Clinical practice with anti-dementia drugs:a revised (second) consensus statement from the British Association for Psychopharmacology

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.

Neurotrophin-3 gene polymorphisms and schizophrenia:no evidence for linkage or association

It has been suggested on the basis of neuropathological and epidemiological evidence that schizophrenia is, at least in part, a neurodevelopmental illness. Some patients show abnormalities in cell position in the medial temporal lobes of their brains. Neurotrophin-3 is one of many proteins essential for the proper growth and development of the nervous system. Therefore the finding of a polymorphism near the promoter region of the gene, alleles of which were associated with the disease, prompted us to attempt replication. In a linkage and association analysis of the same polymorphism using familial schizophrenics and population controls we found no evidence to support the finding. We conclude that mutations or polymorphisms at this gene are unlikely to be involved in the genetic aetiology of schizophrenia.

No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

Pre-operative fasting for intravenous conscious sedation used in dental treatment: are conclusions based on relative risk management or evidence?

Intravenous sedation is a widely used pharmacological method of patient management commonly used in dental surgery for the treatment of anxious patients. Variety exists in fasting regimes between different centres offering dental sedation, with some advocating starvation in line with general anaesthesia protocols and others not enforcing starvation at all. The currently available guidelines on fasting protocols are ambiguous and open to interpretation partly because they are based on expert opinion rather than evidence-based research. This article reviews the available evidence on the subject of pre-operative fasting and discusses current guidelines.

An official American thoracic society research statement: Comparative effectiveness research in pulmonary, critical care, and sleep medicine

Background: Comparative effectiveness research (CER) is intended to inform decision making in clinical practice, and is central to patientcentered outcomes research (PCOR). Purpose: To summarize key aspects of CER definitions and provide examples highlighting the complementary nature of efficacy and CER studies in pulmonary, critical care, and sleep medicine. Methods: An ad hoc working group of the American Thoracic Society with experience in clinical trials, health services research, quality improvement, and behavioral sciences in pulmonary, critical care, and sleepmedicinewas convened. The group used an iterative consensus process, including a reviewbyAmerican Thoracic Society committees and assemblies. Results: The traditional efficacy paradigm relies on clinical trials with high internal validity to evaluate interventions in narrowly defined populations and in research settings. Efficacy studies address the question, "Can it work in optimal conditions?" The CER paradigm employs a wide range of study designs to understand the effects of interventions in clinical settings. CER studies address the question, "Does it work in practice?" The results of efficacy and CER studies may or may not agree. CER incorporates many attributes of outcomes research and health services research, while placing greater emphasis on meeting the expressed needs of nonresearcher stakeholders (e.g., patients, clinicians, and others). Conclusions: CER complements traditional efficacy research by placing greater emphasis on the effects of interventions in practice, and developing evidence to address the needs of the many stakeholders involved in health care decisions. Stakeholder engagement is an important component of CER. Copyright © 2013 by the American Thoracic Society.

Which biomarkers are predictive specifically for cardiovascular or for non-cardiovascular mortality in men? Evidence from the Caerphilly Prospective Study (CaPS)

OBJECTIVE: To examine a panel of 28 biomarkers for prediction of cardiovascular disease (CVD) and non-CVD mortality in a population-based cohort of men.

METHODS: Starting in 1979, middle-aged men in Caerphilly underwent detailed medical examination. Subsequently 2171 men were re-examined during 1989-1993, and fasting blood samples obtained from 1911 men (88%). Fibrinogen, viscosity and white cell count (WCC), routine biochemistry tests and lipids were analysed using fresh samples. Stored aliquots were later analysed for novel biomarkers. Statistical analysis of CVD and non-CVD mortality follow-up used competing risk Cox regression models with biomarkers in thirds tested at the 1% significance level after covariate adjustment.

RESULTS: During an average of 15.4years follow-up, troponin (subhazard ratio per third 1.71, 95% CI 1.46-1.99) and B-natriuretic peptide (BNP) (subhazard ratio per third 1.54, 95% CI 1.34-1.78) showed strong trends with CVD death but not with non-CVD death. WCC and fibrinogen showed similar weaker findings. Plasma viscosity, growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) were associated positively with both CVD death and non-CVD death while total cholesterol was associated positively with CVD death but negatively with non-CVD death. C-reactive protein (C-RP), alkaline phosphatase, gamma-glutamyltransferase (GGT), retinol binding protein 4 (RBP-4) and vitamin B6 were significantly associated only with non-CVD death, the last two negatively. Troponin, BNP and IL-6 showed evidence of diminishing associations with CVD mortality through follow-up.

CONCLUSION: Biomarkers for cardiac necrosis were strong, specific predictors of CVD mortality while many inflammatory markers were equally predictive of non-CVD mortality.

Physical activity assessment in cystic fibrosis: A position statement

Background

The aim of this position statement was to inform the choice of physical activity tools for use within CF research and clinical settings.

Methods

A systematic review of physical activity tools to explore evidence for reliability, validity, and responsiveness. Narrative answers to “four key questions” on motion sensors, questionnaires and diaries were drafted by the core writing team and then discussed at the Exercise Working Group in ECFS Lisbon 2013.

Results and summary

Our current position is that activity monitors such as SenseWear or ActiGraph offer informed choices to facilitate a comprehensive assessment of physical activity, and should as a minimum report on dimensions of physical activity including energy expenditure, step count and time spent in different intensities and sedentary time. The DigiWalker pedometer offers an informed choice of a comparatively inexpensive method of obtaining some measurement of physical activity. The HAES represents an informed choice of questionnaire to assess physical activity. There is insufficient data to recommend the use of one diary over another. Future research should focus on providing additional evidence of clinimetric properties of these and new physical activity assessment tools, as well as further exploring the added value of physical activity assessment in CF.

The scramble for the seas : the ballad evidence of Sir Andrew Barton

The presence and importance of the sea as a factor that has helped shape the history of England since at least the Roman invasions of 55-54 BC (less successful, incidentally, than most of Caesar’s other military ventures ...) need no particular urging or demonstration. Nonetheless, a bird’s-eye view would necessarily survey the waves of invasions and settlements that, one after the other, came dashing over the centuries upon England’s shores; not to mention the requested invasion of 1688, Angles and Saxons, Scandinavians, Normans, they all crossed the whale’s path and cast anchor in England’s green and pleasant land. In the course of this retrospective voyage through the oceans of History, one would inevitably stop at the so-called ‘Discoveries’ of the 15th-16th centuries, meet their navigators, sailors and pirates extolled by Richard Hakluyt (1553?-1616), face an anonymous crowd of merchants and witness the huge expansion of trade, largely to the benefit of the ‘discovering’ countries as prescribed by the economic Gospel Adam Smith (1723-90) would later baptize as “mercantilism”.

Relatório de estágio no departamento central de investigação e acção penal

The means of obtaining evidence, the amount of evidence obtained, the number of defendants related to each criminal case and the gravity of the crimes for which the magistrates of the Department are holders of penal action, define its real importance to the Rule of Law. I have deeply studied the subject of the institution of hierarchical intervention required by the assistant and the application of an opening statement by the defendant, starting from a hypothetical case, provided when the query of an investigation with the subject of the crime of active corruption, where this institution was called as a reaction to the archiving dispatch delivered by the Public Ministry. I have study about the implementation of the institution of provisional suspension of the process, specifically in the scope of fiscal criminality, analyzing the effective satisfaction of the purposes of the sentences in two slopes: general prevention and special prevention. I went for my first time to a Central Court of Criminal Instruction, where I attended the measures of inquiry and instructive debate of a process that culminated with the prosecution and pronunciation of the defendants. In addition to this criminal experience, I have deepened and consolidated the academic knowledge with the study of various criminal cases from various fields in the scope of criminality investigated by the Department. I could therefore check the basis of procedural delays, regarding to our legal system, especially in this type of crime, raising issues that I analyzed and discussed, always in a critical and academic way. I had the opportunity to attend and witness a seminar in the Lisbon Directorate of Finance as well of entering the Centre for Judicial Studies to attend a conference on the International Anti-Corruption Day. Focus on the investigatory importance of the international judicial cooperation, through the various organs, with special interest to EUROJUST. I comprehended the organization and functioning of these communitarian organs and means of communication of procedural acts, in particular, the rogatory letters and european arrest warrants. This involvement is motivated by the moratorium factor of the investigations where rogatory letters are necessary for the acquisition of evidence or information relevant to the good continuation of the process. For this reason the judicial cooperation through the relevant communitarian organs, translates a streamlined response between the competent judicial authorities of the Member States, through the National Member that integrates EUROJUST. This report aims to highlight some of the difficulties and procedural issues that Public Prosecutors of DCIAP and criminal police bodies that assist them, face in combating violent and organized crime, of national and transnational nature, of particular complexity, according to the specifics of criminal types.

Statement from the Sheriff’s Office, Lincoln that there are no writs of execution or extent against Owen Clifford

Statement from the Sheriff’s Office, Lincoln that there are no writs of execution or extent against Owen Clifford. This is signed by Joseph A. Woodruff, March 5, 1869.

Screening for adolescent idiopathic scoliosis: an information statement by the scoliosis research society international task force

Background: Routine screening of scoliosis is a controversial subject and screening efforts vary greatly around the world. METHODS: Consensus was sought among an international group of experts (seven spine surgeons and one clinical epidemiologist) using a modified Delphi approach. The consensus achieved was based on careful analysis of a recent critical review of the literature on scoliosis screening, performed using a conceptual framework of analysis focusing on five main dimensions: technical, clinical, program, cost and treatment effectiveness. FINDINGS: A consensus was obtained in all five dimensions of analysis, resulting in 10 statements and recommendations. In summary, there is scientific evidence to support the value of scoliosis screening with respect to technical efficacy, clinical, program and treatment effectiveness, but there insufficient evidence to make a statement with respect to cost effectiveness. Scoliosis screening should be aimed at identifying suspected cases of scoliosis that will be referred for diagnostic evaluation and confirmed, or ruled out, with a clinically significant scoliosis. The scoliometer is currently the best tool available for scoliosis screening and there is moderate evidence to recommend referral with values between 5 degrees and 7 degrees. There is moderate evidence that scoliosis screening allows for detection and referral of patients at an earlier stage of the clinical course, and there is low evidence suggesting that scoliosis patients detected by screening are less likely to need surgery than those who did not have screening. There is strong evidence to support treatment by bracing. INTERPRETATION: This information statement by an expert panel supports scoliosis screening in 4 of the 5 domains studied, using a framework of analysis which includes all of the World Health Organisation criteria for a valid screening procedure.

La valoración de la prueba testimonial; el paradigmático caso del Coronel Luis Alfonso Plazas Vega

De acuerdo a la coyuntura social por la que atraviesa actualmente la administración de justicia colombiana, en cuanto a la proliferación de injusticias y errores judiciales causados por la valoración probatoria positiva de los falsos testigos, nace nuestro estudio y la respectiva crítica a la estimación superficial que se realiza a la prueba testimonial por parte de algunos de nuestros jueces, y la aceptación sin mayor control que efectúa la Fiscalía General de la Nación. En ese sentido, se realiza una exhaustiva pero concisa investigación al respecto de todos y cada uno de los factores relevantes a la hora de valorar al deponente y su testimonio como medio probatorio, de suerte que establece los diferentes requisitos formales y sustanciales de los cuales debe gozar, tanto el testigo como su declaración, para que puedan ser tomados en cuenta a la hora de tomar una decisión judicial en materia penal. Con base en lo anterior, nuestra monografía consta de una parte teórica y una parte teóricopractica, en la cual se tomó como ejemplo principal, el paradigmático caso del Coronel ® Luis Alfonso Plazas Vega, toda vez que es un proceso que actualmente se encuentra en sede de casación, y aun no tiene un pronunciamiento definitivo por parte de la honorable Corte Suprema de Justicia, por lo cual es posible realizar una crítica constructiva y propia en lo que concierne a la valoración de la prueba testimonial, en el entendido en que no existe una decisión inequívoca. Finalmente, lo que se pretende con este trabajo es explicar de una manera sencilla y de fácil entendimiento la labor que deben realizar los jueces de la República y la Fiscalía, que aunque no es la que toma la decisión, también debería realizar un mínima valoración, o por lo menos una verificación al momento de aportar y darle credibilidad a testigos que son favorables a su teoría del caso. De forma tal que, la administración de justicia debe llevar a cabo una valoración probatoria, específicamente encaminada al estándar probatorio que se le debe atribuir al testimonio, teniendo en cuenta los factores externos e internos que afecten la declaración, y por los cuales se vea influenciada la misma; todo esto, con el fin de evitar los errores judiciales que se han generado a lo largo de nuestra historia, los cuales han conllevado a innumerables injusticias creando gran polémica y un desasosiego por parte de la sociedad civil.

The differential effect on dropout of increasing grades' supply by integrating or expanding schools: evidence from a quasi-experiment in Bogotá

En el año 2002, la Secretaría de Educación de Bogotá estipuló la Resolución 2101 que tenía por objeto asegurar el ciclo de la educación completo en los colegios públicos. El propósito de este trabajo es evaluar el impacto de los mecanismos seguidos a la aplicación de esta política sobre la tasa de deserción escolar. Las escuelas tenían tres mecanismos diferentes para alcanzar el objetivo de la presente resolución: expandir los grados escolares ofertados, integrarse con otros colegios de la zona, o ambos. Para ello, utilizo variables instrumentales para resolver el sesgo causado por el hecho de que los colegios que siguen determinada estrategia eran los que tenían altas tasas de deserción inicialmente. Usando datos sobre las características institucionales y las características socio-demográficas de la población cerca del colegio, evalúo el impacto de estos tres mecanismos sobre las tasas de deserción escolar. Los resultados sugieren que las instituciones que aumentaron los grados experimentan un aumento en el número de estudiantes que abandonan el colegio en 12.1 puntos porcentuales, mientras que las instituciones que complementaron este mecanismo con la integración de un colegio próximo pre existente mostraron una reducción en la tasa de deserción escolar de 9.8 puntos porcentuales.

PPP, UIP and Fisher parity: speculation or rational expectations? Evidence for four Latin American countries

This work aims to test the equilibrium relations of two international macroeconomics models for Colombia, Chile, Mexico and Brazil. The first model is the rational expectation hypothesis (REH) where three key relations will be tested: Purchasing Power Parity (PPP), Uncovered Interest Rate Parity (UIP) and the Fisher Parity condition. The second model follows the line of though of Imperfect Knowledge Economics (IKE) where two equilibrium relations will be tested. According to IKE, even under the assumption that agents are rational, the presence of speculative behavior in financial markets helps explain the long swings often observed in the behavior of exchange rates. The results support the view that the predictions of the IKE model hold for Colombia, while those of the REH hold for both Brazil and Mexico. Mixed findings are obtained for Chile.