Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis.

PURPOSE: Exome (ES) and genome sequencing (GS) are increasingly being utilized for individuals with rare and undiagnosed diseases; however, guidelines on their use remain limited. This study aimed to identify factors associated with diagnosis by ES and/or GS in a heterogeneous population of patients with rare and undiagnosed diseases. METHODS: In this case control study, we reviewed data from 400 diagnosed and 400 undiagnosed randomly selected participants in the Undiagnosed Diseases Network, all of whom had undergone ES and/or GS. We analyzed factors associated with receiving a diagnosis by ES and/or GS. RESULTS: Factors associated with a decreased odds of being diagnosed included adult symptom onset, singleton sequencing, and having undergone ES and/or GS before acceptance to the Undiagnosed Diseases Network (48%, 51%, and 32% lower odds, respectively). Factors that increased the odds of being diagnosed by ES and/or GS included having primarily neurological symptoms and having undergone prior chromosomal microarray testing (44% and 59% higher odds, respectively). CONCLUSION: We identified several factors that were associated with receiving a diagnosis by ES and/or GS. This will ideally inform the utilization of ES and/or GS and help manage expectations of individuals and families undergoing these tests.

Neuroanatomical variability associated with early substance use initiation: Results from the ABCD Study.

The extent to which neuroanatomical variability associated with substance involvement reflects pre-existing risk and/or consequences of substance exposure remains poorly understood. In the Adolescent Brain Cognitive DevelopmentSM (ABCD®) Study, we identify associations between global and regional differences in brain structure and early substance use initiation (i.e., occurring <15 years of age; nsanalytic=6,556-9,804), with evidence that associations precede initiation. Neurodevelopmental variability in brain structure may confer risk for substance involvement.

Wound Bed Preparation 2024: Delphi Consensus on Foot Ulcer Management in Resource-Limited Settings.

GENERAL PURPOSE: To review a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Summarize issues related to wound assessment.2. Identify a class of drugs for the treatment of type II diabetes mellitus that has been shown to improve glycemia, nephroprotection, and cardiovascular outcomes.3. Synthesize strategies for wound management, including treatment in resource-limited settings.4. Specify the target time for edge advancement in chronic, healable wounds.

Chronic wound management in low-resource settings deserves special attention. Rural or underresourced settings (ie, those with limited basic needs/healthcare supplies and inconsistent availability of interprofessional team members) may not have the capacity to apply or duplicate best practices from urban or abundantly-resourced settings. The authors linked world expertise to develop a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. A group of 41 wound experts from 15 countries reached a consensus on wound bed preparation in resource-limited settings. Each statement of 10 key concepts (32 substatements) reached more than 88% consensus. The consensus statements and rationales can guide clinical practice and research for practitioners in low-resource settings. These concepts should prompt ongoing innovation to improve patient outcomes and healthcare system efficiency for all persons with foot ulcers, especially persons with diabetes.

The role community-based healthcare providers play in managing hard-to-heal wounds.

It is common for community-based healthcare providers (CHPs)-many of whom have not received specialised training in wound care-to deliver initial and ongoing management for various wound types and diverse populations. Wounds in any setting can rapidly transition to a stalled, hard-to-heal wound (HTHW) that is not following a normal healing trajectory. Failure to recognise or address issues that cause delayed healing can lead to increased costs, healthcare utilisation and suffering. To encourage early intervention by CHPs, a panel of wound care experts developed actionable evidence-based recommendations for CHPs delineating characteristics and appropriate care in identifying and treating HTHWs. A HTHW is a wound that fails to progress towards healing with standard therapy in an orderly and timely manner and should be referred to a qualified wound care provider (QWCP) for advanced assessment and diagnosis if not healed or reduced in size by 40%-50% within 4 weeks. HTHWs occur in patients with multiple comorbidities, and display increases in exudate, infection, devitalised tissue, maceration or pain, or no change in wound size. CHPs can play an important initial role by seeing the individual's HTHW risk, addressing local infection and providing an optimal wound environment. An easy-to-follow one-page table was developed for the CHP to systematically identify, evaluate and treat HTHWs, incorporating a basic toolkit with items easily obtainable in common office/clinic practice settings. A flow chart using visual HTHW clinical cues is also presented to address CHPs with different learning styles. These tools encourage delivery of appropriate early interventions that can improve overall healthcare efficiency and cost.

Participation in a national diagnostic research study: assessing the patient experience.

INTRODUCTION: The Undiagnosed Diseases Network (UDN), a clinical research study funded by the National Institutes of Health, aims to provide answers for patients with undiagnosed conditions and generate knowledge about underlying disease mechanisms. UDN evaluations involve collaboration between clinicians and researchers and go beyond what is possible in clinical settings. While medical and research outcomes of UDN evaluations have been explored, this is the first formal assessment of the patient and caregiver experience. METHODS: We invited UDN participants and caregivers to participate in focus groups via email, newsletter, and a private participant Facebook group. We developed focus group questions based on research team expertise, literature focused on patients with rare and undiagnosed conditions, and UDN participant and family member feedback. In March 2021, we conducted, recorded, and transcribed four 60-min focus groups via Zoom. Transcripts were evaluated using a thematic analysis approach. RESULTS: The adult undiagnosed focus group described the UDN evaluation as validating and an avenue for access to medical providers. They also noted that the experience impacted professional choices and helped them rely on others for support. The adult diagnosed focus group described the healthcare system as not set up for rare disease. In the pediatric undiagnosed focus group, caregivers discussed a continued desire for information and gratitude for the UDN evaluation. They also described an ability to rule out information and coming to terms with not having answers. The pediatric diagnosed focus group discussed how the experience helped them focus on management and improved communication. Across focus groups, adults (undiagnosed/diagnosed) noted the comprehensiveness of the evaluation. Undiagnosed focus groups (adult/pediatric) discussed a desire for ongoing communication and care with the UDN. Diagnosed focus groups (adult/pediatric) highlighted the importance of the diagnosis they received in the UDN. The majority of the focus groups noted a positive future orientation after participation. CONCLUSION: Our findings are consistent with prior literature focused on the patient experience of rare and undiagnosed conditions and highlight benefits from comprehensive evaluations, regardless of whether a diagnosis is obtained. Focus group themes also suggest areas for improvement and future research related to the diagnostic odyssey.

The Influence of Absorbent Products on Skin Integrity: A Scoping Review.

PURPOSE: Absorbent products are commonly used to absorb urine and fecal matter and to mitigate potential skin complications such as incontinence-associated dermatitis (IAD). Evidence concerning the effect these products have on skin integrity is limited. This scoping review aimed to explore the evidence/literature on the effect of absorbent containment products on skin integrity. METHOD: A scoping literature review. SEARCH STRATEGY: The electronic databases CINAHL, Embase, MEDLINE, and Scopus were searched for published articles between 2014 and 2019. Inclusion criteria were studies that focused on urinary and/or fecal incontinence, use of incontinent absorbent containment products, impact on skin integrity, and published in English. The search identified a total of 441 articles that were identified for the title and abstract review. FINDINGS: Twelve studies met inclusion criteria and were included in the review. Variability in the study designs did not allow firm conclusions regarding which absorbent products contributed to or prevented IAD. Specifically, we found variations in assessment of IAD, study settings, and types of products used. IMPLICATIONS: There is insufficient evidence to support the effectiveness of one product category over another for maintaining skin integrity in persons with urinary or fecal incontinence. This paucity of evidence illustrates the need for standardized terminology, a widely used instrument for assessment of IAD, and identification of a standard absorbent product. Additional research using both in vitro and in vivo models, along with real-world clinical studies, is needed to enhance current knowledge and evidence of the impact of absorbent products on skin integrity.

A Cost-Effectiveness Model to Determine Ostomy-Related Costs of Care and Health Outcomes Among People With an Ostomy in Canada Using a Ceramide-Infused Skin Barrier.

PURPOSE: The aim of this study was to determine whether a difference exists in the financial impact of the use of a 2-piece ceramide-infused skin barrier (CIB) versus standard of care barrier (SOC) in Ontario and Alberta using a cost-effectiveness model over a 1-year period for people with a fecal or urinary ostomy. DESIGN: A cost-effectiveness model adapted from a previously published work. SUBJECTS AND SETTING: The model was populated with data inputs from a hypothetical cohort of 1000 individuals in Ontario and 4000 in Alberta. Model results were assessed for robustness via the use of deterministic and probabilistic sensitivity analyses. The provinces of Ontario and Alberta were chosen because cost data were readily accessible. The combined population of these provinces accounts for 50% of Canada's population. RESULTS: An expected cost savings of Can$443.13 (US $322.60) and Can$243.84 (US $177.52) per user for the hypothetical cohort of 1000 individuals in Ontario and 4000 in Alberta per year was obtained for those using a CIB versus a non-infused skin barrier in Ontario and Alberta, respectively. The incremental cost effectiveness ratio (ICER) of CIB to SOC per peristomal skin complication (PSC) avoided and per quality-adjusted life day (QALD) gained was approximately Can$2702 (US $1967)/PSC and Can$1266 (US $922)/QALD for Ontario and approximately Can$1487 (US $1083)/PSC and Can$697 (US $507)/QALD for Alberta. Analysis indicated CIBs remained cost-effective across all sensitivity analyses performed. CONCLUSIONS: Finding suggest that a CIB is cost-effective when compared to a barrier not infused with ceramide when applied to persons with an ostomy and residing in the provinces of Alberta and Ontario.

Electronic consultation use by advanced practice nurses in older adult care-A descriptive study of service utilization data.

AIMS AND OBJECTIVES: To describe characteristics of service utilization by advanced practice nurses (APNs) employing an electronic consultation (eConsult) service in their care for older adults. BACKGROUND: Canada's aging population is projected to place unprecedented demands on the healthcare system. APNs, which include clinical nurse specialists (CNSs) and nurse practitioners (NPs), are nurses with advanced knowledge who can independently provide age-appropriate care. eConsult is a secure web-based platform enabling asynchronous, provider-to-provider communication. APNs can send and receive eConsults to address patient-specific concerns. METHODS: This is a retrospective analysis of eConsult utilization and user survey data for cases completed in 2019, reported in line with the STROBE guidelines. Eligible eConsults included those that had APN involvement (as a referrer or responder) and were concerning an older patient (≥65 years). Descriptive statistics were used to analyse service utilization and survey response data. RESULTS: Of 430 eligible eConsults, 421 (97.9%) were initiated by NPs and the rest by physicians. 23 (5.3%) were received by a CNS, of which 14 (3.3%) involved an NP-to-CNS exchange. Median specialist response interval was 0.9 days. 53% of eConsults was for dermatology, haematology, cardiology, gastroenterology and endocrinology. 73% of eConsults avoided a face-to-face referral after the consultation. In 90% of eConsults, APNs rated the service as helpful and/or educational. CONCLUSIONS: Through eConsult, APNs can collaborate with each other and physicians to access and provide a breadth of advice facilitating timely specialist-informed care for older patients, thus helping to alleviate some of the demands placed on the healthcare system. RELEVANCE TO CLINICAL PRACTICE: There is an opportunity for APNs to further adopt eConsult into their clinical practice, and this can, in turn, support the integration of the APN role in the health workforce. PATIENT OR PUBLIC CONTRIBUTION: Current APN eConsult users were involved in the study design and interpretation of results.

Individual-, peer-, and parent-level substance use-related factors among 9- and 10-year-olds from the ABCD Study: Prevalence rates and sociodemographic differences.

Background: Although a relatively large body of research has identified multiple factors associated with adolescent substance use, less is known about earlier substance-related factors during preadolescence, including curiosity to use substances. The present study examined individual-, peer-, and parent-level domains pertaining to substance use and how these domains vary by sociodemographic subgroups and substance type. Methods: Participants were 11,864 9- and 10-year-olds from the baseline sample of the Adolescent Brain Cognitive Development (ABCD) Study. Youth-reported measures were curiosity to use substances and perceived peer substance use. Parent-reported measures were availability of and rules about substances. Generalized logistic mixed models (GLMM) were used to compare these measures across alcohol, nicotine, and marijuana and across sociodemographic subgroupings (sex, race/ethnicity, household income, and family history of alcohol problems). GLMM was then used to examine predictors of curiosity to use by substance type. Results: The most striking descriptive differences were found between race/ethnicity and income categories (e.g., positive associations between greater income and greater availability of alcohol). In multivariable analyses, greater curiosity to use alcohol was associated with being male, higher household income, perceived peer alcohol use, and easy alcohol availability; greater curiosity to use nicotine was associated with being male, perceived peer cigarette use, easy availability of cigarettes, and no parental rules about cigarette use. Conclusions: This study identified substance use-related individual-, peer-, and parent-level factors among a diverse, national sample. Findings highlight the importance of considering sociodemographic and substance-specific variability and may help identify risk and protective factors preceding adolescent substance use.

Electronic Consultation by Advanced Practice Nurses to Improve Access to Specialist Care for Older Adults.

Older adults face several challenges when accessing specialist care. Advanced practice nurses (APNs) can perform an important role in primary care for older adults, particularly when bolstered with digital tools. In the current study, we conducted a multiple case study of electronic consultations (eConsults) involving APNs to assess how these practitioners use the service to improve access to care. All eConsults submitted by or to an APN in 2019 on behalf of patients aged ≥65 years were reviewed to identify examples from six settings representative of the range of advanced nursing practices. For each setting, a final case was chosen using an iterative process and stratified by specialty and type of advice. Included cases were assessed using a conceptual framework for health care access. Selected cases illustrate how APNs can be effective users of eConsults in a diversity of health care settings. The framework allowed for an in-depth study of access over the range of interactions that take place among patients, caregivers, providers, and the health care system. [Journal of Gerontological Nursing, 48(4), 33-40.].

Measuring retention within the adolescent brain cognitive development (ABCD)SM study.

The Adolescent Brain Cognitive Development (ABCD)SM study aims to retain a demographically diverse sample of youth and one parent across 21 sites throughout its 10-year protocol while minimizing selective (systematic) attrition. To evaluate the effectiveness of these efforts, the ABCD Retention Workgroup (RW) has employed a data-driven approach to examine, track, and intervene via three key metrics: (1) which youth completed visits late; (2) which youth missed visits; and (3) which youth withdrew from the study. The RW actively examines demographic (race, education level, family income) and site factors (visit satisfaction, distance from site, and enrollment in ancillary studies) to strategize efforts that will minimize disengagement and loss of participating youth and parents. Data showed that the most robust primary correlates of late visits were distance from study site, race, and parental education level. Race, lower parental education level, parental employment status, and lower family income were associated with higher odds of missed visits, while being enrolled in one of the ancillary studies was associated with lower odds of missed visits. Additionally, parents who were primary Spanish speakers withdrew at slightly higher rates. These findings provide insight into future targets for proactive retention efforts by the ABCD RW.

A pragmatic randomised controlled clinical study to evaluate the use of silicone dressings for the treatment of skin tears.

One of the most common types of skin breakdown in ageing populations is skin tears. The International Skin Tear Advisory Panel advocates for special attention to be paid to dressing selection related to skin tear management. The panel recommends choosing dressings that will promote the maintenance of moisture balance, suit the local wound environment, protect peri-wound skin, control or manage exudate and infection, and optimise caregiver time. It is paramount that dressings protect the fragile nature of the skin associated with those who at heightened risk for skin tear development. To compare the effectiveness of soft silicone dressings (a contact layer and/or foam) for the healing of skin tears with local practices that do not include soft silicone dressings. The study was a pragmatic randomised controlled prospective study. One hundred and twenty-six individuals from two long-term care facilities in Ontario Canada who presented with skin tears were randomised into the treatment group using either soft silicone dressings (a contact layer and/or foam) or the control group using non-adhesive dressings. The current study demonstrated that 96.9% (n = 63) of skin tears in the treatment group healed over a 3-week period compared with 34.4% (n = 21) in the control group. The proportion of wound healing experienced at week 2 was 89.2% (n = 58) in the treatment group compared with 27.9% (n = 17) in the control group. There was a significantly greater reduction in wound surface area relative to baseline in the treatment group (2.9 cm2 ) compared with the control group (0.6 cm2 ) (χ2  = 21.792 P < .0001) at week 1. Survival analysis data supported that skin tears healed 50% faster in the treatment group (11 days) compared with the control group (22 days) (χ2  = 59.677 P < .0001). The expected healing trajectory of acute wounds, including skin tears, if proper wound bed preparation is realised and infection is controlled, is 7 to 21 days. Results of this study suggest the use of silicone dressings support wound healing and aid in wound closure within the expected healing trajectory, with faster complete wound closure and mean healing times compared with non-silicone dressing for the treatment of STs.

Patients as Partners in Rare Disease Diagnosis and Research.

There is great value in understanding the patient perspective in rare disease diagnosis and research, and in partnering actively with patients and their families throughout the process. Meaningful and respectful interaction between patients and researchers leads to learning on both sides, and ultimately, to better research outcomes. Researchers can help patients understand how research is conducted and what the latest advances and perceived gaps in research are, and patients, who have direct experience living with their health conditions, can impart to researchers what is most important to them. We describe our engagement with patients in the Undiagnosed Diseases Network (UDN) program, as well as the lessons we have learned to date. In the UDN, patients have been instrumental in bringing meaning to the work of clinicians and researchers, building patient communities, making the network aware of unmet patient needs, advocating for additional research funding, and disseminating UDN research findings. Although patient engagement in the UDN has already had a significant positive impact on our work, we continue to strive to involve patients earlier in the process, in the research design itself, and in addressing power dynamics that may arise between clinicians, researchers, and patients.