Cost-effectiveness analysis of medical management versus conservative surgery for early tubal pregnancy.

STUDY QUESTION: Is conservative surgery (laparoscopic salpingotomy) cost-effective, using fertility as the endpoint compared with medical management (Methotrexate) in women with an early tubal pregnancy? SUMMARY ANSWER: Conservative surgery appeared slightly, but not statistically significantly, more effective than medical management but also more costly. WHAT IS KNOWN ALREADY: Women with an early tubal pregnancy treated with medical therapy (Methotrexate) or conservative surgery (laparoscopic salpingotomy) have comparable future intrauterine pregnancy rates by natural conception. Also, cost-minimisation studies have shown that medical therapy was less expensive than conservative surgery, but there is no cost-effectiveness study comparing these two treatments with fertility as the endpoint. STUDY DESIGN, SIZE, DURATION: A multicentre randomised controlled trial-based (DEMETER study) cost-effectiveness analysis of conservative surgery compared with medical therapy in women with an early tubal pregnancy was performed. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Included women had an ultrasound that confirmed an early tubal pregnancy. They were randomly allocated to conservative surgery or to medical therapy. The study clinical outcome was the intrauterine pregnancy rate. The payer's perspective was considered. Costs of conservative surgery and medical therapy were compared. The analysis was performed according to the intention-to-treat principle. Missing variables were imputed using the fully conditional method. To characterise uncertainty and to provide a summary of it, a non-parametric bootstrap resampling was executed and cost-effectiveness accessibility curves were constructed. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, costs per woman in the conservative surgery group and in the medical therapy group were 2627€ and 2463€, respectively, with a statistically significant difference of +164€. Conservative surgery resulted in a marginally, but non-significant (P = 0.46), higher future intrauterine pregnancy rate compared to medical therapy (0.700 vs. 0.649); leading, after bootstrap, to an incremental cost-effectiveness ratio of 1299€ (95% CI = -29 252; +29 919). Acceptability curves showed that conservative surgery could be considered a cost-effective treatment at a threshold of 3201€ for one additional future intrauterine pregnancy. LIMITATIONS, REASONS FOR CAUTION: A limitation was that monetary valuation was carried out using 2016 euros while the DEMETER study took place from 2005 to 2009. Anyway, the results would not have been very different given the marginal changes in the health insurance reimbursement tariffs during this period. WIDER IMPLICATIONS OF THE FINDINGS: Conservative surgery can be considered a cost-effective treatment, if the additional cost of 3201€ per additional future intrauterine pregnancy is an acceptable financial effort for the payer. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: NCT 00137982.

Chronic exposure of rats to noise: relationship between long-term memory deficits and slow wave sleep disturbances.

Noise is now recognized as a serious health problem in our modern societies. Although its deleterious and direct effects on cognitive tasks (long-term memory, mental arithmetic activity, visual tasks, etc.) are clearly admitted, no studies have determined a delayed indirect effect of noise on cognitive processes. Furthermore, the link between sleep disturbances related to environmental noise (EN) exposure and these indirect deteriorations of human performances has never been demonstrated. This could be due to inappropriate evaluation of sleep as well as to uncontrolled and confounding factors such as sex, age, and also inter-individual vulnerability. Based on a recently validated animal model [Rabat A, Bouyer JJ, Aran JM, Le Moal M, Mayo W. Chronic exposure to an environmental noise permanently disturbs sleep in rats: inter-individual vulnerability. Brain Res 2005;1059:72-82], aims of the present study were (i) to determine long-term memory (LTM) deficits following a chronic exposure to EN and (ii) to link these behavioral problems to sleep disturbances related to EN. For this purpose in a first experiment, LTM performances were evaluated before and following 9 days of EN. Results show LTM deficits following a chronic exposure to EN with inter-individual vulnerability. Vulnerability profile was related to the psychobiological profile of rats. Results of the second experiment show LTM deficits correlated to both debt of slow wave sleep (SWS) and to daily decrease of SWS bout duration. Our results demonstrate that chronic exposure to noise indirectly disturbs LTM possibly through SWS disturbances and suggest a possible role of the stress hormonal axis in these biological effects of noise.

Chronic exposure to an environmental noise permanently disturbs sleep in rats: inter-individual vulnerability.

Chronic exposure to an environmental noise (EN) induces sleep disturbances. However, discrepancies exist in the literature since many contradictory conclusions have been reported. These disagreements are largely due to inappropriate evaluation of sleep and also to uncontrolled and confounding factors such as sex, age and also inter-individual vulnerability. Based on a recently validated animal model, aims of the present study were (i) to determine the effects of a chronic exposure to EN on sleep and (ii) to evaluate the inter-individual vulnerability of sleep to EN. For this purpose, rats were exposed during 9 days to EN. Results show that a chronic exposure to EN restricts continually amounts of slow wave sleep (SWS) and paradoxical sleep (PS) and fragments these two sleep stages with no habituation effect. Results also evidence the existence of subpopulations of rats that are either resistant or vulnerable to these deleterious effects of EN on sleep and especially on SWS amounts, bouts number and bout duration. Furthermore, importance of SWS debt and daily decrease of SWS bout duration are correlated to each others and both correlate to the amplitude of the locomotor reactivity to novelty, a behavioral measure of reactivity to stress. This last result suggests that this psychobiological profile of subjects, known to induce profound differences in neural and endocrine systems, could be responsible for their SWS vulnerability under a chronic EN exposure.

[Regulation pathways of expectancy behavior in the cat: histologic study]. / Voies de régulation du comportement d'attente chez le chat: étude histologique.

In the behaving cat, motion expectancy of an event to occur (for a prey to appear) is accompanied by the development of 14 Hz electrocortical mu rhythms in the hand subarea of cortical somatic area SI. Our first aim here was to identify subcortical sites projecting to this cortical mu focus, using localised retrograde HRP marking. The only site thus labelled was the thalamic zone well known to project to the cortical mu area, and to act as a generator for the mu rhythms (ventral posterior nucleus, VP); no other deep structure could be identified, that could have been considered as a putative zone for control of cortical mu. We then injected minute amounts of HRP into the thalamic mu zone; labelled neurones were located (apart from those expected in the relays of the somatic pathway) in locus coeruleus (bilaterally) and ipsilaterally in the thalamic nuclei anteroventralis and laterodorsalis. In brief then, it seems that the regulation of the VP-SI mu channel (that we could previously demonstrate), by other deep structures is exerted upon the thalamic side.

[Localized frontoparietal beta rhythms and focused attention in animals]. / Rythmes bêta fronto-pariétaux focalisés et attention dirigée chez l'animal.

In normal cats and monkeys, fronto-parietal beta rhythms (averages: 36 and 18 c/sec, respectively) were considered as a sign of focused attention, since they appeared during several different situations having in common that the subject's attention was drawn by a signal or an object of the environment. These regular rhythmic activities, often with a high amplitude, are localized within two small cortical foci. At least one set of beta rhythms corresponds to the end station of a thalamocortical system originating in the posterior group (POm), and are controlled by a dopaminergic system the somas of which are situated in the ventral mesencephalic tegmentum (area A10). Eight percent of the VMT cells, studied with micropipettes in normal awake cats, suddenly increased their spontaneous activity 1 sec before the beginning of the rhythmic volleys. Considering the analogy between these rhythms and the human frontal beta rhythms, it is suggested that these data may contribute to the study of attention in man, whether in a healthy state or suffering from mental disease.

Thalamic rhythms in cat during quiet wakefulness and immobility.

In this study we tried to get some more information on the cortical 'mu' rhythms in normal cat and their thalamic pacemaker. Mu (14 c/sec) activity develops when the animal is motionless, in a state of 'quiet waking.' It is distinct from other sensorimotor rhythms, with distinct cortical distributions, distinct frequencies and appearing under different behavioural and environmental conditions. The cortical mu focus was shown to be centred within a restricted part of area SI, in the forepaw and wrist projection field. The related thalamic focus was localized in a small zone of the VP nucleus that also corresponded to the hand and wrist projection area. A coherence study confirmed the close relationship between the two foci, thalamic and cortical. After unilateral electrolytic destruction of the thalamic area, a small mu activity persisted, on the ipsilateral cortex, originating from the opposite side. After bilateral lesion of the VP foci, no mu activity could ever be recorded on either side, while the other sensorimotor rhythms were left intact.

Somatosensory rhythms in the awake cat: a single unit exploration of their thalamic concomitant in nucleus ventralis posterior and vicinity.

A microelectrode study was performed in n. ventralis posterior (VP) of the fully alert cat, to study the correlation between thalamic unit activity and the cortical synchronized 14 c/sec rhythms that develop in the somatic area I for forepaw and wrist projections, when the animal is in a state of "quiet waking". (i) Only a small proportion of VP cells underwent changes during the studied cortical rhythms. (ii) None of these cells were typical thalamo-cortical relay cells carrying tactile messages to the cortex. (iii) Cells altering their discharge were of two types, rhythmic (R) cells, discharging at the frequency of the cortical rhythms, and tonic (T) cells, displaying an overall, sustained change during the whole sequence of cortical 14 c/sec. (iv) Among R cells, some were long axon thalamo-cortical cells and others, likely to be interneurones. (v) Some T cells increased their firing rate during rhythmic trains, others came into silence during the same period. (vi) The thalamic circuitry responsible for this particular set of "quiet waking rhythms" is discussed.

Fast fronto-parietal rhythms during combined focused attentive behaviour and immobility in cat: cortical and thalamic localizations.

In the cat, fronto-parietal mu rhythms belonging to the 'high frequency range' (35-45 c/sec) develop as the animal becomes immobile in an attitude of focused attention. Two cortical foci were identified, one anterior in the precruciate area, the other posterior in the periansate cortex (posterior parietal area). A thalamic focus, in an area belonging to the medial portion of the posterior thalamic group, appears to be a pacemaker for the posterior cortical focus alone.

Selective modification of spontaneous ECoG rhythms of the cat somesthetic cortex by psychoactive drugs: behavioral correlates.

Three psychoactive drugs with known central effects were administered to the freely moving cat in order to study their action on spontaneous rhythmic activities recorded from the primary somesthetic cortex, which are analogous to the rolandic mu rhyhm in man. The ECoG patterns obtained are qualitatively identical to those of the normal subject, but their temporal organization is profoundly disturbed by the action of the drugs. The normal ECoG consists of three rhythmic systems with distinct frequencies and displays a considerable time variability. In contrast, psychoactive drugs induce a stabilized pattern with only one type (or at most two types) of rhythm prevailing for one or several hours, which never occurs under normal conditions. These ECoG rhythms underlie various behavioral states. Under d-amphetamine, correspondence remains excellent between behavior and ECoG; under Ditran, complete dissociation occurs; finally, LSD represents a borderline case in which ECoG and behavior are partially correlated and partially dissociated.