In this work, we report a drug delivery system based on the pH-responsive self-assembly and -disassembly behaviors of peptides. Here, a systematically designed histidine-rich lipidated peptide (NP1) is presented to encapsulate and deliver an anticancer drug ellipticine (EPT) into two model cells: non-small-cell lung carcinoma and Chinese hamster ovary cells. The mechanism of pH-responsive peptide self-assembly and -disassembly involved in the drug encapsulation and release process are extensively investigated. We found that NP1 could self-assemble as a spherical nanocomplex (diameter = 34.43 nm) in a neutral pH environment with EPT encapsulated and positively charged arginine amino acids aligned outward and EPT is released in an acidic environment due to the pH-triggered disassembly. Furthermore, the EPT-encapsulating peptide could achieve a mass loading ability of 18% (mass of loaded-EPT/mass of NP1) with optimization. More importantly, it is revealed that the positively charged arginine on the periphery of the NP1 peptides could greatly facilitate their direct translocation through the negatively charged plasma membrane via electrostatic interaction, instead of via endocytosis, which provides a more efficient uptake pathway.

Background As the urgent care landscape evolves, specialized musculoskeletal urgent care centers (MUCCs) are becoming more prevalent. MUCCs have been offered as a convenient, cost-effective option for timely acute orthopaedic care. However, a recent “secret-shopper” study on patient access to MUCCs in Connecticut demonstrated that patients with Medicaid had limited access to these orthopaedic-specific urgent care centers. To investigate how generalizable these regional findings are to the United States, we conducted a nationwide secret-shopper study of MUCCs to identify determinants of patient access. Questions/purposes (1) What proportion of MUCCs in the United States provide access for patients with Medicaid insurance? (2) What factors are associated with MUCCs providing access for patients with Medicaid insurance? (3) What barriers exist for patients seeking care at MUCCs? Methods An online search of all MUCCs across the United States was conducted in this cross-sectional study. Three separate search modalities were used to gather a complete list. Of the 565 identified, 558 were contacted by phone with investigators posing over the telephone as simulated patients seeking treatment for a sprained ankle. Thirty-nine percent (216 of 558) of centers were located in the South, 13% (71 of 558) in the West, 25% (138 of 558) in the Midwest, and 24% (133 of 558) in New England. This study was given an exemption waiver by our institution’s IRB. MUCCs were contacted using a standardized script to assess acceptance of Medicaid insurance and identify barriers to care. Question 1 was answered through determining the percentage of MUCCs that accepted Medicaid insurance. Question 2 considered whether there was an association between Medicaid acceptance and factors such as Medicaid physician reimbursements or MUCC center type. Question 3 sought to characterize the prevalence of any other means of limiting access for Medicaid patients, including requiring a referral for a visit and disallowing continuity of care at that MUCC. Results Of the MUCCs contacted, 58% (323 of 558) accepted Medicaid insurance. In 16 states, the proportion of MUCCs that accepted Medicaid was equal to or less than 50%. In 22 states, all MUCCs surveyed accepted Medicaid insurance. Academic-affiliated MUCCs accepted Medicaid patients at a higher proportion than centers owned by private practices (odds ratio 14 [95% CI 4.2 to 44]; p < 0.001). States with higher Medicaid physician reimbursements saw proportional increases in the percentage of MUCCs that accepted Medicaid insurance under multivariable analysis (OR 36 [95% CI 14 to 99]; p < 0.001). Barriers to care for Medicaid patients characterized included location restriction and primary care physician referral requirements. Conclusion It is clear that musculoskeletal urgent care at these centers is inaccessible to a large segment of the Medicaid-insured population. This inaccessibility seems to be related to state Medicaid physician fee schedules and a center’s affiliation with a private orthopaedic practice, indicating how underlying financial pressures influence private practice policies. Ultimately, the refusal of Medicaid by MUCCs may lead to disparities in which patients with private insurance are cared for at MUCCs, while those with Medicaid may experience delays in care. Going forward, there are three main options to tackle this issue: increasing Medicaid physician reimbursement to provide a financial incentive, establishing stricter standards for MUCCs to operate at the state level, or streamlining administration to reduce costs overall. Further research will be necessary to evaluate which policy intervention will be most effective. Level of Evidence Level II, prognostic study.

Objective: Patients may call urgent care centers (UCCs) with urgent surgical conditions but may not be properly referred to a higher level of care. This study aims to characterize how UCCs manage Medicaid and privately insured patients who present with an emergent condition. Methods: Using a standardized script, we called 1245 randomly selected UCCs in 50 states on 2 occasions. Investigators posed as either a Medicaid or a privately-insured patient with symptoms of an incarcerated inguinal hernia. Rates of direct emergency department (ED) referral were compared between insurance types. Results: A total of 1223 (98.2%) UCCs accepted private insurance and 981 (78.8%) accepted Medicaid. At the 971 (78.0%) UCCs that accepted both insurance types, direct-to-ED referral rates for private and Medicaid patients were 27.9% and 33.8%, respectively. Medicaid patients were significantly more likely than private patients to be referred to the ED [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.09–1.60]. Private patients who were triaged by a clinician compared to nonclinician staff were over 6 times more likely to be referred to the ED (OR 6.46, 95% CI 4.63–9.01). Medicaid patients were nearly 9 times more likely to have an ED referral when triaged by a clinician (OR 8.72, 95% CI 6.19–12.29). Conclusions: Only one-third of UCCs across the United States referred an apparent emergent surgical case to the ED, potentially delaying care. Medicaid patients were more likely to be referred directly to the ED versus privately insured patients. All patients triaged by clinicians were significantly more likely to be referred to the ED; however, the disparity between private and Medicaid patients remained.

No abstract

Background: As the demand for dementia care grows rapidly worldwide, heavy “caregiver burden” has been associated with stress and depression. Even so, standard metrics for interdisciplinary research of caregiver burden are limited. Objective: The objective of the present review is to recommend valid, reliable, and comprehensive self-report instruments of caregiver burden. Methods: A systematic review was performed using four databases, searched in April 2021. Articles that established or evaluated self-report instruments for dementia caregiver burden were included, while studies that involved non-dementia caregivers or did not clearly define caregiver burden were excluded. Established guidelines for reliability and agreement studies were used to assess quality and risk of bias. Assessments of self-report instruments were made based on reliability, validity, feasibility, and quality of psychometric evaluations, and comparative evaluations were presented in visual form using radar graphs. Results: Search terms yielded 1,720 articles, and 40 were included in the systematic review after excluding those of low quality. Based on the results of these studies, we recommend the Zarit Burden Interview, Screen for Caregiver Burden, Caregiver Burden Interview, and Burden Scale for Family Caregivers, due to their validity, reliability, and inclusion of multiple subjective and objective dimensions of burden. Conclusion: Targeting specific sources of caregiver burden can help prevent negative outcomes for both dementia patients and caregivers. Future studies should apply self-report instruments to measure and address caregiver burden longitudinally.