Drug-induced liver injury

Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paractamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature, since affected individuals represent only a small proportion of those treated with such drugs. In many cases the mechanism for idiosyncrasy is immune mediation and is often identified by genetic risk determined by HLA variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, though recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued especially in the presence of elevated transaminases (AST/ALT ≥5ULN) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefit of N-acetylcysteine in early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory

Natural history and outcomes in drug induced autoimmune hepatitis

Aim: Drug-induced autoimmune hepatitis (DIAIH) remains poorly characterized. Our aim was to assess natural history and outcomes in DIAIH. Methods: This was a retrospective cohort study. Results: Eighty-two patients with autoimmune hepatitis (AIH) were identified, 11 (13.4%) with DIAIH, implicated drugs being nitrofurantoin (n = 4), statins (n = 4), herbal remedies (n = 2) and diclofenac (n = 1). Female sex, acute onset, elevated serum globulins/immunoglobulin G, fibrosis stage (Ishak), cirrhosis at onset, moderate–severe portal inflammation, interface and lobular hepatitis, remission, relapse and poor outcome were similar in those with DIAIH and AIH (P > 0.05). The former were however more likely to be aged 60 years or more and take longer to relapse on immunosuppression discontinuation (P = <0.05). On Kaplan–Meier analysis, probability of poor outcome was similar in those with DIAIH and AIH (log–rank test, 0.339). On comparing those with (n = 4) and without nitrofurantoin (n = 7) DIAIH, the former were older, had longer duration of drug use prior to DIAIH diagnosis, higher fibrosis stage and were less likely to relapse upon immunosuppression discontinuation. Conclusion: Approximately 15% of patients with AIH have DIAIH with similar outcomes, although the latter are older with a propensity for late relapse, mandating long-term follow up

A new measure for multi-professional medical team communication: design and methodology for multilingual measurement development

BackgroundAs implementation science in global health continues to evolve, there is a need for valid and reliable measures that consider diverse linguistic and cultural contexts. A standardized, reproducible process for multilingual measure development may improve accessibility and validity by participants in global health settings. To address this need, we propose a rigorous methodology for multilingual measurement development. We use the example of a novel measure of multi-professional team communication quality, a determinant of implementation efforts.MethodsThe development and translation of this novel bilingual measure is comprised of seven steps. In this paper, we describe a measure developed in English and Spanish, however, this approach is not language specific. Participants are engaged throughout the process: first, an interprofessional panel of experts and second, through cognitive interviewing for measure refinement. The steps of measure development included: (1) literature review to identify previous measures of team communication; (2) development of an initial measure by the expert panel; (3) cognitive interviewing in a phased approach with the first language (English); (4): formal, forward-backward translation process with attention to colloquialisms and regional differences in languages; (5) cognitive interviewing repeated in the second language (Spanish); (6) language synthesis to refine both instruments and unify feedback; and (7) final review of the refined measure by the expert panel.ResultsA draft measure to assess quality of multi-professional team communication was developed in Spanish and English, consisting of 52 questions in 7 domains. This measure is now ready for psychometric testing.ConclusionsThis seven-step, rigorous process of multilingual measure development can be used in a variety of linguistic and resource settings. This method ensures development of valid and reliable tools to collect data from a wide range of participants, including those who have historically been excluded due to language barriers. Use of this method will increase both rigor and accessibility of measurement in implementation science and advance equity in research and practice

Elucidating the role of melatonin or sugar beet pulp pellet in physiological improvement characteristics and promoting the growth of Moringa oleifera under lead stress

Pot experiments were conducted to evaluate the effect of root and foliar uptake of Pb on Moringa oleifera plants. The levels of Pb used in the experiments were 100 and 400 ppm Pb. The lead application affected the growth, photosynthetic pigment, carbohydrates, proline, oxidative stress biomarkers, mineral contents, and Pb accumulation in Moringa plants. The growth parameters, chlorophyll, Na, K, and Ca content declined in the case of soil or foliar Pb application. The foliar lead application revealed a more negative effect on the growth of moringa plants than the soil application. However, Pb-stressed moringa plants increased carbohydrates, proline, H2O2, MDA, electrolyte leakage, Pb, and Mg content. In addition, the possible role of melatonin (MEL) and sugar beet pulp pellets (SBP) in ameliorating lead toxicity and enhancement of phytoremediation was investigated. It was found that supplemental addition of MEL or SBP increases the growth parameters, photosynthetic pigments, carbohydrates, proline, and minerals compared to stressed moringa plants. Moreover, a decrease in hydrogen peroxide, lipid peroxidation, and electrolyte leakage was observed under MEL and SBP treatments. The ameliorating effect of SBP was more pronounced than that of MEL. Furthermore, MEL application enhanced the phytoremediation capacity of moringa plants

Development and pilot testing of PROACTIVE: A pediatric onco‐critical care capacity and quality assessment tool for resource‐limited settings

Abstract Background Nearly 90% children with cancer reside in low‐ and middle‐income countries, which face multiple challenges delivering high‐quality pediatric onco‐critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center‐specific reports, and identification of common POCC challenges. Methods The original 119 consensus‐derived PROACTIVE indicators were converted into 182 questions divided between 2 electronic surveys for intensivists and oncologists managing critically ill pediatric cancer patients. Alpha‐testing was conducted to confirm face‐validity with four pediatric intensivists. Eleven centers representing diverse geographic regions, income levels, and POCC services conducted beta‐testing to evaluate usability, feasibility, and applicability of PROACTIVE. Centers' responses were scored and indicators with mean scores ≤75% in availability/performance were classified as common POCC challenges. Results Alpha‐testing ensured face‐validity and beta‐testing demonstrated feasibility and usability of PROACTIVE (October 2020–June 2021). Twenty‐two surveys (response rate 99.4%) were used to develop center‐specific reports. Adjustments to PROACTIVE were made based on focus group feedback and surveys, resulting in 200 questions. Aggregated data across centers identified common POCC challenges: (1) lack of pediatric intensivists, (2) absence of abstinence and withdrawal symptoms monitoring, (3) shortage of supportive care resources, and (4) limited POCC training for physicians and nurses. Conclusions PROACTIVE is a feasible and contextually appropriate tool to help clinicians and organizations identify challenges in POCC services across a wide range of resource‐levels. Widespread use of PROACTIVE can help prioritize and develop tailored interventions to strengthen POCC services and outcomes globally