User-centered healthcare IT: meaningful or meaningless?

This panel aims to discuss concepts, assumptions and visions of user- centered information technology for healthcare. It presents two opposite views on the subject. The discussion is informed by findings of three research projects evaluating the implementation of e-prescribing systems, electronic transmission of prescriptions, and electronic health records in the UK. The timeliness and perhaps urgency of such a debate are due to the incessantly increasing worldwide computerization of healthcare, concurrent to an ambiguity of the effect of IT on care processes, outcomes and user satisfaction

NGO Partnership Project: Integration of Service Delivery by Large Multi-Service Non Government Providers, Final Report

The research on which this report was based was commissioned by the Department of Family and Community Services (FaCS) in 2001. The purpose of the study was to shed light on developments in service integration by large, multi-service, non-governmental organisations (NGOs) in the community welfare sector. A sample of 10 national and State-based NGOs was selected for the study in consultation with the Department. These represent major service providers in a range of welfare and community service fields. Nine of the 10 organisations agreed, when approached, to take part in the study. Interviews were carried out, either face-to-face or by telephone, with both senior and operational management in the organisations. Summary drafts of the interviews were returned to respondents for comment and checking. Limited review of annual reports and other documents was also undertaken

The Lantern Vol. 58, No. 2, Summer 1991

• We All Fall Up • Clerical Nightmares • The Brass Bed • Mon Amour • The Lady of J. Alfred Prufrock • Forbidden Places • Edge of the Dance • Crystal World • Saturday, July 12, 1978, 4:59 pm • Of You I Think • Just Another Statistic • A $16 Word in a$4.99 Trashcan • Souvenir • The Jester • Against a Rock • I Wish I Were a Fish • Too Small, Too Weak • Somewheres in N.Y.C. • Stuck Up • Patterns • I Should Tell You Now • Me, Tommy, and Miss May • Two Hands • All-Natural, Organically Grown Macadamia Butter • Irony of a Suburban Deathhttps://digitalcommons.ursinus.edu/lantern/1138/thumbnail.jp

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). METHODS: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage. RESULTS: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed. CONCLUSIONS: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01862003

HER2-HER3 heterodimer quantification by FRET-FILM and patient subclass analysis of the COIN colorectal trial

BACKGROUND: The phase 3 MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. METHODS: HER2-HER3 dimerization was quantified by 'FLIM Histology' in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy +/-cetuximab. Bayesian latent class analysis (LCA) and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation and cetuximab on progression-free survival (PFS) and overall survival (OS). All statistical tests were two-sided. RESULTS: LCA on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS: 1624 days [95%CI=1466-1816] vs 461 [95%CI=431-504]): Class 1 (15.6%) showed a benefit from cetuximab in OS (HR = 0.43 [95%CI=0.25-0.76]; p = 0.004). Class 2 showed an association of increased HER2-HER3 with better OS (HR = 0.64 [95%CI=0.44-0.94]; p = 0.02). A class prediction signature was formed and tested on an independent validation cohort (N = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (N = 1,630) based on 10 baseline clinicopathological and genetic covariates. CONCLUSIONS: Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment

The Lantern Vol. 59, No. 2, Summer 1992

• Mr. Foley\u27s Toboggan • I Close the Door to the Bathroom • Insomniac Scribbles • And Then There Were Four • Goodbye, Ace • Silicone\u27s a Manmade Matter • The Nineteenth Hole • Upon Visiting Manor Care • Little Boys • Obsessed • Life • Shakespearean Shakedown • Violets and Morning Glories • Mr. Cope Takes His Secretary to Lunch • Winter Eyes • Triptych • These Hot, Humid Nights • The Car\u27s Place in His Heart • Saturday Night • The Windows of a Clean House • An Harmonious Thunk • Nomads • My Watch at Mass • Dave\u27s Fine Print • K.P. Duty • Serendipityhttps://digitalcommons.ursinus.edu/lantern/1141/thumbnail.jp

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd

Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration

A biosensor for the RhoA GTPase illustrates its activation patterns in both the front and rear of migrating lymphocytes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Causal inference and large‐scale expert validation shed light on the drivers of SDM accuracy and variance

Aim: To develop a causal understanding of the drivers of Species distribution model (SDM) performance. Location: United Kingdom (UK). Methods: We measured the accuracy and variance of SDMs fitted for 518 species of invertebrate and plant in the UK. Our measure of variance reflects variation among replicate model fits, and taxon experts assessed model accuracy. Using directed acyclic graphs, we developed a causal model depicting plausible effects of explanatory variables (e.g. species' prevalence, sample size) on SDM accuracy and variance and quantified those effects using a multilevel piecewise path model. Results: According to our model, sample size and niche completeness (proportion of a species' niche covered by sampling) directly affect SDM accuracy and variance. Prevalence and range completeness have indirect effects mediated by sample size. Challenging conventional wisdom, we found that the effect of prevalence on SDM accuracy is positive. This reflects the facts that sample size has a positive effect on accuracy and larger sample sizes are possible for widespread species. It is possible, however, that the omission of an unobserved confounder biased this effect. Previous studies, which reported negative correlations between prevalence and SDM accuracy, conditioned on sample size. Main conclusions: Our model explicates the causal basis of previously reported correlations between SDM performance and species/data characteristics. It also suggests that niche completeness has similarly large effects on SDM accuracy and variance as sample size. Analysts should consider niche completeness, or proxies thereof, in addition to sample size when deciding whether modelling is worthwhile