[Scientific medicine and care relationship: From the therapeutic alliance to the therapeutic effect of the alliance]. / Médecine scientifique et relation de soin : de l'alliance thérapeutique à l'effet thérapeutique de l'alliance.

The new paradigm of precision medicine in oncology questions today the respective place of evidence-based medicine and doctor-patient relationship. Based on the results of a randomized study comparing the efficacy of a homeopathic molecule in the prevention of nausea and vomiting induced by chemotherapy in non-metastatic breast cancer, this article extends and develops the discussion of maintaining an unresolved tension between medical art and medical science, between care and cure. This tension sets a base for the authors of the therapeutic alliance in medicine, defined as a dialectic constantly adjourned between the alliance of the doctor with the patient and his therapy, and the therapeutic effect of this alliance. Because if a policy or a public opinion were to promote an exclusively rational medicine deprived of the field of relation to care, or on the contrary a medicine based only on clinical sense and intuition, then respectively the ethics of care and the progress of therapy would be threatened. It is advisable to be aware of erring from the truth, amplified today by social networks, as much due to a tide of scientific positivism, as an excess of the "good caring soul". Taking into account the therapeutic alliance makes it possible to no longer oppose scientific medicine and care relationship.

Personality Modulates the Efficacy of Art Intervention on Chronic Pain in a Population of Patients with Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) mainly occurs in elderly individuals. Comorbidities and chronic pain are frequent in this population. Previous studies revealed that personality modulates both chronic pain (CP) andADoccurrence and evolution. Moreover, as pain treatments can induce side-effects, non-drugs treatments, such as art interventions, are interesting alternative therapies for decreasing CP in these patients. OBJECTIVE: Our aim was to assess the potential role of personality traits on art intervention efficacy for reducing CP in a population of patients with mild AD. METHODS: Design: multicenter randomized controlled trial. Fifty mild AD patients underwent a 12-week art intervention including singing and painting groups. Personality was assessed with the Big Five Inventory before the sessions. CP was measured with Numeric Rating Scale (NRS) [Usual pain (NRS-U) and most Intense pain (NRS-I)], Simple Visual Scale [Usual pain (SVS-U) and most Intense pain (SVS-I)] and Brief Pain Inventory (BPI) before and after the sessions. The influence of personality traits on CP evolution before and after art intervention was assessed with multiple linear regression models. RESULTS: A positive association was observed between neuroticism and the evolution of three CP measures including NRS-U (B = 0.34, p = 0.01), SVS-U (B = 0.20, p = 0.04), and BPI-U (B = 0.46, p = 0.02) evolution. No significant relationship was observed between neuroticism and NRS-I, SVS-I and BPI-R evolution. CONCLUSIONS: Our findings suggest that neuroticism can decrease the efficacy of group art intervention on pain in patients with mild AD. Individual therapies could be more appropriate for these patients. These results emphasize the interest of taking into account patients' personality before proposing them to participate to a group therapy.

Can Musical or Painting Interventions Improve Chronic Pain, Mood, Quality of Life, and Cognition in Patients with Mild Alzheimer's Disease? Evidence from a Randomized Controlled Trial.

BACKGROUND: Among non-pharmacological therapies, musical intervention is often used for patients with Alzheimer's disease (AD) and patients presenting chronic pain. However, their efficacy is still under debate. OBJECTIVE: Our aim was to determine the efficacy of choral singing versus painting sessions on chronic pain, mood, quality of life, and cognition in AD patients. METHODS: In this multicenter randomized controlled trial, 59 mild AD patients were randomized to a 12-week singing (SG; n = 31) or painting group (PG; n = 28). Chronic pain, anxiety, depression, and quality of life were assessed before, after, and 1 month after the sessions. Cognitive abilities were assessed before and after interventions. The evolution of these different measures was assessed with mixed linear models. The primary data analysis was by intention-to-treat, and completed by a 'per protocol' approach. RESULTS: Both singing and painting interventions led to significant pain reduction (Time effect: F = 4.71; p = 0.01), reduced anxiety (Time effect: F = 10.74; p < 0.0001), improved Quality of Life (Time effect: F = 6.79; p = 0.002), improved digit span (F = 12.93; p = 0.001), and inhibitory processes (Time effect: F = 4.93; p = 0.03). Depression was reduced over time in PG only (Time x Group effect: F = 4.53; p = 0.01). Verbal Memory performance remained stable over time in SG, but decreased in PG (Time x group effect: F = 9.29; p = 0.004). CONCLUSION: Findings suggest that singing and painting interventions may reduce pain and improve mood, quality of life, and cognition in patients with mild AD, with differential effects of painting for depression and singing for memory performance.

[Chronic pain: emotional and cognitive consequences]. / Douleur chronique: son retentissement émotionnel et cognitif.

Chronic pain which had become a major public health problem, is always accompanied with emotional and cognitive disorders. These comorbidities are circular and auto generated as in low back pain or in somatoform pain as fibromyalgia. Cerebral imagery of pain show the superposition of emotional and cognitive circuits especially in frontal regions from where come the descending control of pain. Therefore common areas regulate the three functions. Consequences on semiology and treatment of chronic pain are discussed.

Chronic low-back pain modulation is enhanced by hypnotic analgesic suggestion by recruiting an emotional network: a PET imaging study.

This study aimed to characterize the neural networks involved in patients with chronic low-back pain during hypnoanalgesia. PET was performed in 2 states of consciousness, normal alertness and hypnosis. Two groups of patients received direct or indirect analgesic suggestion. The normal alertness state showed activations in a cognitive-sensory pain modulation network, including frontotemporal cortex, insula, somatosensory cortex, and cerebellum. The hypnotic state activated an emotional pain modulation network, including frontotemporal cortex, insula, caudate, accumbens, lenticular nuclei, and anterior cingulate cortex (ACC). Direct suggestion activated cognitive processes via frontal, prefrontal, and orbitofrontal cortices, while indirect suggestion activated a widespread and more emotional network including frontal cortex, anterior insula, inferior parietal lobule, lenticular nucleus, and ACC. Confirmed by visual analog scale data, these results suggest that chronic pain modulation is greater with hypnosis, which enhances both activated networks.

Visual imagery processing and knowledge of famous names in Alzheimer's disease and MCI.

The study of memory for famous people and visual imagery retrieval was investigated in patients in the early stages of Alzheimer's disease (AD) and in the prodromal stage of AD, so-called Mild Cognitive Impairment (MCI). Fifteen patients with AD (MMSE > or = 23), 15 patients with amnestic MCI (a-MCI) and 15 normal controls (NC) performed a famous names test designed to evaluate the semantic and distinctive physical features knowledge of famous persons. Results indicated that patients with AD and a-MCI generated significantly less physical features and semantic biographical knowledge about famous persons than did normal control participants. Additionally, significant differences were observed between a-MCI and AD patients in all tasks. The present findings confirm recent studies reporting semantic memory impairment in MCI. Moreover, the current findings show that mental imagery is lowered in a-MCI and AD and is likely related to the early semantic impairment.

Lack of specific gray matter alterations in restless legs syndrome in elderly subjects.

Magnetic resonance imaging studies using voxel-based morphometry (VBM) have been inconsistent in demonstrating volumetric differences in patients with restless legs syndrome (RLS). Since treatment, age and selection of patients may introduce a methodological bias, we conducted optimized VBM analyses in unmedicated elderly subjects reporting RLS. Two hundred-four voluntaries, 65.9 +/- 0.6 year-old, free of any significant medical condition and without previous neurological or psychiatric medication, participated at the study. After exclusion of subjects having sleep-related breathing disorders and previous silent infarct, 71 subjects, 54 without RLS (RLS-) and 17 having RLS (RLS+) were analyzed. No structural change in gray matter density was found in RLS+ subjects compared to RLS- subjects. Subjects with RLS+ symptoms showed a small gray matter volume in the left occipital region without, however, statistical significance. VBM analysis did not show any significant change in subcortical and cortical gray matter in unmedicated elderly subjects with RLS symptoms. These results confirm the lack of specificity of thalamic and subcortical changes in restless legs syndrome.

[Non pharmacologic treatment of neuropathic pain]. / Traitements non médicamenteux de la douleur neuropathique.

Nondrug treatments of neuropathic pain should always begin at the same time as pharmacologic treatment. There are three types of nondrug treatment for neuropathic pain: physical, surgical, and "psychocorporal" and psychotherapeutic treatment. Transcutaneous electrical nerve stimulation (TENS) is a simple physical treatment that strengthens local inhibitory controls and is indicated in focal neuropathic pain when upstream stimulation is possible for a superficial sensitive nerve trunk. Destructive surgery is represented today by "DREZotomy", destruction of nociceptive fibers and their dorsal root entry zones. It is indicated essentially in intractable pain due to plexus avulsion. Functional surgery is implanted electric stimulation--either spinal or central (encephalic)--of structures that exert inhibitory control on the pain pathways. Spinal stimulation is performed at the level of the posterior spinal cord and is indicated essentially in segmental mononeuropathies refractory to drug treatment. Central stimulation is performed at the motor cortex and is indicated for refractory central pain. "Psychocorporal" techniques (relaxation, sophrology, hypnosis) are useful to reduce anxiety and neurovegetative hypertonicity, both factors that aggravate neuropathic pain.

Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study.

To investigate brain mechanisms whereby electrical stimulation of the motor cortex (MCS) may induce pain relief in patients with neuropathic pain, cerebral blood flow (CBF) changes were studied using H2O PET in 19 consecutive patients treated with MCS for refractory neuropathic pain. Patients were studied in three conditions, (a) before MCS (Baseline, stimulator stopped 4 weeks before), (b) during a 35-min period of MCS and (c) during a 75-min period after MCS had been discontinued (OFF). Compared to Baseline, turning on the stimulator was associated with CBF increase in the contralateral (anterior) midcingulate cortex (aMCC, BA24 and 32) and in the dorso-lateral prefrontal (BA10) cortices. The most important changes of CBF were observed in the 75 min after discontinuation of MCS (OFF). This post-stimulation period was associated with CBF increases in a large set of cortical and subcortical regions (from posterior MCC (pMCC) to pregenual (pg) ACC, orbitofrontal cortex, putamen, thalami, posterior cingulate and prefrontal areas) and in the brainstem (mesencephalon/periaqueductal grey (PAG) and pons). CBF changes in the post-stimulation period correlated with pain relief. Functional connectivity analysis showed significant correlation between pgACC and PAG, basal ganglia, and lower pons activities, supporting the activation of descending ACC-to-PAG connections. MCS may act in part through descending (top-down) inhibitory controls that involve prefrontal, orbitofrontal and ACC as well as basal ganglia, thalamus and brainstem. These hemodynamic changes are lengthened and might therefore underlie the long-lasting clinical effects that largely outlast the actual stimulation periods.

On the relation between sensory deafferentation, pain and thalamic activity in Wallenberg's syndrome: a PET-scan study before and after motor cortex stimulation.

Decrease of thalamic blood flow contralateral to neuropathic pain has been described by several groups, but its relation with sensory deafferentation remains unclear. Here we report one instance where the thalamic effects of sensory deafferentation could be dissociated from those of neuropathic pain. A 50-year-old patient underwent a left medullary infarct leading to right-sided thermal and pain hypaesthesia up to the third right trigeminal division, as well as in the left face. During the following months the patient developed neuropathic pain limited to the left side of the face. Although the territory with sensory loss was much wider in the right (non painful) than in the left (painful) side of the body, PET-scan demonstrated significant reduction of blood flow in the right thalamus (contralateral to the small painful area) relative to its homologous region. After 3 months of right motor cortex stimulation the patient reported 60% relief of his left facial pain, and a new PET-scan showed correction of the thalamic asymmetry. We conclude that thalamic PET-scan hypoactivity contralateral to neuropathic pain does not merely reflect deafferentation, but appears related to the pain pathophysiology, and may be normalized in parallel with pain relief. The possible mechanisms linking thalamic hypoactivity and pain are discussed in relation with findings in epileptic patients, possible compensation phenomena and bursting thalamic discharges described in animals and humans. Restoration of thalamic activity in neuropathic pain might represent one important condition to obtain successful relief by analgesic procedures, including cortical neurostimulation.

Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy.

Thirty-one patients with medically refractory neuropathic pain were included in a prospective evaluation of motor cortex stimulation. The long-term outcome was evaluated using five variables: (a) rate (percentage) of pain relief, (b) pain scores as assessed on VAS, (c) postoperative decrease in VAS scores, (d) reduction in analgesic drug intake, (e) a dichotomic (yes/no) response to the question whether the patient would accept, under similar circumstances, to be operated on again. Pain relief was rated as excellent (>70 % pain relief) in 10 % of cases, good (40-69 %) in 42 %, poor (10-39 %) in 35 % and negligible (0-9 %) in 13 %. Intake of analgesic drugs was decreased in 52 % of patients and unchanged in 45 % (unavailable data in 3 %), with complete withdrawal of analgesic drugs in 36 % of patients. Twenty-one patients (70 %) declared themselves favourable to re-intervention if the same beneficial outcome could be guaranteed. Neither preoperative motor status, pain characteristics, type or localisation of lesions, quantitative sensory testing, Somatosensory Evoked Potentials, nor the interval between pain and surgery were found to predict the efficacy of MCS. The level of pain relief, as evaluated in the first month following implantation was a strong predictor of long-term relief (regression analysis, R=0.744; p<0.0001). These results confirm that MCS can be a satisfactory and durable alternative to medical treatments in patients with refractory pain, and suggest that the efficacy of MCS may be predicted in the first month of therapy.

Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic humans.

BACKGROUND: Plant sterols reduce cholesterol absorption, which leads to a decrease in plasma and LDL-cholesterol concentrations. Plant sterols also lower plasma concentrations of carotenoids and alpha-tocopherol, but the mechanism of action is not yet understood. OBJECTIVES: The aims of this clinical study were to determine whether plant sterols affect the bioavailability of beta-carotene and alpha-tocopherol in normocholesterolemic men and to compare the effects of plant sterol esters and plant free sterols on cholesterol absorption. DESIGN: Twenty-six normocholesterolemic men completed the double-blind, randomized, crossover study. Subjects consumed daily, for 1 wk, each of the following 3 supplements: a low-fat milk-based beverage alone (control) or the same beverage supplemented with 2.2 g plant sterol equivalents provided as either free sterols or sterol esters. During this 1-wk supplementation period, subjects consumed a standardized diet. RESULTS: Both of the milks enriched with plant sterols induced a similar (60%) decrease in cholesterol absorption. Plant free sterols and plant sterol esters reduced the bioavailability of beta-carotene by approximately 50% and that of alpha-tocopherol by approximately 20%. The reduction in beta-carotene bioavailability was significantly less with plant free sterols than with plant sterol esters. At the limit of significance (P = 0.054) in the area under the curve, the reduction in alpha-tocopherol bioavailability was also less with plant free sterols than with plant sterol esters. CONCLUSIONS: Both plant sterols reduced beta-carotene and alpha-tocopherol bioavailability and cholesterol absorption in normocholesterolemic men. However, plant sterol esters reduced the bioavailability of beta-carotene and alpha-tocopherol more than did plant free sterols.

Evidence for a selective deficit in automatic activation of positive information in patients with Alzheimer's disease in an affective priming paradigm.

Using an affective priming paradigm, we studied the automatic and unconscious activation of emotional information in long-term memory. Participants had to judge target words preceded by various primes as positive or negative. The primes were masked and the SOA between the onset of primes and the onset of targets was 50 ms. Our results showed that in patients with dementia of the Alzheimer type (DAT), the negativity bias was preserved and the emotional priming effect was perturbed with positive targets. In control participants, this priming effect was restricted to negative targets. These findings are discussed in terms of preserved automatic activation of emotional information in Alzheimer's disease (AD) and in terms of an early deficit of the left hemisphere in AD making positive information more vulnerable to disease.