Substance users' perspective of pain management in the acute care environment.

The aim of this exploratory study was to examine substance users' perspectives towards their acute pain management in the acute hospital setting. Barriers to optimal pain management in the substance user population include: altered physiologic responses to analgesia; cultural values; and health professionals' perceptions of drug-seeking behaviours.

Identification and characterisation of the early differentiating cells in neural differentiation of human embryonic stem cells.

One of the challenges in studying early differentiation of human embryonic stem cells (hESCs) is being able to discriminate the initial differentiated cells from the original pluripotent stem cells and their committed progenies. It remains unclear how a pluripotent stem cell becomes a lineage-specific cell type during early development, and how, or if, pluripotent genes, such as Oct4 and Sox2, play a role in this transition. Here, by studying the dynamic changes in the expression of embryonic surface antigens, we identified the sequential loss of Tra-1-81 and SSEA4 during hESC neural differentiation and isolated a transient Tra-1-81(-)/SSEA4(+) (TR-/S4+) cell population in the early stage of neural differentiation. These cells are distinct from both undifferentiated hESCs and their committed neural progenitor cells (NPCs) in their gene expression profiles and response to extracellular signalling; they co-express both the pluripotent gene Oct4 and the neural marker Pax6. Furthermore, these TR-/S4+ cells are able to produce cells of both neural and non-neural lineages, depending on their environmental cues. Our results demonstrate that expression of the pluripotent factor Oct4 is progressively downregulated and is accompanied by the gradual upregulation of neural genes, whereas the pluripotent factor Sox2 is consistently expressed at high levels, indicating that these pluripotent factors may play different roles in the regulation of neural differentiation. The identification of TR-S4+ cells provides a cell model for further elucidation of the molecular mechanisms underlying hESC neural differentiation.

Fibroblast growth factor receptor 1 promotes proliferation and survival via activation of the mitogen-activated protein kinase pathway in bladder cancer.

Fibroblast growth factor receptors (FGFR) play key roles in proliferation, differentiation, and tumorigenesis. Many urothelial carcinomas contain activating point mutations or increased expression of FGFR3. However, little is known about the role of other FGFRs. We examined FGFR expression in telomerase-immortalized normal human urothelial cells, urothelial carcinoma cell lines, and tumor samples and showed that FGFR1 expression is increased in a high proportion of cell lines and tumors independent of stage and grade. To determine the role of FGFR1 in low-stage bladder cancer, we overexpressed FGFR1 in telomerase-immortalized normal human urothelial cells and examined changes in proliferation and cell survival in response to FGF2. FGFR1 stimulation increased proliferation and reduced apoptosis. To elucidate the mechanistic basis for these alterations, we examined the signaling cascades activated by FGFR1. FRS2alpha and PLCgamma were activated in response to FGF2, leading to activation of the mitogen-activated protein kinase pathway. The level of mitogen-activated protein kinase activation correlated with the level of cyclin D1, MCL1, and phospho-BAD, which also correlated with FGFR-induced proliferation and survival. Knockdown of FGFR1 in urothelial carcinoma cell lines revealed differential FGFR1 dependence. JMSU1 cells were dependent on FGFR1 expression for survival but three other cell lines were not. Two cell lines (JMSU1 and UMUC3) were dependent on FGFR1 for growth in soft agar. Only one of the cell lines tested (UMUC3) was frankly tumorigenic; here, FGFR1 knockdown inhibited tumor growth. Our results indicate that FGFR1 has significant effects on urothelial cell phenotype and may represent a useful therapeutic target in some cases of urothelial carcinoma.

Use of pro re nata medications in acute inpatient care.

OBJECTIVES: Available evidence suggests that the use of 'as needed' (PRN; from the Latin pro re nata: for an occasion that has arisen) medications has remained a standard aspect of treatment in acute inpatient mental health units over a number of years despite lack of evidence from controlled clinical trials. The practice is one in which doctors and nurses are interdependent; that is, while doctors prescribe the medications, professional nurses are the ones who make the clinical decisions to administer them. The aim of the present study was to provide a detailed description of the circumstances surrounding the use of PRN medications across four inpatient units in Sydney. METHODS: The medical records of all patients admitted for >24h during a 2 month period were retrospectively audited for details regarding prescriptions and administrations of PRN medications. RESULTS: A total of 420 records were reviewed, producing a total of 3868 PRN medication administrations. Ninety-seven per cent of all patients were prescribed PRN medications and 93.8% were prescribed regular medications. The most frequently prescribed medications were second-generation antipsychotics for regular use along with benzodiazepine for PRN use. Nearly 84% of patients received at least one PRN medication during their admission, while patients diagnosed with personality disorder received more PRNs per day. The most common reason for PRN administration was patient agitation. The results indicated poor documentation in the prescription and documentation of PRN administrations. Also, the findings show that a small subset of the patients (5%) received >30% of all PRN medications. CONCLUSION: PRN medication use has endured as standard practice and the results of the present study are consistent with the reported frequency of use increasing slightly over the years. The combination of second-generation antipsychotics as regular medications and benzodiazepines for PRN medication is consistent with recommended treatment guidelines. The small subset of patients who were overrepresented in the PRN administrations is noteworthy.