Drug-induced liver injury in the elderly: Consensus statements and recommendations from the IQ-DILI Initiative

The elderly demographic is the fastest-growing segment of the world\u27s population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug-drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events such as serious forms of drug-induced liver injury (DILI). It has been a longstanding shortcoming that elderly individuals are often a vulnerable population underrepresented in clinical trials. As such, an improved understanding of DILI in the elderly is a high-priority, unmet need. This challenge is underscored by recent documents put forward by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) that encourage data collection in the elderly and recommend improved practices that will facilitate a more inclusive approach. To establish what is already known about DILI in the elderly and pinpoint key gaps of knowledge in this arena, a working definition of elderly is required that accounts for both chronologic and biologic ages and varying states of frailty. In addition, it is critical to characterize the biological role of aging on liver function, as well as the different epidemiological factors such as polypharmacy and inappropriate prescribing that are common practices. While data may not show that elderly people are more susceptible to DILI, DILI due to specific drugs might be more common in this population. Improved characterization of DILI in the elderly may enhance diagnostic and prognostic capabilities and improve the way in which liver safety is monitored during clinical trials. This summary of the published literature provides a framework to understand and evaluate the risk of DILI in the elderly. Consensus statements and recommendations can help to optimize medical care and catalyze collaborations between academic clinicians, drug manufacturers, and regulatory scientists to enable the generation of high-quality research data relevant to the elderly population

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

18 years of Romanian national program of liver transplant - a retrospective analysis of 924 patients operated

Center of General Surgery and Liver Transplantation “Dan Setlacec”, Fundeni Clinical Institute, Bucharest, Romania, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroducere: Transplantul hepatic (TH) a devenit un tratament stabil pentru boala hepatică în stadiu final, cu peste 20.000 de proceduri la nivel mondial anual. Prelegerea prezintă și analizează înființarea și rezultatele Programului Național Român al TH. Material și metode: Între aprilie 2000 și decembrie 2018, 924 pacienti au efectuat 964 operatii de TH în România. Raportul dintre bărbați și femei a fost de 546/378, în timp ce raportul adult / pediatric a fost de 857/67, cu o vârstă medie de 46 de ani (mediană de 50 de ani, interval de 7 luni - 68 de ani). Principalele indicații TH au fost ciroza VHB (270 pac., 29%), CHC (196 pac., 21%) și ciroza VHC (141 pac., 15%). Rezultate: TH de la donator aflat in moarte cerebrala a fost efectuat în 805 de cazuri: TH total în 778 de cazuri, TH împărțit (split) în 20 de cazuri, LT redus în 5 cazuri, LT accesoriu în 1 caz și domino LT în 1 pac. TH de la donator inrudit a fost efectuat în 159 de pacienti:cu hemificat drept la113 pac (12%), secțiune laterală stânga la 30 pac (3%), cu hemificat stang la 14 pac (1,5%) și LDLT dual graft la 2 pacienti. Rata generală de morbiditate majoră a fost de 42% (cel puțin clasa IIIB Clavien-Dindo), în timp ce mortalitatea perioperatorie a fost de 8%. Rata de retransplantare a fost de 4,3% (40 de pac). Pe termen lung, ratele de supraviețuire estimate la pacienți cu 1, 3 și 5 ani au fost de 88%, 82% și, respectiv, 79%. Concluzii: Programul național de transplant hepatic abordează toate cauzele insuficienței hepatice acute și cronice sau a tumorilor hepatice la adulți și copii, folosind toate tehnicile chirurgicale, cu rezultate bune pe termen lung. Programul a evoluat constant în timp, ceea ce a dus la scăderea ratei mortalității pe lista de așteptare. * * * Introduction: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The lecture presents and analyzes the setting-up and results of the Romanian National Program of LT. Material and methods: Between April 2000 and December 2018, 924 pts received 964 LTs in Romania. Male/female ratio was 546/378, while adult/pediatric ratio was 857/67, with a mean age of 46 years (median 50 yrs; range 7 months – 68 yrs). Main LT indications were HBV cirrhosis (270 pts; 29%), CHC (196 pts; 21%), and HCV cirrhosis (141 pts; 15%). Results: Deceased donor LT was performed in 805 cases: whole LT in 778 cases, split LT in 20 cases, reduced LT in 5 cases, accesory LT in 1 case, and domino LT in 1 pt. Living donor LT was performed in 159 pts: right hemiliver in 113 pts (12%), left lateral section in 30 pts (3%), left hemiliver in 14 pts (1.5%), and dual graft LDLT in 2 pts. Overall major morbidity rate was 42% (at least IIIB Clavien-Dindo class), while perioperative mortality was 8%. Retransplantation rate was 4.3% (40 pts). Long-term overall 1, 3, and 5-year estimated survival rates for patients were 88%, 82%, and 79%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)