Acupuncture as a complex intervention for depression: A consensus method to develop a standardised treatment protocol for a randomised controlled trial

Objective: To standardise a complex intervention by defining the characteristic (specific) components of treatment for a randomised controlled trial of acupuncture as an intervention for individuals who have been diagnosed with depression using a consensus method. Methods: A nominal group technique was used. Potential components of the acupuncture intervention were generated from the literature, experts and participants. These were categorised as constant or variable, the latter including active management techniques (such as providing relevant explanations), auxiliary techniques (such as auricular acupuncture), and other aspects of patient care (such as offering life-style and dietary advice), all of which were underpinned by defined theoretical frameworks. Participants were selected on the basis of their experience and training, to encompass a diverse range of styles of traditional acupuncture practice in the UK, and all rated components in two rounds. Results: Fifteen practitioners rated 52 variable components in the first round and 55 in the second. There was group support for 16 active management components, three auxiliary techniques and five areas of life-style support, all driven by eight theoretical diagnostic and treatment frameworks. For the 39 components that were rated twice, group support increased between rounds from 75 to 79% (z=-2.2, p=0.03), while the absolute average deviation from the median dropped from 1.04 to 0.83 (z=-2.5, p=0.011). Conclusion: Standardising the characteristic components of a complex intervention for a randomised controlled trial of acupuncture for depression using a consensus approach is feasible. The method can be generalised to other clinical situations and other treatment modalities. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved

Acupuncture, or non-directive counselling versus usual care for the treatment of depression: a pilot study

<p>Abstract</p> <p>Background</p> <p>Depression is one of the most common reasons for consulting in primary care. Acupuncture is a popular complementary therapy choice for depression but its evidence base is poor with more robust high quality trials being required. More than half of depressed patients experience painful symptoms, with severe pain being associated with poor response to antidepressants. Acupuncture may have much to offer as an intervention for depression that also helps alleviate pain. Non-directive counselling is the most widely used psychological approach for depression in NHS settings, and provides a useful pragmatic comparison for acupuncture that would, according to our pre-trial qualitative research, be of high interest to doctors and patients.</p> <p>Methods and design</p> <p>The pilot study uses five arms and involves a pragmatic design. All patients will continue to receive usual care. Four groups of patients will be allocated to acupuncture, or non-directive counselling, in addition to usual GP care. The acupuncture and counselling arms will be further split into two groups to explore different treatment regimens. The primary outcome measure is the BDI II. Potentially eligible patients will be screened for depression using the PHQ-9, which is also a secondary outcome measure. Other secondary measures include the SF 36 bodily pain subscale, the CORE OM, the WBQ-12 and the EQ5D. Health economic data will be collected and measures of therapeutic engagement will be used to compare patient's views of therapists and GPs. The study will employ a fully randomised preference design with collection of data on patient preferences and prior expectations.</p> <p>Discussion</p> <p>This study has been implemented, and data are currently being analysed to inform the design of a full scale trial. Two practical operational issues that impacted on study implementation are discussed. Firstly, the challenge of recruiting depressed patients via GP consultation. Secondly, the problem of poor uptake and high attrition for counselling and acupuncture, which appeared to be associated with poor questionnaire return, and resulted in missing data. These problems may be relevant to other researchers working in the area of depression, or similar illnesses, where patients may lack motivation and energy to engage in research, or attend for treatment.</p> <p>Trial Registration</p> <p>Current Controlled Trials (ISRCTN 59267538)</p

Developing a randomised controlled trial of acupuncture for depression

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Absorption, Distribution, Metabolism, and Excretion (ADME) of Capmatinib (INC280) in Healthy Male Volunteers and In Vitro Aldehyde Oxidase Phenotyping of the Major Metabolite

Capmatinib (INC280), a highly selective and potent inhibitor of the MET receptor tyrosine kinase, has demonstrated clinically meaningful efficacy and a manageable safety profile in patients with advanced NSCLC harboring MET exon 14 skipping mutations. We investigated the absorption, distribution, metabolism, and excretion of capmatinib in six healthy male volunteers after a single peroral dose of 600 mg 14C-labeled capmatinib. The mass balance, blood and plasma radioactivity, and plasma capmatinib concentrations were determined along with metabolite profiles in plasma, urine, and feces. The metabolite structures were elucidated using mass spectrometry and comparing with reference compounds. The parent compound accounted for most of the radioactivity in plasma (42.9 ± 2.9%). The extent of oral absorption was estimated to be 49.6%; the maximum concentration (Cmax) of capmatinib in plasma was reached at 2 h (median Tmax). The apparent mean elimination half-life of capmatinib in plasma was 7.84 h. Apparent distribution volume (Vz/F) of capmatinib during the terminal phase was moderate to high (geometric mean 473 L). Metabolic reactions involved lactam formation, hydroxylation, N-dealkylation, formation of a carboxylic acid, hydrogenation, N oxygenation, glucuronidation, and combinations thereof. The most abundant metabolite, M16 was formed by imidazo-triazinone formation (lactam formation). Absorbed capmatinib was eliminated mainly by metabolism and subsequent biliary/fecal and renal excretion. Excretion of radioactivity was complete after 7 days. In vitro studies demonstrated that CYP3A was the major P450 enzyme subfamily involved in hepatic microsomal metabolism, and M16 formation was mainly catalyzed by cytosol aldehyde oxidase