El concepto jurídico de la sangre y sus derivados desde la perspectiva del derecho comunitario y español

El presente trabajo pretende analizar desde el punto de vista del Derecho farmacéutico el concepto jurídico dela sangre y sus derivados, concepto que ha de servirnos para valorar la situación de la sangre y los hemoderivadosy su inclusión o no dentro de la normativa existente para los medicamentos de uso humano. Para conseguirestablecer unos criterios adecuados sobre esta cuestión, en primer lugar hemos de definir el concepto jurídico demedicamento, que no parece claro, a pesar de las distintas definiciones que aporta la legislación. Estas definiciones,en ocasiones pueden parecer ambiguas y presentar zonas fronterizas no definidas que necesitan de un nuevoavance que consiga reflejar con claridad el concepto jurídico de medicamento. Para conseguir determinar conmayor precisión el concepto de medicamento hemos de utilizar de forma reiterada las diversas sentencias queaporta la jurisprudencia comunitaria en la materia, que ha debido de interpretar y aclarar en más de una ocasiónla indefinición que presenta la normativa para determinar de forma clara y meridiana el concepto de medicamento.Una vez definido el concepto de medicamento, pretendemos observar cómo quedan incorporados a esta definiciónlos medicamentos derivados de la sangre y plasma humanos, así como las zonas fronterizas que este tipode medicamentos presentan

Measuring benefits and patients' satisfaction when glasses are not needed after cataract and presbyopia surgery: scoring and psychometric validation of the Freedom from Glasses Value Scale (FGVS©)

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to reduce the number of items, create a scoring method and assess the psychometric properties of the Freedom from Glasses Value Scale (FGVS), which measures benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal intraocular lens (IOL) surgery.</p> <p>Methods</p> <p>The 21-item FGVS, developed simultaneously in French and Spanish, was administered by phone during an observational study to 152 French and 152 Spanish patients who had undergone cataract or presbyopia surgery at least 1 year before the study. Reduction of items and creation of the scoring method employed statistical methods (principal component analysis, multitrait analysis) and content analysis. Psychometric properties (validation of the structure, internal consistency reliability, and known-group validity) of the resulting version were assessed in the pooled population and per country.</p> <p>Results</p> <p>One item was deleted and 3 were kept but not aggregated in a dimension. The other 17 items were grouped into 2 dimensions ('global evaluation', 9 items; 'advantages', 8 items) and divided into 5 sub-dimensions, with higher scores indicating higher benefit of surgery. The structure was validated (good item convergent and discriminant validity). Internal consistency reliability was good for all dimensions and sub-dimensions (Cronbach's alphas above 0.70). The FGVS was able to discriminate between patients wearing glasses or not after surgery (higher scores for patients not wearing glasses). FGVS scores were significantly higher in Spain than France; however, the measure had similar psychometric performances in both countries.</p> <p>Conclusions</p> <p>The FGVS is a valid and reliable instrument measuring benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal IOL surgery.</p

HBV Infection in Relation to Consistent Condom Use: A Population-Based Study in Peru

Data on hepatitis B virus (HBV) prevalence are limited in developing countries. There is also limited information of consistent condom use efficacy for reducing HBV transmission at the population level. The study goal was to evaluate the prevalence and factors associated with HBV infection in Peru, and the relationship between anti-HBc positivity and consistent condom use.Data from two different surveys performed in 28 mid-sized Peruvian cities were analyzed. Participants aged 18-29 years were selected using a multistage cluster sampling. Information was collected through a validated two-part questionnaire. The first part (face-to-face) concerned demographic data, while the second part (self-administered using handheld computers) concerned sexual behavior. Hepatitis B core antibody (anti-HBc) was tested in 7,000 blood samples. Prevalences and associations were adjusted for sample strata, primary sampling units and population weights. Anti-HBc prevalence was 5.0% (95%CI 4.1%-5.9%), with the highest prevalence among jungle cities: 16.3% (95%CI 13.8%-19.1%). In the multivariable analysis, Anti-HBc positivity was directly associated with geographic region (highlands OR = 2.05; 95%CI 1.28-3.27, and jungle OR = 4.86; 95%CI 3.05-7.74; compared to coastal region); and inversely associated with age at sexual debut (OR = 0.90; 95%CI 0.85-0.97). Consistent condom use, evaluated in about 40% of participants, was associated with reduced prevalence (OR = 0.34; 95%CI 0.15-0.79) after adjusting for gender, geographic region, education level, lifetime number of sex partners, age at sexual debut and year of survey.Residence in highlands or jungle cities is associated with higher anti-HBc prevalences, whereas increasing age at sexual debut were associated with lower prevalences. Consistent condom use was associated with decreased risk of anti-HBc. Findings from this study emphasize the need of primary prevention programs (vaccination) especially in the jungle population, and imply that condom use promotion might be a potential strategy to prevent HBV infection

FSP27 Promotes Lipid Droplet Clustering and Then Fusion to Regulate Triglyceride Accumulation

Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173–220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120–140 are essential but not sufficient for LD enlargement, whereas amino acids 120–210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation

Leaky doors: private captivity as a prominent source of bird introductions in Australia

The international pet trade is a major source of emerging invasive vertebrate species. We used online resources as a novel source of information for accidental bird escapes, and we investigated the factors that influence the frequency and distribution of bird escapes at a continental scale. We collected information on over 5,000 pet birds reported to be missing on animal websites during the last 15 years in Australia. We investigated whether variables linked to pet ownership successfully predicted bird escapes, and we assessed the potential distribution of these escapes. Most of the reported birds were parrots (> 90%), thus, we analysed factors associated with the frequency of parrot escapes. We found that bird escapes in Australia are much more frequent than previously acknowledged. Bird escapes were reported more frequently within, or around, large Australian capital cities. Socio-economic factors, such as the average personal income level of the community, and the level of human modification to the environment were the best predictors of bird escapes. Cheaper parrot species, Australian natives, and parrot species regarded as peaceful or playful were the most frequently reported escapees. Accidental introductions have been overlooked as an important source of animal incursions. Information on bird escapes is available online in many higher income countries and, in Australia, this is particularly apparent for parrot species. We believe that online resources may provide useful tools for passive surveillance for non-native pet species. Online surveillance will be particularly relevant for species that are highly reported, such as parrots, and species that are either valuable or highly commensal.Miquel Vall-llosera, Phillip Casse

The effect of the COACH program (Continuity Of Appropriate pharmacotherapy, patient Counselling and information transfer in Healthcare) on readmission rates in a multicultural population of internal medicine patients

BACKGROUND: Medication errors occur frequently at points of transition in care. The key problems causing these medication errors are: incomplete and inappropriate medication reconciliation at hospital discharge (partly arising from inadequate medication reconciliation at admission), insufficient patient information (especially within a multicultural patient population) and insufficient communication to the next health care provider. Whether interventions aimed at the combination of these aspects indeed result in less discontinuity and associated harm is uncertain. Therefore the main objective of this study is to determine the effect of the COACH program (Continuity Of Appropriate pharmacotherapy, patient Counselling and information transfer in Healthcare) on readmission rates in patients discharged from the internal medicine department. METHODS/DESIGN: An experimental study is performed at the internal medicine ward of a general teaching hospital in Amsterdam, which serves a multicultural population. In this study the effects of the COACH program is compared with usual care using a pre-post study design. All patients being admitted with at least one prescribed drug intended for chronic use are included in the study unless they meet one of the following exclusion criteria: no informed consent, no medication intended for chronic use prescribed at discharge, death, transfer to another ward or hospital, discharge within 24 hours or out of office hours, discharge to a nursing home and no possibility to counsel the patient.The intervention consists of medication reconciliation, patient counselling and communication between the hospital and primary care healthcare providers.The following outcomes are measured: the primary outcome readmissions within six months after discharge and the secondary outcomes number of interventions, adherence, patient's attitude towards medicines, patient's satisfaction with medication information, costs, quality of life and finally satisfaction of general practitioners and community pharmacists.Interrupted time series analysis is used for data-analysis of the primary outcome. Descriptive statistics is performed for the secondary outcomes. An economic evaluation is performed according to the intention-to-treat principle. DISCUSSION: This study will be able to evaluate the clinical and cost impact of a comprehensive program on continuity of care and associated patient safety. TRIAL REGISTRATION: Dutch trial register: NTR151

Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle

Neuronal activity within the central nervous system (CNS) strictly depends on homeostasis and therefore does not tolerate uncontrolled entry of blood components. It has been generally believed that under normal conditions, the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB) prevent immune cell entry into the CNS. This view has recently changed when it was realized that activated T cells are able to breach the BBB and the BCSFB to perform immune surveillance of the CNS. Here we propose that the immune privilege of the CNS is established by the specific morphological architecture of its borders resembling that of a medieval castle. The BBB and the BCSFB serve as the outer walls of the castle, which can be breached by activated immune cells serving as messengers for outside dangers. Having crossed the BBB or the BCSFB they reach the castle moat, namely the cerebrospinal fluid (CSF)-drained leptomeningeal and perivascular spaces of the CNS. Next to the CNS parenchyma, the castle moat is bordered by a second wall, the glia limitans, composed of astrocytic foot processes and a parenchymal basement membrane. Inside the castle, that is the CNS parenchyma proper, the royal family of sensitive neurons resides with their servants, the glial cells. Within the CSF-drained castle moat, macrophages serve as guards collecting all the information from within the castle, which they can present to the immune-surveying T cells. If in their communication with the castle moat macrophages, T cells recognize their specific antigen and see that the royal family is in danger, they will become activated and by opening doors in the outer wall of the castle allow the entry of additional immune cells into the castle moat. From there, immune cells may breach the inner castle wall with the aim to defend the castle inhabitants by eliminating the invading enemy. If the immune response by unknown mechanisms turns against self, that is the castle inhabitants, this may allow for continuous entry of immune cells into the castle and lead to the death of the castle inhabitants, and finally members of the royal family, the neurons. This review will summarize the molecular traffic signals known to allow immune cells to breach the outer and inner walls of the CNS castle moat and will highlight the importance of the CSF-drained castle moat in maintaining immune surveillance and in mounting immune responses in the CNS

Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases

Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. Weevaluated whether PSVs inBRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.Peer reviewe