The Lantern Vol. 69, No. 1, Fall 2001

• Frets • Burn • The Amish-Man • City Children • Coasting West • Futile • Oxymoron • Fleeting Reflection • Pink Geraniums • Moving • Running: Arcola • Expectations • One Time Deal • We Slept • Faraway Field • My Own Giselle • My Father\u27s Will • Meet Me in Montana • Pride is a Lawn Mower • Gloss • 2% Low Fat • Bits of Tuesday • This is not a Pipe • What Ifs • Reconnection • A Bell Called Emily • The Elevatorhttps://digitalcommons.ursinus.edu/lantern/1159/thumbnail.jp

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

VA Healthcare Costs of a Collaborative Intervention for Chronic Pain in Primary Care

Background: Chronic pain is costly to individuals and the healthcare system, and is often undertreated. Collaborative care models show promise for improving treatment of patients with chronic pain. The objectives of this article are to report the incremental benefit and incremental health services costs of a collaborative intervention for chronic pain from a veterans affairs (VA) healthcare perspective. Methods: Data on VA treatment costs incurred by participants were obtained from the VA\u27s Decision Support System for all utilization except certain intervention activities which were tracked in a separate database. Outcome data were from a cluster-randomized trial of a collaborative intervention for chronic pain among 401 primary care patients at a VA medical center. Intervention group participants received assessments and care management; stepped-care components were offered to patients requiring more specialized care. The main outcome measure was pain disability-free days (PDFDs), calculated from Roland-Morris Disability Questionnaire scores. Results: Participants in the intervention group experienced an average of 16 additional PDFDs over the 12-month follow-up window as compared with usual care participants; this came at an adjusted incremental cost of $364 per PDFD for a typical participant. Important predictors of costs were baseline medical comorbidities, depression severity, and prior year\u27s treatment costs. Conclusion: This collaborative intervention resulted in more pain disability-free days and was more expensive than usual care. Further research is necessary to identify if the intervention is more cost-effective for some patient subgroups and to learn whether pain improvements and higher costs persist after the intervention has ended