The Patient's perspective: A review of the results from a radiotherapy patient experience survey in the North-West of England.

INTRODUCTION: A patient experience survey was undertaken for patients completing radiotherapy at the three Northwest of England Radiotherapy Providers. METHODS: A previously reported National Radiotherapy Patient Experience Survey was adapted and undertaken in the Northwest of England. Quantitative data was analysed to establish trends. Frequency distribution was applied to appraise the number of participants selecting each of the pre-determined responses. Thematic analysis of free text responses was conducted. RESULTS: The questionnaire received 653 responses from the 3 providers across seven departments. Thematic analysis revealed 3 themes; logistics, information and operational. CONCLUSION: The results indicate that the majority of patients are satisfied with their treatment and care. Patients' responses indicate areas for improvements. Expectancy theory states that an individual's satisfaction is related to the difference between expected service and the service received. Consequently, when reviewing services and developing improvement it is important to understand patients' expectations. This regional survey starts to capture what people receiving radiotherapy expect from the service and the professionals delivering their treatment. IMPLICATIONS FOR PRACTICE: This survey responses make a case for reviewing the information provision pre and post radiotherapy. This includes clarifying the understanding of consent for treatment including the intended benefits and potential late effects. There is an argument to offer information sessions prior to radiotherapy to achieve more relaxed and informed patients. A recommendation from this work is for the radiotherapy community undertake a national radiotherapy patient experience survey, facilitated via the 11 Radiotherapy ODNs. A national radiotherapy survey has multiple benefits to inform improvements in practice. This includes benchmarking services against national averages. This approach is aligned with the principles of the service specification in terms of reducing variation and increasing quality.

4-4-(Anilinomethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-ylbenzoic acid derivatives as potent anti-gram-positive bacterial agents.

A collection of potent antimicrobials consisting of novel 1,3-bis-benzoic acid and trifluoromethyl phenyl derived pyrazoles has been synthesized and tested for antibacterial activity. The majority of trifluoromethyl phenyl derivatives are highly potent growth inhibitors of Gram-positive bacteria and showed low toxicity to human cultured cells. In particular, two compounds (59 and 74) were selected for additional studies. These compounds are highly effective against Staphylococcus aureus as shown by a low minimum inhibitory concentration (MIC), a bactericidal effect in time-kill assays, moderate inhibition of biofilm formation as well as biofilm destruction, and a bactericidal effect against stationary phase cells representing non-growing persister cells. Multistep resistance assays showed a very low tendency for S. aureus and Enterococcus faecalis to develop resistance through mutation. Additionally, in vivo mouse model studies showed no harmful effects at doses up to 50 mg/kg using 14 blood plasma organ toxicity markers or TUNEL assay in liver and kidney. Investigations into the mode of action by performing macromolecular synthesis inhibition studies showed a broad range of inhibitory effects, suggesting targets that have a global effect on bacterial cell function.

Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors.

The phosphoinositide 3-kinases (PI3Ks) constitute an important family of lipid kinase enzymes that control a range of cellular processes through their regulation of a network of signal transduction pathways, and have emerged as important therapeutic targets in the context of cancer, inflammation and cardiovascular diseases. Since the mid-late 1990s, considerable progress has been made in the discovery and development of small molecule ATP-competitive PI3K inhibitors, a number of which have entered early phase human trials over recent years from which key clinical results are now being disclosed. This review summarizes progress made to date, primarily on the discovery and characterization of class I and dual class I/IV subtype inhibitors, together with advances that have been made in translational and clinical research, notably in cancer.

Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome.

Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses. IP results from mutations in the gene for NF-kappaB essential modulator (NEMO), with deletion of exons 4-10 of NEMO accounting for >80% of new mutations. Male fetuses inheriting this mutation and other "null" mutations of NEMO usually die in utero. Less deleterious mutations can result in survival of males subjects, but with ectodermal dysplasia and immunodeficiency. Male patients with skin, dental, and ocular abnormalities typical of those seen in female patients with IP (without immunodeficiency) are rare. We investigated four male patients with clinical hallmarks of IP. All four were found to carry the deletion normally associated with male lethality in utero. Survival in one patient is explained by a 47,XXY karyotype and skewed X inactivation. Three other patients possess a normal 46,XY karyotype. We demonstrate that these patients have both wild-type and deleted copies of the NEMO gene and are therefore mosaic for the common mutation. Therefore, the repeat-mediated rearrangement leading to the common deletion does not require meiotic division. Hypomorphic alleles, a 47,XXY karyotype, and somatic mosaicism therefore represent three mechanisms for survival of males carrying a NEMO mutation.

Parallel synthesis of isatin-based serine protease inhibitors.

The synthesis of N-functionalised isatins using parallel, solution synthesis is described. Functionalised polymers were employed as stoichiometric and catalytic reagents as well as purification media in the exercise, and the derivatives were screened against a panel of serine proteases; high percentage inhibition was observed in several cases.

Gallium diffusion in human root dentin: quantitative measurements by pulsed Nd:YAG laser ablation combined with an inductively coupled plasma mass spectrometer.

OBJECTIVE: The purpose of this work was to determine if gallium nitrate placed in human root canals would diffuse across root dentin and reach concentrations high enough to inhibit osteoclasts (approximately 10(-4) M). BACKGROUND DATA: External root resorption by osteoclasts is a common sequela of dental trauma. If not detected and treated, it can lead to the loss of a tooth. Gallium has recently been reported to inhibit osteoclastic resorption in vitro. METHODS: Roots were cleaned and shaped using standard endodontic procedures and the tips sealed with cyanoacrylate cement. The root canal space was filled with an aqueous solution of 1.0 M gallium nitrate chelated with 1.0 M sodium citrate buffer (pH 7.2). The roots were then sectioned longitudinally into two equal halves. Each half was fixed to a translation stage that moved at a constant rate beneath a frequency-quadrupled Nd-YAG laser (266 nm) laser that was used to sample the concentration of 43Ca, 69Ga, and 71Ga by laser ablation across the thickness of root dentin to the periodontal surface. The plume of ablated dentin was swept into an inductively heated plasma chamber by argon gas and hence into a mass spectrometer. RESULTS: Quantitative analyses of the distribution of gallium showed it was highest adjacent to the root canal space and fell as more peripheral sites were sampled but then rose slightly at the external boundary of the root which is covered with a thin layer of atubular cementum. CONCLUSIONS: Even the lowest concentrations of gallium found in peripheral root dentin exceeded the 10(-4) M concentration required to inhibit osteoclastic activity. This simple endodontic treatment should undergo clinical trials to determine its efficacy in vivo. The laser ablation, inductively coupled mass spectrometry method is a powerful analytic tool for measuring spatial distribution of materials in mineralized tissues.

Parallel solution synthesis of pyridinethiones, pyridinones and thienopyridines.

The parallel solution synthesis of three classes of heterocycles is described. Arrays of pyridinethiones, pyridinones and thienopyridines were prepared using one-step chemistry starting from readily accessible building blocks. The latter class of compounds was accessed by utilising a library-from-library approach.

Violence to staff in a general hospital setting.

The problem of aggression to staff in a general hospital was examined from the perspective of Poyner & Warne's (1986) model of workplace violence. A total of 396 staff (39% response rate) provided information on their experience of violence in the past year and a subsample were additionally interviewed about their current levels of mental health (GHQ). Some 72 staff (21% of respondents had been physically assaulted and 90% of these assaulted staff worked beyond the accident and emergency department, e.g. in medical wards. Nurses were physically assaulted, threatened and verbally abused at higher rates than other professionals. Employee factors (younger age, shorter National Health Service experience and attendance at violence training) were significantly associated with assault (P < 0.05). Postoperative confusion, receiving treatment and delayed treatment were common precursors of aggression. Mental health was significantly worse amongst staff exposed to threats (P < 0.01). This exploratory study establishes that violence is a problem across a number of general hospital departments and occupations and we argue that effective training should be made more available for staff at risk of assault.