Appropriateness of methadone maintenance treatment for opiate addiction: evaluation by an expert panel.

With some 30,000 dependent persons, opiate addiction constitutes a major public health problem in Switzerland. The Swiss Federal Office of Public Health (FOPH) has long played a leading role in the prevention and treatment of opiate addiction and in research on effective means of containing the epidemic of opiate addiction and its consequences. Major milestones on that path have been the successive "Methadone reports" published by that Office and providing guidance on the care of opiate addiction with substitution treatment. In view of updating the recommendations for the appropriateness of substitution treatment for opiate addiction, in particular for the prescription of methadone, the FOPH commissioned a multi-component project involving the following elements. A survey of current attitudes and practices in Switzerland related to opiate substitution treatment Review of Swiss literature on methadone substitution treatment Review of international literature on methadone substitution treatment National Methadone Substitution Conference Multidisciplinary expert panel to evaluate the appropriateness of substitution treatment. The present report documents the process and summarises the results of the latter element above. The RAND appropriateness method (RAM) was used to distil from literature-based evidence and systematically formulated expert opinion, areas where consensus exist on the appropriateness (or inappropriateness) of methadone maintenance treatment (MMT) and areas where disagreement or uncertainty persist and which should be further pursued. The major areas which were addressed by this report are Initial assessment of candidates for MMT Appropriate settings for initiation of MMT (general and special cases) Appropriateness of methadone supportive therapy Co-treatments and accompanying measures Dosage schedules and pharmacokinetic testing Withdrawal from MMT Miscellaneous questions Appropriateness of other (non-methadone) substitution treatment Summary statements for each of the above categories are derived from the panel meeting and presented in the report. In the "first round", agreement was observed for 31% of the 553 theoretical scenarios evaluated. The "second round" rating, following discussion of divergent ratings, resulted in a much higher agreement among panellists, reaching 53% of the 537 scenarios. Frank disagreement was encountered for 7% of all scenarios. Overall 49% of the clinical situations (scenarios) presented were considered appropriate. The areas where at least 50% of the situations were considered appropriate were "initial assessment of candidates for MMT", the "appropriate settings for initiation of MMT", the "appropriate settings for methadone supportive treatment" and "Appropriateness of other (non-methadone) substitution treatment". The area where there was the least consensus on appropriateness concerned "appropriateness of withdrawal from MMT" (6%). The report discusses the implications and limitations of the panel results and provides recommendations for the dissemination, application, and future use of the criteria for the appropriateness of MMT. The RAND Appropriateness Method proved to be an accepted and appreciated method to assess the appropriateness of methadone maintenance treatment for opiate addicts. In the next step, the results of the expert panel process must now be combined with those of the Swiss and international literature reviews and the survey of current attitudes and practices in Switzerland, to be synthesized into formal practice guidelines. Such guidelines should be disseminated to all concerned, promoted, used and rigorously evaluated for compliance and outcome.

Evoked axonal oxytocin release in the central amygdala attenuates fear response.

The hypothalamic neuropeptide oxytocin (OT), which controls childbirth and lactation, receives increasing attention for its effects on social behaviors, but how it reaches central brain regions is still unclear. Here we gained by recombinant viruses selective genetic access to hypothalamic OT neurons to study their connectivity and control their activity by optogenetic means. We found axons of hypothalamic OT neurons in the majority of forebrain regions, including the central amygdala (CeA), a structure critically involved in OT-mediated fear suppression. In vitro, exposure to blue light of channelrhodopsin-2-expressing OT axons activated a local GABAergic circuit that inhibited neurons in the output region of the CeA. Remarkably, in vivo, local blue-light-induced endogenous OT release robustly decreased freezing responses in fear-conditioned rats. Our results thus show widespread central projections of hypothalamic OT neurons and demonstrate that OT release from local axonal endings can specifically control region-associated behaviors.

Disseny i desenvolupament d'un esquema criptogràfic per gestionar de forma segura els historials mèdics dels pacients a través d'una xarxa de comunicacions.

Desenvolupament d'un esquema criptogràfic per gestionar de forma segura els historials mèdics dels pacients através d'una xarxa de comunicacions. L'aplicació proporciona les propietatsbàsiques de seguretat que hem esmentat, a més de la propietat de no-repudique permet assegurar que una informació referent a una visita ha estat introduïda per un metge autoritzat i concret.

Field evaluation of effectiveness of the BG-Sentinel, a new trap for capturing adult Aedes aegypti (Diptera: Culicidae)

In recent years, the development of new tools to gather field information about vector ecological parameters has increased. This report evaluated the BG-Sentinel Trap (BGS-Trap), a promising new attempt to improve collection of the dengue vector, Aedes aegypti. The efficacy of the BGS-Trap was compared with the CDC backpack aspirator, one of the commonest used methods for capturing adult mosquitoes. BGS-Traps captured significantly more Ae. aegypti males (chi2 = 21.774, df = 1, P < 0.05) and females (chi2 = 56.007, df = 1, P < 0.05) than CDC aspirator during all days of field collection. However, CDC aspirator was significantly more efficient to capture Culex quinquefasciatus males (chi2 = 5.681, df = 1, P < 0.05) and females (chi2 = 6.553, df = 1, P < 0.05). BGS-Traps captured host-seeking females (varying between 68.75 to 89.8%) in detriment of females in other behavioral and physiological stages. BGS-Traps proved to be efficient and can be used for monitoring adult mosquito populations.

Asma en la edad pediátrica : proceso asistencial integrado

Este documento (2003), junto con el de Asma en la edad adulta (2004), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma del adulto : proceso asistencial integrado

Este documento (2004), junto con el de Asma en la edad pediátrica (2003), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma : proceso asistencial integrado

Este Proceso (2012) integra los dos publicados anteriormente de Asma en la edad pediátrica (2003) y Asma en la edad adulta (2004). Fichero en formato pdf, publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Effect of long-term administration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons.

BACKGROUND. Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. DESIGN. This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs).The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. RESULTS. The baseline levels of uric acid were higher in the MFT group.Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004).In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03),and the FEUA was higher (P = 0.04).The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03).In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). CONCLUSIONS. Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy.The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.

Change in mutation patterns of Plasmodium vivax dihydrofolate reductase (Pvdhfr) and dihydropteroate synthase (Pvdhps) in P. vivax isolates from malaria endemic areas of Thailand

Malaria is the most important public health problem in several countries. In Thailand, co-infections of Plasmodium vivax and Plasmodium falciparum are common. We examined the prevalence and patterns of mutations in P. vivax dihydrofolate reductase (Pvdhfr) and P. vivax dihydropteroate synthase (Pvdhps) in 103 blood samples collected from patients with P. vivax infection who had attended the malaria clinic in Mae Sot, Tak Province during 2009 and 2010. Using nested polymerase chain reaction-restriction fragment length polymorfism, we examined single nucleotide polymorphisms-haplotypes at amino acid positions 13, 33, 57, 58, 61, 117 and 173 of Pvdhfr and 383 and 553 of Pvdhps. All parasite isolates carried mutant Pvdhfr alleles, of which the most common alleles were triple mutants (99%). Eight different types of Pvdhfr and combination alleles were found, as follows: 57I/58R/117T, 57I/58R/117T, 57I/58R/117T/N, 57L/58R/117T, 57L/58R/117T, 58R/61M/117N, 58R/61M/117N and 13L/57L/58R/117T. The most common Pvdhfr alleles were 57I/58R/117T (77.7%), 57I/58R/117T/N (1%), 57L/58R/117T (5.8%) and 58R/61M/117N (14.5%). The most common Pvdhfr alleles were 57I/58R/117T (77.7%), 57I/58R/117T/N (1%), 57L/58R/117T (5.8%) and 58R/61M/117N (14.5%). Additionally, we recovered one isolate of a carrying a quadruple mutant allele, 13L/57L/58R/117T. The most prevalent Pvdhps allele was a single mutation in amino acid 383 (82.5%), followed by the wild-type A383/A553 (17.5%) allele. Results suggest that all P. vivax isolates in Thailand carry some combination of mutations in Pvdhfr and Pvdhps. Our findings demonstrate that development of new antifolate drugs effective against sulfadoxine-pyrimethamine-resistant P. vivax is required.

Evaluación económica de la monoterapia con tocilizumab frente a adalimumab en artritis reumatoide.

BACKGROUND Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy, in reducing signs and symptoms of adult rheumatoid arthritis (RA) when methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the study was to analyze the cost-effectiveness of TCZ vs ADA in these patients. METHODS Economic evaluation of the cost per response or remission of TCZ vs ADA from ADACTA (time horizon: 24 weeks). Clinical response criteria ACR or disease remission criteria, DAS28. PERSPECTIVE National Health System. The costs included (acquisition, administration and monitoring of medicines; € 2012) were obtained from Spanish sources. Simple univariate sensitivity analyzes were performed. RESULTS ACR20, ACR50 and ACR70 response rates with TCZ and ADA were obtained in 65% and 49.4% (p <0.01), 47.2% and 27.8% (p <0.01); and 32.5% and 17.9% (p <0.01) of patients, respectively. DAS28 remission occurred in 39.9% and 10.5%, respectively (p <0.0001). The cost per response was lower with TCZ than with ADA (ACR20: € 8,105 and € 11,553; ACR50: € 11,162 and € 20,529; ACR70: € 16,211 and € 31,882) respectively. The cost of DAS28 remission was € 13,204 and € 54,352, respectively. Treatment with TCZ was dominant (more effective, with lower costs vs ADA) in all scenarios analyzed. CONCLUSIONS According to this analysis, in Spain TCZ monotherapy is an efficient strategy vs ADA for treating RA patients intolerant to MTX or in which there is inappropriate response.

The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement.

Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the efficiency of Ag recognition deviated by fivefold or more. Here we report that the functional CTL response (cytotoxicity and IFN-gamma production) correlated with the rate of TCR-ligand complex dissociation, but not the avidity of TCR-ligand binding. While peptide antagonists exhibited very rapid TCR-ligand complex dissociation, slightly slower dissociation was observed for strong agonists. Conversely and surprisingly, weak agonists typically displayed slower dissociation than the wild-type agonists. Acceleration of TCR-ligand complex dissociation by blocking CD8 participation in TCR-ligand binding increased the efficiency of Ag recognition in cases where dissociation was slow. In addition, permanent TCR engagement by TCR-ligand photocross-linking completely abolished sustained intracellular calcium mobilization, which is required for T cell activation. These results indicate that the functional CTL response depends on the frequency of serial TCR engagement, which, in turn, is determined by the rate of TCR-ligand complex dissociation.

Mélanges de poésie.

Poème de Tobie (1). — Mag. Alexandri Laus sapientiae divinae {40). — Pièces de vers composées par Jo. Prevost (89), Fr, Caulier (90), Lud. Hurillon (91, 93), J. Mentel (94), N. Leon. Bursarius (95), J. Fr. Mondolot. (96), Fr. Boutard (99), Am. du Mas (106), Car. Thiery (112), Ben. Thibaud (113), Fr. de Clermont Thoury (139), Pet, Neveletus. Doschius (169), Car. Fr. Thiery (184), Seb. Tripier (276), Franc. Linant (323), Jos. Rosset (351), Rob. Wallery (363), Ren. Pr. Tassin (371), Jo. Henr. Wentsel (373). — Extr. du ms. 553 du Vatican (104). — Lettre des religieux de Tiron à Jean Casimir, roi de Pologne (178). — Épitaphes et inscriptions modernes, plusieurs composées par Mabillon. — Deux vieilles épitaphes de l'église de: Lagny (262). Inscription antique de Vicence (311). — Distiques de l'abbé Serlon (355). Épitaphe. de Ratherius (356). — Qq. pièces en français et en italien.

Wildflower areas within revitalized agricultural matrices boost small mammal populations but not breeding Barn Owls

Agro-ecosystems have recently experienced dramatic losses of biodiversity due to more intensive production methods. In order to increase species diversity, agri-environment schemes provide subsidies to farmers who devote a fraction of their land to ecological compensation areas (ECA). Several studies have shown that invertebrate biodiversity is actually higher in ECA than in nearby intensively cultivated farmland. It remains poorly understood, however, to what extent ECA also favour vertebrates, such as small mammals and their predators, which would contribute to restore functioning food chains within revitalized agricultural matrices. We studied small mammal populations among eight habitat types - including wildflower areas, a specific ECA in Switzerland - and habitat selection (radiotracking) by the barn owl Tyto alba, one of their principal predators. Our prediction was that habitats with higher abundances of small mammals would be more visited by foraging Barn owls during the period of chicks' provisioning. Small mammal abundance tended to be higher in wildflower areas than in any other habitat type. Barn owls, however, preferred to forage in cereal fields and grassland. They avoided all types of crops other than cereals, as well as wildflower areas, which suggests that they do not select their hunting habitat primarily with respect to prey density. Instead of prey abundance, prey accessibility may play a more crucial role: wildflower areas have a dense vegetation cover, which may impede access to prey for foraging owls. The exploitation of wildflower areas by the owls might be enhanced by creating open foraging corridors within or around wildflower areas. Wildflower areas managed in that way might contribute to restore functioning food chains within agro-ecosystems.