Dysregulated lung stroma drives emphysema exacerbation by potentiating resident lymphocytes to suppress an epithelial stem cell reservoir.

Aberrant tissue-immune interactions are the hallmark of diverse chronic lung diseases. Here, we sought to define these interactions in emphysema, a progressive disease characterized by infectious exacerbations and loss of alveolar epithelium. Single-cell analysis of human emphysema lungs revealed the expansion of tissue-resident lymphocytes (TRLs). Murine studies identified a stromal niche for TRLs that expresses Hhip, a disease-variant gene downregulated in emphysema. Stromal-specific deletion of Hhip induced the topographic expansion of TRLs in the lung that was mediated by a hyperactive hedgehog-IL-7 axis. 3D immune-stem cell organoids and animal models of viral exacerbations demonstrated that expanded TRLs suppressed alveolar stem cell growth through interferon gamma (IFNγ). Finally, we uncovered an IFNγ-sensitive subset of human alveolar stem cells that was preferentially lost in emphysema. Thus, we delineate a stromal-lymphocyte-epithelial stem cell axis in the lung that is modified by a disease-variant gene and confers host susceptibility to emphysema.

Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.

Vascular permeability is frequently associated with inflammation and is triggered by a cohort of secreted permeability factors such as vascular endothelial growth factor (VEGF). Here, we show that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and is independent of VEGF. Global or endothelial-specific deletion of PR blocks physiological vascular permeability in the uterus, whereas misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of an endothelial genome-wide transcriptional profile with chromatin immunoprecipitation sequencing revealed that PR induces an NR4A1 (Nur77/TR3)-dependent transcriptional program that broadly regulates vascular permeability in response to progesterone. Silencing of NR4A1 blocks PR-mediated permeability responses, indicating a direct link between PR and NR4A1. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely, and venous-specific regulation of vascular barrier function that is critical for embryo implantation.

Cognitive Abilities and Collaboration in Couples in Type 1 Diabetes Management.

Managing type 1 diabetes involves coordinating complex daily behaviors that may rely on the cognitive abilities of people with diabetes (PWD) and spouses, especially as couples collaborate surrounding diabetes care. The aims of the study were to examine whether 1) the cognitive abilities of PWD and their spouses predicted lower A1C, 2) collaborating with a spouse with higher cognitive abilities was especially beneficial for PWD with lower cognitive abilities, and 3) the benefit of the cognitive abilities of PWD and their spouse occurred through better self-care. Couples (n = 199) were recruited with one member diagnosed with type 1 diabetes (PWD 52% female sex, average age 46.81 years, average duration of diabetes 27 years; spouses 48% female sex; average age 46.40 years). PWD and spouses completed fluid (trail making tests from the Delis-Kaplan Executive Function System) and crystallized (information subtest from the Wechsler Adult Intelligence Scale-4th Edition) ability tests. PWD rated their spouse's collaboration in diabetes and reported self-care behaviors through surveys. A1C was assessed as a measure of blood glucose through a blood assay. Multiple regressions revealed that spouses' crystallized ability was the only statistically significant predictor, with higher values associated with lower A1C (t = -2.17, P <0.05). The interaction of crystallized ability of PWD × spouse crystallized ability × collaboration indicated that PWD with lower ability tended to benefit more when they collaborated with a spouse who scored higher in ability (t = -2.21, P <0.05). Mediational analyses indicated that spouses' crystallized ability was associated with lower A1C through better self-care behaviors of PWD (B = 0.03, SE = 0.01, P <0.01). We conclude that PWD benefit from the cognitive abilities of their spouses through better self-care behaviors that are important for maintaining lower A1C across adulthood.

Continuous glucose monitoring with data sharing in older adults: A qualitative study.

AIMS: This study examined the perceptions of the SHARE plus intervention and its effects on communication, collaboration, and involvement in day-to-day diabetes management in older adults with Type 1 diabetes (T1D) and their care partners. BACKGROUND: The SHARE plus intervention includes continuous glucose monitoring with a data sharing app that allows care partners to view glucose data on a smartphone and receive alerts. People with T1D and their care partners are educated about communication strategies, problem-solving strategies, and action planning when using glucose data sharing. DESIGN: Qualitative descriptive design. METHODS: Older adults with T1D wore a continuous glucose monitor for 3 months (n = 10). Care partners (n = 10) used a data-sharing app. The SHARE plus intervention consisted of one 90-min education session. Semi-structured interviews were conducted across 10 dyads (person with diabetes and care partner) following the 12-week study. A qualitative description and a constant comparison approach were used to examine similarities and differences in experiences. Interviews were transcribed, coded, and analysed for common themes. The manuscript adheres to COREQ EQUATOR checklist. RESULTS: The SHARE plus intervention increased diabetes knowledge across the dyads, improving confidence and helping partners understand how to navigate symptoms and behaviours and when to intervene. Dyads worked together to optimise diabetes management through improved communication, collaboration, and management of disagreements. Although the majority of persons with diabetes and their care partners reported no conflictual communication, disagreements about diabetes management remained in some dyads. The SHARE plus intervention impacted care partners in various ways from a psychological perspective. While live-in-care partners felt peace of mind, care partners living away from persons with diabetes had some increased worry and concern. CONCLUSION: The SHARE plus intervention results can help guide future development of diabetes dyadic care and education interventions using diabetes technology. RELEVANCE TO CLINICAL PRACTICE: The SHARE plus intervention is a brief, practical intervention that can help diabetes clinicians improve communication and collaboration among spouses living with older adults with T1D who use continuous glucose monitoring with data sharing. PATIENT CONTRIBUTION: A person with diabetes was part of the research team and assisted with design of the intervention and subsequent interviews and analysis.

Hospital Admissions and Mortality in Patients With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND/OBJECTIVES: Anti-neutrophil cytoplasmic antibody-associated vasculitis has reported hospital mortality rates ranging between 10% and 20% with inadequate information regarding causes and outcomes of these hospitalizations. Characterization of outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis can improve patient care and prognostication following hospitalization. METHODS: A medical records review of all hospitalizations between October 1, 2015, and December 31, 2018, of adults with granulomatosis with polyangiitis or microscopic polyangiitis at a single academic medical center was performed. Chart review confirmed diagnoses in patients identified by International Classification of Diseases, Tenth Revision code. Vasculitis activity was determined based on clinical data and treatment during the hospitalization. Differences in outcome measures were analyzed using Fisher exact test, t test, and Wilcoxon signed-rank test. RESULTS: Of the 127 hospitalizations among 54 patients, active vasculitis was identified in 43 hospitalizations (33.9%). A total of 15 patients with active disease, including 10 patients with a new diagnosis, required intensive care unit (ICU)-level care. Of 84 hospitalizations when vasculitis was inactive, infection was diagnosed in 31 admissions (36.9%), with inactive disease representing 44% of all ICU admissions. Overall mortality was 7% for hospitalized patients and 15% for those admitted to the ICU. An additional 5 patients died within 28 days of discharge, for an overall mortality rate of 17%. All 4 hospital deaths and 3 of 5 postdischarge deaths were in the setting of known infection. CONCLUSION: Most hospitalizations and patient deaths were in the context of inactive vasculitis, with infection being the most common cause. Infection and ICU admission were associated with patient death.

Diabetes stress contagion among romantic partners: a daily diary investigation.

The stress of diabetes management not only affects persons with type 1 diabetes (PWD) but also their social network. We examined the extent to which romantic partners of PWD (n = 199) identified their most significant daily stressor as diabetes-related (i.e., partner diabetes stress) using a 14-day daily diary design. Utilizing a communal coping framework, we examined appraisal and communication as predictors of partner diabetes stress and examined links of partner diabetes stress to supportive/unsupportive behavior and mood by assessing each construct daily. We also examined whether a survey measure of partner anxious attachment moderated these links. Results showed that viewing diabetes as a shared problem and greater diabetes communication were associated with greater partner diabetes stress. Partner diabetes stress was linked to partner provision of greater supportive and unsupportive behavior-especially so for anxiously attached partners. Importantly, partner diabetes stress was not linked to mood for PWDs or partners.

Equity in the Provision of Diabetes Self-Management Education and Support.

Diabetes self-management education and support (DSMES) interventions must be accessible to all people with diabetes. To address equity in the delivery of DSMES, interventions should consider the unique needs of various populations. This article outlines the needs of a wide range of populations, including people with diabetes who are racially or ethnically diverse; have limited English proficiency or literacy; are deaf or hard of hearing; are blind or have low vision; are neurodiverse; live with learning disabilities or intellectual or developmental disabilities; have dementia or cognitive impairment; or are of sexual and/or gender minority. The authors discuss how best to tailor DSMES to meet the needs of these diverse groups.

Financial Barriers in Emerging Adults With Type 1 Diabetes: A Qualitative Analysis.

Background: Emerging adulthood is a period fraught with challenging life transitions for many and is especially difficult for individuals with type 1 diabetes, as they encounter more obstacles to independently managing their diabetes. We examined the barriers faced by emerging adults and parents of emerging adults with type 1 diabetes and the impact these barriers had on their lives. Methods: Emerging adults and parents of emerging adults with type 1 diabetes were recruited from primary care and specialty clinics and via social media posts. In the parent study, semi-structured interviews were conducted to understand what supported and did not support diabetes self-management. Interviews were transcribed, coded, and analyzed for common themes. This sub-analysis analyzed data related to financial challenges in accessing diabetes management equipment and supplies. Results: This study included emerging adults with type 1 diabetes (n = 33; mean age 20 ± 2.9 years) and parents of emerging adults with type 1 diabetes (n = 17; mean age 47.5 ± 6.9 years). The majority of emerging adults used an insulin pump and continuous glucose monitoring system (n = 24 [73%]). Four main themes emerged related to access to care: 1) affordability of diabetes management tools, 2) managing insurance, 3) communication with pharmacies and health care providers, and 4) emotional consequences of financial stress. Conclusion: The current health system is challenging for emerging adults with type 1 diabetes and parents and is causing substantial emotional and financial stress. Future research is needed to address interventions for helping emerging adults and their parents navigate the cost of living with diabetes.

SHARE plus: Delivering a Telehealth CGM Data-Sharing Intervention to Older Adults and Their Care Partners.

Care partners of older adults with type 1 diabetes often become part of the diabetes care team but lack knowledge of how to become involved with glucose management. This article describes a study confirming the feasibility of SHARE plus, a telehealth intervention involving continuous glucose monitoring and data-sharing to assist these individuals in working together on diabetes management. The intervention provides a strategy for increasing remote patient monitoring and facilitating care partner involvement in diabetes management.

Continuous Glucose Monitoring Plus an Online Peer Support Community Reinforces Healthy Behaviors in Hispanic Adults With Type 2 Diabetes.

Background: Previous research has suggested beneficial glycemic outcomes for people with type 2 diabetes with the use of continuous glucose monitoring (CGM); yet, there is a dearth of data examining CGM in diverse populations. Additionally, the use of online peer support communities (OPSCs) can further support the application of CGM information to improve health behaviors. The purpose of this qualitative study was to assess participant experiences with a CGM+OPSC intervention. Methods: Semi-structured interviews were conducted after a 12-week combined CGM+OPSC intervention with Hispanic, Spanish-speaking people with type 2 diabetes not using insulin. The OPSC was managed by five trained bilingual peer facilitators. Interviews were conducted in Spanish. Audio recordings were translated and transcribed and then reviewed by the interviewer for accuracy. Emergent themes were identified through inductive thematic analysis. Results: Twenty-six participants completed interviews. Three main themes emerged from the data: 1) CGM supports participants' understanding of the relationship between glucose levels and health behaviors such as healthy eating, being active, taking medication, stress reduction, and improving sleep; 2) the OPSC reinforced how to make healthy choices through personal experiments, collective learning, and social support; and 3) CGM+OPSC supports behavior change and increases confidence. Conclusion: When combined, CGM+OPSC interventions appear to create a positive feedback loop to reinforce and optimize healthy behaviors for diabetes self-management in individuals with type 2 diabetes who are not on insulin. The provision of such an intervention tailored to Hispanic, Spanish-speaking individuals has the potential to address the health care disparity seen in this population.

Personal Continuous Glucose Monitoring Use Among Adults with Type 2 Diabetes: Clinical Efficacy and Economic Impacts.

PURPOSE OF REVIEW: This article reviews recent clinical efficacy research and economic analysis of the use of personal continuous glucose monitoring (CGM) in type 2 diabetes (T2D). RECENT FINDINGS: Studies from the past 5 years include a variety of randomized controlled trials, meta-analyses, and other studies which generally favor CGM over self-monitoring of blood glucose (SMBG) in T2D, especially among people with T2D treated with insulin. Concurrently, some studies show no significant difference, but there is no evidence of worse outcomes with CGM. CGM is frequently associated with greater reduction in HbA1c than is SMBG. HbA1c reductions tend to be greater when baseline HbA1c is higher. Reductions in hypoglycemia and hyperglycemia have also been demonstrated with CGM in people with T2D, as have comfort with, preference for, and psychosocial benefits of CGM compared to SMBG. There is a small but growing evidence base on the economics and cost-effectiveness of CGM in T2D. CGM has been clearly demonstrated to have clinical benefits in people with T2D, especially among those treated with insulin. Economic and cost-effectiveness data are more scant but are generally favorable. CGM should be an important consideration in the management of T2D, and its use is likely to increase as efficacy data accumulate further and as costs associated with CGM gradually decrease.

Couples Managing Type 1 Diabetes Using Diabetes Technology.

OBJECTIVE: Diabetes technology has improved the lives of people with diabetes (PWD), but there is little research on how insulin pumps and continuous glucose monitoring (CGM) affect couples' relationships. The purpose of this study was to examine how the use of diabetes technology affects couple interactions. METHODS: In a secondary data analysis, we used a multiple-method qualitative analysis, including a constant-comparison approach, to examine similarities and differences in couple interactions related to diabetes technology. PWD and their spouses were interviewed separately, using a semi-structured interview guide; the interviews primarily focused on how couples coped with type 1 diabetes. RESULTS: Participants (n = 134 couples) were using an insulin pump or CGM system. Average age was 44 ± 12.05 years for PWD and 44 ± 12.62 years for spouses. Couples' average length of relationship was 18 ± 12.50 years. Among the PWD, 54 used a pump only, 12 used CGM only, and 68 used both. Four main themes emerged: 1) diabetes technology facilitates shared diabetes management for couples, 2) diabetes technology facilitates spousal involvement in diabetes care, 3) diabetes technology is a source of relationship tension, and 4) diabetes technology causes positive/negative responses to sleep and alarms. CONCLUSION: Overall, couples perceived diabetes technology as having a positive effect on their relationship by increasing collaboration, promoting communication, and reducing diabetes burden and vigilance. Technology also was perceived to increase relationship tension, lifestyle inconveniences, and positive/negative responses regarding sleep and alarms. Involvement of spouses in diabetes technology education should be considered.

Exploring the Impact of Dementia in Samoan Culture: A Qualitative Study on Community Perspective.

Purpose: Explore if and how American Samoan cultural norms influence caregivers' knowledge, attitudes, and care choices for person's living with Alzheimer's Dementia (AD).Design: This pilot study used mixed methods.Methods: 1) Quantitative survey: measuring knowledge/attitudes towards AD (n = 80); 2) Qualitative techniques: a) Focus groups (n= 54) with caregivers; b) Semi-structured interviews (n=26) with health professionals; and c) In-depth interviews (n=3) with key informants. Emergent themes were created using data from all methods.Findings: Quantitative analyses revealed 50% of participants identified AD as normal aging, 83% as mental illness. The majority of participants believed elders with AD do not experience pain (70%) and should be cared for solely at home (74%). Qualitative evidence showed dissonance between cultural norms of respect for elders, familial caregiving duty, shame in others observing elders' dementia-related behaviours, and the current language used to describe AD.Conclusions: Our findings show a need for developing and disseminating culturally sensitive terminology for AD to destigmatize and transmute attitudes, knowledge and care choices for elders living with AD.Clinical Evidence: American Samoan terminology for dementia is discordant with its cultural norms, thus shaping caregivers' perceptions of AD and influencing care choices for managing AD symptoms.

The Role of Self-regulation Failures and Self-care in the Link Between Daily Sleep Quality and Blood Glucose Among Adults with Type 1 Diabetes.

BACKGROUND: Sleep, a process that restores the body's ability to self-regulate, may be one important factor affecting self-care behaviors and blood glucose (BG) levels. The link between sleep quality, self-care behaviors, and BG levels may occur by sleep-altering daily self-regulatory failures. PURPOSE: This study examined whether the relation between sleep quality and self-care behaviors occurred through self-regulation failures and whether the relation between sleep quality and BG levels occurred through self-regulation failures and self-care behaviors sequentially. METHODS: One hundred and ninety-nine adults with type 1 diabetes (T1D) completed an online questionnaire for 14 days in which they reported sleep quality, self-regulation failures, and self-care behaviors. BG levels were gathered from glucometers. Analyses involved multilevel mediation models and focused on daily within-person and between-person variability of sleep quality. RESULTS: Better daily sleep quality was associated with higher self-care behaviors at both within-person and between-person levels, and self-regulation failures mediated the association between daily sleep quality and daily self-care behaviors at both within-person and between-person levels. Better daily sleep quality was associated with better BG levels at the within-person level and self-regulation behaviors and self-care behaviors sequentially mediated the association between daily sleep quality and daily BG levels at the within-person level. CONCLUSION: This study provides a process account of the importance of daily sleep quality of adults with T1D, as well as one potential mechanism-self-regulation-that may explain the effect of sleep quality on diabetes outcomes.

The benefits of daily exercise on blood glucose levels and affect among adults with type 1 diabetes.

The purpose of this study was to investigate the concurrent and lagged effects of daily exercise on daily blood glucose level and affect among persons with type 1 diabetes (T1D). 199 persons with T1D (Mage = 46.82) completed a 14-day diary in which they reported on their engagement in moderate to vigorous exercise for 30 min and positive and negative affect. Daily blood glucose (BG) was gathered through study-provided glucometers. Multilevel modeling examined the effects of daily variability in (within-person effects) and average levels of (between-person effects) daily exercise on BG and affect. On days when persons with T1D reported they exercised moderately to vigorously for 30 min, they had lower mean BG, higher risk for low BG, lower negative affect, and higher positive affect on the same day as well as lower mean BG on the following day. Engaging in daily exercise is important in managing daily blood glucose and affect among persons with T1D, but can be complicated by hypoglycemia.

Yours, Mine, and Ours: A Qualitative Analysis of the Impact of Type 1 Diabetes Management in Older Adult Married Couples.

OBJECTIVE: The purpose of this study was to understand perceptions of diabetes management responsibilities and the impact of diabetes on day-to-day activities in older adulthood for individuals with type 1 diabetes and their spouses. DESIGN AND METHODS: This qualitative content analysis used a constant-compare approach to analyze individual interviews conducted with older adults and their spouses. People with type 1 diabetes (PWD) and their spouses were interviewed regarding how they coped or dealt with diabetes, what activities they carried out or avoided because of diabetes, and how they appraised diabetes as an individual or shared problem. RESULTS: Participants (n = 52) included 26 older adults with diabetes (mean age 69 years, SD 2.56 years; 38.5% female) and their spouses (mean age 68 years, SD 5.11 years; 61.5% female). Half of the PWD (50%) and the majority of spouses (76.9%) appraised diabetes as a shared issue. Five themes emerged from the interview data: 1) Perceptions pf PWD of spouse involvement in diabetes care, 2) PWD underestimated the impact of diabetes on their spouse's daily lives, 3) gendered nature of spouses supporting diabetes management, 4) evolution of diabetes and the relationship across developmental time, and 5) differences in diabetes management among couples. CONCLUSION: Older adults with type 1 diabetes and their spouses have different perspectives regarding diabetes support and responsibility and may not always realize what support is being provided or needed to optimize effective diabetes management. Advancing age with or without diabetes complications may necessitate that spouses provide diabetes support. Diabetes management training for spouses would likely be helpful.

Experience With a Care Process Model in the Evaluation of Pediatric Musculoskeletal Infections in a Pediatric Emergency Department.

OBJECTIVES: Care process models (CPMs) for certain conditions have improved clinical outcomes in children. This study describes the implementation and impact of a CPM for the evaluation of musculoskeletal infections in a pediatric emergency department (ED). METHODS: A retrospective pre-post intervention study was performed to analyze the impact of a musculoskeletal infection CPM. Patients were identified retrospectively through electronic order history for imaging of an extremity or joint and recommended laboratory tests. Clinical outcomes evaluated included hospital length of stay (LOS), time to magnetic resonance imaging (MRI), time to administration of antibiotics, hospital admission rate, and 30-day readmission rate. RESULTS: Musculoskeletal infection evaluations completed in the ED were reviewed from 1 year before implementation (n = 383) and 2 years after implementation (n = 1219) of the CPM. A significant improvement in the time to antibiotic administration for all patients (4.3 vs 3.7 hours, P < 0.05) and for patients with confirmed musculoskeletal infections (9.5 vs 4.9 hours, P < 0.05) was observed after the implementation of the CPM. The overall time to MRI (13.2 vs 10.3 hours, P = 0.29) and hospital LOS (4.7 vs 3.7 days, P = 0.11) were improved for all patients but were not statistically significant. The admission rate and 30-day readmission were similar before and after the implementation of the CPM. CONCLUSIONS: The implementation of a musculoskeletal infection CPM has standardized the approach to the evaluation and diagnosis of musculoskeletal infections resulting in a significant decrease in the time to administer antibiotics and a downward trend in time to MRI and hospital LOS.

Transplantation of hepatitis C virus (HCV) antibody positive, nucleic acid test negative donor kidneys to HCV negative patients frequently results in seroconversion but not HCV viremia.

Anecdotal reports have suggested that transplantation of hepatitis C virus (HCV) antibody positive (Ab+)/nucleic acid test negative (NAT-) donor kidneys into HCV negative recipients is not associated with HCV transmission. We reviewed our center's outcomes of 32 HCV negative patients who received kidney allografts from 25 donors who were HCV Ab+/NAT-. The mean recipient age was 56.9 ± 12.1 years and the mean donor age was 41.5 ± 14 years, with a median Kidney Donor Profile Index (KDPI) of 68%. Twelve donors (48%) met Public Health Service (PHS) increased risk status. All patients received antithymocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and steroid maintenance immunosuppression. With a mean follow-up posttransplant of 10 ± 2.7 months, 1- and 3- month serum creatinine levels were 1.7 ± 0.8 and 1.3 ± 0.4, respectively, and patient and graft survival rates were 100% and 97%, respectively. Fourteen patients (44%) seroconverted and became HCV Ab+ posttransplant. However, all 32 patients were HCV RNA negative at 1- and 3- months posttransplant, and 27 and 8 patients tested at 6- and 12-months posttransplant, respectively, remain HCV RNA negative. In conclusion, transplantation of HCV Ab+/NAT- kidneys to HCV negative recipients frequently causes HCV Ab seroconversion but not HCV viremia.

Patterns and severity of vascular amyloid in Alzheimer's disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer's disease.

In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vascular disease, we additionally aimed to explore the role of APOE genotype in CAA severity and subtypes. Plaque formation was greater in DS and missense APP mutations than in APPdup, sEOAD and sLOAD cases. Conversely, CAA was more severe in APPdup and missense APP mutations, and in DS, compared to sEOAD and sLOAD. When stratified by CAA subtype from 1 to 4, there were no differences in plaque scores between the groups, though in patients with APPdup, APP mutations and sEOAD, types 2 and 3 CAA were more common than type 1. Conversely, in DS, sLOAD and controls, type 1 CAA was more common than types 2 and 3. APOE ε4 allele frequency was greater in sEOAD and sLOAD compared to APPdup, missense APP mutations, DS and controls, and varied between each of the CAA phenotypes with APOE ε4 homozygosity being more commonly associated with type 3 CAA than types 1 and 2 CAA in sLOAD and sEOAD. The differing patterns in CAA within individuals of each group could be a reflection of variations in the efficiency of perivascular drainage, this being less effective in types 2 and 3 CAA leading to a greater burden of CAA in parenchymal arteries and capillaries. Alternatively, as suggested by immunostaining using carboxy-terminal specific antibodies, it may relate to the relative tissue burdens of the two major forms of Aß, with higher levels of Aß40 promoting a more 'aggressive' form of CAA, and higher levels of Aß42(3) favouring a greater plaque burden. Possession of APOE ε4 allele, especially ε4 homozygosity, favours development of CAA generally, and as type 3 particularly, in sEOAD and sLOAD.

Effect of an Asthma Guideline in 2 Pediatric Emergency Departments and an Urgent Care Center.

OBJECTIVES: The objective of this study was to evaluate ordering of albuterol via metered-dose inhaler with spacer (MDI-spacer), length of stay (LOS), and 72-hour return rates before and after publication of an internally developed pediatric asthma clinical practice guideline (CPG). METHODS: The internally developed CPG reflected national recommendations. It was explained at faculty meetings by a respected clinician and published on the intranet on February 6, 2012. We performed a retrospective study of visits from January 1, 2009, to October 31, 2014, by children aged 2 to 17 years with a primary diagnosis of asthma and discharged from a target site (2 pediatric emergency departments and 1 urgent care center). We excluded critical/emergent visits and those by patients who transferred to the emergency department/urgent care center from another facility or were admitted. We extracted data for 37 months before and 33 months after CPG implementation (post-CPG) using a single electronic health record system. RESULTS: Albuterol delivery via MDI-spacer increased by 33.95% (P < 0.0001) during 1-month post-CPG implementation with no significant subsequent decrease. An unexpected decline was noted for median LOS before CPG implementation (-1.24 minutes; P < 0.0001). For MDI-spacer-treated patients post-CPG, decreased median LOS was maintained and there was decreased variability of the median LOS (P < 0.001). For nebulizer-treated patients post-CPG, median LOS increased (.95 minutes; P = 0.033). No change was observed for 72-hour return rates. CONCLUSIONS: Implementation of an asthma CPG increased ordering of albuterol via MDI-spacer. The increase was sustained over time in all study sites. Decreased variability in median LOS for MDI-spacer patients was observed post-CPG. Median LOS for those treated with MDI-spacer exclusively remained unchanged in the post-CPG period, whereas post-CPG LOS increased in those who received nebulized albuterol.