Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence.

BACKGROUND: People who use illicit opioids are more likely to be admitted to hospital than people of the same age in the general population. Many admissions end in discharge against medical advice, which is associated with readmission and all-cause mortality. Opioid withdrawal contributes to premature discharge. We sought to understand the barriers to timely provision of opioid substitution therapy (OST), which helps to prevent opioid withdrawal, in acute hospitals in England.MethodsWe requested policies on substance dependence management from 135 National Health Service trusts, which manage acute hospitals in England, and conducted a document content analysis. Additionally, we reviewed an Omitted and Delayed Medicines Tool (ODMT), one resource used to inform critical medicine categorisation in England. We worked closely with people with lived experience of OST and/or illicit opioid use, informed by principles of community-based participatory research. RESULTS: Eighty-six (64%) trusts provided 101 relevant policies. An additional 44 (33%) responded but could not provide relevant policies, and five (4%) did not send a definitive response. Policies illustrate procedural barriers to OST provision, including inconsistent application of national guidelines across trusts. Continuing community OST prescriptions for people admitted in the evening, night-time, or weekend was often precluded by requirements to confirm doses with organisations that were closed during these hours. 42/101 trusts (42%) required or recommended a urine drug test positive for OST medications or opioids prior to OST prescription. The language used in many policies was stigmatising and characterised people who use drugs as untrustworthy. OST was not specifically mentioned in the reviewed ODMT, with 'drugs used in substance dependence' collectively categorised as posing low risk if delayed and moderate risk if omitted. CONCLUSIONS: Many hospitals in England have policies that likely prevent timely and effective OST. This was underpinned by the 'low-risk' categorisation of OST delay in the ODMT. Delays to continuity of OST between community and hospital settings may contribute to inpatient opioid withdrawal and increase the risk of discharge against medical advice. Acute hospitals in England require standardised best practice policies that account for the needs of this patient group

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

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Parliament and prayer book: the theology and ecclesiology behind the Prayer Book Crisis

This thesis considers the doctrinal and ecclesiological trends that were present during the construction of the revised Book of Common Prayer of 1927. Through the use of the records of both Convocations and of the National/Church Assembly, it looks at the discussions that took place within the Church of England during the construction of the revised Book. By analysing these debates, it considers the doctrinal shifts that were taking place within the Church of England after the ritual controversies of the nineteenth century. Focussing on the Communion service and the reservation of the elements for the communion of the sick, the thesis shows how much of what had been seen as ritualist had become part of the ‘mainstream’ of the Church. It challenges the idea that the revision process stalled in the First World War both by demonstrating how the process continued at the same pace during the war as it had done pre-1914, but also by showing how the birth of the National Assembly that took place during the war was born out of the revision process and a desire to avoid Parliamentary scrutiny of any revision. This will also demonstrate how the revision process created an atmosphere in which many in the Church of England had serious discussions about radically altering the ecclesiology of the Church, specifically in the area of Church-State relations. It will link into my previous work on the growth of ‘Two Kingdoms’ theology in the Church by showing how the revision process made many decide the State, in Parliament, should not have the right to debate and approve the liturgy of the Church of England. Examining the revision process in the National Assembly it will show the growth of lay power in the Church through the integral role they played in the revision process in the 1920s. Through the parliamentary debates, it will show how Parliament reasserted its right to decide the liturgy and doctrine of the Church of England, at the same time as many within the Church had decided they did not have that right. Finally it will examine how the rejection of the revised Books of 1927 and 1928 led to radical ecclesiological thinking within the Church, with many from the very top of the hierarchy advocating forms of disestablishment

'To our earthly view Dietrich is dead’: George Bell’s Eulogy for Dietrich Bonhoeffer

No abstract available

The Church of England and the Third Reich: a case study in Church-State relations

Abstract not currently available

Perilaku mengajar = the act teaching, buku 2, ed.6/ Cruickshank

xx, 248 hal.: ill.; tab.; 29 cm

Perilaku mengajar = the act teaching, buku 2, ed.6/ Cruickshank

xx, 248 hal.: ill.; tab.; 29 cm