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BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve motor milestones and in death or the need for mechanical ventilation by 2 years of age. We studied functional replacement of the mutated gene encoding survival motor neuron 1 (SMN1) in this disease. METHODS: Fifteen patients with SMA1 received a single dose of intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA encoding the missing SMN protein. Three of the patients received a low dose (6.7×1013 vg per kilogram of body weight), and 12 received a high dose (2.0×1014 vg per kilogram). The primary outcome was safety. The secondary outcome was the time until death or the need for permanent ventilatory assistance. In exploratory analyses, we compared scores on the CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) scale of motor function (ranging from 0 to 64, with higher scores indicating better function) in the two cohorts and motor milestones in the high-dose cohort with scores in studies of the natural history of the disease (historical cohorts). RESULTS: As of the data cutoff on August 7, 2017, all 15 patients were alive and event-free at 20 months of age, as compared with a rate of survival of 8% in a historical cohort. In the high-dose cohort, a rapid increase from baseline in the score on the CHOP INTEND scale followed gene delivery, with an increase of 9.8 points at 1 month and 15.4 points at 3 months, as compared with a decline in this score in a historical cohort. Of the 12 patients who had received the high dose, 11 sat unassisted, 9 rolled over, 11 fed orally and could speak, and 2 walked independently. Elevated serum aminotransferase levels occurred in 4 patients and were attenuated by prednisolone. CONCLUSIONS: In patients with SMA1, a single intravenous infusion of adeno-associated viral vector containing DNA coding for SMN resulted in longer survival, superior achievement of motor milestones, and better motor function than in historical cohorts. Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952 .).
Subject(s)
Genetic Therapy , Spinal Muscular Atrophies of Childhood/therapy , Survival of Motor Neuron 1 Protein/genetics , Cohort Studies , Dependovirus , Disease-Free Survival , Female , Genetic Therapy/adverse effects , Genetic Vectors , Historically Controlled Study , Humans , Infant , Infant, Newborn , Infusions, Intravenous , Liver Diseases/etiology , Male , Motor Skills , Nutritional Support , Respiration, Artificial , Spinal Muscular Atrophies of Childhood/genetics , Spinal Muscular Atrophies of Childhood/physiopathologyABSTRACT
Female college students report higher rates of stress than their male peers. Ineffective stress management contributes to a variety of concerning health outcomes. A number of factors have been shown to promote resilience to stress, such as experiencing positive social support. Few studies have examined if gender-specific social support impacts resilience. The present study investigates if gender-specific social support uniquely contributes to resilience among nontraditional college female students. Participants (N = 57) aged 21 to 54 completed an online survey assessing resilience and perceived social support from females and males. Participants with higher levels of perceived female social support reported higher levels of resilience than those with lower levels of perceived female social support. Perceived male social support was not significantly related to resilience when examined in conjunction with perceived female social support. These findings suggest that perceived female social support may uniquely contribute to resilience in nontraditional female students.
Subject(s)
Social Support , Students , Humans , Male , Female , Universities , Surveys and QuestionnairesABSTRACT
OBJECTIVE: The goal was to elicit adolescents' and young adults' (AYAs) perspectives about how to implement the Six Core Elements of Healthcare Transition within rheumatology care. METHODS: AYAs (ages 16-28 years old) with self-reported rheumatic conditions were recruited through patient organizations and social media. In Phase One (qualitative [QUAL]), 90-minute focus groups were facilitated to elicit AYAs' reactions to Six Core Elements content. In Phase Two (quantitative; QUAN), a national survey was conducted to determine generalizability of recommendations extracted from Phase One. Mixed methods analyses were conducted by a multidisciplinary team of social science researchers, pediatric rheumatologists, and patients. RESULTS: Although focus group participants (n = 39) were previously unfamiliar with the Six Core Elements, they reacted favorably to its format and content. Participants provided suggestions for how to logistically execute each component in the clinic. Additionally, 3 overarching recommendations emerged that focused on motivating AYAs to engage: 1) frame health care transition as an opportunity for empowerment; 2) implement a structured education plan; and 3) consider the role of parents. In line with qualitative findings, survey participants (n = 137) reported that they would prefer to learn most transitional skills from and discuss developmentally specific topics with their rheumatology team. Participants reported they would likely complete programs to learn transitional skills from allied professionals, via patient portals, or in group settings. CONCLUSION: Incorporating patient perspectives into research and clinical practice is an opportunity to strengthen educational programs. AYAs emphasized the importance of gaining independence and becoming empowered through the health care transition process with structured support from their rheumatology teams.
Subject(s)
Rheumatic Diseases , Rheumatology , Transition to Adult Care , Child , Humans , Young Adult , Adolescent , Adult , Patient Transfer , Rheumatic Diseases/diagnosis , Rheumatic Diseases/therapy , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Patients with autoimmune rheumatic diseases (ARDs) are at greater risk of COVID-19 infection and hospitalization, increasing the stress and uncertainty already associated with unpredictable conditions. These may be heightened for patients with ARDs from underrepresented minority backgrounds. This study aimed to explore patient experiences and ARD-related challenges during the first year of the pandemic. METHODS: Between December 2020 and May 2021, 60-minute semistructured interviews were conducted with English- and Spanish-speaking adults, aged 18 years or older with self-reported diagnosis of ARD, via phone or videoconferencing using an interview guide on living with an ARD during the pandemic. Analysis combined methods of phenomenology and content analysis through three steps: 1) summarizing interviews, 2) iteratively refining units of meaning, and 3) axial and selective coding to determine cross-cutting themes. Study procedures were conducted by a multidisciplinary team, a majority also diagnosed with ARDs. RESULTS: The research team interviewed 22 patients (39.8 ± 15.7 years old; 82.8% female; 31.8% Hispanic or Latino/a/x) with ARDs. Themes included 1) information access and understanding, 2) problem solving access to health care, 3) balancing risks, and 4) mental health implications. Within these themes, patients from underrepresented minority backgrounds faced unique challenges. CONCLUSION: Patients with ARDs require direct and timely communication about their risk of COVID-19 morbidity and mortality and require increased support for psychosocial and ARD-related implications of the pandemic. Health care systems must consider ways to support patients who are balancing chronic disease management with risk reduction for contracting emerging COVID-19 variants.
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OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Rheumatology , Humans , United States , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/therapeutic use , Diet , Exercise TherapyABSTRACT
OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Rheumatology , Humans , United States , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/therapeutic use , Diet , Exercise TherapyABSTRACT
PURPOSE: The sciatic nerve innervates the hamstring muscles. Occasionally, the sciatic nerve is injured along with a hamstring muscle. Detailed biomechanical and sensory thresholds of these structures are not well-characterized. Therefore, we designed a prospective study that explored high-resolution ultrasound (US) at multiple sites to evaluate properties of the sciatic nerve, including cross-sectional area (CSA) and shear-wave elastography (SWE). We also assessed SWE of each hamstring muscle at multiple sites. Mechanical algometry was obtained from the sciatic nerve and hamstring muscles to assess multi-site pressure pain threshold (PPT). METHODS: Seventy-nine asymptomatic sciatic nerves and 147 hamstring muscles (25 males, 24 females) aged 18-50 years were evaluated. One chiropractic radiologist with 4.5 years of US experience performed the evaluations. Sciatic nerves were sampled along the posterior thigh at four sites obtaining CSA, SWE, and algometry. All three hamstring muscles were sampled at two sites utilizing SWE and algometry. Descriptive statistics, two-way ANOVA, and rater reliability were assessed for data analysis with p ≤ 0.05. RESULTS: A significant decrease in sciatic CSA from proximal to distal was correlated with increasing BMI (p < 0.001). Intra-rater and inter-rater reliability for CSA was moderate and poor, respectively. Elastographic values significantly increased from proximal to distal with significant differences in gender and BMI (p = 0.002). Sciatic PPT significantly decreased between sites 1 and 2, 1 and 3, and 1 and 4. Significant correlation between gender and PPT was noted as well as BMI (p < 0.001). Hamstring muscle elastographic values significantly differed between biceps femoris and semitendinosus (p < 0.001) and biceps femoris and semimembranosus (p < 0.001). All three hamstring muscles demonstrated increased PPT in males compared to females (p < 0.001). In addition, PPT of the biceps femoris correlated with BMI (p = 0.02). CONCLUSION: High-resolution US provided useful metrics of sciatic nerve size and biomechanical properties. PPT for the normal sciatic nerve and hamstring muscles was obtained for future clinical application.
Subject(s)
Hamstring Muscles , Adolescent , Adult , Female , Hamstring Muscles/diagnostic imaging , Hamstring Muscles/innervation , Hamstring Muscles/physiology , Humans , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Sciatic Nerve/diagnostic imaging , Sciatic Nerve/physiology , Sensory Thresholds , Young AdultABSTRACT
OBJECTIVE: Spondylolysis is 1 of the most common sources of low back pain in children and adolescents; however, there is still a great deal of confusion in regard to etiology, clinical presentation, and diagnostic imaging findings. It is imperative for clinicians to recognize that persistent low back pain is strongly indicative of spondylolysis, especially in high-performance athletes. This case series demonstrates a comprehensive diagnostic spectrum of spondylolysis and its treatment in 2 competitive adolescent cheerleaders. CLINICAL FEATURES: In case 1, a 12-year-old female competitive cheerleader presented with a gradual onset of subacute low back pain. Comprehensive clinical examination indicated imaging studies that identified bilateral L5 grade 1 stress reaction, consisting of neural arch bone marrow edema (BME). Treatment included spinal adjustments, rehabilitation, and myofascial therapy. In case 2, 15-year-old female competitive cheerleader presented with insidious chronic low back pain that was provocative with extension. Magnetic resonance imaging revealed a left L5 grade 1 pars interarticularis stress reaction. Computed tomography demonstrated right L5 pars grade 3 and left L5 healing spondylolysis. Treatment included spinal adjustments and rehabilitation exercises. She was also seen by a physical therapist who prescribed a lumbar spine flexion brace. INTERVENTION AND OUTCOME: Diagnosis of BME and spondylolysis led to temporary cessation of cheerleading activities in cases 1 and 2. The individual in case 1 self-discharged with a list of rehabilitation exercises and was lost to follow-up. The individual in case 2 was able to return to sport pain free approximately 5 weeks after seeking treatment. CONCLUSION: Spondylolysis is common in adolescent athletes, and the presence of BME precedes spondylolysis. Primary spine providers could consider this diagnosis in any adolescent, especially an athlete, who has persistent low back pain. Timely diagnosis will optimize treatment outcomes.
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BACKGROUND: This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1). METHODS: This study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: (1) early dosing/low motor, dosed age less than three months with scores <20 (n = 3), (2) late dosing, dosed at age three months or greater (n = 6), and (3) early dosing/high motor, dosed age less than three months with scores ≥20 (n = 3). RESULTS: Early dosing/low motor group demonstrated a mean gain of 35.0 points from a mean baseline of 15.7, whereas the late dosing group had a mean gain of 23.3 from a mean baseline of 26.5. The early dosing/high motor group quickly reached a mean score of 60.3, near the scale maximum (64), from a mean baseline of 44.0. Despite a lower baseline motor score, the early dosing/low motor group achieved sitting unassisted earlier than the late dosing group (mean age: 17.0 vs 22.0 months). The early dosing/high motor group reached this milestone earliest (mean age: 9.4 months). CONCLUSIONS: The rapid, significant motor improvements among infants with severe SMA1 treated with AVXS-101 at an early age highlight the importance of newborn screening and early treatment and demonstrate the therapeutic potential of AVXS-101 regardless of baseline motor function.
Subject(s)
Genetic Therapy , Motor Disorders/therapy , Outcome Assessment, Health Care , SMN Complex Proteins/therapeutic use , Spinal Muscular Atrophies of Childhood/therapy , Age Factors , Dependovirus , Female , Follow-Up Studies , Genetic Vectors , Humans , Infant , Male , Motor Disorders/etiology , Severity of Illness Index , Spinal Muscular Atrophies of Childhood/complicationsABSTRACT
BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma®) gene replacement therapy, are emerging. OBJECTIVE: This study evaluated the effectiveness of AVXS-101 in infants with spinal muscular atrophy type 1 (SMA1) compared with a prospective natural history cohort and a cohort of healthy infants. METHODS: Twelve SMA1 infants received the proposed therapeutic dose of AVXS-101 (NCT02122952). Where possible, the following outcomes were compared with a natural history cohort of SMA1 infants (nâ=â16) and healthy infants (nâ=â27) enrolled in the NeuroNEXT (NN101) study (NCT01736553): event-free survival, CHOP-INTEND scores, motor milestone achievements, compound muscle action potential (CMAP), and adverse events. RESULTS: Baseline characteristics of SMA1 infants in the AVXS-101 and NN101 studies were similar in age and genetic profile. The proportion of AVXS-101-treated infants who survived by 24 months of follow-up was higher compared with the NN101 study (100% vs 38%, respectively). The average baseline CHOP-INTEND score for NN101 SMA1 infants was 20.3, worsening to 5.3 by age 24 months; the average baseline score in AVXS-101-treated infants was 28.2, improving to 56.5 by age 24 months. Infants receiving AVXS-101 achieved motor milestones, such as sitting unassisted and walking. Improvements in CMAP peak area were observed in AVXS-101-treated infants at 6 and 24 months (means of 1.1 and 3.2 mV/s, respectively). CONCLUSIONS: In this study, AVXS-101 increased the probability of survival, rapidly improved motor function, and enabled motor milestone achievement in SMA1 infants.
Subject(s)
Genetic Therapy , Spinal Muscular Atrophies of Childhood/therapy , Female , Humans , Infant , Kaplan-Meier Estimate , Male , Prospective Studies , Spinal Muscular Atrophies of Childhood/genetics , Treatment OutcomeABSTRACT
We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy. Cancer Immunol Res; 6(3); 288-94. ©2018 AACR.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Exanthema/chemically induced , Fatigue/chemically induced , Female , Humans , Hypothyroidism/chemically induced , Male , Middle Aged , Treatment OutcomeABSTRACT
Erik H. Erikson published his groundbreaking theory of 8 stages of lifelong psychosocial development in 1950. His theory expanded psychoanalytic concepts of psychosexual development to include the importance of social dynamics; it transcended then-current thinking that psychological development culminated in early adulthood, acknowledging that systematic human development continues throughout the entire life cycle. The theory made Erikson a pioneer in developmental psychology. His last authored book, Vital Involvement in Old Age, rearticulated and elaborated 3 principles that, in different words, are rooted in his original theory of healthy life cycle development: (1) Dynamic Balance of Opposites; (2) Vital Involvement; and (3) Life in Time. Using a lens informed by knowledge gained over the past 30 years and by reflections of one of the original researchers on that project, the current manuscript seeks to spark new interest in Erikson's late-life contribution. It explains the principles in new detail, links them to relevant research, and suggests ways they could enable Erikson's ideas to further enrich gerontological practice and research.
Subject(s)
Aging/psychology , Psychoanalytic Theory , Psychology, Developmental/history , History, 20th Century , Human Development , Humans , MaleABSTRACT
BACKGROUND: To increase understanding of the healthcare transition (HCT) process for young people living with Juvenile Idopathic Arthritis (JIA) by examining: 1) the extent to which youth report discussing HCT topics with their rheumatologist and 2) the association between youth perceptions of autonomy support from their rheumatologist and HCT discussions. METHODS: Data are from an online survey of youth in the United States with rheumatologic conditions (n= 134). HCT discussion was measured by 4 questions from the National Survey of Children with Special Health Care Needs. Youth perception of autonomy support was measured using a validated 6-item scale. RESULTS: One third of the youth (33.7%) reported talking to their rheumatologist about transferring to adult medicine. Less than half (40.8%) of respondents talked with their rheumatologist about adult healthcare needs, and less than a quarter (22.0%) discussed acquiring health insurance as an adult. Nearly two-thirds of respondents (62.7%) reported that their rheumatologist usually/always encourages self-care responsibility. Multivariate analyses revealed significant associations between rheumatologist support for youth autonomy and HCT counseling. CONCLUSION: The low frequency of HCT counseling reported indicates a continuing need to increase awareness among rheumatologist in the USA. The strong associations between rheumatologist's support for youth autonomy and HCT counseling suggest that developmentally "in-tune" providers may deliver the best guidance about transition planning for youth living with arthritis.
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INTRODUCTION: The objective of this study was to identify challenges that teens experience while living with juvenile arthritis (JA) from the perspective of youth and young adults with JA. METHOD: Focus group interviews were conducted with youth (aged 14-21 years) and young adults (aged 22-29 years) with JA using a semi-structured interview protocol that included questions about the challenges adolescents experience while living with arthritis. RESULTS: Challenges of living with JA were identified in the areas of (a) health care, (b) relationships, (c) school, (d) physical, and (e) individual. However, distinct perspectives emerged between youth and young adult participants. For youth, challenges were situated in present time and focused heavily on interpersonal situations. Alternatively, young adults reported challenges that illuminated their experiences of movement from adolescence into young adulthood (e.g., independently managing their JA and disclosure to dating partners). DISCUSSION: Findings from this study display complex and multifaceted experiences that teens face while living with arthritis. Experiences associated with arthritis were not limited to being described as health care-related challenges; rather, arthritis permeates multiple contexts in adolescents' lives.