Consumo entre juventud norteamericana: un dilema paradójico

Los Estados Unidos ha recibido inmigrantes de más de 150 países, y entre ellos, hay gran diferencias en tradiciones sobre el consumo del alcohol. Como resultado, hay una falta de consenso sobre normas nacionales. La situación de heterogeneidad de valores y opiniones se ha designado ambivalencia cultural. Una tradición dominante de valores se basa en puritanismo. Así, casi todos los estados en el país establecieron una edad mínima de 21 años para comprar bebidas alcohólicas. Una ley nacional que bajó la edad de votar desde 21 hasta 18 fue el estímulo por la bajada de la edad para comprar bebidas alcohólicas a 18 o 19 años en 35 de los 50 estados. Una reacción conservadora influyó el restablecimiento de la edad legal a 21 años después de 1984.La prohibición del alcohol a los menores de 21 años ha tenido poco éxito. Entre los consumidores de escuelas secundarias, los jóvenes en los EE.UU. muestran una tasa de embriaguez frecuente que es un poco más alta que la media aritmética de los europeos. Una medida del consumo total por grupo etário revaló que los de 12 a 20 años constan el 15.4% de la población total de 12 años y mayores, y ellos consumen el 19.7% del alcohol producido. También, los de 18 hasta 20 años bebieron una media aritmétrica de 51 bebidas por mes por persona, en contraste con 33 mensualmente por parte de los de 21 años y más, una diferencia superior del 54% por parte de la juventud. El sitio de consumo por parte de los universitarios debajo de la edad legal es primariamente en fiestas en alojamientos privados fuera del campo universitario en el que el 65% asiste por lo menos mensualmente. Los de 21 años y mayores beben con iqual frecuencia en fiestas privadas y en bares donde ellos pueden asistir legalmente.Claro que la política de proteger la inocencia y la virtud de la juventud ha fracasado casi completamente. Personas de 18 años no creen que se necesitan esta protección en que ellos son adultos en todas las otras áreas de la vida. Debido a ambivalencia cultural, la mayoría de adultos norteamericanos creen que se require más madurez para escoger una bebida alcohólica en contraste con escoger participación en las otras actividades de la vida adulta. Lo que la ley efectua es que los de 18 a 20 años no consumen frecuentemente en bares públicos, sino que en fiestas privadas en que se desarrolla un sentido de comunidad y una contracultura en oposición al control de los mayores

A novel dried blood spot-LCMS method for the quantification of methotrexate polyglutamates as a potential marker for methotrexate use in children

Objective: Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). Methods: DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 μl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 μm, 2.1x150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization. Key Results: The method was linear over the range 5-400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique. Conclusions and Clinical Relevance: The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology. © 2014 Hawwa et al

Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011

The internal structure and composition of a plate-boundary-scale serpentinite shear zone: the Livingstone Fault, New Zealand

Abstract. Deciphering the internal structure and composition of large serpentinite-dominated shear zones will lead to an improved understanding of the rheology of the lithosphere in a range of tectonic settings. The Livingstone Fault in New Zealand is a terrane-bounding structure that separates the basal portions (peridotite; serpentinised peridotite; metagabbros) of the Dun Mountain Ophiolite Belt from the quartzofeldspathic schists of the Caples and Aspiring Terrane. Field and microstructural observations from 11 localities along a strike length of ca. 140 km show that the Livingstone Fault is a steeply dipping, serpentinite-dominated shear zone tens of metres to several hundred metres wide. The bulk shear zone has a pervasive scaly fabric that wraps around fractured and faulted pods of massive serpentinite, rodingite and partially metasomatised quartzofeldspathic schist up to a few tens of metres long. S–C fabrics and lineations in the shear zone consistently indicate a steep east-side-up shear sense, with significant local dispersion in kinematics where the shear zone fabrics wrap around pods. The scaly fabric is dominated (>98 % vol) by fine-grained (≪10 µm) fibrous chrysotile and lizardite–polygonal serpentine, but infrequent (<1 % vol) lenticular relicts of antigorite are also preserved. Dissolution seams and foliation surfaces enriched in magnetite, as well as the widespread growth of fibrous chrysotile in veins and around porphyroclasts, suggest that bulk shear zone deformation involved pressure–solution. Syn-kinematic metasomatic reactions occurred along all boundaries between serpentinite, schist and rodingite, forming multigenerational networks of nephritic tremolite veins that are interpreted to have caused reaction hardening within metasomatised portions of the shear zone. We propose a conceptual model for plate-boundary-scale serpentinite shear zones which involves bulk-distributed deformation by pressure–solution creep, accompanied by a range of physical (e.g. faulting in pods and wall rocks; smearing of magnetite along fault surfaces) or chemical (e.g. metasomatism) processes that result in localised brittle deformation within creeping shear zone segments

No change in calculated creatinine clearance after tenofovir initiation among Thai patients

Objectives Thai patients have a lower average body weight than patients from western Europe or the USA. Tenofovir is largely prescribed at the standard dosage of 300 mg once daily: therefore, the per kilogram dose is higher in Thailand than in the USA. We asked the question whether this higher per kilogram dose was associated with more nephrotoxicity. Methods Thai patients from the Staccato trial were treated with tenofovir/lamivudine combined with ritonavir-boosted saquinavir. Creatinine values were measured before the start of tenofovir and then every 12 weeks. Renal function was assessed using the Cockcroft-Gault formula and the MDRD formula. To compare CLCR before and after tenofovir, the t-paired or Wilcoxon signed rank tests were used. One-way analysis of variance and Spearman's correlation coefficient were used to study CLCR longitudinally. Results CLCR remained stable after a median of 21 weeks on tenofovir (difference of +1.06 mL/min; 95% CI −2.7-4.8, P = 0.58), even among patients with underlying diseases. The mean CLCR remained stable across time (P = 0.17). Conclusions We did not find renal dysfunction on tenofovir among Thai patients included in the Staccato trial. Tenofovir could be safely prescribed at a standard dosage of 300 mg once daily in the Thai populatio

Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial

Background: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT0093134

Chronic Oedema and the older person: The effects of ageing upon treatment outcomes

Chronic oedema (CO) and lymphoedema (LO) are long-term conditions that can become more complicated or are more likely to develop with age. The ageing process can involve alterations in the structures that support the normal function of the lymphatic system or put it at greater risk of damage. The main three components (skin care, exercise and compression therapy) within the management of CO/LO can become more difficult to apply with age. This is because of reduced healing rates, decreased cardiovascular capacity and deterioration in vascular and arterial structures. The impact of ageing and how this can affect patients and treatment outcomes requires careful consideration

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment