Preparing for the unexpected: Recommendations for returning secondary findings in late-stage cancer care.

PURPOSE: We conducted qualitative interviews with patients with cancer and providers to identify gaps in clinical care and highlight care delivery solutions for the return of secondary germline findings. METHODS: Twelve patients and 19 cancer providers from the United States were interviewed between January 2019 and May 2021. Interviews elicited feedback about patient information needs, emotional responses to secondary findings, and recommendations for improving pre-test education. RESULTS: Patients' responses ranged from gratitude to regret, depending on how much pre-test counseling they received before tumor testing. Providers cited insufficient clinic time as a major barrier to pretest education, favoring online support tools and standardized pre-test education models. Providers had differing perspectives on how pre-test education should be integrated into clinical workflows but agreed that it should include the differences between somatic and germline testing, the likelihood of medically actionable findings, and the possibility of being referred to a genetics provider. CONCLUSION: The spectrum of participants' responses to their secondary findings underscores the importance of adequate pre-test discussions before somatic sequencing. Although educational interventions could address patients' information needs and augment traditional pre-test counseling, health care systems, labs, and genetic providers may be called on to play greater roles in pre-test education.

Factors Associated with Positive SARS-CoV-2 Test Results in Outpatient Health Facilities and Emergency Departments Among Children and Adolescents Aged <18 Years - Mississippi, September-November 2020.

As of December 14, 2020, children and adolescents aged <18 years have accounted for 10.2% of coronavirus disease 2019 (COVID-19) cases reported in the United States.* Mitigation strategies to prevent infection with SARS-CoV-2, the virus that causes COVID-19, among persons of all ages, are important for pandemic control. Characterization of risk factors for SARS-CoV-2 infection among children and adolescents can inform efforts by parents, school and program administrators, and public health officials to reduce SARS-CoV-2 transmission. To assess school, community, and close contact exposures associated with pediatric COVID-19, a case-control study was conducted to compare exposures reported by parents or guardians of children and adolescents aged <18 years with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing (case-patients) with exposures reported among those who received negative SARS-CoV-2 RT-PCR test results (control participants). Among 397 children and adolescents investigated, in-person school or child care attendance ≤14 days before the SARS-CoV-2 test was reported for 62% of case-patients and 68% of control participants and was not associated with a positive SARS-CoV-2 test result (adjusted odds ratio [aOR] = 0.8, 95% confidence interval [CI] = 0.5-1.3). Among 236 children aged ≥2 years who attended child care or school during the 2 weeks before SARS-CoV-2 testing, parents of 64% of case-patients and 76% of control participants reported that their child and all staff members wore masks inside the facility (aOR = 0.4, 95% CI = 0.2-0.8). In the 2 weeks preceding SARS-CoV-2 testing, case-patients were more likely to have had close contact with a person with known COVID-19 (aOR = 3.2, 95% CI = 2.0-5.0), have attended gatherings† with persons outside their household, including social functions (aOR = 2.4, 95% CI = 1.1-5.5) or activities with other children (aOR = 3.3, 95% CI = 1.3-8.4), or have had visitors in the home (aOR = 1.9, 95% CI = 1.2-2.9) than were control participants. Close contacts with persons with COVID-19 and gatherings contribute to SARS-CoV-2 infections in children and adolescents. Consistent use of masks, social distancing, isolation of infected persons, and quarantine of those who are exposed to the virus continue to be important to prevent COVID-19 spread.

A qualitative study of perceptions of meaningful change in spinal muscular atrophy.

BACKGROUND: This qualitative study examined how individuals with Spinal Muscular Atrophy (SMA), their caregivers, and clinicians defined meaningful change, primarily in the Type II and non-ambulant type III patient populations, associated with treatment of this condition. In addition, we explored participants' views about two measures of motor function routinely used in clinical trials for these SMA subtypes, namely the expanded version of the Hammersmith Functional Motor Scale (HFMSE) and the Upper Limb Module (ULM). METHODS: The 123 participants (21 with SMA, 64 parents, and 11 clinicians), recruited through SMA advocacy organizations, participated in one of 16 focus groups or 37 interviews. The sessions were audio-recorded, and verbatim transcripts were analyzed using a grounded theory approach. RESULTS: For the participants, meaningful change was relative to functional ability, and small changes in motor function could have an important impact on quality of life. Because patients and families feared progressive loss of functional ability, the participants saw maintenance of abilities as a meaningful outcome. They believed that measures of motor function covered important items, but worried that the HFMSE and ULM might not be sensitive enough to capture small changes. In addition, they felt that outcome measures should assess other important features of life with SMA, including the ability to perform daily activities, respiratory function, swallowing, fatigue, and endurance. CONCLUSIONS: Given the heterogeneity of SMA, it is important to expand the assessment of treatment effects to a broader range of outcomes using measures sensitive enough to detect small changes.

Understanding the experiences and needs of individuals with Spinal Muscular Atrophy and their parents: a qualitative study.

BACKGROUND: The clinical features of SMA, which range along a spectrum of severity, are relatively well described. In contrast, the literature on how individuals with SMA and their families experience this condition is limited. To address this gap, we undertook a qualitative study with individuals affected by SMA Types I, II and III, parents of those affected, and clinicians. METHODS: We completed 16 focus group sessions and 37 interviews in the US with 96 participants including: 21 with individuals with SMA; 64 parents of individuals affected by SMA; and 11 clinicians who specialize in the care of SMA patients. RESULTS: The Diagnostic Journey: Families reported substantial diagnostic delays owing to: 1) lack of awareness and knowledge about SMA; 2) the difficulty of distinguishing normal from abnormal development; and 3) the challenge of differential diagnosis. Lack of sensitivity in how clinicians communicated this potentially devastating diagnosis compounded parents' negative impressions. Newborn Screening: Parents generally held positive views about adding SMA to newborn screening panels. For example, it would: 1) enable earlier access to care; 2) shorten the diagnostic journey; and 3) give families more time to prepare to care for a disabled child. Some noted negative outcomes such as prematurely affecting a parent's relationship with a child before symptoms are evident. The Psychosocial Impact of Living with SMA: Ten thematic areas characterized the impact: 1) confronting premature death; 2) making difficult treatment choices; 3) fearing the loss of functional ability; 4) coming to terms with lost expectations; 5) loss of sleep and stress; 6) stigma; 7) limitations on social activities; 8) independence; 9) uncertainty and helplessness; and 10) family finances. CONCLUSIONS: The results of this study suggest high levels of burden experienced by individuals with SMA and their families. The difficulties of living with SMA begin with the long and often arduous process of finding a diagnosis for their child. Newborn screening for SMA is seen as an important step toward shortening this journey. The psychosocial effects of coping with SMA are substantial and wide ranging both for the individual living with this condition and family members of affected individuals.

Perceptions of erectile dysfunction and phosphodiesterase type 5 inhibitor therapy in a qualitative study of men and women in affected relationships.

Erectile dysfunction negatively affects men and women in relationships; however, the subjective experience of erectile dysfunction and phosphodiesterase-type 5 inhibitor therapy remains poorly understood. The authors therefore characterized participants' subjective understanding of erectile dysfunction and phosphodiesterase-type 5 inhibitor therapy using individual interviews with affected heterosexual men (n = 58) and women (n = 65). Responses were characterized by 6 psychosocial domains: explanation of the experience, emotional responses, socially expected responses, value of sex, communication with the partner, and treatment expectations. The findings may aid clinicians in relating to men with erectile dysfunction and thus potentially improve effectiveness of therapy.

Nonpharmacological interventions to promote sleep and rest among hospitalized pediatric patients in general pediatric wards: a best practice implementation project.

OBJECTIVES: The aim of this implementation project was to improve compliance with best practice regarding nonpharmacological interventions used to promote sleep and rest in hospitalized pediatric patients in a nonintensive care setting. INTRODUCTION: Hospitalized children endure numerous hindrances to sleep and rest, including, but not limited to, noise, pain, anxiety, and interruptions for nursing care. Evidence suggests that a multifaceted approach to sleep promotion can reduce the length of time to sleep onset and the length of nighttime awakenings. It is widely accepted, however, rarely practiced, that proven, low-cost, and noninvasive strategies exist to promote sleep and restoration of hospitalized pediatric patients, which fosters healing and recovery. METHODS: This project used the JBI Evidence Implementation framework. A baseline audit of 22 nurses' and 31 patients'/parents'/caregivers' receipt of education on strategies to promote sleep and rest was obtained via survey; baseline data were also obtained from nurses regarding whether or not a multifaceted approach to sleep promotion is utilized and/or if an evidence-based protocol regarding sleep promotion is in place. Targeted strategies, including a protocol and nurse/patient education of multifaceted approaches to sleep, were then implemented, and a follow-up audit of 25 nurses and 32 patients/caregivers was completed. RESULTS: Overall, postimplementation audits revealed 93% compliance with best practice, a 78% increase from baseline audits of 15%. Baseline data revealed poor knowledge of and/or compliance with each of the four audit criteria: nurse education on strategies to promote sleep and rest, the use of an evidence-based protocol regarding sleep promotion, a multifaceted approach to sleep promotion, and patient and/or caregiver education regarding sleep promotion. Postimplementation data, however, showed improvement in each of these areas. CONCLUSION: Deficiencies in best practice recommendations for the promotion of sleep and rest in pediatric patients admitted to general wards were identified, interventions were implemented, and results were beneficial. Further investigation could be taken to assess the long-term effectiveness of interventions and/or sleep quality of patients while hospitalized. Moreover, postimplementation audits should be administered to parents near the end of their stay, after they have had time to implement optional interventions, if they choose.

Physician experiences with and perceptions of risk evaluation and mitigation strategy programs with elements to assure safe use.

PURPOSE: The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to require risk evaluation and mitigation strategy (REMS) programs for drugs with important safety concerns. REMS can have elements to assure safe use (ETASU), such as patient registries, dispensing restrictions, and physician training and certification requirements. We aimed to understand physician experiences with and perceptions of a selection of ETASU REMS. METHODS: Physicians prescribing 1 of 4 ETASU REMS-covered drugs: natalizumab, riociguat, sodium oxybate, and vigabatrin. STUDY DESIGN: Descriptive phenomenological study based on semi-structured phone interviews. DATA COLLECTION/EXTRACTION METHODS: Qualitative content analysis to summarize physician responses to open-ended questions. RESULTS: Of 31 physicians (14 female), 6 prescribed riociguat, 6 vigabatrin, 7 sodium oxybate, and 12 natalizumab (5 for Crohn's disease, 7 for multiple sclerosis), most demonstrated good understanding of the rationale for and requirements of the ETASU REMS but believed that the programs had limited effect on clinical practice. Some physicians reported that the ETASU REMS made them more comfortable with prescribing covered drugs due to heightened oversight, facilitated discussions about treatment, and were likely more beneficial for non-specialists. Concerns were raised about the administrative effort needed to comply with the programs and the potential misuse of patient health information transmitted to manufacturers. CONCLUSIONS: Physicians are generally aware of ETASU REMS and get reassurance from the additional oversight, but the programs can be better integrated into clinical workflows and can be designed to better protect patient health information.

Meaningful Improvements in Rett Syndrome: A Qualitative Study of Caregivers.

BACKGROUND: Rett syndrome is a rare neurodevelopmental disorder primarily affecting females. This syndrome is associated with many comorbidities and impairments related to motor function, breathing, sleep, expressive language, and repetitive hand movements. The Rett Syndrome Behaviour Questionnaire (RSBQ) is one measure used to assess changes in Rett syndrome-related manifestations or core symptoms. Little is known about how caregivers think about meaningful changes in the items that make up the RSBQ scale. METHODS: This qualitative study explored how caregivers of individuals with Rett syndrome viewed changes in the symptoms covered in the RSBQ. We conducted semistructured interviews with 40 caregivers and employed thematic analysis, identifying themes using an iterative process. RESULTS: Two factors characterized caregivers' thoughts about meaningful changes in Rett syndrome manifestations. First, general features of these symptoms rendered them bothersome: the extent of bother compared to other symptoms, if or how they prevented desirable behaviors and their temporal qualities. Second, caregivers evaluated the meaning of improvements by considering the decrease in bother and the potential benefits of change. Improvements had social and psychological consequences for individuals with Rett syndrome and caregivers. In addition, implications for health, fine and gross motor skills, and communication were also substantial.

"I was able to still be her mom"--parenting at end of life in the pediatric intensive care unit.

OBJECTIVES: The death of a child in the pediatric intensive care unit is perhaps one of the most devastating and challenging experiences a parent can ever endure. This article examines how parents of children dying in the pediatric intensive care unit understood their role and discusses implications for clinical care and policy. DESIGN: Retrospective, qualitative study. SETTING: Two pediatric intensive care units located in children's hospitals within academic medical centers in the northeastern United States. SUBJECTS: Parents of 18 children who died in the pediatric intensive care unit. INTERVENTIONS: Semistructured telephone interviews, digitally recorded and transcribed. MEASUREMENTS AND MAIN RESULTS: Many of the factors deemed important by the parents related to their capacity to be a "good parent" to their child throughout his or her stay in the pediatric intensive care unit. Specifically, parents sought meaningful ways to express and assert their parenthood across three domains: 1) providing love, comfort, and care; 2) creating security and privacy for the family; and 3) exercising responsibility for what happens to one's child. CONCLUSIONS: Parents' ability to fulfill the essential features of their role as parents of children dying in the pediatric intensive care unit shapes how they perceive the quality of the experience. Pediatric intensive care unit clinical care and policies can and should uphold and protect these features enabling parents to feel that, despite the outcome, they had done their best on behalf of their children.

Effectiveness of trauma-informed, school-based interventions for children with a history of trauma or adverse experiences: an umbrella review protocol.

OBJECTIVE: The objective of this review is to synthesize evidence regarding the effectiveness of trauma-informed, school-based interventions for children with a history of trauma or adverse experiences as they pertain to academic performance and health outcomes, including behavior, mental health, and socio-emotional functioning. INTRODUCTION: Children and adolescents who face prolonged adverse experiences or trauma have a predisposition toward emotional, behavioral, mental, and physical health problems. Few children or adolescents who endure the repercussions of constant stress and hardships, or survivors of one or more types of trauma, receive the appropriate screening and diagnosis; therefore, they do not receive tailored care or interventions. INCLUSION CRITERIA: This review will include research syntheses pertaining to school-based, trauma-informed interventions for children and adolescents between the ages of 4 and 18 years with a history of adverse experiences or trauma. Comparisons will be made across all known school-based, trauma-informed interventions. This review will consider systematic reviews that include the following outcomes: mental health, behavior, academic performance, and/or socio-emotional functioning. METHODS: The search strategy will aim to locate both published and unpublished systematic reviews. An initial limited search of MEDLINE (PubMed) and CINAHL (EBSCO) will identify articles on the topic. The search strategy will be adapted for each included information source. Articles published in English will be considered for inclusion and no date limits will apply. Two independent reviewers will critically appraise eligible studies. Extracted data will be tabulated and presented along with a narrative summary.

Treatment Goals for Achondroplasia: A Qualitative Study with Parents and Adults.

INTRODUCTION: Achondroplasia is characterized by disproportionate short stature accompanied by other changes to the musculoskeletal system. Individuals with this condition typically experience a variety of medical complications. As pharmacologic treatments continue to be developed for the treatment of achondroplasia, it is important to understand treatment goals among those affected by achondroplasia and the factors that shape their goals. METHODS: This qualitative study is based on semi-structured interviews with 19 parents of children with achondroplasia and five adults with achondroplasia in the USA. We employed thematic analysis using an iterative process to identify themes across the interviews. RESULTS: Participants had two goals for pharmacologic treatment of achondroplasia: ameliorating complications associated with the condition and increasing stature to overcome functional limitations and psychosocial challenges. Complications of particular concern were chronic pain and surgeries to repair spinal, ear, nose, and throat (ENT) problems, and neurological sequelae. Increased height would enhance independence, help individuals to fit in socially, and avoid social stigma. Countervailing factors included the importance of stature to their identity and the concern that the condition would remain despite treatment. CONCLUSIONS: This study offers evidence about how individuals affected by achondroplasia think about the pharmacologic treatment of this condition, including both the benefits of ameliorating complications and increasing height. The findings can offer practical insights for parents of children considering treatment, treating physicians, and decision-makers evaluating coverage decisions for treatment of achondroplasia.

Patients' roles in governance of learning: Results from a qualitative study of 16 learning healthcare systems.

Patient and family engagement has been identified as key to fulfilling Learning Healthcare Systems' (LHSs') promise as a model for improving clinical care, catalyzing research, and controlling costs. Little is known, however, about the state of patient engagement in the learning mission of these systems or about what governance structures and processes facilitate such engagement. Here, we report on an interview study of 99 patient and employee leaders in 16 systems. We found both variable levels of engagement and broad agreement that shared governance of learning remains a work in progress. We also identified a range of practices that can support or thwart development of an organizational culture conducive to shared governance, including transparency, capacity building, infrastructure investment, leadership, attention to diversity of patient partners, and committee structures. In LHSs with most sophisticated shared governance, both employees and patients contribute to building a democratic learning culture.

Patient and Caregiver Experiences With and Perceptions of Risk Evaluation and Mitigation Strategy Programs With Elements to Assure Safe Use.

Importance: The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to impose safety requirements on drugs with important risks, such as prescriber certification or routine laboratory testing, to ensure that the benefits of use outweighed the risks. However, little is known about patient and caregiver experiences with these Risk Evaluation and Mitigation Strategy (REMS) programs with Elements to Assure Safe Use (ETASU). Objective: To understand patient and caregiver experiences with and perceptions of REMS programs with ETASU. Design, Setting, and Participants: This qualitative study included semistructured qualitative phone interviews conducted between 2016 and 2017, with initial analysis performed in 2017 and reanalysis performed in 2021. Adult patients prescribed natalizumab or sodium oxybate, adult patients or caregivers of adult patients prescribed vigabatrin, and adult female patients of reproductive age prescribed riociguat were included. Main Outcomes and Measures: Assessment of knowledge, decision-making, medication access, and perceptions of medical privacy. Results: Among 63 participants, 46 (73%) were female. Twenty-five participants (40%) had taken natalizumab, 10 (16%) riociguat, 15 (24%) sodium oxybate, and 10 (16%) vigabatrin. One participant had taken both natalizumab and vigabatrin; 4 (6%) were caregivers of patients using vigabatrin. Most participants expressed knowledge of REMS program requirements, but many lacked the insight that these requirements were part of an FDA-mandated special safety program and expressed difficulty understanding program education materials. REMS requirements made some participants more likely to initiate treatment. However, many reported burdens accessing medication, including the need to travel to certified prescribers or pharmacies. Manufacturer access to personal health information was also controversial, although some participants expressed an altruistic desire to assist others. Conclusions and Relevance: This qualitative study found that REMS programs with ETASU reassured patients and their caregivers about drug safety and helped support medication initiation. However, steps are needed to improve the quality of REMS educational materials, promote efficient medication access, and protect patient privacy.

Engaging Patients in Precision Oncology: Development and Usability of a Web-Based Patient-Facing Genomic Sequencing Report.

PURPOSE: Evidence-based somatic and germline sequencing has transformed cancer care and improves patient outcomes. However, patients' low genetic literacy and misunderstanding of their own genomic results poses a threat to the realization of precision oncology. To optimize patient genomic comprehension, we developed a Web-based, patient-directed, genomic sequencing education and return-of-results tool, HOPE-Genomics. METHODS: The HOPE-Genomics prototype included somatic and germline sequencing results, embedded multimedia genomic education, and interactive features (eg, request for genetic counseling). Between January and April 2018, we elicited feedback on tool usability and comprehensiveness through participant surveys, 4 focus groups of patients with cancer and their family members, and 3 provider focus groups (comprising 8 patients, 5 family members, and 19 providers). RESULTS: We identified themes in patient/family tool-related responses, including the desire to view a patient-friendly report, a desire to receive multiple types of genomic information (eg, prognostic and uncertain), high acceptability of report content, and interest in tool-enabled access to genetic counseling. Major themes from the clinician focus groups included believing the tool could help patients formulate questions and facilitate patients' communication of results to family members. However, there were diverse responses from all participants in terms of tool implementation (ie, timing and nature of report release). Some participants preferred report release before meeting with the provider, and others preferred it during the appointment. Additionally, some clinicians were concerned about providing prognostic and treatment information through the tool. CONCLUSION: There was high acceptability and interest from patients, family members, and providers in a patient-directed genomics report. Future work will determine whether direct-to-patient reporting of genomic results improves patient knowledge, care engagement, and compliance with genomically guided interventions.

Assessing symptoms of hypogonadism by self-administered questionnaire: qualitative findings in patients and controls.

BACKGROUND: Current screening instruments for hypogonadism lack adequate specificity and diagnostic accuracy. A new self-administered questionnaire of hypogonadism symptoms is being developed to address this need. The process for questionnaire development and results from the first (qualitative) phase are presented. METHODS: Qualitative interviews were conducted based on a new conceptual model of hypogonadism and according to standards for questionnaire development. An item pool was generated from focus groups and in-depth interviews with two groups of hypogonadal patients, treated (N = 26) and untreated (N = 26), and age-equivalent controls (N = 28). Standardized scoring of the qualitative interviews was used to confirm conceptual domains in the model and to generate questionnaire items for further validation. RESULTS: Key domains identified in both patients and controls included: (a) physical function; (b) bodily signs and symptoms; (c) sexual function and libido; (d) sleep function; (e) mood and affective function; (f) memory and cognitive function. The final domain is distress or bother associated with hypogonadism symptoms. This domain was only relevant to the patient groups. CONCLUSIONS: The first stage in the design of a new hypogonadism screener has been completed. Seven domains were identified and draft items were developed in each domain according to current standards of patient-reported outcomes.

Preferences for Return of Genetic Results Among Participants in the Jackson Heart Study and Framingham Heart Study.

BACKGROUND: Surveys suggest that most research participants desire access to secondary (incidental) genomic findings. However, few studies clarify whether preferences vary by the nature of the finding. METHODS: We surveyed members of the JHS (Jackson Heart Study, n=960), the FHS (Framingham Heart Study; n=955), and African American members of the FHS Omni cohort (n=160) who had consented to genomic studies. Each factorial survey included 3 vignettes, randomly selected from a set of 64, that described a secondary genomic result. Vignettes varied systematically by 5 factors identified by expert panels as salient: phenotype severity, actionability (preventability), reproductive significance, and relative and absolute risk of the phenotype. Respondents indicated whether they would want to receive the result. Data were analyzed separately by cohort using generalized linear mixed models. RESULTS: Response rates ranged from 67% to 73%. Across vignettes, 88% to 92% of respondents would definitely or probably want to learn the result. In multivariate analyses among JHS respondents, desire for results was associated with positive attitudes towards genetic testing, lower education, higher subjective numeracy, and younger age, but not with any of the 5 factors. Among FHS respondents, desire for results was associated with higher absolute risk, preventability, reproductive risk, and positive attitudes towards genetic testing. Among FHS Omni respondents, desire for results was associated with positive attitudes towards genetic testing and younger age. CONCLUSIONS: Most genetic research participants desire return of secondary genetic results. Several factors identified by expert panels as salient are associated with preferences among FHS, but not JHS or FHS Omni, participants.

Attitudes Toward Genetics and Genetic Testing Among Participants in the Jackson and Framingham Heart Studies.

Genetic analysis has become integral to many large cohort studies. However, little is known about longitudinal cohort study participants' attitudes toward genetics and genetic testing. We analyzed data from a survey of participants in the Jackson Heart Study (n = 960), Framingham Heart Study (n = 955), and Framingham Heart Study-Omni Cohort (n = 160). Based on a three-question attitude scale, most participants had positive attitudes toward genetic testing (median score = 4.3-5/5). Participants were also asked to select words to describe their attitudes toward genetics. More respondents endorsed the positive words "hopeful" (60%-70%), "optimistic" (44%-64%), "enthusiastic" (35%-43%), or "excited" (28%-30%) than the negative words "cautious" (35%-38%), "concerned" (25%-55%), "worried" (6%-13%), "pessimistic" (2%-5%), or "horrified" (1%-5%). Characteristics associated with favorable attitudes were greater genetics knowledge, higher subjective numeracy, experience with genetic testing, less frequent religious attendance, and not being employed. These findings demonstrate variation in attitudes even among participants in long-standing cohort studies, indicating a need for ongoing participant engagement and education.

Elimination of the fibrinogen integrin αMß2-binding motif improves renal pathology in mice with sickle cell anemia.

Sickle cell anemia (SCA) is caused by a point mutation in the ß-globin gene that leads to devastating downstream consequences including chronic hemolytic anemia, episodic vascular occlusion, and cumulative organ damage resulting in death. SCA patients show coagulation activation and inflammation even in the absence of vascular occlusion. The coagulation factor fibrinogen is not only central to hemostasis but also plays important roles in pathologic inflammatory processes, in part by engaging neutrophils/macrophages through the αMß2 integrin receptor. To determine whether fibrin(ogen)-mediated inflammation is a driver of SCA-associated pathologies, hematopoietic stem cells from Berkeley sickle mice were transplanted into homozygous Fibγ390-396A mice that express normal levels of a mutant form of fibrin(ogen) that does not engage αMß2 Fibγ390-396A mice with SCA displayed an impressive reduction of reactive oxygen species (ROS) in white blood cells (WBCs), decreased circulating inflammatory cytokines/chemokines, and significantly improved SCA-associated glomerular pathology highlighted by reduced glomerulosclerosis, inflammatory cell infiltration, ischemic lesions, mesangial thickening, mesangial hypercellularity, and glomerular enlargement. In addition, Fibγ390-396A mice with SCA had improved glomerular protective responses and podocyte/mesangial transcriptional signatures that resulted in reduced albuminuria. Interestingly, the fibrinogen γ390-396A mutation had a negligible effect on cardiac, lung, and liver functions and pathologies in the context of SCA over a year-long observation period. Taken together, our data support that fibrinogen significantly contributes to WBC-driven inflammation and ROS production, which is a key driver of SCA-associated glomerulopathy, and may represent a novel therapeutic target against irreversible kidney damage in SCA.

Psychosocial issues in hepatitis C: a qualitative analysis.

BACKGROUND: Despite demonstrated prevalence of psychosocial problems among hepatitis C (HCV) patients, little is known about how these problems develop, why they are sustained, and how clinical providers can effectively intervene. OBJECTIVE: The authors used a qualitative approach to investigate the nature of psychosocial issues in HCV. METHOD: Focus groups were conducted with HCV patients. RESULTS: Participants discussed significant feelings of anger, depression, and stigma associated with the diagnosis and noted that these feelings/experiences isolated them from potential sources of social support. CONCLUSION: Results have important implications for clinical providers and suggest pathways by which HCV-related psychosocial factors may interact with and affect quality of life.