Hepatic p-nitrophenetole O-deethylation Activity in Mice depends on Diet Composition

The present study investigated effects of various commercial diets, of protein and of fat 1evels in semisynthetic diets, and of fiber content and type on hepatic O-deethylation of p-nitrophenetole in mice. A high fat content increased and a high fiber content decreased the hepatic p-nitrophenetole O-deethylation activity. The activity in mice kept on different commercial feedings differed significantly. The level of hepatic microsomal cytochrome P-450 activity affects the toxicity of many compounds. Thus, standardization of commercial feeds for experimental animals used in toxicological and pharmacological studies is needed to avoid the potential risk of misleading conclusions

Risk Thresholds and Risk Classifications Pose Problems for Person-Centred Care.

Classification of a continuous risk score into risk levels is common. However, while the absolute risk score is essential, it is arguably unethical to label anyone at 'high, moderate or low risk' of a serious event, simply because management based on a single criterion (e.g. avoiding the target condition) has been determined to be effective or cost-effective at a population level. Legally, mono-criterial risk labeling can inhibit the obtaining of a fully-informed, preference-based consent, since multiple considerations (various benefits and harms) matter to most individuals, not only the single criterion that is the basis of the provided risk category. These ethical and legal challenges can be met by preference-sensitive multi-criteria decision support tools. In this future vision paper, we demonstrate, at a conceptual proof-of-method level, how such decision support can and should be developed without reference to risk-level classifications. The statin decision is used as illustration, without any empirical claims

Separating Risk Assessment from Risk Management Poses Legal and Ethical Problems in Person-Centred Care.

Accelerating progress in screening technologies, e.g. genetic testing, means more individuals are facing the stressful decision of whether to request the test. Fully-informed and preference-based consent, as well as ethical practice, requires the full range of benefits and harms from any test or treatment to be identified and assessed from the individual's point of view. For both ethical and legal reasons, we see the decision on whether to undertake a genetic screening test being increasingly seen, in future, as calling for a personalised analysis of the full range of subsequent management options. The conventional dissociation of 'risk assessment' and 'risk management' phases is thereby ruled out. One way of addressing the resulting challenge is through personalised multi-criterial decision support tools. In this vision paper we provide conceptual proof of method of how such an interactive online tool could function. The polygenetic genetic screening decision is used, solely as illustration

Preference-Sensitive Apomediative Decision Support Is Key to Facilitating Self-Produced Health.

In the health capital model, the main function of health services is not to produce health, but to support the person in their self-production investments. In the health context there are three types of decision support tools, depending on the role of the provider (e.g. clinician) and person. Non-mediative tools are designed to help the clinician decide what is best for the patient. Intermediative Patient Decision Aids are designed to help the clinician and patient decide together, in an encounter, what is best for the patient. Apomediative Personalised Decision Support Tools are designed to help the person decide what is best for themselves, including whether to seek a professional consultation and/or to prepare for, and engage in, an intermediative consultation. Only preference-sensitive apomediative support tools ensure that the key requirements of self-produced health are met, along with legally informed and preference-based consent to any subsequent provider action. The desirable form of apomediative support is a publicly accessible, direct-to-citizen, provider-independent, multi-criteria analysis-based decision support of the sort available in many other areas of self-production. Which (UK), Tænk (Denmark), Choice (Australia) and numerous other comparison magazines and websites provide independent multi-criterial support for decisions on, for example, which food and transport to buy to self-produce nutrition and movement. A personalised decision support tool for the statin decision is provided as illustration: Should I go to my general practitioner and ask for a statin prescription or go to discuss taking statins, in the light of the preliminary opinion of the tool

Dual Purpose, Dual Audience: MCDA-Based Tools Can Simultaneously Support Personal Health Decisions and Educate Persons and Clinicians.

In this vision paper we envisage paradigmatic change transforming the health professional from the empowered agent of a dependent patient into the final decision supporter of an empowered person; a person who comes equipped with the preliminary opinion of an apomediative personalised decision support tool and the enhanced health decision literacy it produces. The anomalies in the current paradigm that will produce this change arise from unworkable attempts to combine multicriterial personal preferences and the best available evidence in a medical reasoning model. Multi-Criteria Decision Analysis (MCDA)-based decision support tools provide one mechanism for achieving this synthesis in a transparent way in a specific case whilst, simultaneously, increasing the generic health decision literacy and competencies of both person and clinician. The educational task for both is less than might be expected because of their familiarity, as consumers, with the many comparison websites and magazines for products and services using an informal version of MCDA. The educational task, particularly for the clinician, is primarily one of acknowledging that MCDA is a decision competence that has the potential, not only to enhance decision quality, but also facilitate communication between person and professional, who will now be talking the same decisional language. Experience from developing the MyBoneHealth tool confirms both the feasibility and challenges of delivering a MCDA-based decision support and educational tool

The Evaluation of Decision Support Tools Requires a Measure of Decision Quality That Has Content and Construct Validity in Person-Centred Care.

The evaluation of decision aids and support interventions requires a multi-attribute index which can be calculated for both aid and comparator/s. The Decision Conflict Scale (DCS) is such an index and has been widely used in this context, the recent Cochrane review Decision aids for people facing health treatment or screening decisions reporting its use in 63 of the 105 studies included. However, while the DCS may be a valid measure for the eponymous construct - decision conflict - it lacks both content and construct validity for the evaluation of decision aids. It lacks content validity for this task because of the 3 items which make up its Uncertainty subscale, which penalize an aid that correctly reports the situation is one of decisional equipoise or near equipoise. A 'false clarity' bias in aid presentation is encouraged by being rewarded. In this paper we confirm that the inclusion of the Uncertainty subscale in the DCS has inappropriate empirical consequences for decision aid evaluation. Excluding the Uncertainty items would address this content invalidity, but the DCS would still lack construct validity, since the construct being measured is being treated, and inappropriately psychometrically validated, as a reflective rather than formative one. The component scales (items) of an index for a formative construct need to be preference-weighted, in ethical person-centred care by the individual at the point of decision. We argue that the most appropriate formative construct for use in decision aid evaluation is decision quality, and suggest MyDecisionQuality (MDQ) as the first formative index that can claim to both possess content and construct validity for the measurement of decision quality. However, like all multi-criterial formative metrics, the construct that MDQ measures is constructed by the measure and has no existence independent of it

Who should decide how much and what information is important in person-centred health care?

Most guidelines for clinical practice, and especially those for the construction of decision support tools, assume that the individual person (the patient) needs to be in possession of information of particular sorts and amount in order to qualify as having made an 'informed decision'. This often implicitly segues into the patient having made a 'good decision'. In person-centred health care, whether, in what form, and with what weight, 'information' is included as a criterion of decision quality is a matter for the person involved, to decide in the light of their own values, preferences, and time and resource constraints

Repetitive Activation of the Corticospinal Pathway by Means of rTMS may Reduce the Efficiency of Corticomotoneuronal Synapses

Low-frequency rTMS applied to the primary motor cortex (M1) may produce depression of motor-evoked potentials (MEPs). This depression is commonly assumed to reflect changes in cortical circuits. However, little is known about rTMS-induced effects on subcortical circuits. Therefore, the present study aimed to clarify whether rTMS influences corticospinal transmission by altering the efficiency of corticomotoneuronal (CM) synapses. The corticospinal transmission to soleus α-motoneurons was evaluated through conditioning of the soleus H-reflex by magnetic stimulation of either M1 (M1-conditioning) or the cervicomedullary junction (CMS-conditioning). The first facilitation of the H-reflex (early facilitation) was determined after M1- and CMS-conditioning. Comparison of the early facilitation before and after 20-min low-frequency (1 Hz) rTMS revealed suppression with M1- (−17 ± 4%; P = 0.001) and CMS-conditioning (−6 ± 2%; P = 0.04). The same rTMS protocol caused a significant depression of compound MEPs, whereas amplitudes of H-reflex and M-wave remained unaffected, indicating a steady level of motoneuronal excitability. Thus, the effects of rTMS are likely to occur at a premotoneuronal site—either at M1 and/or the CM synapse. As the early facilitation reflects activation of direct CM projections, the most likely site of action is the synapse of the CM neurons onto spinal motoneuron

Increasing User Involvement in Health Care and Health Research Simultaneously: A Proto-Protocol for "Person-as-Researcher" and Online Decision Support Tools.

BACKGROUND: User involvement is appearing increasingly on policy agendas in many countries, with a variety of proposals for facilitating it. The belief is that it will produce better health for individuals and community, as well as demonstrate greater respect for the basic principles of autonomy and democracy. OBJECTIVE: Our Web-based project aims to increase involvement in health care and health research and is presented in the form of an umbrella protocol for a set of project-specific protocols. We conceptualize the person as a researcher engaged in a continual, living, informal "n-of-1"-type study of the effects of different actions and interventions on their health, including those implying contact with health care services. We see their research as primarily carried out in order to make better decisions for themselves, but they can offer to contribute the results to the wider population. We see the efforts of the "person-as-researcher" as contributing to the total amount of research undertaken in the community, with research not being confined to that undertaken by professional researchers and institutions. This view is fundamentally compatible with both the emancipatory and conventional approaches to increased user involvement, though somewhat more aligned with the former. METHODS: Our online decision support tools, delivered directly to the person in the community and openly accessible, are to be seen as research resources. They will take the form of interactive decision aids for a variety of specific health conditions, as well as a generic one that supports all health and health care decisions through its focus on key aspects of decision quality. We present a high-level protocol for the condition-specific studies that will implement our approach, organized within the Populations, Interventions, Comparators, Outcomes, Timings, and Settings (PICOTS) framework. RESULTS: Our underlying hypothesis concerns the person-as-researcher who is equipped with a prescriptive, transparent, expected value-based opinion-an opinion that combines their criterion importance weights with the Best Estimates Available Now for how well each of the available options performs on each of those outcomes. The hypothesis is that this person-as-researcher is more likely to be able to position themselves as an active participant in a clinical encounter, if they wish, than someone who has engaged with a descriptive decision aid that attempts to work with their existing cognitive processes and stresses the importance of information. The precise way this is hypothesis tested will be setting-specific and condition-specific and will be spelled out in the individual project protocols. CONCLUSIONS: Decision resources that provide fast access to the results of slower thinking can provide the stimulus that many individuals need to take a more involved role in their own health. Our project, advanced simply as one approach to increased user involvement, is designed to make progress in the short term with minimal resources and to do so at the point of decision need, when motivation is highest. Some basic distinctions, such as those between science and non-science, research and practice, community and individual, and lay and professional become somewhat blurred and may need to be rethought in light of this approach

Illusory Sensation of Movement Induced by Repetitive Transcranial Magnetic Stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement