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Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events (ADEs), hospitalization, and wasteful utilization of resources. We randomized 400 hospitalized patients aged ≥ 65 years to receive either the usual pharmaceutical care (control) or screening with STOPP/START criteria followed up with recommendations to their attending physicians (intervention). The Medication Appropriateness Index (MAI) and Assessment of Underutilization (AOU) index were used to assess prescribing appropriateness, both at the time of discharge and for 6 months after discharge. Unnecessary polypharmacy, the use of drugs at incorrect doses, and potential drug-drug and drug-disease interactions were significantly lower in the intervention group at discharge (absolute risk reduction 35.7%, number needed to screen to yield improvement in MAI = 2.8 (95% confidence interval 2.2-3.8)). Underutilization of clinically indicated medications was also reduced (absolute risk reduction 21.2%, number needed to screen to yield reduction in AOU = 4.7 (95% confidence interval 3.4-7.5)). Significant improvements in prescribing appropriateness were sustained for 6 months after discharge.

Background inappropriate prescribing encompasses acts of commission i.e. giving drugs that are contraindicated or unsuitable, and acts of omission i.e. failure to prescribe drugs when indicated due to ignorance of evidence base or other irrational basis e.g. ageism. There are considerable published data on the prevalence of inappropriate prescribing; however, there are no recent published data on the prevalence of acts of omission. The aim of this study was to calculate the prevalence of acts of prescribing omission in a population of consecutively hospitalised elderly people. Methods a screening tool (screening tool to alert doctors to the right treatment acronym, START), devised from evidencebased prescribing indicators and arranged according to physiological systems was prepared and validated for identifying prescribing omissions in older adults. Data on active medical problems and prescribed medicines were collected in 600 consecutive elderly patients admitted from the community with acute illness to a teaching hospital. On identification of an omitted medication, the patient's medical records were studied to look for a valid reason for the prescribing omission. Results using the START list, we found one or more prescribing omissions in 57.9% of patients. In order of prevalence, the most common prescribing omissions were: statins in atherosclerotic disease (26%), warfarin in chronic atrial fibrillation (9.5%), anti-platelet therapy in arterial disease (7.3%) and calcium/vitamin D supplementation in symptomatic osteoporosis (6%). Conclusion failure to prescribe appropriate medicines is a highly prevalent problem among older people presenting to hospital with acute illness. A validated screening tool (START) is one method of systematically identifying appropriate omitted medicines in clinical practice.

Host-tumor interaction is considered critical in carcinogenesis, tumor invasion, and metastasis. To explore the reciprocal effects of host-tumor interaction, we developed a system to assess the gene expression patterns of A2058 human melanoma cells cocultured in fibrillar collagen with HS-68 primary human fibroblasts. The gene expression pattern of the cocultured A2058 cells was only modestly affected, whereas the HS-68 fibroblast gene expression pattern was significantly altered. Interleukin-11 and inhibitor of DNAbinding domain-1 gene expression in the cocultured A2058 cells was down-regulated, indicative of a proinflammatory response and resistance to apoptosis, respectively. The overall pattern of up-regulated genes indicated triggering of the proinflammatory process. In addition, the melanoma growth and migration stimulatory chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts. These results were corroborated by additional coculture experiments with the melanoma cell lines WM-164, BLM, and SK-Mel-28 and immunohistochemistry on invasive human melanoma sections. Taken together, these results indicate that tumor cells cause a proinflammatory and melanoma growth-promoting response in stromal fibroblasts. The role of inflammation in carcinogenesis, tumor promotion, invasion, and metastasis is viewed as being increasingly important and the results of these studies underscore this as well as identify certain key proteins that are expressed as a result of the complex interactive processes in the host-tumor microenvironment. (Cancer Res 2005; 65(10): 4134-46)

BackgroundDespite advanced nursing roles having a research competency, participation in research is low. There are many barriers to participation in research and few interventions have been developed to address these. This paper aims to describe the implementation of an intervention to increase research participation in advanced clinical nursing roles and evaluate its effectiveness.MethodsThe implementation of the intervention was carried out within one hospital site. The evaluation utilised a mixed methods design and a implementation science framework. All staff in advanced nursing roles were invited to take part, all those who were interested and had a project in mind could volunteer to participate in the intervention. The intervention consisted of the development of small research groups working on projects developed by the nurse participant/s and supported by an academic and a research fellow. The main evaluation was through focus groups. Output was analysed using thematic analysis. In addition, a survey questionnaire was circulated to all participants to ascertain their self-reported research skills before and after the intervention. The results of the survey were analysed using descriptive statistics. Finally an inventory of research outputs was collated.ResultsIn the first year, twelve new clinical nurse-led research projects were conducted and reported in six peer reviewed papers, two non-peer reviewed papers and 20 conference presentations. The main strengths of the intervention were its promptness to complete research, to publish and to showcase clinical innovations. Main barriers identified were time, appropriate support from academics and from peers. The majority of participants had increased experience at scientific writing and data analysis.ConclusionThis study shows that an intervention, with minor financial resources; a top down approach; support of a hands on research fellow; peer collaboration with academics; strong clinical ownership by the clinical nurse researcher; experiential learning opportunities; focused and with needs based educational sessions, is an intervention that can both increase research outputs and capacity of clinically based nurses. Interventions to further enhance nursing research and their evaluation are crucial if we are to address the deficit of nurse-led patient-centred research in the literature.Electronic supplementary materialThe online version of this article (doi:10.1186/s12912-017-0214-6) contains supplementary material, which is available to authorized users.

To validate STOPPFrail, a list of explicit criteria for potentially inappropriate medication (PIM) use in frail older adults with limited life expectancy. Design A Delphi consensus survey of an expert panel comprising academic geriatricians, clinical pharmacologists, palliative care physicians, old age psychiatrists, general practitioners and clinical pharmacists. Setting Ireland. Subjects Seventeen panellists. Methods STOPPFrail criteria were initially created by the authors based on clinical experience and literature appraisal. Criteria were organised according to physiological system; each criterion accompanied by an explanation. Using Delphi consensus methodology, panellists ranked their agreement with each criterion on a 5-point Likert scale and provided written feedback. Criteria with a median Likert response of 4/5 (agree/strongly agree) and a 25 th centile of ≥4 were included in the final list. Results All panellists completed 3 Delphi rounds. Thirty criteria were proposed; 27 were accepted. The first two criteria suggest deprescribing medications without indication or where compliance is poor. The remaining 25 criteria include lipid-lowering therapies, alpha-blockers for hypertension, antiplatelets, neuroleptics, memantine, proton-pump-inhibitors, H2-receptor antagonists, antispasmodic agents, theophylline, leukotriene antagonists, calcium supplements, bone anti-resorptive therapy, selective oestrogen receptor modulators, non-steroidal anti-inflammatories, corticosteroids, 5-alpha-reductase inhibitors, alpha-1-selective blockers, muscarinic antagonists, oral diabetic agents, ACE-inhibitors, angiotensin receptor blockers, systemic oestrogens, multivitamins, nutritional supplements and prophylactic antibiotics. Consensus could not be reached on the inclusion of acetyl-cholinesterase inhibitors. Full consensus was reached on exclusion of anticoagulants and anti-depressants from the list. Conclusion STOPPFrail comprises 27 criteria relating to medications that are potentially inappropriate in frail older patients with limited life expectancy. STOPPFrail may assist physicians in deprescribing medications in these patients.

Atrolysin A and jararhagin are class P-III snake venom metalloproteinases (SVMPs) with three distinct domains: a metalloproteinase, a disintegrin-like and a cysteinerich. The metalloproteinase and the disintegrin-like domains of atrolysin A and jararhagin contain peptide sequences that interact with K K2L L1 integrin and inhibit the platelet responses to collagen. Recently, the recombinant cysteine-rich domain of atrolysin A was shown to have similar e¡ects, but the sequence(s) responsible for this is unknown. In this report, we demonstrate two complete peptide sequences from the homologous cysteine-rich domains of atrolysin A and jararhagin that inhibit both platelet aggregation by collagen and adhesion of K K2-expressing K562 cells to this protein. In addition, the peptide e¡ects on platelets do not seem to involve an inhibition of GPVI. These results identify, for the ¢rst time, sites in the cysteine-rich domain of SVMPs that inhibit cell responses to collagen and reveal the complexity of the potential biological e¡ects of these enzymes with multifunctional domains. ß

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