Flexible visiting positively impacted on patients, families and staff in an Australian Intensive Care Unit: A before-after mixed method study

Background The admission of a relative to intensive care is stressful for families. To help them support the patient, families need assurance, information and an ability to be near their sick relative. Flexible visiting enables patient access but the impact of this on patients, families and staff is not clear. Objective To assess the impact of flexible visiting from the perspective of patients, families, and Intensive Care Unit (ICU) staff. Methods A before-after mixed method study was used with interviews, focus groups and surveys. Patients were interviewed, family members completed the Family Satisfaction in ICU survey and ICU staff completed a survey and participated in focus groups following the introduction of 21 h per day visiting in a tertiary ICU. The study was conducted within a philosophy of family-centred care. Results All interviewed patients (n = 12) positively evaluated the concept of extended visiting hours. Family members’ (n = 181) overall ‘satisfaction with care’ did not change; however 85% were ‘very satisfied’ with increased visiting flexibility. Seventy-six percent of family visits continued to occur within the previous visiting hours (11 am–8 pm) with the remaining 24% taking place during the newly available visiting hours. Families recognised the priority of patient care with their personal needs being secondary. Three-quarters of ICU staff were ‘satisfied’ with flexible visiting and suggested any barriers could be overcome by role modelling family inclusion. Conclusion Patients, families and ICU staff positively evaluated flexible visiting hours in this ICU. Although only a minority of families took advantage of the increased hours they indicated appreciation for the additional opportunities. Junior staff may benefit from peer-support to develop family inclusion skills. More flexible visiting times can be incorporated into usual ICU practice in a manner that is viewed positively by all stakeholders

Reduced Apaf-1 expression in human cutaneous melanomas

Malignant melanoma is a life-threatening skin cancer due to its highly metastatic character and resistance to radio- and chemotherapy. It is believed that the ability to evade apoptosis is the key mechanism for the rapid growth of cancer cells. However, the exact mechanism for failure in the apoptotic pathway in melanoma cells is unclear. p53, the most frequently mutated tumour suppressor gene in human cancers, is a key apoptosis inducer. However, p53 mutation is only found in 15–20% of melanoma biopsies. Recently, it was found that Apaf-1, a downstream target of p53, is inactivated in metastatic melanoma. Specifically, loss of heterozygosity (LOH) of the Apaf-1 gene was found in 40% of metastatic melanoma. To determine if loss of Apaf-1 expression is indeed involved in melanoma progression, we employed the tissue microarray technology and examined Apaf-1 expression in 70 human primary malignant melanoma biopsies by immunohistochemistry. Our data showed that Apaf-1 expression is significantly reduced in melanoma cells compared with normal nevi (χ2=6.02, P=0.014). Our results also revealed that loss of Apaf-1 was not associated with the tumour thickness, ulceration or subtype, patient's gender, age and 5-year survival. In addition, our in vitro apoptosis assay revealed that overexpression of Apaf-1 can sensitise melanoma cells to anticancer drug treatment. Taken together, our data indicate that Apaf-1 expression is significantly reduced in human melanoma and that Apaf-1 may serve as a therapeutic target in melanoma

High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays

Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level

Surgery and radiotherapy in the treatment of cutaneous melanoma

Adequate surgical management of primary melanoma and regional lymph node metastasis, and rarely distant metastasis, is the only established curative treatment. Surgical management of primary melanomas consists of excisions with 1–2 cm margins and primary closure. The recommended method of biopsy is excisional biopsy with a 2 mm margin and a small amount of subcutaneous fat. In specific situations (very large lesions or certain anatomical areas), full-thickness incisional or punch biopsy may be acceptable. Sentinel lymph node biopsy provides accurate staging information for patients with clinically unaffected regional nodes and without distant metastases, although survival benefit has not been proved. In cases of positive sentinel node biopsy or clinically detected regional nodal metastases (palpable, positive cytology or histopathology), radical removal of lymph nodes of the involved basin is indicated. For resectable local/in-transit recurrences, excision with a clear margin is recommended. For numerous or unresectable in-transit metastases of the extremities, isolated limb perfusion or infusion with melphalan should be considered. Decisions about surgery of distant metastases should be based on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases