Websites about, not for, adolescents? A systematic analysis of online fertility preservation information for adolescent and young adult cancer patients.

PURPOSE: Fertility preservation is an increasingly important topic in adolescent and young adult cancer survivorship, yet treatments remain under-utilized, possibly due to lack of awareness and understanding. The internet is widely used by adolescents and young adults and has been proposed to fill knowledge gaps and advance high-quality, more equitable care. As a first step, this study analyzed the quality of current fertility preservation resources online and identified opportunities for improvement. METHODS: We conducted a systematic analysis of 500 websites to assess the quality, readability, and desirability of website features, and the inclusion of clinically relevant topics. RESULTS: The majority of the 68 eligible websites were low quality, written at college reading levels, and included few features that younger patients find desirable. Websites mentioned more common fertility preservation treatments than promising experimental treatments, and could be improved with cost information, socioemotional impacts, and other equity-related fertility topics. CONCLUSIONS: Currently, the majority of fertility preservation websites are about, but not for, adolescent and young adult patients. High-quality educational websites are needed that address outcomes that matter to teens and young adults, with a priority on solutions that prioritize equity. IMPLICATIONS FOR CANCER SURVIVORS: Adolescent and young adult survivors have limited access to high-quality fertility preservation websites that are designed for their needs. There is a need for the development of fertility preservation websites that are clinically comprehensive, written at appropriate reading levels, inclusive, and desirable. We include specific recommendations that future researchers can use to develop websites that could better address AYA populations and improve the fertility preservation decision making process.

Websites about, not for, adolescents? A systematic analysis of online fertility preservation information for adolescent and young adult cancer patients.

Purpose Fertility preservation is an increasingly important topic in adolescent and young adult cancer survivorship, yet treatments remain under-utilized, possibly due to lack of awareness and understanding. The internet is widely used by adolescents and young adults and has been proposed to fill knowledge gaps and advance high-quality, more equitable care. As a first step, this study analyzed the quality of current fertility preservation resources online and identified opportunities for improvement. Methods We conducted a systematic analysis of 500 websites to assess the quality, readability, and desirability of website features, and the inclusion of clinically relevant topics. Results The majority of the 68 eligible websites were low quality, written at college reading levels, and included few features that younger patients find desirable. Websites mentioned more common fertility preservation treatments than promising experimental treatments, and could be improved with cost information, socioemotional impacts, and other equity-related fertility topics. Conclusions Currently, the majority of fertility preservation websites are about, but not for, adolescent and young adult patients. High-quality educational websites are needed that address outcomes that matter to teens and young adults, with a priority on solutions that prioritize equity. Implications for Cancer Survivors: Adolescent and young adult survivors have limited access to high-quality fertility preservation websites that are designed for their needs. There is a need for the development of fertility preservation websites that are clinically comprehensive, written at appropriate reading levels, inclusive, and desirable. We include specific recommendations that future researchers can use to develop websites that could better address AYA populations and improve the fertility preservation decision making process.

Muscle-directed gene therapy corrects Pompe disease and uncovers species-specific GAA immunogenicity.

Pompe disease is a severe disorder caused by loss of acid α-glucosidase (GAA), leading to glycogen accumulation in tissues and neuromuscular and cardiac dysfunction. Enzyme replacement therapy is the only available treatment. AT845 is an adeno-associated viral vector designed to express human GAA specifically in skeletal muscle and heart. Systemic administration of AT845 in Gaa-/- mice led to a dose-dependent increase in GAA activity, glycogen clearance in muscles and heart, and functional improvement. AT845 was tolerated in cynomolgus macaques at low doses, while high doses caused anti-GAA immune response, inflammation, and cardiac abnormalities resulting in unscheduled euthanasia of two animals. Conversely, a vector expressing the macaque GAA caused no detectable pathology, indicating that the toxicity observed with AT845 was an anti-GAA xenogeneic immune response. Western blot analysis showed abnormal processing of human GAA in cynomolgus muscle, adding to the species-specific effects of enzyme expression. Overall, these studies show that AAV-mediated GAA delivery to muscle is efficacious in Gaa-/- mice and highlight limitations in predicting the toxicity of AAV vectors encoding human proteins in non-human species.

Lack of Toxicity in Nonhuman Primates Receiving Clinically Relevant Doses of an AAV9.U7snRNA Vector Designed to Induce DMD Exon 2 Skipping.

Therapeutic exon skipping as a treatment for Duchenne muscular dystrophy (DMD) has largely concentrated on the delivery of antisense oligomers to treat out-of-frame exon deletions. Here we report on the preclinical development of an adeno-associated virus (AAV)-encapsidated viral vector containing four copies of the noncoding U7 small nuclear RNA (U7snRNA), each targeted to either the splice donor or the splice acceptor sites of DMD exon 2. We have previously shown that delivery of this vector (scAAV9.U7.ACCA) to the Dup2 mouse model results in expression of full-length dystrophin from wild-type DMD mRNA, as well as an internal ribosome entry site (IRES)-driven isoform translated only in the absence of exon 2 (deletion exon 2 [Del2] mRNA). Here we present the data from a rigorous dose escalation toxicity study in nonhuman primates, encompassing two doses (3 × 1013 and 8 × 1013 vg/kg) and two time points (3 and 6 months postinjection). No evidence for significant toxicity was seen by biochemical, histopathologic, or clinical measures, providing evidence for safety that led to initiation of a first-in-human clinical trial.

Exploring unnecessary invasive procedures in the United States: a retrospective mixed-methods analysis of cases from 2008-2016.

BACKGROUND: Unnecessary invasive procedures risk harming patients physically, emotionally, and financially. Very little is known about the factors that provide the motive, means, and opportunity (MMO) for unnecessary procedures. METHODS: This project used a mixed-methods design that involved five key steps: (1) systematically searching the literature to identify cases of unnecessary procedures reported from 2008 to 2016; (2) identifying all medical board, court, and news records on relevant cases; (3) coding all relevant records using a structured codebook of case characteristics; (4) analyzing each case using a MMO framework to develop a causal theory of the case; and (5) identifying typologies of cases through a two-step cluster analysis using variables hypothesized to be causally related to unnecessary procedures. RESULTS: Seventy-nine cases met inclusion criteria. The mean number of documents or sources examined for each case was 36.4. Unnecessary procedures were performed for at least five years in most cases (53.2%); 56.3% of the cases involved 30 or more patients, and 37.5% involved 100 or more patients. In nearly all cases the physician was male (96.2%) and working in private practice (92.4%); 57.0% of the physicians had an accomplice, 48.1% were 50 years of age or older, and 40.5% trained outside the U.S. The most common motives were financial gain (92.4%) and suspected antisocial personality (48.1%), followed by poor problem-solving or clinical skills (11.4%) and ambition (3.8%). The most common environmental factors that provided opportunity for unnecessary procedures included a lack of oversight (40.5%) or oversight failures (39.2%), a corrupt moral climate (26.6%), vulnerable patients (20.3%), and financial conflicts of interest (13.9%). CONCLUSIONS: Unnecessary procedures usually appear motivated by financial gain and occur in settings that have oversight problems. Preventive efforts should focus on early detection by peers and institutions, and decisive action by medical boards and federal prosecutors.