International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

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

Visions and Shadows: A Socio-history of the Mental-health Policy Reform Agenda in Canada

This dissertation offers a critical, contextualizing analysis of government policy and discourse pertaining to mental-health reform in Canada, with a focus on the province of Ontario. It represents my attempt to craft an analysis and contextual history of government policy visions pertaining to mental disorder and wellness. I define the study’s problematic broadly, as an attempt to understand how problems are defined and solutions enacted through institutions organized under the auspices of government, insofar as problems and solutions in public discourse are depicted as pertaining to mental disorder. My investigation proceeds through an analysis of government texts and their social, political and historical context, influenced by Dorothy Smith’s contributions to institutional ethnography and political economy, Arthur Frank’s project of socio-narratology, and, (in a more complicated way), the historical and methodological works of Michel Foucault. My history of reform is in many respects a history of how problems have been constructed and understood, and my deconstruction of discourses of recovery and reform is in many ways an exploration of institutional developments (as well as certain concrete policy proposals that authorized discourse seems to preclude, actively or implicitly). Drawing on literature from policy studies related to policy subsystems and state capacity, I interpret actual policy developments and visionary discourse pertaining to mental-health policy as the vanguard movement of neoliberalism within the Canadian social-welfare state. I suggest that a biomedical era of mental-health discourse may be usefully thought of as giving way to, and merging with, an ascendant economic understanding of disorder itself – the antecedents of which are well-described in Foucault’s analysis in the 1970s of the then-nascent political implications of neoliberalism.Ph.D.2021-11-13 00:00:0

Eviction filings during bans on enforcement throughout the COVID-19 pandemic: an interrupted time series analysis.

OBJECTIVE: Bans on evictions were implemented to reduce the spread of COVID-19 and to protect vulnerable populations during a public health crisis. Our objective was to examine how three bans on eviction enforcement impacted eviction filings from March 2020 through January 2022 in Ontario, Canada. METHODS: Data were derived from eviction application records kept by the Ontario Landlord and Tenant Board. We used segmented regression analysis to model changes in the average weekly filing rates for evictions due to non-payment of rent (L1 filings) and reasons other than non-payment of rent (L2 filings). RESULTS: The average number of weekly L1 and L2 applications dropped by 67.5 (95% CI: 55.2, 79.9) and 31.7 (95% CI: 26.7, 36.6) filings per 100,000 rental dwellings, respectively, following the first ban on eviction enforcement (p &lt; 0.0001). Notably, they did not fall to zero. Level changes during the second and third bans were insubstantial and slope changes for L2 applications varied throughout the study period. The L1 filing rate appeared to increase towards the end of the study period (slope change: 1.3; 95% CI: 0.1, 2.6; p = 0.0387). CONCLUSION: Our findings suggest that while the first ban on eviction enforcement appeared to substantially reduce filing rates, subsequent bans were less effective and none of them eliminated eviction filings altogether. Enacting upstream policies that tackle the root causes of displacement would better equip jurisdictions during future public health emergencies