Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical management of patients with ...progressive neurological decline and multisystem involvement requires a multidisciplinary team with experience in the management of neurodegenerative disorders. Best practice guidelines for the clinical management of patients with these types of rare disorders are critical to ensure prompt diagnosis and initiation of appropriate care. However, there are no published standard global clinical care guidelines for patients with Sanfilippo syndrome. To address this, a literature review was conducted to evaluate the current evidence base and to identify evidence gaps. The findings were reviewed by an international steering committee composed of clinical experts with extensive experience in managing patients with Sanfilippo syndrome. The goal was to create a consensus set of basic clinical guidelines that will be accessible to and informed by clinicians globally, as well as providing a practical resource for families to share with their local care team who may not have experience with this rare disease. This review distills 178 guideline statements into an easily digestible document that provides evidence-based, expert-led recommendations for how to approach common management challenges and appropriate monitoring schedules in the care of patients with Sanfilippo syndrome.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
Sanfilippo syndrome is a rare multisystem disease with no approved treatments. This study explores caregiver perspectives on the most impactful symptoms and patient-relevant clinical ...outcomes assessments. The pediatric onset and progressive neurodegenerative nature of Sanfilippo limits use of self-report in clinical research. This study obtains Sanfilippo caregiver data to support the selection of fit-for-purpose and patient-relevant clinical outcome assessments (COAs).
Methods
We conducted an asynchronous online focus group (n = 11) followed by individual interviews with caregivers (n = 19) of children with Sanfilippo syndrome. All participants reported on the impact of disease symptoms and level of unmet treatment need across Sanfilippo symptom domains. Focus group participants reviewed existing assessments relating to 8 symptom domains (15 total assessments) and provided feedback on meaningfulness and relevance. Focus group data were used to reduce the number of assessments included in subsequent interviews to 8 COAs across 7 symptom domains: communication, eating, sleep, mobility, pain, behavior and adapting. Interview respondents provided data on meaningfulness and relevance of assessments. Data were coded using an item-tracking matrix. Data summaries were analyzed by caregivers’ responses regarding meaningfulness; relevance to Sanfilippo syndrome; and based on caregiver indication of missing or problematic subdomains and items.
Results
Participants’ children were 2–24 years in age and varied in disease progression. Caregivers reported communication and mobility as highly impactful domains with unmet treatment needs, followed closely by pain and sleep. Domains such as eating, adaptive skills, and behaviors were identified as impactful but with relatively less priority, by comparison. Participants endorsed the relevance of clinical outcome assessments associated with communication, eating, sleep, and pain, and identified them as highly favorable for use in a clinical trial. Participants specified some refinements in existing assessments to best reflect Sanfilippo symptoms and disease course.
Discussion
The identification of impactful symptoms to treat and relevant and meaningful clinical outcome assessments supports patient-focused drug development. Our results inform targets for drug development and the selection of primary and secondary outcome assessments with high meaningfulness and face validity to Sanfilippo syndrome caregivers. Assessments identified as less optimal might be refined, replaced, or remain if the clinical trial necessitates.
Abstract The impact of an incentive/reward intervention on college students' intoxication from alcohol consumption at fraternity parties was explored using a group-randomized trial. Participants ...included 702 college students (447 men, 225 women) attending fraternity parties in Blacksburg, VA. Six fraternities were randomly assigned to a control or experimental group, and each of these fraternities hosted two parties. The three fraternities in the experimental group hosted a baseline party first and then hosted an intervention party at which those having a blood alcohol concentration (BAC) level below 0.05 were entered in a $100 cash lottery. The three fraternities in the control group hosted two control (non-intervention) parties. For the experimental fraternities, mean BAC levels were significantly lower at the intervention parties ( M = 0.079) than the baseline parties ( M = 0.098) and the percentage of partygoers with a BAC below 0.08 was significantly higher at intervention parties (40.1%) than at baseline parties (30.6%). This field study supports the efficacy of differential reinforcement in controlling student intoxication at party settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sanfilippo syndrome (MPS III) is a rare, degenerative disorder with no approved therapies. This study explored caregiver perceptions of the burden of Sanfilippo syndrome on the child and family, and ...meaningful benefits that are desired from a non-curative therapy. We used an innovative mixed-method approach with 25 caregivers (biological and step-parents) of children ages 4-36 years old from 17 U.S. states. We conducted three focus groups comprising three activities: (1) formative validity testing of a symptom/staging survey (not described here), (2) moderated exploration of burden and meaningful treatment benefit, and (3) best-worst scaling (BWS) activities to quantify the relative importance of twelve treatment benefits, which arose during activity 2 and thus varied across focus groups. Thematic analysis revealed common themes and the quantitative analysis used ‘best-worst’ scoring to prioritize meaningful benefits from most to least important. Caregivers’ experiences reflect uncertainty and distress related to progression and increased family burden with progressing symptoms. Participants expressed willingness to “try anything” to slow or stop progression. Meaningful benefits to the family included reducing risky and perceived aggressive/impulsive behaviors and improving ability to communicate needs and preferences. For their children, focus group 1 prioritized addressing communication (relative importance score=.50), pain (score=.35), and child unhappiness (score=.33) group 2 prioritized communication (score=.58), frustration (score=.33), and aggressive behavior (score=.31) and group 3 prioritized communication (score=.50), pain (score=.48), and sleep (score=.23). Caregivers reflected on the relevance of communication challenges across disease progression. Consistent with prior reports, most caregivers identified considerable burden. Modest treatment benefits to communication limitations and problematic behaviors would be highly valued, as would reduced pain-especially given caregiver uncertainty regarding the child’s pain experience. Our next steps include using these data to develop a larger BWS survey to prioritize meaningful treatment benefits across stages of MPS III progression. Funding: Cure Sanfilippo Foundation, BioMarin, Lysogene, Sobi, Orchard Therapeutics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
Sanfilippo syndrome (MPS III) is a rare, degenerative condition characterized by symptoms impacting cognitive ability, mobility, behavior, and quality of life. Currently there are no ...approved therapies for this severe life-limiting disease. Integrating patient and caregiver experience data into drug development and regulatory decision-making has become a priority of the Food and Drug Administration and rare disease patient communities.
Methods
This study assesses parents’ perceptions of their child’s Sanfilippo syndrome disease-related symptoms using a research approach that is consistent with the Center for Drug Evaluation and Research (CDER) guidance. This study was initiated by the Cure Sanfilippo Foundation, and all steps in the research process were informed by a multidisciplinary advisory committee, with an objective of informing biopharmaceutical companies and regulatory agencies. We explored caregiver burden, symptoms with greatest impact, and meaningful but unmet treatment needs. Data were collected from 25 parents through three focus groups and a questionnaire. Transcripts were coded and analyzed using inductive thematic analysis, and descriptive analysis of quantitative data was conducted.
Results
Participating parents’ children ranged in age from 4 to 36 years. Participants endorsed high caregiving burden across all stages of the disease. Analysis revealed multiple domains of unmet need that impact child and family quality of life, including cognitive-behavioral challenges in communication, relationships, behavior, anxiety, and child safety; and physical health symptoms including sleep, pain, and mobility. Participants reported placing high value on incremental benefits targeting those symptoms, and on a treatment that would slow or stop symptom progression.
Conclusion
Even modest treatment benefits for Sanfilippo syndrome were shown to be highly valued. Despite high caregiver burden, most parents expressed a willingness to “try anything,” including treatments with potentially high risk profiles, to maintain their child’s current state.
The impact of an incentive/reward intervention on college students' intoxication from alcohol consumption at fraternity parties was explored using a group-randomized trial. Participants included 702 ...college students (447 men, 225 women) attending fraternity parties in Blacksburg, VA. Six fraternities were randomly assigned to a control or experimental group, and each of these fraternities hosted two parties. The three fraternities in the experimental group hosted a baseline party first and then hosted an intervention party at which those having a blood alcohol concentration (BAC) level below 0.05 were entered in a $100 cash lottery. The three fraternities in the control group hosted two control (non- intervention) parties. For the experimental fraternities, mean BAC levels were significantly lower at the intervention parties (M = 0.079) than the baseline parties (M = 0.098) and the percentage of partygoers with a BAC below 0.08 was significantly higher at intervention parties (40.1%) than at baseline parties (30.6%). This field study supports the efficacy of differential reinforcement in controlling student intoxication at party settings. PUBLICATION ABSTRACT
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Attempts by behavior scientists to test interventions designed to promote environmentally-responsible behavior (ERB) have been documented for decades. Numerous behavioral scientists have looked to ...community-based interventions to decrease environment-destructive behaviors, as well as to increase environmental-protective behaviors (Geller, 1995). Litter is one of the most obvious examples of environmental degradation. Litter, defined here as misplaced waste material (Geller, Winett, & Everett, 1982), is a form of environmental pollution that not only degrades the quality of the environment but also proves costly to taxpayers. A wide variety of ecological and monetary benefits result from a decrease in litter. The current research examined the effectiveness of positive vs. negative antecedent messages to reduce littering behavior.
A methodology similar to that used by Geller, Witmer, and Orebaugh (1976), in which handbills containing weekly supermarket specials and special anti-litter message prompts were distributed at local community shopping centers, was used in the current research. In the first study, handbills with no anti-litter messages were distributed for a one-week period to determine percentage of handbills that were littered, and to serve as a baseline. The total percentage of handbills littered was 38.5. A second, web-based, study was conducted to determine the six specific (three positive or gain-framed, and three negative or loss-framed) anti-litter antecedent messages to be added to the handbills. In the third study, handbills with anti-litter messages were distributed for a two-week period. Upon addition of anti-litter prompts, results revealed 36.09% of distributed handbills were littered. Although no significant interactions were found, several significant main effects were found for store location, distribution period, and gender. The gender effect, indicating women littered at significantly higher rates than males, is notable. Survey research in the area of gender differences related to environmental concerns often has often shown modest differences between men and women, with women frequently displaying greater levels of environmental concern as compared to men. Based on behavioral observations (instead of self-report measures frequently used in previous research), the present research demonstrated significantly more women littering than men.
Although slightly more handbills, in terms of total handbill numbers, containing positive antecedents were littered as compared to those containing negative antecedents (which might be interpreted as stronger impact of loss-framed messages), this difference was not statistically significant. Similarly, there were no statistically significant differences found among each of the six anti-litter messages.
Comparisons of Study 1 (baseline) and Study 2 (prompting intervention) revealed significantly more littered handbills in the baseline condition as compared to the anti-litter message condition. These results indicate a beneficial anti-litter effect of the prompts added to handbills.
Conclusions based on the findings of the three studies within the present research are discussed. Implications for policies, public campaigns, and follow-up research designs are noted. Suggestions for future research involving message prompts and ERBs are offered.
Ph. D.
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