The life of Miguel de Cervantes Saavedra : a biographical, literary, and historical study with a tentative bibliography from 1585 to 1892, and an annotated appendix on the Canto de Caliope

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 201

Computerized advice on drug dosage to improve prescribing practice

International audienceComputerized advice on drug dosage to improve prescribing practice (Review) 1 Copyright © 2013 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Data collection and analysis Two review authors independently extracted data and assessed study quality.We grouped the results from the included studies by drug used and the effect aimed at for aminoglycoside antibiotics, amitriptyline, anaesthetics, insulin, anticoagulants, ovarian stimulation, anti-rejection drugs and theophylline. We combined the effect sizes to give an overall effect for each subgroup of studies, using a random-effects model. We further grouped studies by type of outcome when appropriate (i.e. no evidence of heterogeneity). Main results Forty-six comparisons (from 42 trials) were included (as compared with 26 comparisons in the last update) including a wide range of drugs in inpatient and outpatient settings. All were randomized controlled trials except two studies. Interventions usually targeted doctors, although some studies attempted to influence prescriptions by pharmacists and nurses. Drugs evaluated were anticoagulants, insulin, aminoglycoside antibiotics, theophylline, anti-rejection drugs, anaesthetic agents, antidepressants and gonadotropins. Although all studies used reliable outcome measures, their quality was generally low. This update found similar results to the previous update and managed to identify specific therapeutic areas where the computerized advice on drug dosage was beneficial compared with routine care: 1. it increased target peak serum concentrations (standardized mean difference (SMD) 0.79, 95% CI 0.46 to 1.13) and the proportion of people with plasma drug concentrations within the therapeutic range after two days (pooled risk ratio (RR) 4.44, 95% CI 1.94 to 10.13) for aminoglycoside antibiotics; 2. it led to a physiological parameter more often within the desired range for oral anticoagulants (SMD for percentage of time spent in target international normalized ratio +0.19, 95% CI 0.06 to 0.33) and insulin (SMD for percentage of time in target glucose range: +1.27, 95% CI 0.56 to 1.98); 3. it decreased the time to achieve stabilization for oral anticoagulants (SMD -0.56, 95% CI -1.07 to -0.04); 4. it decreased the thromboembolism events (rate ratio 0.68, 95% CI 0.49 to 0.94) and tended to decrease bleeding events for anticoagulants although the difference was not significant (rate ratio 0.81, 95%CI 0.60 to 1.08). It tended to decrease unwanted effects for aminoglycoside antibiotics (nephrotoxicity: RR 0.67, 95% CI 0.42 to 1.06) and anti-rejection drugs (cytomegalovirus infections: RR 0.90, 95% CI 0.58 to 1.40); 5. it tended to reduce the length of time spent in the hospital although the difference was not significant (SMD -0.15, 95% CI -0.33 to 0.02) and to achieve comparable or better cost-effectiveness ratios than usual care; 6. there was no evidence of differences in mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, antirejection drugs and antidepressants. For all outcomes, statistical heterogeneity quantified by I2 statistics was moderate to high. Authors’ conclusions This review update suggests that computerized advice for drug dosage has some benefits: it increases the serum concentrations for aminoglycoside antibiotics and improves the proportion of people for which the plasma drug is within the therapeutic range for aminoglycoside antibiotics. It leads to a physiological parameter more often within the desired range for oral anticoagulants and insulin. It decreases the time to achieve stabilization for oral anticoagulants. It tends to decrease unwanted effects for aminoglycoside antibiotics and anti-rejection drugs, and it significantly decreases thromboembolism events for anticoagulants. It tends to reduce the length of hospital stay compared with routine care while comparable or better cost-effectiveness ratios were achieved. However, there was no evidence that decision support had an effect on mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti-rejection drugs and antidepressants. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimize the effect of computerized advice. Taking into account the high risk of bias of, and high heterogeneity between, studies, these results must be interpreted with caution. P L A I N L A N G U A G E S U M M A R Y Computerized advice on drug dosage to improve prescribing practice (Review) 2 Copyright © 2013 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Computerized advice on drug dosage to improve prescribing practice Background Physicians and other healthcare professionals often prescribe drugs that will only work at certain concentrations. These drugs are said to have a narrow therapeutic window. This means that if the concentration of the drug is too high or too low, they may cause serious side effects or not provide the benefits they should. For example, blood thinners (anticoagulants) are prescribed to thin the blood to prevent clots. If the concentration is too high, people may experience excessive bleeding and even death. In contrast, if the concentration is too low, a clot could form and cause a stroke. For these types of drugs, it is important that the correct amount of the drug be prescribed. Calculating and prescribing the correct amount can be complicated and time-consuming for healthcare professionals. Sometimes determining the correct dose can take a long time since healthcare professionals may not want to prescribe high doses of the drugs initially because they make mistakes in calculations. Several computer systems have been designed to do these calculations and assist healthcare professionals in prescribing these types of drugs. Study characteristics We sought clinical trial evidence from scientific databases to evaluate the effectiveness of these computer systems. The evidence is current to January 2012. We found data from 42 trials (40 randomized controlled trials (trials that allocate people at random to receive one of a number of drugs or procedures) and two non-randomized controlled trials). Key results Computerized advice for drug dosage can benefit people taking certain drugs compared with empiric dosing (where a dose is chosen based on a doctor’s observations and experience)without computer assistance.When using the computer system, healthcare professionals prescribed appropriately higher doses of the drugs initially for aminoglycoside antibiotics and the correct drug dose was reached more quickly for oral anticoagulants. It significantly decreased thromboembolism (blood clotting) events for anticoagulants and tended to reduce unwanted effects for aminoglycoside antibiotics and anti-rejection drugs (although not an important difference). It tended to reduce the length of hospital stay compared with routine care with comparable or better cost-effectiveness. There was no evidence of effects on death or clinical side events for insulin (low blood sugar (hypoglycaemia)), anaesthetic agents, anti-rejection drugs (drugs taken to prevent rejection of a transplanted organ) and antidepressants. Quality of evidence The quality of the studies was low so these results must be interpreted with caution

Supporting Communication Access of People With Communication Disabilities and Communication Differences in UNCRPD‐Ratified Countries: An Integrative Review

Background: The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) recognizes communication accessibility as a fundamental human right. Communication plays a key role in facilitating belonging, sharing and engaging with communities, allowing individuals to connect and forge relationships. Communication is fundamental to well‐being and building a sense of self and identity, as well as establishing and maintaining social roles and vocation. Those with communication disabilities or differences can face many barriers to social participation, inclusion and potential financial implications. Aims: This integrative review explores policy, practices and guidelines that support communication access of adults with communication disabilities and differences in selected English‐speaking countries with UNCRPD‐ratified status and well‐established speech and language therapy services. Methods: An integrative review of the literature was undertaken. A systematic search of the published, peer‐reviewed literature was conducted for empirical research, and a manual search was undertaken to obtain policy, practice, or guidelines, to support communication access at a sectoral/service or community level. A multi‐scalar approach situates the findings within several contexts: international law, national legislation and policy, professional guidelines and evidence from local/national projects. Main Contributions: A multi‐scalar map was developed that positions the findings on communication access within the included countries (Republic of Ireland, Northern Ireland, United Kingdom, Canada, Australia and New Zealand), across local/national programmes and projects (n = 11), professional body and civil society guidance, regional/national legislation and policy specific to communication access and finally the international normative instrument of the UNCRPD. The findings indicate that communication accessibility is recognised as a fundamental human right, but signatory states are required to take appropriate measures to ensure access to information and communication for persons with disabilities. National legislation, policy and practice need further scrutiny in this regard. Conclusions: This review examines the complex phenomenon of communication access for people with communication disabilities and differences. The findings of this review can inform and shape practice with regard to communication accessibility as well as support advocacy efforts and future research in this area. WHAT THIS PAPER ADDS: What is already known on the subject Communication accessibility is a fundamental human right. It can be characterized by the respectful and responsive treatment of individuals with communication disabilities and differences, along with the implementation of strategies and resources and the adaptation of environments, process and systems to facilitate effective communication. What this paper adds to existing knowledge A multi‐scalar map was developed that situates the findings on communication access within the included countries (Republic of Ireland, Northern Ireland, United Kingdom, Canada, Australia and New Zealand), across local/national programmes and projects (n = 11), professional body and civil society guidance, regional/national legislation and policies specific to communication access, and finally the international normative instrument of the UNCRPD. There is a lack of a shared understanding of communication access within empirical research, policy and local and national guidelines across the included countries. In addition, the focus on the right to communication is addressed more explicitly in some groups (and country contexts) than others. What are the practical and clinical implications of this work? This review highlights how multimodal communication is important for accessible communication. Co‐design can also be harnessed to enhance communication access. The review provides an integrated set of data (empirical research, policy and guidelines) that can be used in future research, practice development and advocacy

Evidence for models of diagnostic service provision in the community: literature mapping exercise and focused rapid reviews

Background Current NHS policy favours the expansion of diagnostic testing services in community and primary care settings. Objectives Our objectives were to identify current models of community diagnostic services in the UK and internationally and to assess the evidence for quality, safety and clinical effectiveness of such services. We were also interested in whether or not there is any evidence to support a broader range of diagnostic tests being provided in the community. Review methods We performed an initial broad literature mapping exercise to assess the quantity and nature of the published research evidence. The results were used to inform selection of three areas for investigation in more detail. We chose to perform focused reviews on logistics of diagnostic modalities in primary care (because the relevant issues differ widely between different types of test); diagnostic ultrasound (a key diagnostic technology affected by developments in equipment); and a diagnostic pathway (assessment of breathlessness) typically delivered wholly or partly in primary care/community settings. Databases and other sources searched, and search dates, were decided individually for each review. Quantitative and qualitative systematic reviews and primary studies of any design were eligible for inclusion. Results We identified seven main models of service that are delivered in primary care/community settings and in most cases with the possible involvement of community/primary care staff. Not all of these models are relevant to all types of diagnostic test. Overall, the evidence base for community- and primary care-based diagnostic services was limited, with very few controlled studies comparing different models of service. We found evidence from different settings that these services can reduce referrals to secondary care and allow more patients to be managed in primary care, but the quality of the research was generally poor. Evidence on the quality (including diagnostic accuracy and appropriateness of test ordering) and safety of such services was mixed. Conclusions In the absence of clear evidence of superior clinical effectiveness and cost-effectiveness, the expansion of community-based services appears to be driven by other factors. These include policies to encourage moving services out of hospitals; the promise of reduced waiting times for diagnosis; the availability of a wider range of suitable tests and/or cheaper, more user-friendly equipment; and the ability of commercial providers to bid for NHS contracts. However, service development also faces a number of barriers, including issues related to staffing, training, governance and quality control. Limitations We have not attempted to cover all types of diagnostic technology in equal depth. Time and staff resources constrained our ability to carry out review processes in duplicate. Research in this field is limited by the difficulty of obtaining, from publicly available sources, up-to-date information about what models of service are commissioned, where and from which providers. Future work There is a need for research to compare the outcomes of different service models using robust study designs. Comparisons of ‘true’ community-based services with secondary care-based open-access services and rapid access clinics would be particularly valuable. There are specific needs for economic evaluations and for studies that incorporate effects on the wider health system. There appears to be no easy way of identifying what services are being commissioned from whom and keeping up with local evaluations of new services, suggesting a need to improve the availability of information in this area. Funding The National Institute for Health Research Health Services and Delivery Research programme

Azotobacter genomes: the genome of Azotobacter chroococcum NCIMB 8003 (ATCC 4412)

The genome of the soil-dwelling heterotrophic N2-fixing Gram-negative bacterium Azotobacter chroococcum NCIMB 8003 (ATCC 4412) (Ac-8003) has been determined. It consists of 7 circular replicons totalling 5,192,291 bp comprising a circular chromosome of 4,591,803 bp and six plasmids pAcX50a, b, c, d, e, f of 10,435 bp, 13,852, 62,783, 69,713, 132,724, and 311,724 bp respectively. The chromosome has a G+C content of 66.27% and the six plasmids have G+C contents of 58.1, 55.3, 56.7, 59.2, 61.9, and 62.6% respectively. The methylome has also been determined and 5 methylation motifs have been identified. The genome also contains a very high number of transposase/inactivated transposase genes from at least 12 of the 17 recognised insertion sequence families. The Ac-8003 genome has been compared with that of Azotobacter vinelandii ATCC BAA-1303 (Av-DJ), a derivative of strain O, the only other member of the Azotobacteraceae determined so far which has a single chromosome of 5,365,318 bp and no plasmids. The chromosomes show significant stretches of synteny throughout but also reveal a history of many deletion/insertion events. The Ac-8003 genome encodes 4628 predicted protein-encoding genes of which 568 (12.2%) are plasmid borne. 3048 (65%) of these show > 85% identity to the 5050 protein-encoding genes identified in Av-DJ, and of these 99 are plasmid-borne. The core biosynthetic and metabolic pathways and macromolecular architectures and machineries of these organisms appear largely conserved including genes for CO-dehydrogenase, formate dehydrogenase and a soluble NiFe-hydrogenase. The genetic bases for many of the detailed phenotypic differences reported for these organisms have also been identified. Also many other potential phenotypic differences have been uncovered. Properties endowed by the plasmids are described including the presence of an entire aerobic corrin synthesis pathway in pAcX50f and the presence of genes for retro-conjugation in pAcX50c. All these findings are related to the potentially different environmental niches from which these organisms were isolated and to emerging theories about how microbes contribute to their communities

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

El Quijote filantrópico victoriano: Donna Quixote, de Justin McCarthy

The paper undertakes the analysis of a little known Victorian quixotic novel, Donna Quixote, by Justin McCarthy. In so doing, it places the latter, in the first place, within the conception of quixotism characteristic of the Victorian age and, in the second place, within the previous tradition of female quixotes, particularly as a response to George Eliot’s Middlemarch. Then, the text studies the novel’s originality within the English quixotic tradition, which lies in the way it relates quixotism to both philanthropy and feminism, not just by means of the heroine but also of some quixotic secondary figures, and argues the author’s conservative position in the debate on women’s rights known as the woman question. Finally, the paper illustrates such a position and its ideological context by presenting another “Donna Quixote,” in this case a satiric cartoon on the so-called new woman.El artículo analiza una novela quijotesca victoriana poco conocida, la Donna Quixote de Justin McCarthy. Para ello la sitúa, en primer lugar, dentro de la concepción del quijotismo distintiva de la época victoriana y, en segundo lugar, dentro de la tradición previa de quijotes femeninos, en particular como respuesta a Middlemarch, de George Eliot. A continuación, el texto estudia la originalidad de la novela dentro de la tradición quijotesca inglesa, que procede de la forma en que relaciona quijotismo tanto con filantropía como con feminismo, a través no solo de la protagonista sino de otras figuras quijotescas secundarias, y muestra la posición conservadora de su autor dentro del debate sobre los derechos de la mujer conocido como woman question. Finalmente, el artículo ilustra tal posición y su contexto ideológico presentando otra “Donna Quixote”, en este caso una viñeta satírica, tanto gráfica como literaria, sobre la llamada new woman

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]