A nationwide study of breast reconstruction after mastectomy in patients with breast cancer receiving postmastectomy radiotherapy: comparison of complications according to radiotherapy fractionation and reconstruction procedures.

BACKGROUND: We examined the patterns of breast reconstruction postmastectomy in breast cancer patients undergoing postmastectomy radiotherapy (PMRT) and compared complications based on radiotherapy fractionation and reconstruction procedures. METHODS: Using National Health Insurance Service (NHIS) data (2015-2020), we analysed 4669 breast cancer patients with PMRT and reconstruction. Using propensity matching, cohorts for hypofractionated fractionation (HF) and conventional fractionation (CF) were created, adjusting for relevant factors and identifying grade ≥3 complications. RESULT: Of 4,669 patients, 30.6% underwent HF and 69.4% CF. The use of HF has increased from 19.4% in 2015 to 41.0% in 2020. Immediate autologous (32.9%) and delayed two-stage implant reconstruction (33.9%) were common. Complication rates for immediate (N = 1286) and delayed two-stage (N = 784) reconstruction were similar between HF and CF groups (5.1% vs. 5.4%, P = 0.803, and 10.5% vs. 10.7%, P = 0.856, respectively) with median follow-ups of 2.5 and 2.6 years. HF showed no increased risk of complications across reconstruction methods. CONCLUSION: A nationwide cohort study revealed no significant difference in complication rates between the HF and CF groups, indicating HF for reconstructed breasts is comparable to CF. However, consultation regarding the fractionation for reconstructed breast cancer patients may still be necessary.

Comparing Rates of Undiagnosed Hypertension and Diabetes in Patients With and Without Substance Use Disorders.

BACKGROUND: Individuals with substance use disorders (SUDs) have increased risk for developing chronic conditions, though few studies assess rates of diagnosis of these conditions among patients with SUDs. OBJECTIVE: To compare rates of undiagnosed hypertension and diabetes among patients with and without an SUD. DESIGN: Cross-sectional analysis using electronic health record (EHR) data from 58 primary care clinics at a large, urban, healthcare system in New York. PARTICIPANTS: Patients who had at least two primary care visits from 2019-2022 were included in our patient sample. Patients without an ICD-10 hypertension diagnosis or prescribed hypertension medications and with at least two blood pressure (BP) readings ≥ 140/90 mm were labeled 'undiagnosed hypertension,' and patients without a diabetes diagnosis or prescribed diabetes medications and with A1C/hemoglobin ≥ 6.5% were labeled 'undiagnosed diabetes.' MAIN MEASURES: We calculated the mean number of patients with and without an ICD-10 SUD diagnosis who were diagnosed and undiagnosed for each condition. We used multivariate logistic regression to assess the association between being undiagnosed for each condition, and having an SUD diagnosis, patient demographic characteristics, clinical characteristics (body mass index, Elixhauser comorbidity count, diagnosed HIV and psychosis), the percentage of visits without a BP screening, and the total number of visits during the time period. KEY RESULTS: The percentage of patients with undiagnosed hypertension (2.74%) and diabetes (22.98%) was higher amongst patients with SUD than patients without SUD. In multivariate models, controlling for other factors, patients with SUD had significantly higher odds of having undiagnosed hypertension (OR: 1.81; 95% CI: 1.48, 2.20) and undiagnosed diabetes (OR: 1.93; 1.72, 2.16). Being younger, female, and having an HIV diagnosis was also associated with significantly higher odds for being undiagnosed. CONCLUSIONS: We found significant disparities in rates of undiagnosed chronic diseases among patients with SUDs, compared with patients without SUDs.

Barriers and Facilitators to Establishing Partnerships for Substance Use Disorder Care Transitions Between Safety-Net Hospitals and Community-Based Organizations.

BACKGROUND: The effectiveness of hospital-based transitional opioid programs (TOPs), which aim to connect patients with substance use disorders (SUD) to ongoing treatment in the community following initiation of medication for opioid use disorder (MOUD) treatment in the hospital, hinges on successful patient transitions. These transitions are enabled by strong partnerships between hospitals and community-based organizations (CBOs). However, no prior study has specifically examined barriers and facilitators to establishing SUD care transition partnerships between hospitals and CBOs. OBJECTIVE: To identify barriers and facilitators to developing partnerships between hospitals and CBOs to facilitate care transitions for patients with SUDs. DESIGN: Qualitative study using semi structured interviews conducted between November 2022-August 2023. PARTICIPANTS: Staff and providers from hospitals affiliated with four safety-net health systems (n=21), and leaders and staff from the CBOs with which they had established partnerships (n=5). APPROACH: Interview questions focused on barriers and facilitators to implementing TOPs, developing partnerships with CBOs, and successfully transitioning SUD patients from hospital settings to CBOs. KEY RESULTS: We identified four key barriers to establishing transition partnerships: policy and philosophical differences between organizations, ineffective communication, limited trust, and a lack of connectivity between data systems. We also identified three facilitators to partnership development: strategies focused on building partnership quality, strategic staffing, and organizing partnership processes. CONCLUSIONS: Our findings demonstrate that while multiple barriers to developing hospital-CBO partnerships exist, stakeholders can adopt implementation strategies that mitigate these challenges such as using mediators, cross-hiring, and focusing on mutually beneficial services, even within resource-limited safety-net settings. Policymakers and health system leaders who wish to optimize TOPs in their facilities should focus on adopting implementation strategies to support transition partnerships such as inadequate data collection and sharing systems.

A molecular beacon design for a colorimetric loop-mediated isothermal amplification assay.

In this study, a molecular beacon (MB) was designed for colorimetric loop-mediated isothermal amplification (cLAMP). The length of complementary bases on the MB, guanine and cytosine content (GC content), and hybridization sites of complementary bases were investigated as key factors affecting the design of the MB. We designed MBs consisting of 10, 15, and 20 complementary bases located at both ends of the HRPzyme. In the case of the long dumbbell DNA structure amplified from the hlyA gene of Listeria monocytogenes, possessing a flat region (F1c-B1) of 61 base pairs (bp), an MB was designed to intercalate into the flat region between the F1c and B1 regions of the LAMP amplicons. In the case of the short dumbbell DNA structure amplified from the bcfD gene of Salmonella species possessing a flat region (F1c-B1) length of 6 bp, another MB was designed to intercalate into the LoopF or LoopB regions of the LAMP amplicons. The results revealed that the hybridization site of the MB on the LAMP amplicons was not crucial in designing the MB, but the GC content was an important factor. The highest hybridization efficiencies for LAMP amplicons were obtained from hlyA gene-specific and bcfD gene-specific MBs containing 20- and 15-base complementary sequences, respectively, which exhibited the highest GC content. Therefore, designing MBs with a high GC content is an effective solution to overcome the low hybridization efficiency of cLAMP assays. The results obtained can be used as primary data for designing MBs to improve cLAMP accessibility.

Impact of age at diagnosis on long-term prognosis in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: Although age at disease onset is considered to be a significant factor in the prognosis of Crohn's disease, little is known about its influence on the long-term prognosis of those with intestinal Behçet's disease (BD). This study aimed to evaluate the long-term clinical outcomes of patients with intestinal BD according to age of disease onset. METHODS: Patients diagnosed with intestinal BD at < 18, 18-60, and > 60 years of age were classified into early-onset, adult-onset, and late-onset groups, respectively. The influence of disease onset time on clinical prognosis, including specific medical requirements, BD-related intestinal surgery, hospitalization, and emergency room visits, was compared using the log-rank test in a large cohort of patients with intestinal BD. RESULTS: Among 780 patients, 21 (2.7%), 672 (86.2%), and 87 (11.1%) comprised the early-onset, adult-onset, and late-onset groups, respectively. Patients in the early-onset group were more likely to require immunosuppressants than those in the adult-onset group (P = 0.048). Nine (42.9%), 158 (23.5%), and 18 (20.7%) patients in the early-onset, adult-onset, and late-onset groups, respectively, underwent intestinal resection. The early-onset group exhibited a higher risk for intestinal resection than the late-onset (P = 0.043) and adult-onset (P = 0.030) groups. The late-onset group exhibited a higher risk for BD-related hospitalization than the adult-onset group (P = 0.023). CONCLUSIONS: Age at diagnosis affected the clinical course of intestinal BD, including intestinal surgery, hospitalization, and specific medical requirements. Different treatment strategies should be established according to age at diagnosis.

Zonisamide attenuates pressure overload-induced myocardial hypertrophy in mice through proteasome inhibition.

Myocardial hypertrophy is a pathological thickening of the myocardium which ultimately results in heart failure. We previously reported that zonisamide, an antiepileptic drug, attenuated pressure overload-caused myocardial hypertrophy and diabetic cardiomyopathy in murine models. In addition, we have found that the inhibition of proteasome activates glycogen synthesis kinase 3 (GSK-3) thus alleviates myocardial hypertrophy, which is an important anti-hypertrophic strategy. In this study, we investigated whether zonisamide prevented pressure overload-caused myocardial hypertrophy through suppressing proteasome. Pressure overload-caused myocardial hypertrophy was induced in mice by trans-aortic constriction (TAC) surgery. Two days after the surgery, the mice were administered zonisamide (10, 20, 40 mg·kg-1·d-1, i.g.) for four weeks. We showed that zonisamide administration significantly mitigated impaired cardiac function. Furthermore, zonisamide administration significantly inhibited proteasome activity as well as the expression levels of proteasome subunit beta types (PSMB) of the 20 S proteasome (PSMB1, PSMB2 and PSMB5) and proteasome-regulated particles (RPT) of the 19 S proteasome (RPT1, RPT4) in heart tissues of TAC mice. In primary neonatal rat cardiomyocytes (NRCMs), zonisamide (0.3 µM) prevented myocardial hypertrophy triggered by angiotensin II (Ang II), and significantly inhibited proteasome activity, proteasome subunits and proteasome-regulated particles. In Ang II-treated NRCMs, we found that 18α-glycyrrhetinic acid (18α-GA, 2 mg/ml), a proteasome inducer, eliminated the protective effects of zonisamide against myocardial hypertrophy and proteasome. Moreover, zonisamide treatment activated GSK-3 through inhibiting the phosphorylated AKT (protein kinase B, PKB) and phosphorylated liver kinase B1/AMP-activated protein kinase (LKB1/AMPKα), the upstream of GSK-3. Zonisamide treatment also inhibited GSK-3's downstream signaling proteins, including extracellular signal-regulated kinase (ERK) and GATA binding protein 4 (GATA4), both being the hypertrophic factors. Collectively, this study highlights the potential of zonisamide as a new therapeutic agent for myocardial hypertrophy, as it shows potent anti-hypertrophic potential through the suppression of proteasome.

Clinical characteristics and salivary biomarkers of burning mouth syndrome.

OBJECTIVES: To investigate the clinical characteristics and salivary biomarkers in each type of burning mouth syndrome (BMS) patients. MATERIALS AND METHODS: Ninety-eight postmenopausal female patients with BMS were included. Fifty and 21 patients were assigned to the primary and secondary groups, respectively. Twenty-seven patients with both primary and secondary characteristics were assigned to the intermediate group. Comprehensive clinical characteristics and salivary biomarkers were analyzed. RESULTS: Significant differences in age, proportion of hyposalivator patients based on unstimulated whole saliva (UWS), symptom distribution, severties of burning sensation and effect of oral complaints in daily life (Eff-life), and positive symptom distress index (PSDI) were observed among the three groups. The primary group had significant higher UWS flow rate, fewer UWS hyposalivator proportions, and lesser severity of Eff-life than the secondary group. The intermediate group had significantly greater intensities of burning sensation and Eff-life and higher PSDI score than did the primary group. The primary group had significantly higher cortisol and dehydroepiandrosterone (DHEA) levels in stimulated whole saliva than did the secondary group. CONCLUSIONS: This study's findings show that clinical characteristics differentiate each BMS type. Cortisol and DHEA levels are potential salivary biomarkers for discriminating between the primary and secondary types of BMS.

Trends in the availability of comprehensive services within outpatient substance use treatment facilities from 2018 to 2022.

Background: Little is known regarding the extent to which substance use disorder (SUD) treatment facilities adopt comprehensive services to meet patients' medical and social needs.Objective: To examine trends in the availability of comprehensive services within outpatient SUD treatment facilities from 2018 to 2022.Methods: We used data from the Mental Health and Addiction Treatment Tracking Repository, a national database of SUD treatment facilities (n = 13,793). We examined the availability of four domains of comprehensive services and four types of SUD treatment services from 2018 to 2022. We conducted bivariate and multivariate logistic regression predicting the availability of a comprehensive service model (defined as having at least one service from each service domain), controlling for organizational and community characteristics.Results: Comprehensive services were increasingly offered from 2018 to 2022. In unadjusted and adjusted models, facilities which were externally accredited (OR: 1.50; 95%CI: 1.30-1.74), accepted Medicaid (OR: 1.51; 95%CI: 1.30-1.74), performed community outreach (OR: 2.05; 95%CI: 1.80-2.33), provided naloxone and overdose education (OR: 3.50; 95%CI: 3.06-3.99), had a robust SUD treatment infrastructure (OR: 2.33; 95%CI; 2.08-2.62), and were located in a county with a lower percentage of White residents (OR: 0.99; 95%CI: 0.99-0.99), a higher percentage of residents in poverty (OR: 1.02; 95%CI: 1.00-1.03), and the Northeast compared with the South (OR: 1.21; 95%CI: 1.01-1.45), had significantly higher odds of adopting a comprehensive service model.Conclusion: Findings highlight the importance of factors reflecting experience with organizational change efforts and enhanced external support. Policymakers working to enhance the uptake of comprehensive services should focus on obtaining the financial and technical support necessary to develop these models.

A Year After Implementation of the Telehealth Waiver: Being Offered and Utilizing Video-Specific Telehealth Among Dual-Eligible Medicare Recipients During the COVID-19 Pandemic.

OBJECTIVE: Telehealth is an essential tool to provide access to care while reducing infection exposure for high-risk populations during the COVID-19 pandemic. Our study aims to examine factors associated with telehealth availability and usage among Medicare and dual-eligible recipients 1 year after implementation of the Medicare's temporary telehealth waiver. DESIGN, SETTING, AND PARTICIPANT: A cross-sectional, phone survey with a national representative sample of Medicare recipients. We obtained a final study sample from the Winter 2021 COVID-19 Supplement of Medicare Current Beneficiary Survey dataset (N = 10 586). We examined associations for being offered and having had telehealth visits or any video telehealth visits during the pandemic since November 1, 2020. MAIN OUTCOME MEASURES: Our primary outcomes were being offered any telehealth, being offered any video telehealth, having had any telehealth visit, and having had any video telehealth. RESULTS: Although dual eligibility was not significantly associated with being offered or having had any telehealth services during the pandemic, those who were dual eligible were more likely to have had video telehealth visits (adjusted odds ratio = 1.39, 95% confidence interval 1.04-1.86, P = .03) compared with those with non-dual eligibility. Recipients with disability eligibility, technology access, and severe chronic conditions were more likely to have been offered or have had telehealth. At the same time, those who lived in the nonmetropolitan area were less likely to have been offered or have had telehealth, including video telehealth. CONCLUSIONS: Our findings suggest that the federal waivers to expand telehealth services were successful in continuing care for vulnerable Medicare recipients. The providers' specific outreach and intervention efforts to offer telehealth visits are crucial for dual-eligible recipients. To increase video telehealth uptake, technology access and services to rural areas should be prioritized.

Examining the Relationship Between Local Governmental Expenditures on the Social Determinants of Health and County-Level Overdose Deaths, 2017-2020.

CONTEXT: Prior studies have examined the social determinants of health (SDOH) characteristics of counties with elevated rates of overdose deaths. However, this research often ignores variation in upstream governmental investment in these SDOH categories. OBJECTIVE: To examine the association of local governmental investments in SDOH with drug overdose mortality at the county level, controlling for demographic and socioeconomic characteristics. DESIGN: Longitudinal analysis from 2017 to 2020. SETTING: United States counties. PARTICIPANTS: 3126 counties. MAIN OUTCOME AND MEASURES: The primary study outcome was county overdose death rates per 100 000 population taken from the Centers for Disease Control and Prevention. The main predictor of interest was the per capita average of local governmental expenditures in public health, social service, and education drawn from the U.S. Census of Governments, categorized into quartiles. Covariates included county-level socioeconomic and demographic characteristics as well as county-level SUD services from the AHRQ SDOH Database. RESULTS: In longitudinal multivariate linear regression models with state and year fixed effects, counties in the highest 3 quartiles of SDOH spending had significantly lower rates of overdose deaths compared with counties in the lowest quartile of SDOH spending; in particular, counties in quartile 2 had an average of 9.09 fewer overdose deaths per 100 000 population (95% CI: -12.58, -5.60), counties in quartile 3 had an average of 13.18 fewer deaths per 100 000 population (95% CI: -17.56; -8.80), and counties in quartile 4 had an average of 13.92 deaths per 100 000 population (95% CI: -19.16, -8.68). CONCLUSIONS: Our findings demonstrate that higher levels of local governmental investments in SDOH were associated with significantly lower rates of overdose death in U.S. counties after controlling for socioeconomic and demographic characteristics. Going forward, research should focus on determining causality in this relationship, the mechanisms through which this relationship occurs, as well as assess the impact of local public health expenditures allocated toward SUD prevention and treatment specifically on substance use outcomes at the local level.

The In Vitro and In Vivo Anticancer Effect of Photomed for Photodynamic Therapy: Comparison with Photofrin and Radachlorin.

To overcome the limitation of conventional cancer treatments, photodynamic therapy (PDT) has been introduced as another treatment option. PDT provides a non-invasive, non-surgical way with reduced toxicity. To improve the antitumor efficacy of PDT, we synthesized a novel photosensitizer, a 3-substituted methyl pyropheophorbide-a derivative (Photomed). The purpose of the study was to evaluate the antitumor effect of PDT with Photomed comparing with the clinically approved photosensitizers Photofrin and Radachlorin. The cytotoxicity assay against SCC VII cells (murine squamous cell carcinoma) was performed to determine whether Photomed is safe without PDT and whether Photomed is effective against cancer cells with PDT. An in vivo anticancer efficacy study was also performed using SCC VII tumor-bearing mice. The mice were divided into small-tumor and large-tumor groups to identify whether Photomed-induced PDT is effective for not only small tumors but also large tumors. From in vitro and in vivo studies, Photomed was confirmed to be (1) a safe photosensitizer without laser irradiation, (2) the most effective photosensitizer with PDT against cancers compared to Photofrin and Radachlorin and (3) effective with PDT in treating not only small tumors but also large tumors. In conclusion, Photomed may contribute as a novel, potential photosensitizer for use in PDT cancer treatment.

A Survey of Practice Patterns for Clinical Nodal Staging Prior to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The importance of clinical staging in breast cancer has increased owing to the wide use of neoadjuvant systemic therapy (NST). This study aimed to investigate the current practice patterns regarding clinical nodal staging in breast cancer in real-world settings. MATERIALS AND METHODS: A web-based survey was administered to board-certified oncologists in Korea, including breast surgical, medical, and radiation oncologists, from January to April 2022. The survey included 19 general questions and 4 case-based questions. RESULTS: In total, 122 oncologists (45 radiation, 44 surgical, and 33 medical oncologists) completed the survey. Among them, 108 (88%) responded that clinical staging before NST was primarily performed by breast surgeons. All the respondents referred to imaging studies during nodal staging. Overall, 64 (52.5%) responders determined the stage strictly based on the radiology reports, whereas 58 (47.5%) made their own decision while noting radiology reports. Of those who made their own decisions, 88% referred to the number or size of the suspicious node. Of the 75 respondents involved in prescribing regimens for neoadjuvant chemotherapy, 58 (77.3%) responded that the reimbursement regulations in the selection of NST regimens affected nodal staging in clinical practice. In the case-based questions, high variability was observed among the clinicians in the same cases. CONCLUSIONS: Diverse assessments by specialists owing to the lack of a clear, harmonized staging system for the clinical nodal staging of breast cancer can lead to diverse practice patterns. Thus, practical, harmonized, and objective methods for clinical nodal staging and for the outcomes of post-NST response are warranted for appropriate treatment decisions and accurate outcome evaluation.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Exploring Barriers and Facilitators to Integrating a Harm Reduction Approach to Substance Use in Three Medical Settings.

BACKGROUND: Evidence suggests that harm reduction, a public health strategy aimed at reducing the negative consequences of a risky health behavior without requiring elimination of the behavior itself, may be a promising approach for minimizing drug-related harms while engaging individuals with substance use disorders (SUDs) in care. However, philosophical clashes between the medical and harm reduction models may pose barriers to adopting harm reduction approaches within medical settings. OBJECTIVE: To identify barriers and facilitators to implementing a harm reduction approach toward care within healthcare settings. We conducted semi-structured interviews with providers and staff at three integrated harm reduction and medical care sites in New York. DESIGN: Qualitative study using in-depth and semi-structured interviews. PARTICIPANTS: Twenty staff and providers across three integrated harm reduction and medical care sites across New York state. APPROACH: Interview questions focused on how harm reduction approaches were implemented and demonstrated in practice and barriers and facilitators to implementation, as well as questions based on the five domains of the Consolidated Framework for Implementation Research (CFIR). KEY RESULTS: We identified three key barriers to the adoption of the harm reduction approach that surrounded resource constraints, provider burnout, and interacting with external providers that do not have a harm reduction orientation. We also identified three facilitators to implementation, which included ongoing training both within and external to the clinic, team-based and interdisciplinary care, and affiliations with a larger healthcare system. CONCLUSIONS: This study demonstrated that while multiple barriers to implementing harm reduction informed medical care existed, health system leaders can adopt practices to mitigate barriers to adoption, such as value-based reimbursement models and holistic models of care that address the full spectrum of patient needs.

Electrochemiluminescent determination of sphingomyelin in milk based on polyaniline hydrogel coupled with enzyme-functionalized Au nanoparticles.

In this paper, sphingomyelin (SM) is detected by a polyaniline hydrogel and Au nanoparticles with enzyme modified electrode (GCE/PAniH/AuNPs@enzyme). After a battery of enzymic degradation, SM can generate H2O2 and enhance the electrochemiluminescence (ECL) response of luminol, which endows the sensor with good sensitivity, specifiity and repeatability. Additionally, the proposed ECL biosensor displays good analytical performances with a wide range from 10.0 µg·mL-1 to 250.0 µg·mL-1 as well as a low detection limit of 3.50 µg·mL-1 (S/N = 3). When the ECL biosensor is used in the detection of SM in milk samples, satisfactory results are obtained, indicating that PAniH/AuNPs@enzyme will serve as a promising ECL material in the applications of H2O2-related bioassay in the future.

APP96-110 Elicits Neuroprotective Effects Following Ischemic Insult in Animal Models.

Competitive amyloidogenic pathways play an important role in many neurological diseases such as the onset of various degenerative diseases and ischemic stroke. Overexpression of amyloid precursor protein (APP) and amyloid-beta is modulated via the amyloidogenic pathway, which plays a crucial role in neuroinflammation. During ischemic conditions, the activity of the anti-inflammatory non-amyloidogenic pathway decreases, thus increasing the activity of amyloidogenic pathway. The soluble alpha form of APP (sAPPα), formed via the non-amyloidogenic pathway, exhibits neuroprotective effects against neurological diseases. sAPPα is thought to have a modulatory effect on several cell survival pathways, including its ability to inhibit the phosphoinositide 3-kinases (PI3K) pathway, thereby inhibiting the inflammatory response. The APP derivative, APP96-110, could act as a functional substitute for native sAPPα. Herein, we investigated whether APP96-110 has neuroprotective effects against neuroinflammation and damage following cerebral ischemic stroke. Treatment with diluted APP96-110 (0.005 mg/kg) in mice after 30 min of transient middle cerebral artery occlusion (tMCAO) showed improved motor function and reduced expression of the inflammatory marker CD86. APP96-110 decreased the infarct size and induced an anti-inflammatory response by inhibiting the PI3K pathway. These results suggest that the treatment of APP96-110 is efficacious in reducing neuroinflammation and infarct size in ischemic stroke.

An observational, sequential analysis of the relationship between local economic distress and inequities in health outcomes, clinical care, health behaviors, and social determinants of health.

BACKGROUND: Socioeconomic status has long been associated with population health and health outcomes. While ameliorating social determinants of health may improve health, identifying and targeting areas where feasible interventions are most needed would help improve health equity. We sought to identify inequities in health and social determinants of health (SDOH) associated with local economic distress at the county-level. METHODS: For 3,131 counties in the 50 US states and Washington, DC (wherein approximately 325,711,203 people lived in 2019), we conducted a retrospective analysis of county-level data collected from County Health Rankings in two periods (centering around 2015 and 2019). We used ANOVA to compare thirty-three measures across five health and SDOH domains (Health Outcomes, Clinical Care, Health Behaviors, Physical Environment, and Social and Economic Factors) that were available in both periods, changes in measures between periods, and ratios of measures for the least to most prosperous counties across county-level prosperity quintiles, based on the Economic Innovation Group's 2015-2019 Distressed Community Index Scores. RESULTS: With seven exceptions, in both periods, we found a worsening of values with each progression from more to less prosperous counties, with least prosperous counties having the worst values (ANOVA p < 0.001 for all measures). Between 2015 and 2019, all except six measures progressively worsened when comparing higher to lower prosperity quintiles, and gaps between the least and most prosperous counties generally widened. CONCLUSIONS: In the late 2010s, the least prosperous US counties overwhelmingly had worse values in measures of Health Outcomes, Clinical Care, Health Behaviors, the Physical Environment, and Social and Economic Factors than more prosperous counties. Between 2015 and 2019, for most measures, inequities between the least and most prosperous counties widened. Our findings suggest that local economic prosperity may serve as a proxy for health and SDOH status of the community. Policymakers and leaders in public and private sectors might use long-term, targeted economic stimuli in low prosperity counties to generate local, community health benefits for vulnerable populations. Doing so could sustainably improve health; not doing so will continue to generate poor health outcomes and ever-widening economic disparities.

Association of Medicaid expansion and 1115 waivers for substance use disorders with hospital provision of opioid use disorder services: a cross sectional study.

INTRODUCTION: Opioid-related hospitalizations have risen dramatically, placing hospitals at the frontlines of the opioid epidemic. Medicaid expansion and 1115 waivers for substance use disorders (SUDs) are two key policies aimed at expanding access to care, including opioid use disorder (OUD) services. Yet, little is known about the relationship between these policies and the availability of hospital based OUD programs. The aim of this study is to determine whether state Medicaid expansion and adoption of 1115 waivers for SUDs are associated with hospital provision of OUD programs. METHODS: We conducted a cross-sectional study of a random sample of hospitals (n = 457) from the American Hospital Association's 2015 American Hospital Directory, compiled with the most recent publicly available community health needs assessment (2015-2018). RESULTS: Controlling for hospital characteristics, overdose burden, and socio-demographic characteristics, both Medicaid policies were associated with hospital adoption of several OUD programs. Hospitals in Medicaid expansion states had significantly higher odds of implementing any program related to SUDs (OR: 1.740; 95% CI: 1.032-2.934) as well as some specific activities such as programs for OUD treatment (OR: 1.955; 95% CI: 1.245-3.070) and efforts to address social determinants of health (OR: 6.787; 95% CI: 1.308-35.20). State 1115 waivers for SUDs were not significantly associated with any hospital-based SUD activities. CONCLUSIONS: Medicaid expansion was associated with several hospital programs for addressing OUD. The differential availability of hospital-based OUD programs may indicate an added layer of disadvantage for low-income patients with SUD living in non-expansion states.

Facilitation of team-based care to improve HTN management and outcomes: a protocol for a randomized stepped wedge trial.

BACKGROUND: There are well-established guidelines for treating hypertension (HTN), yet only half of patients with HTN meet the defined target of < 140/90. Team-based care (TBC) is an evidence-based strategy for improving blood pressure (BP) management and control. TBC is defined as the provision of health services by at least two health professionals "who work collaboratively with patients and their caregivers to accomplish shared goals to achieve coordinated, high-quality care". However, primary care practices experience challenges to implementing TBC principles and care processes; these are more pronounced in small independent practice settings (SIPs). Practice facilitation (PF) is an implementation strategy that may overcome barriers to adopting evidence-based TBC to improve HTN management in SIPs. METHODS: Using a stepped wedge randomized controlled trial design, we will test the effect of PF on the adoption of TBC to improve HTN management in small practices (< 5 FTE clinicians) in New York City, and the impact on BP control compared with usual care. We will enroll 90 SIPs and randomize them into one of three 12-month intervention waves. Practice facilitators will support SIPs to adopt TBC principles to improve implementation of five HTN management strategies (i.e., panel management, population health, measuring BP, supporting medication adherence, self-management). The primary outcome is the adoption of TBC for HTN management measured at baseline and 12 months. Secondary outcomes include the rate of BP control and sustainability of TBC and BP outcomes at 18 months. Aggregated data on BP measures are collected every 6 months in all clusters so that each cluster provides data points in both the control and intervention conditions. Using a mixed methods approach, we will also explore factors that influence the effectiveness of PF at the organization and team level. DISCUSSION: This study will provide much-needed guidance on how to optimize adoption and sustainability of TBC in independent primary care settings to reduce the burden of disease related to suboptimal BP control and advance understanding of how facilitation works to improve implementation of evidence-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05413252 .

Hospital adoption of harm reduction and risk education strategies to address substance use disorders.

Background: Hospitals are well-positioned to integrate harm reduction into their workflow. However, the extent to which hospitals across the United States are adopting these strategies remains unknown.Objectives: To assess what factors are associated with hospital adoption of harm reduction/risk education strategies, and trends of adoption across time.Methods: We constructed a dataset marking implementation of harm reduction/risk education strategies for a 20% random sample of nonprofit hospitals in the U.S (n = 489) using 2019-2021 community health needs assessments (CHNAs) and implementation strategies obtained from hospital websites. We used two-level mixed effects logistic regression to test the association between adoption of these activities and organizational and community-level variables. We also compared the proportion of hospitals that adopted these strategies in the 2019-2021 CHNAs to an earlier cohort (2015-2018.)Results: In the 2019-2021 CHNAs, 44.7% (n = 219) of hospitals implemented harm reduction/risk education programs, compared with 34.1% (n = 156) in the 2015-2018 cycle. In our multivariate model, hospitals that implemented harm reduction/risk education programs had higher odds of having adopted three or more additional substance use disorder (SUD) programs (OR: 10.5: 95% CI: 5.35-20.62), writing the CHNA with a community organization (OR: 2.14; 95% CI: 1.15-3.97), and prioritizing SUD as a top three need in the CHNA (OR: 2.63; 95% CI: 1.54-4.47.)Conclusions: Our results suggest that hospitals with an existing SUD infrastructure and with connections to community are more likely to implement harm reduction/risk education programs. Policymakers should consider these findings when developing strategies to encourage hospital implementation of harm reduction activities.