspectives on the child's development and disclosure of results to others. Interviews were audiotaped and analyzed for common themes. Most respondents reported their infants were developing typically. The majority expressed concern about their child's future development given the CNV. They reassured themselves their child was unaffected by: comparing him/her to siblings, scrutinizing the child's appearance and behavior, or following provider reassurances. Even without developmental and neurological concerns, some remained acutely observant of their child's neurocognitive development, leading to enrollment in early intervention or ongoing medical assessments. Mothers who were unconcerned stated they would likely attribute atypical behavior or developmental to the CNV. All interviewees shared the result with pediatricians, relatives, or friends, and many shared across groups. Most shared information with pregnant friends considering prenatal testing, but withheld partial or full information from family members due to stigma, lack of understanding, inability to explain the CNV, or presumptions that the child was unaffected. Research must address the long-term consequences of returning uncertain results for parent-child bonding and costs of ongoing assessment and early intervention for typically developing children. Follow up appointments will permit providers to screen for anxiety and assuage worry in the absence of symptoms. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The goal of this study was to examine children's involvement in consent sessions for exome sequencing research and associations of involvement with provider and parent communication. Participants included 44 children (8-17 years) from five cohorts who were offered participation in an exome sequencing study. The consent sessions were audiotaped, transcribed, and coded. Providers attempted to facilitate the child's involvement in the majority (73%) of sessions, and most (75%) children also verbally participated. Provider facilitation was strongly associated with likelihood of child participation. These findings underscore that strategies such as asking for children's opinions and soliciting their questions show respect for children and may increase the likelihood that they are engaged and involved in decisions about research participation.

In 2% to 3% of cases, prenatal microarray testing detects deletions and duplications in a fetus' genome that are undetected by conventional cytogenetics. Many of these changes are associated with variable or uncertain symptomatology. Little is known about how couples experience uncertain results. This study analyzed 24 interviews with members of 12 heterosexual U.S. couples who received pathogenic or uncertain microarray prenatal testing results. Researchers used narrative analysis to examine couples' understanding and incorporation of findings into decision making regarding pregnancy termination. Couples felt unprepared for these findings and frustrated because scant information was available to aid interpretation. Women sought information and made decisions, and men marginalized their distress to support their wives. A shift in voice from first to second person indicated attempts to normalize emotional responses by making the process "common" to all couples. Families pursuing highly sensitive prenatal testing may need expert guidance to support decision making., (© The Author(s) 2015.)

This study aims to explore how couples' understanding of the nature and consequences of positive prenatal chromosomal microarray analysis (CMA) results impacts decision-making and concern about pregnancy. We interviewed 28 women and 12 male partners after receiving positive results and analyzed the transcripts to assess their understanding and level of concern about the expected clinical implications of results. Participant descriptions were compared to the original laboratory interpretation. When diagnosed prenatally, couples' understanding of the nature and consequences of copy number variants (CNVs) impacts decision-making and concern. Findings suggest women, but less so partners, generally understand the nature and clinical implications of prenatal CMA results. Couples feel reassured, perhaps sometimes falsely so, when a CNV is inherited from a "normal" parent and experience considerable uncertainty when a CNV is de novo, frequently precipitating a search for additional information and guidance. Five factors influenced participants' concern including: the pattern of inheritance, type of possible phenotypic involvement, perceived manageability of outcomes, availability and strength of evidence about outcomes associated with the CNV, and provider messages about continuing the pregnancy. A good understanding of results is vital as couples decide whether or not to continue with their pregnancy and seek additional information to assist in pregnancy decision-making.

Genetic counselors frequently are called upon to assist patients in understanding the implications of prenatal testing information for their pregnancies and their family's lives. The introduction of highly sensitive testing such as chromosomal microarray has generated additional kinds of uncertainty into the prenatal period. Counselors may feel uncomfortable or inadequately prepared to engage in discussions with prospective parents who are faced with making critical, and timely, decisions about a pregnancy based on uncertain information. As highly sensitive prenatal testing becomes routine in prenatal care, counselors may be in search of approaches to prenatal counseling, as well as specific skills to approach, engage with, and help families find resolution in such challenging circumstances. To assist genetic counselors, we describe practice skills and provide language for approaching conversations with prospective parents. When clinicians regularly provide care to patients and families making life-altering decisions under conditions of significant uncertainty, discomfort is common and compassion fatigue is likely. We make recommendations directly to the genetic counselor working in reproductive and perinatal settings to enhance training and self-care and to decrease discomfort in balancing the scientific- and art- demands of genetic counseling.

The transdisciplinary field of genomics is revolutionizing conceptualizations of health, mental health, family formation, and public policy. Many professions must rapidly acquire genomic expertise to maintain state-of-the-art knowledge in their practice. Calls for social workers to build genomic capacity come regularly, yet social work education has not prepared practitioners to join the genomics workforce in providing socially just, ethically informed care to all clients, particularly those from vulnerable and marginalized groups. The authors suggest a set of action steps for bringing social work skills and practice into the 21st century. They propose that good genomic practice entails bringing social work values, skills, and behaviors to genomics. With education and training, social workers may facilitate socially just dissemination of genomic knowledge and services across practice domains. Increased genomic literacy will support the profession's mission to address disparities in health, health care access, and mortality., (© 2016 National Association of Social Workers.)

Unlabelled: Sample size calculations determine the number of participants required to have sufficiently high power to detect a given treatment effect. In this review, we examined the reporting quality of sample size calculations in 172 publications of double-blind randomized controlled trials of noninvasive pharmacologic or interventional (ie, invasive) pain treatments published in European Journal of Pain, Journal of Pain, and Pain from January 2006 through June 2013. Sixty-five percent of publications reported a sample size calculation but only 38% provided all elements required to replicate the calculated sample size. In publications reporting at least 1 element, 54% provided a justification for the treatment effect used to calculate sample size, and 24% of studies with continuous outcome variables justified the variability estimate. Publications of clinical pain condition trials reported a sample size calculation more frequently than experimental pain model trials (77% vs 33%, P < .001) but did not differ in the frequency of reporting all required elements. No significant differences in reporting of any or all elements were detected between publications of trials with industry and nonindustry sponsorship. Twenty-eight percent included a discrepancy between the reported number of planned and randomized participants. This study suggests that sample size calculation reporting in analgesic trial publications is usually incomplete. Investigators should provide detailed accounts of sample size calculations in publications of clinical trials of pain treatments, which is necessary for reporting transparency and communication of pre-trial design decisions., Perspective: In this systematic review of analgesic clinical trials, sample size calculations and the required elements (eg, treatment effect to be detected; power level) were incompletely reported. A lack of transparency regarding sample size calculations may raise questions about the appropriateness of the calculated sample size., (Copyright © 2015 American Pain Society. All rights reserved.)

As a result of modern treatments, the life of women who test positive for BRCA mutations may be plotted along the arc of preventive medicine rather than the slope of diagnostics. Despite evidence supporting the benefits of risk reduction, protocols for early detection and prevention among women from families affected by hereditary breast and ovarian cancer (HBOC) are not yet proven, and clinical trials have not been undertaken for patients aged 18 to 25. The absence of psychosocial data may leave genetic counselors without uniform guidance on how to manage the care of these patients. This project sought to investigate perspectives on counseling 18-25 year-old patients from families with hereditary cancer syndromes, with specific emphasis on HBOC, given their unique developmental, familial, and medical challenges. Certified genetic counselors were recruited through the NSGC's Cancer Genetics Special Interest Group listserv. Researchers constructed an online survey which included 41 items and elicited information about: counselor demographics, training, and practice settings; approaches to cancer risk assessment; and common challenges in work with 18- to 25-year-old patients. The survey was also informed by previous work by researchers with 18 to 25-year-olds with BRCA gene mutations. Eighty-six surveys were completed. Researchers used a combination of grounded theory and content analysis for open-ended responses, supported and triangulated with statistical analysis to maximize the interpretation of data. Genetic counselors who responded to this survey experience 18-25 year old patients presenting for cancer risk assessment differently than older patients, and some reported adapting their counseling style to address these differences. Respondents differed in the extent to which they felt well-versed in the developmental needs of patients in this age group. Respondents aged 39 and under reported feeling familiar with this stage in life, having more recently completed it; respondents aged 40 and over reported they were less familiar with, and more interested in learning about, this age group. A primary challenge in cancer risk assessment of these patients, reported primarily by counselors aged 39 and under, is navigating family dynamics in counseling sessions and addressing the developmentally labile young adult. With respect to BRCA-related cancer risk, where penetrance is incomplete, onset in early adulthood is rare. Evidence-based treatment/prevention options exist, but providers may not have clarity regarding how or when to provide directive counsel. A rich understanding of the themes inherent in how people grow and change over time might enhance the counselor's capacity to assess patients and their family members. The integration of a developmental approach to genetic counseling has the potential to reduce the imperative for non-directive counseling.

Background: Rare diseases pose transitioning challenges owing to limited provider expertise and changing healthcare systems. The timeframe and developmental changes of emerging adulthood overlap with the transition of patients with cystinosis from pediatric to adult-oriented healthcare., Methods: This study utilized techniques of qualitative grounded theory to explore the experiences of adults aged 18-47 with cystinosis, and their parents, with a focus on the transition to adulthood and adult-oriented care. Forty-six individuals from 21 families were recruited online and at cystinosis conferences to participate in focus groups and/or individual interviews. The constant comparative method was used to conduct both line-by-line and focused coding of verbatim transcripts., Results: The following elements were reported to be critical to the transition to adulthood and adult-oriented care: gaining skills and responsibility for disease management, progressing toward autonomy while remaining connected to caregivers, and having strong communication with and between providers., Conclusions: Data analysis identified behaviors and relationships that support and/or threaten autonomy and treatment adherence. Participants described institutional, relational, and practical barriers to transition. Suggestions for improving transitioning include: identifying patient/family strengths and improving pediatric-adult provider partnerships and communication. Further research is needed into the experience of patients before and after transition to adult-oriented care.

Unlabelled: Peer-reviewed publications of randomized clinical trials (RCTs) are the primary means of disseminating research findings. "Spin" in RCT publications is misrepresentation of statistically nonsignificant research findings to suggest treatment benefit. Spin can influence the way readers interpret clinical trials and use the information to make decisions about treatments and medical policies. The objective of this study was to determine the frequency with which 4 types of spin were used in publications of analgesic RCTs with nonsignificant primary analyses in 6 major pain journals. In the 76 articles included in our sample, 28% of the abstracts and 29% of the main texts emphasized secondary analyses with P values <.05; 22% of abstracts and 29% of texts emphasized treatment benefit based on nonsignificant primary results; 14% of abstracts and 18% of texts emphasized within-group improvements over time, rather than primary between-group comparisons; and 13% of abstracts and 10% of texts interpreted a nonsignificant difference between groups in a superiority study as comparable effectiveness. When considering the article conclusion sections, 21% did not mention the nonsignificant primary result, 22% were presented with no uncertainty or qualification, 30% did not acknowledge that future research was required, and 8% recommended the intervention for clinical use., Perspective: This article identifies relatively frequent "spin" in analgesic RCTs. These findings highlight a need for authors, reviewers, and editors to be more cognizant of how analgesic RCT results are presented and attempt to minimize spin in future clinical trial publications., (Copyright © 2015 American Pain Society. All rights reserved.)

Objective: To identify patient, study, and site factors associated with assay sensitivity in clinical trials of pharmacologic treatments for osteoarthritis (OA) pain., Methods: We examined associations between study characteristics and the standardized effect size (SES) in a database of 171 publicly available randomized clinical trials of pharmacologic treatment for OA pain. The included trials 1) evaluated oral, topical, or transdermal treatments, 2) had treatment durations of ≥7 days, 3) used parallel-group or crossover designs, 4) included patients with OA of the knee, hip, and/or hand, and 5) were placebo controlled and double blind. Crossover trials were excluded, because complete information was available for only 2 of 20 treatment conditions., Results: There was considerable heterogeneity in the SES among the examined trials. A multiple meta-regression analysis indicated that trials with shorter treatment period durations and those that did not permit concomitant analgesics had significantly greater assay sensitivity. In univariate analyses of efficacious treatments, trials conducted outside North America and those with a minimum baseline pain intensity score (as defined by the inclusion criterion) of ≥40 (0-100 scale) had a significantly larger SES, although these relationships were not significant in the multiple meta-regression analysis., Conclusion: The analyses examined potentially modifiable correlates of study SES and showed that longer treatment durations and allowing concomitant analgesics in randomized clinical trials of OA pain are associated with reduced assay sensitivity. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of false-negative outcomes in randomized clinical trials of efficacious treatments for OA pain., (Copyright © 2014 by the American College of Rheumatology.)

Assessment of treatment safety is 1 of the primary goals of clinical trials. Organizations and working groups have created reporting guidelines for adverse events (AEs). Previous research examining AE reporting for pharmacologic clinical trials of analgesics in major pain journals found many reporting inadequacies, suggesting that analgesic trials are not adhering to existing AE reporting guidelines. The present systematic review documented AE reporting in 3 main pain journals for nonpharmacologic, noninterventional (NP/NI) trials examining pain treatments. To broaden our pool of nonpharmacologic trials, we also included trials examining acupuncture, leech therapy, and noninvasive stimulation techniques (eg, transcutaneous electrical nerve stimulation). We documented AE reporting at 2 levels of specificity using coding manuals based on the Consolidated Standards of Reporting Trials (CONSORT) harms reporting standards and Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) AE reporting checklist. We identified a number of inadequacies in AE reporting across the 3 journals. For example, using the ACTTION coding manual, we found that less than one-half of the trials reported specific AE assessment methods; approximately one-third of the trials reported withdrawals due to AEs for each study arm; and about one-fourth of the trials reported all specific AEs. We also examined differences in AE reporting across several trial characteristics, finding that AE reporting was generally more detailed in trials with patients versus those using healthy volunteers undergoing experimentally evoked pain. These results suggest that investigators conducting and reporting NP/NI clinical trials are not adequately describing the assessment and occurrence of AEs., (Copyright © 2014 International Association for the Study of Pain. All rights reserved.)

Despite research on BRCA1/2 mutation carriers attitudes towards preimplantation genetic diagnosis (PGD), considerably less is known about individuals' experience with its use. Through case reports of BRCA1/2 mutation carriers' thoughts on, and use of, PGD, this paper highlights how the option of PGD is experienced and negotiated in the context of reproductive and life-course goals. Drawing on qualitative interviews with 38 BRCA1/2 mutation carriers, this article focuses on a subsample of 10 interviewees who sought consultation for, and/or attempted, PGD, with in-depth reports of 3 cases and summary decisions of the remaining 7. Three couples decided against PGD, and one was deciding at the time of the interview. Interviewees discuss key aspects of their experience prior to, and going through, PGD for BRCA1/2, including potential challenges of becoming pregnant through PGD and of heightened pressure to achieve their reproductive goals more quickly. Despite considerable focus on ethical issues in screening embryos for mutations associated with adult-onset cancer risk, less attention has been paid to the technical, logistical, and related psychosocial issues. Narrative case reports may help individuals develop appropriate expectations of PGD for BRCA prepare for possibly challenging decisions and outcomes, and ultimately determine whether it is compatible with their reproductive goals.

Performing multiple analyses in clinical trials can inflate the probability of a type I error, or the chance of falsely concluding a significant effect of the treatment. Strategies to minimize type I error probability include prespecification of primary analyses and statistical adjustment for multiple comparisons, when applicable. The objective of this study was to assess the quality of primary analysis reporting and frequency of multiplicity adjustment in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and PAIN®). A total of 161 randomized controlled trials investigating noninvasive pharmacological treatments or interventional treatments for pain, published between 2006 and 2012, were included. Only 52% of trials identified a primary analysis, and only 10% of trials reported prespecification of that analysis. Among the 33 articles that identified a primary analysis with multiple testing, 15 (45%) adjusted for multiplicity; of those 15, only 2 (13%) reported prespecification of the adjustment methodology. Trials in clinical pain conditions and industry-sponsored trials identified a primary analysis more often than trials in experimental pain models and non-industry-sponsored trials, respectively. The results of this systematic review demonstrate deficiencies in the reporting and possibly the execution of primary analyses in published analgesic trials. These deficiencies can be rectified by changes in, or better enforcement of, journal policies pertaining to requirements for the reporting of analyses of clinical trial data., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Purpose: Young women who have been identified as carrying a deleterious mutation in BRCA1 or BRCA2 face a unique set of challenges related to managing cancer risk during a demographically-dense stage of life. They may struggle with decision-making in the absence of clear age-specific guidelines for medical management and because they have not yet fully developed the capacity to make life-altering decisions confidently. This study sought a patient-centered perspective on the dilemmas faced by 18-24 year olds who completed BRCA1/2 gene mutation testing prior to their 25(th) birthdays., Patients and Method: This study integrated qualitative data from three independent investigations of BRCA1/2-positive women recruited through cancer risk clinics, hospital-based research centers, and online organizations. All 32 participants were women aged 21-25 who tested positive for a BRCA1/2 gene mutation between 2 and 60 months prior to data collection. Investigators used techniques of grounded theory and interpretive description to conduct both within and cross-study analysis., Results: Participants expressed needs for (1) greater clarity in recommendations for screening and prevention before age 25, especially with consideration of early and regular exposure to radiation associated with mammography or to hormones used in birth control, and (2) ongoing contact with providers to discuss risk management protocols as they become available., Conclusions: Health care needs during the young adult years evolve with the cognitive capacity to address abrupt and pressing change. Specific needs of women in this population include a desire to balance autonomous decision-making with supportive guidance, a need for clear, accurate and consistent medical recommendations. Optimally, these women are best cared for by a team of genetically-oriented providers as part of a sustained program of ongoing support, rather than seen in an episodic, crisis-driven fashion. A discussion of insurance issues and provider-patient cultural differences is presented.

The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non-industry-sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, "demoting" a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry-sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed., (Copyright © 2013 International Association for the Study of Pain. All rights reserved.)