Chemotherapy with cytochalasin congeners in vitro and in vivo against murine models.

Background Despite inherent differences between the cytoskeletal networks of malignant and normal cells, and the clinical antineoplastic activity of microtubule-directed agents, there has yet to be a microfilament-directed agent approved for clinical use. One of the most studied microfilament-directed agents has been cytochalasin B, a mycogenic toxin known to disrupt the formation of actin polymers. Therefore, this study sought to expand on our previous work with the microfilament-directed agent, along with other less studied cytochalasin congeners. Materials and Methods We determined whether cytochalasin B exerted significant cytotoxic effects in vitro on adherent M109 lung carcinoma and B16BL6 and B16F10 murine melanomas, or on suspension P388/ADR murine leukemia cells. We also examined whether cytochalasin B, its reduced congener 21, 22-dihydrocytochalasin B (DiHCB), or cytochalasin D could synergize with doxorubicin (ADR) against ADR-resistant P388/ADR leukemia cells, and produce significant cytotoxicity in vitro. For in vivo characterization, cytochalasins B and D were administered intraperitoneally (i.p.) to Balb/c mice challenged with drug sensitive P388-S or multidrug resistant P388/ADR leukemias. Results Cytochalasin B demonstrated higher cytotoxicity against adherent lung carcinoma and melanoma cells than against suspension P388/ADR leukemia cells, as assessed by comparative effects on cell growth, and IC50 and IC80 values. Isobolographic analysis indicated that both cytochalasin B and DiHCB demonstrate considerable drug synergy with ADR against ADR-resistant P388/ADR leukemia, while cytochalasin D exhibits only additivity with ADR against the same cell line. In vivo, cytochalasins B and D substantially increased the life expectancy of mice challenged with P388/S and P388/ADR leukemias, and in some cases, produced long-term survival. Conclusion Taken together, it appears that cytochalasins have unique antineoplastic activity that could potentiate a novel class of chemotherapeutic agents.

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration.

Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic agent that prevents actin polymerization, thereby inhibiting cytokinesis. Although cytochalasin B has been extensively studied in vitro, only limited data are available to assess its in vivo potential. Cytochalasin B was administered to Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether the agent could affect an established i.d. tumor when the compound is administered s.c. in the region of the i.d. tumor, but not in direct contact with it. Cytochalasin B was also administered either i.p. or s.c. at a distant site or i.v. to determine whether it could affect the long-term development of an established i.d. tumor. Cytochalasin B was then liposome encapsulated to determine whether the maximum tolerated dose (MTD) of the compound could be increased, while reducing immunosuppression that we have previously characterized. Liposomal cytochalasin B was also administered to mice challenged i.d. with M109 lung carcinoma to assess its chemotherapeutic efficacy. The results can be summarized as follows: 1) cytochalasin B substantially delayed the growth of i.d. M109 tumor nodules, inhibited metastatic progression in surrounding tissues, and produced long-term cures in treated mice; 2) liposomal cytochalasin B increased the i.p. MTD by more than 3-fold, produced a different distribution in tissue concentrations, and displayed antitumor effects against M109 lung carcinoma similar to non-encapsulated cytochalasin B. These data show that cytochalasin B exploits unique chemotherapeutic mechanisms and is an effective antineoplastic agent in vivo in pre-clinical models, either in bolus form or after liposome encapsulation.

A reimagined discharge lounge as a way to an efficient discharge process.

Faced with inherent inefficiencies built into transfer of a patient from emergency department (ED) to an inpatient bed, we determined that the timely availability of an inpatient bed was essential to improving efficiency and flow. Lack of beds early in the day was a major cause for delays and backup in the ED, which in turn placed the ED at risk for overcrowding and diversion. Review of the discharge process revealed that only 33.4% of discharges were completed prior to noon, and on average took 126 minutes from the time a discharge order was written to the time the patient actually left their inpatient bed. To achieve our goals of improving patient flow and discharge efficiency, we proposed a new project, called the "Discharge Hospitality Center (DHC)." Our previous attempt at creating a "discharge lounge" was unsuccessful. However, we learned from that endeavor which then allowed us to completely redesign the new DHC project and incorporate ongoing feedback from all stakeholders, sharing performance metrics regularly, and collectively searching for ways to overcome barriers and improve performance together. Strict eligibility criteria were created, and every patient was screened for DHC eligibility daily at our multidisciplinary discharge planning meeting. This multidisciplinary group made the final decision about eligibility for the DHC, and took responsibility for distributing the list of eligible patients to the acute care nursing floors immediately after their early morning meeting. Using the list of patients appropriate for the DHC, the acute floor nursing teams developed standard work for prioritization of DHC eligible patients for discharge, which more reliably allowed those patients to leave their inpatient beds earlier in the day. We found there was no need for dedicated staff at our DHC, as after discharge all outpatient procedures and policies applied. Our outcomes were quite favorable. Four months after the DHC project was launched, ED stays over 6 hours decreased from 24.6 to 15.8%, discharges before noon increased from 33.4 to 41.5%, and time improved from 126 down to 84 minutes from the time a discharge order was written to the time the patients actually left their inpatient bed. We reviewed all patients who went to the DHC on the subject of readmission and found two that were unavoidable (whether or not the DHC was used), and one patient nearly missed his ride home as he sat in the wrong location for transport pickup. In conclusion, a DHC can be successfully designed through integration and collaboration with stakeholders which can be a valuable tool to improve discharge efficiency and patient flow.

Integrating Physician Services in the Home: evaluation of an innovative program.

OBJECTIVE: To evaluate a new program, Integrating Physician Services in the Home (IPSITH), to integrate family practice and home care for acutely ill patients. DESIGN: Causal model, mixed-method, multi-measures design including comparison of IPSITH and non-IPSITH patients. Data were collected through chart reviews and through surveys of IPSITH and non-IPSITH patients, caregivers, family physicians, and community nurses. SETTING: London, Ont, and surrounding communities, where home care is coordinated through the Community Care Access Centre. PARTICIPANTS: A total of 82 patients receiving the new IPSITH program of care (including 29 family physicians and 1 nurse practitioner), 82 non-randomized matched patients receiving usual care (and their physicians), community nurses, and caregivers. MAIN OUTCOME MEASURES: Emergency department (ED) visits and satisfaction with care. Analysis included a process evaluation of the IPSITH program and an outcomes evaluation comparing IPSITH and non-IPSITH patients. RESULTS: Patients and family physicians were very satisfied with the addition of a nurse practitioner to the IPSITH team. Controlling for symptom severity, a significantly smaller proportion of IPSITH patients had ED visits (3.7% versus 20.7%; P = .002), and IPSITH patients and their caregivers, family physicians, and community nurses had significantly higher levels of satisfaction (P < .05). There was no difference in caregiver burden between groups. CONCLUSION: Family physicians can be integrated into acute home care when appropriately supported by a team including a nurse practitioner. This integrated team was associated with better patient and system outcomes. The gains for the health system are reduced strain on hospital EDs and more satisfied patients.

Interprofessional education: a nurse practitioner impacts family medicine residents' smoking cessation counselling experiences.

This qualitative research paper describes a successful example of interprofessional education with family medicine residents (FMR) by a nurse practitioner (NP) colleague. The educational impact of the NP role in regard to smoking cessation counselling is revealed by the analysis of 16 semi-structured interviews using a phenomenological approach. The key themes depicted the NP as an educator and mentor, encourager and referral resource. Outcomes of improved knowledge, skills, and motivation towards providing smoking cessation counselling are described. This research provides some understanding of how professional students' learning and practice can be affected by a member of another profession through direct and indirect approaches. The experiences identified how interprofessional education and collaborative clinical practice can affect FMRs' attitudes, knowledge and behaviours. This learning can guide us in enhancing the quality of education provided to all health care professionals.

Evolving the delivery of acute care services in the home.

To serve escalating acute care caseloads, physicians affiliated with one Canadian home care program have piloted a project to integrate physician services into the home (IPSITH). This paper presents the 18-month qualitative evaluation. Phenomenological methodology and in-depth interviewing were used to construct a holistic interpretation of the implementation from the experiences of all involved: patients, family caregivers, physicians, case managers, community nurses and the project's nurse practitioner. Findings revealed the central role of the nurse practitioner, who served as a clinical expert, care coordinator and case manager. Several unsolved issues were identified: the extent to which home care is a viable alternative to hospitalization, the feasibility of physician involvement, redundancies with hospital emergency services, and the limitations of system resources for funding such services. The researchers conclude that full-scale long-term integration of physician services in the home may require macro-level decisions about system design, resource allocation, and professional regulations.