Inhaled Medicines for Targeting Non-Small Cell Lung Cancer.

Throughout the years, considerable progress has been made in methods for delivering drugs directly to the lungs, which offers enhanced precision in targeting specific lung regions. Currently, for treatment of lung cancer, the prevalent routes for drug administration are oral and parenteral. These methods, while effective, often come with side effects including hair loss, nausea, vomiting, susceptibility to infections, and bleeding. Direct drug delivery to the lungs presents a range of advantages. Notably, it can significantly reduce or even eliminate these side effects and provide more accurate targeting of malignancies. This approach is especially beneficial for treating conditions like lung cancer and various respiratory diseases. However, the journey towards perfecting inhaled drug delivery systems has not been without its challenges, primarily due to the complex structure and functions of the respiratory tract. This comprehensive review will investigate delivery strategies that target lung cancer, specifically focusing on non-small-cell lung cancer (NSCLC)-a predominant variant of lung cancer. Within the scope of this review, active and passive targeting techniques are covered which highlight the roles of advanced tools like nanoparticles and lipid carriers. Furthermore, this review will shed light on the potential synergies of combining inhalation therapy with other treatment approaches, such as chemotherapy and immunotherapy. The goal is to determine how these combinations might amplify therapeutic results, optimizing patient outcomes and overall well-being.

Preparation, characterization and wound-healing effect of PEGylated nanoliposomes loaded with oleuropein.

Chronic wounds have become a major concern for healthcare systems, as they have been related to diabetic foot ulcers, venous leg ulcers and pressure ulcers. Oleuropein is an active compound that is extracted from olive leaves and it has the ability to reduce injury to tissues owing to its antioxidant effect, hence improving wound healing. The poor pharmacokinetics of oleuropein have limited its use clinically. This work is aimed toward studying the impact of PEGylated and non-PEGylated nanoliposomes loaded with oleuropein, as a carrier model, on wound-healing activity. The thin film hydration method was used to compose PEGylated and non-PEGylated liposomes, both loaded with oleuropein. The results indicated that each free, PEGylated and non-PEGylated composition was within the limit of optimum nanoliposome characterization. The results showed that non-PEGylated compositions produced higher efficiency in encapsulation (47.09 ± 10.06%) than the PEGylated ones (20.97 ± 10.52%). The PEG-nanoliposomes loaded with oleuropein (PEG-oleu) had mean size, charge and polydispersity index of 129.35 nm, -9.55 mV and 0.1010, respectively. The scratch assay results proved that PEGylated liposomal compositions have a more rapid wound-healing activity than non-PEGylated ones at different time intervals at 0, 2, 24 and 28 h.

Integration in mixed-methods studies: existing practices, considerations and recommendations for pharmacy research.

Mixed methods research is increasingly used to investigate complex issues in health and healthcare. Purposeful integration of the qualitative and quantitative strands has a significant potential to yield insights that exceed the value of a study's constituent qualitative and quantitative components alone. The philosophical foundations of mixed methods in pragmatism support the importance of integration as a focus of designing and conducting mixed methods research. Integration can be facilitated by considering and employing study components such as distinct mixed methods research questions, sampling strategies, data transformations, joint data displays and integrated narrative discussions. This manuscript explores the importance of integration in mixed-methods research, provides examples of these techniques used in pharmacy research and offers practical recommendations for implementing these techniques.

Cellular and molecular basis of therapeutic approaches to breast cancer.

In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment of both primary and metastatic breast cancers. It's a well-known fact that treating breast cancer is still a challenging endeavour even though physicians have a fantastic toolset of the latest treatment options at their disposal. Due to limitations of current clinical treatment options, traditional chemotherapeutic drugs, and surgical options are still required to address this condition. In recent years, there have been several developments resulting in a wide range of treatment options. This review article discusses the cellular and molecular foundation of chemotherapeutic drugs, endocrine system-based treatments, biological therapies, gene therapy, and innovative techniques for treating breast cancer.

Identifying Services Provided in Community Pharmacy Practice Settings.

Background: To better address their patients' needs, community pharmacists are expanding from their traditional role of dispensing to managing medications and providing other care. Objective: This study characterized services reported by pharmacists practicing in community pharmacy settings in the 2019 National Pharmacist Workforce Study (NPWS). Methods: The 2019 NPWS was conducted via an online survey. E-mails containing survey links were sent to a systematic random sample of 96,110 U.S. pharmacists. The survey allowed tailoring of questions related to specific practice settings and for respondents in community pharmacies included reporting on delivery of twelve services. Other descriptive characteristic questions included community pharmacy type, staffing, monitoring activities, self-reported workload, and respondent demographics. An index was created by summing the number of yes responses for the service questions. This index served as the dependent variable in an ordinary least squares regression examining the association of work setting characteristics with the index. Results: Usable responses were received from 2,150 community pharmacists. The top four services were: administer vaccines (91.1%), patient medication assistance program (83.7%), naloxone dispensing (72.8%) and medication synchronization (67.2%). The regression model was significant, with supermarket pharmacies having a higher service index than large chains. Elevated service index scores were associated with more technicians on duty, CPESN participation, direct communication with primary care providers, practicing under a CPA and monitoring activities. Conclusions: Pharmacy operational characteristics were important influences on the delivery of services in community pharmacies. These findings can help inform the continuing transformation of community pharmacy practice.

Matrix metalloproteinase 2 is a target of the RAN-GTP pathway and mediates migration, invasion and metastasis in human breast cancer.

RAS-related nuclear protein(RAN) is a nuclear shuttle and normally regulates events in the cell cycle. When overexpressed in cultured cells, it causes increases in cell migration/invasion in vitro and its overexpression is associated with early breast cancer patient deaths in vivo. However, the underlying mechanism is unknown. The effect of RAN overexpression on potential targets MMP2, ATF3, CXCR3 was investigated by Real-Time PCR/Western blots in the triple receptor negative breast cancer(TRNBC) cell line MDA-MB231 and consequent biological effects were measured by cell adhesion, cell migration and cell invasion assays. Results showed that knockdown of RAN lead to a reduction of MMP2 and its potential regulators ATF3 and CXCR3. Moreover, knockdown of ATF3 or CXCR3 downregulated MMP2 without affecting RAN, indicating that RAN regulates MMP2 through ATF3 and CXCR3. Knockdown of RAN and MMP2 reduced cell adhesion, cell migration and cell growth in agar, whilst overexpression of MMP2 reversed the knockdown of RAN. Furthermore, immunohistochemical staining for RAN and MMP2 are positively associated with each other in the same tumour and separately with patient survival times in breast cancer specimens, suggesting that a high level of RAN may be a pre-requisite for MMP2 overexpression and metastasis. Moreover, positive immunohistochemical staining for both RAN and MMP-2 reduces further patient survival times over that for either protein separately. Our results suggest that MMP2 expression can stratify progression of breast cancers with a high and low incidence of RAN, both RAN and MMP2 in combination can be used for a more accurate patient prognosis. SIMPLE SUMMARY: Ran is an important regulator of normal cell growth and behaviour. We have established in cell line models of breast cancer (BC) a molecular pathway between RAN and its protein-degrading effector MMP-2 and properties related to metastasis in culture. Using immunohistochemistry (IHC) staining of primary BCs, we have shown that RAN and MMP-2 are on their own significantly associated with patient demise from metastatic BC. Moreover, when staining for MMP-2 is added to that for RAN in the primary tumours, there is a significant decrease in patient survival time over that for either protein alone. Thus a combination of staining for RAN and MMP2 is an excellent marker for poor prognosis in breast cancer.

Evaluating the coaches' experience in the Flip the Pharmacy program.

BACKGROUND: The Flip the Pharmacy (FtP) program aims to transform pharmacy practice to be patient centered and professionally sustainable through hands-on peer coaching, where the peer coaches' roles are to support their teams and provide them with feedback. There is a need to describe the coaches' experiences in transforming pharmacy practice, to better use coaching in future programs. OBJECTIVES: This study aims to (1) describe peer coaches' experiences in cohort 1 year 1 of the FtP program, (2) identify barriers and facilitators for program implementation, and (3) provide recommendations for future coaches. METHODS: A qualitative design used semistructured telephone interviews with all 7 peer coaches at FtP Team Iowa. They were interviewed about their coaching approach, experiences, and perceived facilitators and barriers to FtP program implementation by 30 pharmacies. The transcripts were coded by 2 researchers independently using thematic analysis, the emergent codes were discussed until agreement was reached, and then codes were aggregated and organized. RESULTS: Coaches' experience contained 3 themes: training received in preparation for the program, role clarity, and pharmacy visits (face to face vs. virtual). Themes also emerged for perceived facilitators and barriers to program implementation. Opportunities and recommendations contained 3 themes: accountability, in which the coach has clear expectations and uses consistent reporting; knowledge sharing, where peer coaches can exchange ideas and experiences; and training, where coaches can receive technical and interpersonal training. CONCLUSION: Consistency and role clarity for the coaches can be increased by training on communication with teams, setting clear expectations, and providing a system for sharing their experiences and knowledge. Peer coaches can help establish service value that can improve contract opportunities and program execution through routinizing workflow. More research should be done about the effects of peer coaches' roles on sustaining practice transformation for successful service execution.

Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions.

The Signal Transducer and Activator of Transcription 3 (STAT3) protein is encoded on chromosome 17q21. The SH2 and the DNA binding domains are critical structural components of the protein, together with tyrosine and serine residues that initiate phosphorylation. STAT3 interacts with DNA directly and functions in cells as both a signal transducer and a transcription factor. Its cytoplasmic activation results in dimerisation and nuclear translocation, where it is involved in the transcription of a large number of target genes. STAT3 is hyperactive in cancer cells as a result of upstream STAT3 mutations or enhanced cytokine production in the tumour environment. The STAT3 signalling pathway promotes many hallmarks of carcinogenesis and metastasis, including enhanced cell proliferation and survival, as well as migration and invasion into the extracellular matrix. Recent investigations into novel STAT3-based therapies describe a range of innovative approaches, such as the use of novel oligonucleotide drugs. These limit STAT3 binding to its target genes by attaching to SH2 and DNA-binding domains. Yet, despite these significant steps in understanding the underpinning mechanisms, there are currently no therapeutic agents that addresses STAT3 signalling in a clinically relevant manner.

Using journey mapping to understand the patient experience with selecting a Medicare part D plan using a pharmacy consultation service.

Background: Patient experience with community pharmacy services can be informed by human-centered design principles and approaches. Pharmacy services may benefit from detailed evaluations of consumer experience and patient-centered service design. Objectives: To use an online journey mapping platform to understand the patient experience with selecting a Medicare Part D plan for individuals that did, and did not, use a free, pharmacy-led, Medicare Part D consultation service. Methods: This was a two-group cross-sectional survey study in a single, rural community pharmacy. Surveys consisted of 7 demographic items, 30 Likert-type items, and 7 open-ended response items. The pharmacy used purposeful convenience sampling to distribute a paper survey to individuals 65 years of age and older currently enrolled in Medicare Part D between June and August 2019. Surveys were distributed to 36 patients currently enrolled in a Medicare Part D plan, with 18 surveys distributed to patients who had previously used a pharmacy-led Medicare Part D consultation service and 18 surveys distributed to patients who did not use the service. Surveys were uploaded to an online journey mapping platform, producing data visualizations for each group. Multiple choice survey items were analyzed using descriptive statistics, wth service user and nonuser groups compared using Mann-Whitney U tests. Open-ended survey responses were coded by the research team using an inductive approach. Results: In total, 36 surveys were returned to the community pharmacy for a response rate of 100%. The journey map platform generated Persona, Empathy, and Current Journey outputs, which mapped Good Experiences and Bad Experiences within the Medicare Part D plan selection experience. Personas differed in their median household incomes ($25,000-$39,999 for service users compared to $50,000-$74,999 for nonusers). Empathy and Current Journey outputs showed that service users had a wider variety of emotions compared to non-users. Mann-Whitney U tests yielded 5 items with statistically significant differences (p-values <0.05) in the plan-selection experience, with both groups similarly uncertain about their plan decision. Qualitative responses indicate patient trust was universally important to a complex decision-making process. Conclusions: An online journey mapping platform provided insight into how patients experience a pharmacy service that extends beyond satisfaction. For community pharmacies providing Medicare Part D plan consultation services, pharmacies should consider how they can improve the service experience through communication style and patient-centered service design.

An evaluation of community pharmacies' actions under value-based payment.

OBJECTIVE: To determine actions taken by community pharmacies to be successful under a value-based pharmacy program (VBPP). METHOD: An exploratory sequential mixed methods approach was used to evaluate pharmacies participating in the VBPP, with qualitative data collected and analyzed in the first phase, followed by quantitative measurement through a 30-item survey instrument in the second phase. RESULTS: The qualitative data showed that participating pharmacies were more involved with adherence and cardiovascular and diabetes metrics than with other metrics. Depression metrics received the lowest overall involvement. For total cost of care, different approaches were used; 5 pharmacies used the dashboard to identify likely high-cost patients they could try to manage, and 4 pharmacies monitored adherence to avoid complications that could contribute to increased cost. For the survey response rate was 72.6% (n = 53). The mean perception of level of success was 53.06 ± 20.15 (mean ± SD). Activities with the highest priority were adherence (1.98 ± 0.97) and diabetes care (2.04 ± 0.83), and the activity with the lowest priority was depression care (3.60 ± 1.10). The most frequently mentioned challenge was time availability, and the most common improvement suggestion was better communication between the insurer and providers. CONCLUSION: In conclusion, this study found that community pharmacies were transforming their practices to be successful under a commercial value-based payment program. The pharmacies tended to build on care processes already established (e.g., medication adherence, patients with diabetes or cardiovascular conditions) and developed new processes to address emerging metrics and associated patient needs (e.g., collecting and documenting blood pressure and hemoglobin A1c levels). Future research is needed to identify best practices for patient care and pharmacy success under broad VBPPs such as the one studied here.