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Evidence for the changing regimens of acetylcysteine.

ABSTRACT: Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dose was empirically derived four decades ago and has not changed since. This regimen is associated with a high rate of adverse effects due mainly to the high initial peak acetylcysteine concentration. Furthermore, there are concerns that the acetylcysteine concentration is not adequate for 'massive' overdoses and that the dose and duration may need to be altered. Various novel regimens have been proposed, looking to address these issues. Many of these modified regimens aim to decrease the rate of adverse reactions by slowing the loading dose and thereby decrease the peak concentration. We used a published population pharmacokinetic model of acetylcysteine to simulate these modified regimens. We determined mean peak and 20 h acetylcysteine concentrations and area under the under the plasma concentration-time curve to compare these regimens. Those regimens that resulted in a lower peak acetylcysteine concentration have been shown in studies to have a lower rate of adverse events. However, these studies were too small to show whether they are as effective as the traditional regimen. Further research is still needed to determine the optimum dose and duration of acetylcysteine that results in the fewest side-effects and treatment failures. Indeed, a more patient-tailored approach might be required, whereby the dose and duration are altered depending on the paracetamol dose ingested or paracetamol concentrations.

SUBMITTER: Chiew AL

PROVIDER: S-EPMC4767192 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Evidence for the changing regimens of acetylcysteine.

Chiew Angela L AL Isbister Geoffrey K GK Duffull Stephen B SB Buckley Nicholas A NA

British journal of clinical pharmacology 20151123 3

Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dose was empirically derived four decades ago and has not changed since. This regimen is associated with a high rate of adverse effects due mainly to the high initial peak acetylcystei ...[more]

PMID: 26387650

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Project description:BackgroundGeneral practitioners (GPs), or family practitioners, are tasked with prescribing medications that can be harmful to the community if they are inappropriately prescribed or used (e.g. opioids). Educational programs, such as educational outreach (EO), are designed to change the behaviour of health professionals. The purpose of this study was to identify the efficacy of EO programs at changing the prescribing behaviour of GPs.MethodsThis study included an evidence and practice review, comprising a rapid review supplemented by interviews with people who are familiar with EO implementation for regulation purposes. Seven databases were searched using terms related to health professionals and prescribing. Systematic and narrative reviews published in English after 2007 were included. Non-statistical analysis was used to report intervention efficacy. Three government representatives participated in semi-structured interviews to aid in understanding the relevance of review findings to the Victorian context. Interviews were transcribed verbatim and thematically analysed for emerging themes.ResultsFourteen reviews were identified for the evidence review. Isolated (e.g. EO program delivered by itself) and multifaceted (e.g. EO program supplemented by other interventions) programs were found to change prescribing behaviours. However, limited evidence suggests that EO can successfully change prescribing behaviours specific to GPs. Isolated EO can successfully change health professional prescribing behaviours, although cheaper alternatives such as letters might be just as effective. Multifaceted EO can also successfully change health professional prescribing behaviours, especially in older adults, but it remains unclear as to what combination of interventions works best. Success factors for EO reported by government representatives included programs having practical rather than didactic foci; making EO compulsory; focussing EO on preventing adverse events; using monetary or professional development incentives; and in-person delivery.ConclusionsEducational outreach can successfully change prescribing behaviours but evidence specific to GPs is lacking. Key characteristics of EO that could optimise success include ensuring the EO program is tailored, involves practical learning and uses incentives that are meaningful to clinicians.

Project description:Comparative effectiveness research (CER) calls for substantial changes in the way clinical research is conducted, interpreted and practically applied in the USA, in order to produce useful clinical evidence. Departing from classic efficacy and effectiveness research, the evolving CER paradigm requires structural and substantive innovations that address three basic questions: what works? for whom? and in whose hands? Addressing these questions will require fundamental changes in the approach to clinical research that include: the use of active treatments (or comparators) versus placebos in the comparisons of treatments, innovative or 'alternative' research methods, the specification and a priori design of studies to account for important subgroups, accounting for the nested nature of healthcare delivery in design and analysis of CER, the simultaneous study of multiple treatments or treatment modalities, the study of multiple outcomes (benefits and harms) for each treatment compared, and the reassessment of the value of different study designs in the hierarchy of collective 'evidence'. In order to aid individual providers and patients in making informed, personalized treatment decisions, guided by the best evidence possible, CER studies must generalize to a broad range of subgroups reflecting the spectrum of patients, providers and health systems that populate real-world practice settings. Without expansion in the scope, conduct and subsequent interpretation of clinical research reflected in the issues outlined above, CER will fall short of its potential for informing evidence-based practice and personalized medicine. The current paradigm for conducting, interpreting and applying clinical research does not meet the needs of optimal generalizability and application to individual physician-patient efforts to identify the most effective treatment, and therefore does not support the basic requirements of CER. The proposed changes should neither require decades nor exorbitant budgets to achieve. Using two examples, prostate cancer, and comparisons of single medications, we illustrated how the proposed changes in clinical research, matching strategy to each application, might be addressed.

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Evidence for the changing regimens of acetylcysteine.

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Evidence for the changing regimens of acetylcysteine.

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