Perceptions of paramedic educators on assessments used in the first year of a paramedic programme: a qualitative exploration.

BACKGROUND: In Ireland, there are currently three educational institutions (recognised institutions- RIs) providing paramedic programmes, accredited by the regulator, the Pre-Hospital Emergency Care Council (PHECC). Each RI assesses their students in-house, and in order to acquire a licence to practice, students must also pass summative assessments provided by PHECC. These assessments comprise multiple choice questions, short answer questions and skills assessments. The objective of this study was to explore the perceptions and experiences of paramedic educators of assessments used within their institution and by the regulator to provide insights that could inform the future design of paramedic assessments. METHODS: A qualitative study with an interpretivist approach and purposive sampling strategy was performed. Semi-structured interviews were conducted with educators from one RI, across their three sites. Data were analysed using an inductive approach to thematic analysis. RESULTS: Four major themes were identified in the data: improving assessments by enhancing authenticity, modifying the current process of assessment, aligning the PHECC and RI examinations and opportunities to use assessment as learning. CONCLUSIONS: This study identifies perceived deficits and opportunities in the assessments currently used for paramedic students and ways in which these assessments could be improved. While participants were relatively content with their own RI assessments, they identified ways to improve both the RI and PHECC assessments. Modifying some of the current methods could be a useful first step. In particular, assessments used by PHECC could be improved by reflecting 'real-world' practice. The inclusion of additional assessment methods by PHECC, a continuous assessment process or devolvement of the entire assessment suite, to the RI/University has the potential to enhance assessments, particularly summative assessments, for paramedic students.

Convergence and translation: attitudes to inter-professional learning and teaching of creative problem-solving among medical and engineering students and staff.

BACKGROUND: Healthcare worldwide needs translation of basic ideas from engineering into the clinic. Consequently, there is increasing demand for graduates equipped with the knowledge and skills to apply interdisciplinary medicine/engineering approaches to the development of novel solutions for healthcare. The literature provides little guidance regarding barriers to, and facilitators of, effective interdisciplinary learning for engineering and medical students in a team-based project context. METHODS: A quantitative survey was distributed to engineering and medical students and staff in two universities, one in Ireland and one in Belgium, to chart knowledge and practice in interdisciplinary learning and teaching, and of the teaching of innovation. RESULTS: We report important differences for staff and students between the disciplines regarding attitudes towards, and perceptions of, the relevance of interdisciplinary learning opportunities, and the role of creativity and innovation. There was agreement across groups concerning preferred learning, instructional styles, and module content. Medical students showed greater resistance to the use of structured creativity tools and interdisciplinary teams. CONCLUSIONS: The results of this international survey will help to define the optimal learning conditions under which undergraduate engineering and medicine students can learn to consider the diverse factors which determine the success or failure of a healthcare engineering solution.

Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2.

OBJECTIVE: Notch signalling pathways are critical for angiogenesis and endothelial cell (EC) fate; however the mechanisms regulating these processes in the inflamed joint remain to be elucidated. Here, we examine whether Notch signalling mediates vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2)-induced vascular function. METHODS: Notch-1 intracellular domain (Notch-1 IC), Notch-4 IC, Delta-like-ligand 4, Hes-related transcriptional repressors-1 and 2 (Hrt-1, Hrt-2) mRNA and/or protein expression was measured by Real-time PCR and/or western blot. VEGF/Ang2 induced EC function was assessed using transwell invasion chambers, matrigel tube formation assays and wound repair scratch assays±Notch-1 siRNA or an γ-secretase inhibitor N-(N-(3,5-Difluorophenacetyl-L-alanly))-S-phenylglycine-t-Butyl Ester (DAPT) in RA synovial explants or human microvascular EC. Interleukin (IL)-6 and IL-8 were measured by ELISA and MMP2 and 9 by gelatine zymography. RESULTS: Notch-1 IC and Notch-4 IC protein expressions were demonstrated in RA and psoriatic arthritis synovial biopsies, with minimal expression observed in Osteoarthritis (OA). VEGF and Ang2 induced Notch-1 IC/ Notch-4 IC protein expression in synovial explant cultures and human microvascular EC levels were further potentiated by VEGF/Ang2 stimulation in combination. Notch-1, Delta-like-ligand 4, and Hrt-2 mRNA expression were significantly induced by VEGF and Ang2 alone and in combination. Furthermore VEGF/Ang2-induced EC invasion, angiogenesis and migration were inhibited by Notch-1 siRNA or DAPT. Conditioned media from VEGF/Ang2 stimulated RA synovial explants induced EC tube formation, an effect that was inhibited by DAPT. Finally, DAPT significantly decreased VEGF/Ang2 induced IL-6, IL-8, MMP2 and 9 expressions in RA synovial explants. CONCLUSIONS: Notch-1 mediates VEGF/Ang2-induced angiogenesis and EC invasion in inflammatory arthritis.

Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

OBJECTIVE: To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. METHODS: The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. RESULTS: Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of <20 mm Hg (<3% O2) than in those with tissue PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. CONCLUSION: Our findings indicate that Notch-1 is expressed in synovial tissue and that increased NICD expression is associated with low in vivo tissue PO2. Furthermore, Notch-1/HIF-1α interactions mediate hypoxia-induced angiogenesis and invasion in inflammatory arthritis.

Medical school attrition-beyond the statistics a ten year retrospective study.

BACKGROUND: Medical school attrition is important--securing a place in medical school is difficult and a high attrition rate can affect the academic reputation of a medical school and staff morale. More important, however, are the personal consequences of dropout for the student. The aims of our study were to examine factors associated with attrition over a ten-year period (2001-2011) and to study the personal effects of dropout on individual students. METHODS: The study included quantitative analysis of completed cohorts and qualitative analysis of ten-year data. Data were collected from individual student files, examination and admission records, exit interviews and staff interviews. Statistical analysis was carried out on five successive completed cohorts. Qualitative data from student files was transcribed and independently analysed by three authors. Data was coded and categorized and key themes were identified. RESULTS: Overall attrition rate was 5.7% (45/779) in 6 completed cohorts when students who transferred to other medical courses were excluded. Students from Kuwait and United Arab Emirates had the highest dropout rate (RR = 5.70, 95% Confidence Intervals 2.65 to 12.27;p < 0.0001) compared to Irish and EU students combined. North American students had a higher dropout rate than Irish and EU students; RR = 2.68 (1.09 to 6.58;p = 0.027) but this was not significant when transfers were excluded (RR = 1.32(0.38, 4.62);p = 0.75). Male students were more likely to dropout than females (RR 1.70, .93 to 3.11) but this was not significant (p = 0.079).Absenteeism was documented in 30% of students, academic difficulty in 55.7%, social isolation in 20%, and psychological morbidity in 40% (higher than other studies). Qualitative analysis revealed recurrent themes of isolation, failure, and despair. Student Welfare services were only accessed by one-third of dropout students. CONCLUSIONS: While dropout is often multifactorial, certain red flag signals may alert us to risk of dropout including non-EU origin, academic struggling, absenteeism, social isolation, depression and leave of absence. Psychological morbidity amongst dropout students is high and Student Welfare services should be actively promoted. Absenteeism should prompt early intervention. Behind every dropout statistic lies a personal story. All medical schools have a duty of care to support students who leave the medical programme.

"If we build it, will it stay?" A case study of the sustainability of whole-system change in London.

CONTEXT: The long-term sustainability of whole-system change programs is rarely studied, and when it is, it is inevitably undertaken in a shifting context, thereby raising epistemological and methodological questions. This article describes a transferable methodology that was developed to guide the evaluation of a three-year follow-up of a large health care change program in London, which took place during a period of economic turbulence and rapid policy change. METHOD: Using a mixed-method organizational case study design, we studied three services (stroke, kidney, and sexual health) across primary and secondary care. Each had received £5 million (US$7.8 million) in modernization funding in 2004. In 2010/2011, we gathered data on the services and compared them with data from 2004 to 2008. The new data set contained quantitative statistics (access, process, and outcome metrics), qualitative interviews with staff and patients, documents, and field notes. Our data analysis was informed by two complementary models of sustainability: intervention-focused (guided by the question, What, if anything, of the original program has been sustained?) and system-dynamic (guided by the question, How and why did change unfold as it did in this complex system?). FINDINGS: Some but not all services introduced in the original transformation effort of 2004-2008 were still running; others had ceased or been altered substantially to accommodate contextual changes (e.g., in case mix, commissioning priorities, or national policies). Key cultural changes (e.g., quality improvement, patient centeredness) largely persisted, and innovative ideas and practices had spread elsewhere. To draw causal links between the original program and current activities and outcomes, it was necessary to weave a narrative thread with multiple intervening influences. In particular, against a background of continuous change in the local health system, the sustainability of the original vision and capacity for quality improvement was strongly influenced by (1) stakeholders' conflicting and changing interpretations of the targeted health need; (2) changes in how the quality cycle was implemented and monitored; and (3) conflicts in stakeholders' values and what each stood to gain or lose. CONCLUSIONS: The sustainability of whole-system change embodies a tension between the persistence of past practice and the adaptation to a changing context. Although the intervention-focused question, What has persisted from the original program? (addressed via a conventional logic model), may be appropriate, evaluators should qualify their findings by also considering the system-dynamic question, What has changed, and why? (addressed by producing a meaningful narrative).

Medical student empathy and breaking bad news communication in a simulated consultation.

OBJECTIVES: This study examined the relationship between self-reported empathy and breaking bad news (BBN) communication skills performance in a sample of undergraduate medical students (n = 100) in the clinical years of their program. METHODS: Correlational and regression analysis examined the relationship between Jefferson Scale of Physician Empathy (JSPE-S) and Empathy Quotient (EQ) scores, and communication skills performance based on students' application of the SPIKES protocol to a BBN scenario in a simulated encounter. RESULTS: Higher BBN communication skills performance was positively correlated with scores on the "Social Skills" EQ sub-scale (r (99) = 0.31, p = 0.002), which measures spontaneous and context-independent use of social skills. Multiple regression confirmed that "Social Skills" sub-scale variation predicted BBN score variation (B = 2.17, 95% CI = 0.65-3.69, p < 0.01). A weak positive association was also observed between BBN score and the "Standing in Patient's Shoes" JSPE sub-scale (r (99) = 0.22, p = 0.03). CONCLUSIONS: Findings suggest that specific aspects of dispositional empathy may moderate BBN communications skills competence in medical students. PRACTICE IMPLICATIONS: A better understanding of the moderating role of personality may lead to more tailored BBN communications skills training interventions and improved transfer of skills to workplace settings.

Notch and vascular smooth muscle cell phenotype.

The Notch signaling pathway is critical for cell fate determination during embryonic development, including many aspects of vascular development. An emerging paradigm suggests that the Notch gene regulatory network is often recapitulated in the context of phenotypic modulation of vascular smooth muscle cells (VSMC), vascular remodeling, and repair in adult vascular disease following injury. Notch ligand receptor interactions lead to cleavage of receptor, translocation of the intracellular receptor (Notch IC), activation of transcriptional CBF-1/RBP-Jkappa-dependent and -independent pathways, and transduction of downstream Notch target gene expression. Hereditary mutations of Notch components are associated with congenital defects of the cardiovascular system in humans such as Alagille syndrome and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Recent loss- or gain-of-function studies have provided insight into novel Notch-mediated CBF-1/RBP-Jkappa-dependent and -independent signaling and cross-regulation to other molecules that may play a critical role in VSMC phenotypic switching. Notch receptors are critical for controlling VSMC differentiation and dictating the phenotypic response following vascular injury through interaction with a triad of transcription factors that act synergistically to regulate VSMC differentiation. This review focuses on the role of Notch receptor ligand interactions in dictating VSMC behavior and phenotype and presents recent findings on the molecular interactions between the Notch components and VSMC-specific genes to further understand the function of Notch signaling in vascular tissue and disease.

Sonic Hedgehog induces Notch target gene expression in vascular smooth muscle cells via VEGF-A.

OBJECTIVE: Notch, VEGF, and components of the Hedgehog (Hh) signaling pathway have been implicated in vascular morphogenesis. The role of Notch in mediating hedgehog control of adult vascular smooth muscle cell (SMC) growth and survival remains unexplored. METHODS AND RESULTS: In cultured SMCs, activation of Hh signaling with recombinant rShh (3.5 mug/mL) or plasmid encoded Shh increased Ptc1 expression, enhanced SMC growth and survival and promoted Hairy-related transcription factor (Hrt) expression while concomitantly increasing VEGF-A levels. These effects were significantly reversed after Hh inhibition with cyclopamine. Shh-induced stimulation of Hrt-3 mRNA and SMC growth and survival was attenuated after inhibition of Notch-mediated CBF-1/RBP-Jk-dependent signaling with RPMS-1 while siRNA knockdown of Hrt-3 inhibited SMC growth and survival. Recombinant VEGF-A increased Hrt-3 mRNA levels while siRNA knockdown abolished rShh stimulated VEGF-A expression while concomitantly inhibiting Shh-induced increases in Hrt-3 mRNA levels, proliferating cell nuclear antigen (PCNA), and Notch 1 IC expression, respectively. Hedgehog components were expressed within intimal SMCs of murine carotid arteries after vascular injury concomitant with a significant increase in mRNA for Ptc1, Gli(2), VEGF-A, Notch 1, and Hrts. CONCLUSIONS: Hedgehog promotes a coordinate regulation of Notch target genes in adult SMCs via VEGF-A.

An e-Delphi Study to Identify Priority Areas for Education on Advance Care Planning in COPD Management.

BACKGROUND: Individuals with COPD typically experience a gradual deterioration in health, with exacerbations and increased health-care utilization in the years before death. As such, adequate planning of future care is necessary. The objective of this research was to identify gaps in health-care professionals' knowledge related to advance care planning (ACP) for patients with COPD and to prioritize content of future educational interventions for health-care professionals accordingly. METHODS: A modified e-Delphi technique with 2 rounds of rating was used. After a literature review and expert consultation, a multidisciplinary panel developed 40 statements. Statements that did not achieve consensus in round 1 were re-presented in round 2, together with new statements developed after participant feedback. Health-care professionals with expertise in caring for people with COPD were asked to rate the importance of including each of the 40 topics in future educational interventions related to ACP and COPD by using a 5-point Likert scale. Average scores for each topic were calculated and expressed as percentages. Consensus on each topic was achieved if it obtained a score of ≥80%. RESULTS: Thirty-eight health-care professionals were invited to participate, of whom, 21 (55%) took part in both rounds. Consensus was achieved for 32 of 40 statements (80%) in round 1 and for 5 of 10 statements (50%) in round 2. All statements relating to "COPD and palliative care" and "legislation for ACP" achieved consensus after one round. CONCLUSIONS: This study uncovered specific topics that related to ACP and COPD that health-care professionals believe should be included in future educational interventions. In particular, there is a clear need for training that addresses the legal issues surrounding ACP, and information on the best timing and content of ACP discussions with patients with COPD. Such training may enable health-care professionals to incorporate ACP into routine COPD management and, ultimately, improve patient care.

Advance Care Planning for Individuals With Chronic Obstructive Pulmonary Disease: A Scoping Review of the Literature.

CONTEXT: Individuals with chronic obstructive pulmonary disease (COPD) typically experience a gradual worsening of the illness in the years before death. Owing to difficulties in predicting the disease trajectory or the timing of acute exacerbations, advance care planning (ACP) may be of particular importance for individuals with COPD. OBJECTIVES: The objective of this study was to review and summarize the available literature on current practices around ACP in COPD. METHODS: A scoping review of the literature was conducted following the Arksey and O'Malley framework. Original research studies of any design were included. RESULTS: Twenty-eight studies were included. Across studies, there was agreement that ACP should be incorporated into routine COPD management. There was evidence that this does not occur in everyday practice, with conversations tending to focus on day-to-day symptom management. Barriers included prognosis uncertainty, insufficient time and training, and a lack of protocols for who is responsible for initiating ACP. Facilitators included the use of transition points for identifying the appropriate time to initiate ACP, and an increased focus on ACP in professional education. The occurrence of repeated episodes of acute care was identified as a key transition point for identifying the palliative stage of COPD and an appropriate time to initiate ACP. CONCLUSION: The findings of this review confirm agreement among health care professionals and patients with COPD and their carers that ACP should be incorporated into routine COPD management. The use of transition points may help health care professionals overcome the barrier of prognosis uncertainty and identify patients who might benefit from ACP.

Advance care planning in COPD: guidance development for healthcare professionals.

OBJECTIVES: To examine current practices, attitudes and levels of confidence related to advance care planning (ACP) in patients with chronic obstructive pulmonary disease (COPD) among healthcare professionals working in Ireland. This will inform future clinical guidance development. METHODS: A cross-sectional survey of healthcare professionals. RESULTS: There were 143 participants (109 general practitioners, 25 nurses, 7 physiotherapists and 2 consultant physicians). The majority (82%, n=117) cared for patients with COPD weekly, but only 23% (n=33) had initiated ACP with a patient with COPD over the previous 6 months. Overall, 59% (n=85) answered ≥6 of 8 general knowledge questions correctly. Participants demonstrated positive attitudes towards ACP (mean score 3.6/5.0), but confidence levels were low (2.2/4.0). Most thought ACP was appropriate for patients with severe or very severe COPD (71%, n=101%, and 91%, n=130, respectively) but were unsure or felt that it was not appropriate for those with mild-moderate COPD. However, almost all participants (97%, n=139) stated that if a patient expressed a desire to have ACP discussions, they would comply. Topics most likely to be discussed related to diagnosis and treatment options. Death and end-of-life issues were rarely discussed. The death of a family member or friend and participation in support groups were identified as new 'triggers' for initiating ACP. CONCLUSIONS: Targeted education to improve general knowledge and confidence levels among healthcare professionals, together with initiatives to increase public awareness of ACP so that patients themselves might be more inclined to start the discussion, may help increase the uptake of ACP for this patient group.

Control of antiviral innate immune response by protein geranylgeranylation.

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates the recruitment of caspase-8 and cFLIPL to the MAVS signalosome and the subsequent cleavage of Ripk1 that terminates MAVS signaling. Consistently, mice with myeloid deficiency of protein geranylgeranylation showed improved survival upon influenza A virus infection. Our work revealed a critical role of protein geranylgeranylation in regulating antiviral innate immune response.

Cyclic strain inhibits Notch receptor signaling in vascular smooth muscle cells in vitro.

Notch signaling has been shown recently to regulate vascular cell fate in adult cells. By applying a uniform equibiaxial cyclic strain to vascular smooth muscle cells (SMCs), we investigated the role of strain in modulating Notch-mediated growth of SMCs in vitro. Rat SMCs cultured under conditions of defined equibiaxial cyclic strain (0% to 15% stretch; 60 cycles/min; 0 to 24 hours) exhibited a significant temporal and force-dependent reduction in Notch 3 receptor expression, concomitant with a significant reduction in Epstein Barr virus latency C promoter-binding factor-1/recombination signal-binding protein of the Jkappa immunoglobulin gene-dependent Notch target gene promoter activity and mRNA levels when compared with unstrained controls. The decrease in Notch signaling was Gi-protein- and mitogen-activated protein kinase-dependent. In parallel cultures, cyclic strain inhibited SMC proliferation (cell number and proliferating cell nuclear antigen expression) while significantly promoting SMC apoptosis (annexin V binding, caspase-3 activity and bax/bcl-x(L) ratio). Notch 3 receptor overexpression significantly reversed the strain-induced changes in SMC proliferation and apoptosis to levels comparable to unstrained control cells, whereas Notch inhibition further potentiated the changes in SMC apoptosis and proliferation. These findings suggest that cyclic strain inhibits SMC growth while enhancing SMC apoptosis, in part, through regulation of Notch receptor and downstream target gene expression.

Adrenoceptor and cholinoceptor modulation of rat pulmonary vein cardiac muscle contractility.

Cardiac muscle extends into mammalian pulmonary veins for variable distances according to species. This study has addressed the autonomic control of electrically paced cardiac muscle of the pulmonary vein of the rat. Contractile responses of Wistar rat pulmonary veins were investigated under isometric conditions in vitro. Vessels were electrically paced at 1 Hz (10 V, 1 ms pulse width). Acetylcholine (ACh, 1 nM-10 microM) attenuated the contractile response (maximum inhibition at 1 microM, 41+/-15%, mean+/-SD). The attenuation was inhibited by atropine (p<0.05) and partially inhibited (7+/-4%, mean+/-SD, p<0.01) by removal of the endothelium. Noradrenaline (NA, 1 nM-10 microM) augmented the cardiac muscle contractility in a fashion partially inhibited by atenolol; augmentation at 10 microM was reduced from 169+/-9% (n=6) to 135+/-9% (n=5), (p<0.05). The ability of ACh to attenuate the contractile responses was unaffected by the presence of NA. In conclusion, ACh has a muscarinic receptor-mediated negative inotropic effect upon the cardiac muscle of the pulmonary vein of the rat mediated in part by the endothelium. The cardiac muscle expresses a positive inotropic response to NA partly mediated by beta1-adrenoceptors that can be antagonised by ACh. Therefore, pulmonary vein cardiac muscle function is modulated by competing autonomic influences which may be of significance to the generation of atrial fibrillation events.

Modification of oral dosage forms for the older adult: An Irish prevalence study.

Age-related pharmacological changes complicate oral dosage form (ODF) suitability for older adults. The aim of this study was to investigate the appropriateness of ODF for older adults by determining the prevalence of ODF modifications in an aged care facility in Ireland. Drug charts for eligible patients were obtained. Details of all medications administered were recorded. ODF modifications were examined to determine if they were evidence-based: defined as complying with the product license or best practice guidelines (BPG). In total, of 111 patients, 35.1% received at least one modified medicine. Medicines were most commonly modified to facilitate fractional dosing (82.0%). Of the 68 instances of medicine modification, 35.3% complied with the product license. Of the 44 unlicensed modifications, 14 complied with BPG. Therefore, 44.1% of modifications were not evidence-based. This study highlights that clinicians have to routinely tailor commercial ODF to meet older patients' needs despite the lack of an evidence-base for almost half of these modifications. The main factor contributing to these modifications is the lack of appropriate, licensed dosage forms. However, reimbursement policies also play a role. Research is needed to optimise medicine administration and to provide clinicians with much needed evidence to support their daily practice.

Place of death and its predictors for local patients registered at a comprehensive cancer center.

PURPOSE: To help with planning of a palliative care program, we reviewed the place of death of patients who were registered at our comprehensive cancer center and explored factors that predicted death in the hospital versus death at home. PATIENTS AND METHODS: A retrospective study was undertaken of local patients who were registered at the University of Texas M.D. Anderson Cancer Center and died during the 1997/1998 fiscal year. Data from the institutional tumor registry and from the State of Texas Bureau of Vital Statistics file were collected and analyzed. The main outcome measures were place of death, patient characteristics associated with place of death, and time from registration at the institution to death. RESULTS: Of 1,793 local patients, 251 (14%) died at M.D. Anderson Cancer Center; the remaining 86% died elsewhere. A total of 617 (34%) died at home, and 929 (52%) died in an acute hospital setting (including M.D. Anderson). A total of 1,040 (58%) died within 2 years of registration. The risk of hospital death versus home death increased for patients with cancer at a hematologic site (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.8 to 6.8) and black ethnicity (OR, 1.9; 95% CI, 1.4 to 2.6) and decreased for patients who paid with Medicare (OR, 0.71; 95% CI, 0.57 to 0.90). CONCLUSION: Most patients died in an acute care hospital setting and within 2 years of registration. Our data show some predictors of hospital death for cancer patients and suggest that better hospital palliative care services and integrated palliative care systems that bridge community and acute hospitals are needed.

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.

Notch 1 and 3 receptor signaling modulates vascular smooth muscle cell growth, apoptosis, and migration via a CBF-1/RBP-Jk dependent pathway.

Vascular smooth muscle cell (SMC) fate decisions (cell growth, migration, and apoptosis) are fundamental features in the pathogenesis of vascular disease. We investigated the role of Notch 1 and 3 receptor signaling in controlling adult SMC fate in vitro by establishing that hairy enhancer of split (hes-1 and -5) and related hrt's (hrt-1, -2, and -3) are direct downstream target genes of Notch 1 and 3 receptors in SMC and identified an essential role for nuclear protein CBF-1/RBP-Jk in their regulation. Constitutive expression of active Notch 1 and 3 receptors (Notch IC) resulted in a significant up-regulation of CBF-1/RBP-Jk-dependent promoter activity and Notch target gene expression concomitant with significant increases in SMC growth while concurrently inhibiting SMC apoptosis and migration. Moreover, inhibition of endogenous Notch mediated CBF-1/RBP-Jk regulated gene expression with a non-DNA binding mutant of CBF-1, a Notch IC deleted of its delta RAM domain and the Epstein-Barr virus encoded RPMS-1, in conjunction with pharmacological inhibitors of Notch IC receptor trafficking (brefeldin A and monensin), resulted in a significant decrease in cell growth while concomitantly increasing SMC apoptosis and migration. These findings suggest that endogenous Notch receptors and downstream target genes control vascular cell fate in vitro. Notch signaling, therefore, represents a novel therapeutic target for disease states in which changes in vascular cell fate occur in vivo.

Survey of Health Care Workers Suggests Unmet Palliative Care Needs in Parkinson's Disease.

The aim of this study was to investigate the knowledge, attitudes, and previous training of Irish health care workers (HCWs) in palliative care in end-stage Parkinson's disease (PD). A survey was distributed to HCWs, including neurologists, geriatricians, general practitioners, nurses, and allied health professionals, in acute and community settings in the Republic of Ireland. Three-hundred and six surveys were returned (32% average response rate). Most HCWs (90%) believed that people with PD have palliative care needs; however, 76% of HCWs also said that these needs are "never" or only "sometimes" met. These unmet needs are reflected in relatively few people with PD being referred to specialist palliative care; 48% of hospital consultants had referred no patients in the previous 6 months, and just 7% had referred more than 10. Just 8% of the HCWs surveyed reported having any training on the palliative care aspects of PD, and 97% expressed an interest in receiving further education. Respondents wanted all topics pertinent to palliative care in PD covered, and many felt that they also needed further information on PD in general. People with PD are seen to have palliative care needs; however, the findings suggest that these needs are not being met. There is a discrepancy between best practice recommendations for palliative care in PD and the beliefs and practices of HCWs. Further education in palliative care in PD is needed to ensure better quality of care for people with PD.