Wound management provided by advanced practice nurses: a scoping review.

OBJECTIVE: The objective of the review was to map the similarities and differences in the wound care practices of nurse practitioners, clinical nurse specialists, and advanced practice registered nurses, globally. INTRODUCTION: Advanced practice nurses have graduate education and advanced scope of practice. Adding advanced wound care training to their skillset provides an opportunity for advanced practice nurses to provide wound care. INCLUSION CRITERIA: This review considered for inclusion advanced practice nurses globally who are registered nurses with graduate-level education and advanced training (certification/education) in wound care in any setting. METHODS: The review was conducted using JBI methodology for scoping reviews. The databases searched included MEDLINE, CINAHL, ProQuest Nursing and Allied Health, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus, and ProQuest Dissertations and Theses. To reflect changes in the advanced practice nursing scope of practice, searches were limited to articles published from 2011. Articles in languages other than English were translated. Two reviewers independently reviewed titles and abstracts; relevant sources were retrieved in full and reviewed. An additional independent reviewer resolved any disagreements. Data were extracted using a data extraction tool. Extracted data included similarities and differences in wound care practice (type of wound, practice setting, treatments). RESULTS: There were 2504 abstracts screened, and 158 were screened at full text. Seven articles were included in this review: 3 sources from the United States, 2 from Australia, and 1 each from Canada and The Netherlands. All 7 sources focused on nurse practitioners; wound care education varied from certification in wound ostomy to a master's education in wounds. The practice setting varied; there were 2 primary care clinics; 2 community clinics; 1 wound care center; a suburban hospital, and a study that included tertiary, community, and residential care. Treatments varied, but sources specific to pressure injuries discussed assessments, cleansing, dressings, topical products, and offloading surfaces/equipment, and 1 examined the impact of hiring nurse practitioners as wound care consultants. Sources that discussed treatments for various wounds described comprehensive assessments, diagnostic investigations, referrals, wound management, and medications prescribed. Outcomes included improved healing, decreased incidence, increased patient satisfaction, access to care, and reduced referrals for additional care. CONCLUSIONS: This review outlined the characteristics of advanced practice nurses and their practice settings, types of wounds, and treatments provided. The findings demonstrated positive results with advanced practice nurses providing wound care. Many articles regarding advanced practice nurses with advanced wound care expertise lack the description of the graduate-level education and/or the specifics regarding wound care certification. This prevents comparison of advanced practice nurses with each other and other providers on the impact that advanced practice nurses have on the health care system in relation to wound care, including cost, access to services, and patient satisfaction.

Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4+ and CD8+ T cells. Co-culturing CD4+ with autologous CD8+ T cells from ART-suppressed HIV+ donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8+ T cells. This trispecific antibody mediates CD4+ and CD8+ T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection.

A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cells.

Effective antitumour immunity depends on the orchestration of potent T cell responses against malignancies1. Regression of human cancers has been induced by immune checkpoint inhibitors, T cell engagers or chimeric antigen receptor T cell therapies2-4. Although CD8 T cells function as key effectors of these responses, the role of CD4 T cells beyond their helper function has not been defined. Here we demonstrate that a trispecific antibody to HER2, CD3 and CD28 stimulates regression of breast cancers in a humanized mouse model through a mechanism involving CD4-dependent inhibition of tumour cell cycle progression. Although CD8 T cells directly mediated tumour lysis in vitro, CD4 T cells exerted antiproliferative effects by blocking cancer cell cycle progression at G1/S. Furthermore, when T cell subsets were adoptively transferred into a humanized breast cancer tumour mouse model, CD4 T cells alone inhibited HER2+ breast cancer growth in vivo. RNA microarray analysis revealed that CD4 T cells markedly decreased tumour cell cycle progression and proliferation, and also increased pro-inflammatory signalling pathways. Collectively, the trispecific antibody to HER2 induced T cell-dependent tumour regression through direct antitumour and indirect pro-inflammatory/immune effects driven by CD4 T cells.

SAR439859, a Novel Selective Estrogen Receptor Degrader (SERD), Demonstrates Effective and Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models.

Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. However, substantial evidence indicates a continued role for ER signaling in tumor progression. Selective estrogen receptor degraders (SERD), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties. Furthermore, activating mutations in the ER have emerged as a resistance mechanism to current endocrine therapies. New oral SERDs with improved drug properties are under clinical investigation, but the biological profile that could translate to improved therapeutic benefit remains unclear. Here, we describe the discovery of SAR439859, a novel, orally bioavailable SERD with potent antagonist and degradation activities against both wild-type and mutant Y537S ER. Driven by its fluoropropyl pyrrolidinyl side chain, SAR439859 has demonstrated broader and superior ER antagonist and degrader activities across a large panel of ER+ cells, compared with other SERDs characterized by a cinnamic acid side chain, including improved inhibition of ER signaling and tumor cell growth. Similarly, in vivo treatment with SAR439859 demonstrated significant tumor regression in ER+ breast cancer models, including MCF7-ESR1 wild-type and mutant-Y537S mouse tumors, and HCI013, a patient-derived tamoxifen-resistant xenograft tumor. These findings indicate that SAR439859 may provide therapeutic benefit to patients with ER+ breast cancer, including those who have resistance to endocrine therapy with both wild-type and mutant ER.

Pan-TGFß inhibition by SAR439459 relieves immunosuppression and improves antitumor efficacy of PD-1 blockade.

TGFß is a pleiotropic cytokine that may have both tumor inhibiting and tumor promoting properties, depending on tissue and cellular context. Emerging data support a role for TGFß in suppression of antitumor immunity. Here we show that SAR439459, a pan-TGFß neutralizing antibody, inhibits all active isoforms of human and murine TGFß, blocks TGFß-mediated pSMAD signaling, and TGFß-mediated suppression of T cells and NK cells. In vitro, SAR439459 synergized with anti-PD1 to enhance T cell responsiveness. In syngeneic tumor models, SAR439459 treatment impaired tumor growth, while the combination of SAR439459 with anti-PD-1 resulted in complete tumor regression and a prolonged antitumor immunity. Mechanistically, we found that TGFß inhibition with PD-1 blockade augmented intratumoral CD8+ T cell proliferation, reduced exhaustion, evoked proinflammatory cytokines, and promoted tumor-specific CD8+ T cell responses. Together, these data support the hypothesis that TGFß neutralization using SAR439459 synergizes with PD-1 blockade to promote antitumor immunity and formed the basis for the ongoing clinical investigation of SAR439459 in patients with cancer (NCT03192345).

Discovery of SARxxxx92, a pan-PIM kinase inhibitor, efficacious in a KG1 tumor model.

N-substituted azaindoles were discovered as potent pan-PIM inhibitors. Lead optimization, guided by structure and focused on physico-chemical properties allowed us to solve inherent hERG and permeability liabilities, and provided compound 27, which subsequently impacted KG-1 tumor growth in a mouse model.

Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer.

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (43d), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.

Discovery of N-substituted 7-azaindoles as Pan-PIM kinases inhibitors - Lead optimization - Part III.

N-substituted azaindoles were discovered as promising pan-PIM inhibitors. Lead optimization is described en route toward the identification of a clinical candidate. Modulation of physico-chemical properties allowed to solve inherent hERG and permeability liabilities. Compound 17 showed tumor growth inhibition in a KG1 tumor-bearing mouse model.

Overcoming Challenges in School-Wide Survey Administration.

School-based surveys provide a useful method for gathering data from youth. Existing literature offers many examples of data collection through school-based surveys, and a small subset of literature describes methodological approaches or general recommendations for health promotion professionals seeking to conduct school-based data collection. Much less is available on real-life logistical challenges (e.g., minimizing disruption in the school day) and corresponding solutions. In this article, we fill that literature gap by offering practical considerations for the administration of school-based surveys. The protocol and practical considerations outlined in the article are based on a survey conducted with 11,681 students from seven large, urban public high schools in the southeast United States. We outline our protocol for implementing a school-based survey that was conducted with all students school-wide, and we describe six types of key challenges faced in conducting the survey: consent procedures, scheduling, locating students within the schools, teacher failure to administer the survey, improper administration of the survey, and minimizing disruption. For each challenge, we offer our key lessons learned and associated recommendations for successfully implementing school-based surveys, and we provide relevant tools for practitioners planning to conduct their own surveys in schools.

Discovery of N-substituted 7-azaindoles as Pan-PIM kinase inhibitors - Lead series identification - Part II.

N-Substituted azaindoles have been discovered as pan-PIM kinase inhibitors. Initial SAR, early ADME and PK/PD data of a series of compounds is described and led to the identification of promising pan-PIM inhibitors which validated our interest in the 7-azaindole scaffold and led us to pursue the identification of a clinical candidate.

The Importance of School Staff Referrals and Follow-Up in Connecting High School Students to HIV and STD Testing.

This study examined predictors of having received HIV and sexually transmitted disease (STD) testing and having been referred by school staff for HIV/STD testing. In 2014, students in seven high schools completed paper-and-pencil questionnaires assessing demographic characteristics, sexual behavior, referrals for HIV/STD testing, and HIV/STD testing. The analytic sample ( n = 11,303) was 50.7% female, 40.7% Hispanic/Latino, 34.7% Black/African American (non-Hispanic), and mean age was 15.86 ( SD = 1.22). After controlling for demographic characteristics, significant predictors of reporting having been tested for HIV or STDs were reporting having received a referral for HIV/STD testing (odds ratio [ OR] = 3.18; 95% CI = [2.14, 4.70]) and reporting staff following-up on the referral ( OR = 3.29; 95% CI = [1.31, 8.23]). Students reporting referrals had significantly higher odds of being male ( OR = 2.49; 95% CI = [1.70, 3.65]), "other" or multiracial (non-Hispanic; compared to White, non-Hispanic; OR = 2.72; 95% CI = [1.35, 5.46]), sexual minority ( OR = 3.80; 95% CI = [2.57, 5.62]), and sexually experienced ( OR = 2.58; 95% CI = [1.76, 3.795]). School staff referrals with follow-up may increase HIV/STD testing among students.