Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.

Mothers’ perspectives on utilization of maternal health services in Rural Health Units in Luzon: A qualitative study

Introduction@#Despite implementing various maternal health care programs and integrating these into Service Delivery Networks, the Philippines continues to have high maternal mortality. Identifying factors that impede the utilization of available maternal care services may help reduce maternal morbidity and mortality and bridge the gap between the need and actual use of such services among mothers in the community. @*Objectives@#This study identified barriers, hindrances, and other factors influencing mothers in availing maternal health services in Luzon, the largest island in the country and the area that accounted for more than half of total maternal mortality. @*Methods@#Eight focus group discussions participated in by a total of 78 pregnant women and mothers were conducted across all of the eight regions of Luzon. In each session, the participants were asked to answer questions based on a semi-structured interview guide. The interviews were recorded, translated and back-translated, transcribed, and compiled before analysis by the deductive-dominant approach using NVivo12. @*Results@#Factors affecting maternal health service utilization center on the capacity of health facilities to provide services like evaluation of the progress of pregnancy, laboratory examinations, free medicines, and immunizations; and on region-bound individual factors. The availability of skilled health personnel and lack of financial resources were the most common subthemes. @*Conclusion@#This study identified some key factors that deter patients from availing of existing maternal health services in Luzon. Eliminating these barriers will not only help strengthen local health infrastructure and improve service delivery but also promote the utilization of such services, leading to better maternal outcomes.

Mosaic fungal individuals have the potential to evolve within a single generation.

Although cells of mushroom-producing fungi typically contain paired haploid nuclei (n + n), most Armillaria gallica vegetative cells are uninucleate. As vegetative nuclei are produced by fusions of paired haploid nuclei, they are thought to be diploid (2n). Here we report finding haploid vegetative nuclei in A. gallica at multiple sites in southeastern Massachusetts, USA. Sequencing multiple clones of a single-copy gene isolated from single hyphal filaments revealed nuclear heterogeneity both among and within hyphae. Cytoplasmic bridges connected hyphae in field-collected and cultured samples, and we propose nuclear migration through bridges maintains this nuclear heterogeneity. Growth studies demonstrate among- and within-hypha phenotypic variation for growth in response to gallic acid, a plant-produced antifungal compound. The existence of both genetic and phenotypic variation within vegetative hyphae suggests that fungal individuals have the potential to evolve within a single generation in response to environmental variation over time and space.

Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial.

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.

Persistence of apremilast in moderate-to-severe psoriasis: a real-world analysis of 14 147 apremilast- and methotrexate-naive patients in the French National Health Insurance database.

BACKGROUND: Real-world data on the persistence of apremilast vs. methotrexate are inconclusive. OBJECTIVES: To assess and compare the long-term persistence of apremilast and methotrexate in a large cohort of patients with psoriasis. METHODS: All adult patients with psoriasis registered in the French national health insurance database ('Système National des Données de Santé') between 2009 and 2017 were eligible for inclusion. The study population comprised apremilast- and methotrexate-naive patients, defined as those with a first prescription of apremilast or methotrexate. Levels of persistence were compared using a Cox model with propensity-score matching that included potential confounders (notably age, sex, psoriatic arthritis, comorbidities and previous exposure to topical and systemic treatments). RESULTS: In this nationwide population-based cohort, 14 147 adult patients with psoriasis (mean age 52·3 years, 55·2% male) were found to be naive to both apremilast and methotrexate. After propensity-score matching, two subgroups of 4805 patients with similar baseline characteristics were included, of whom 3207 apremilast-treated patients and 2736 methotrexate-treated patients discontinued their treatment. Kaplan-Meier survival propensity-score analyses revealed a discontinuation rate of 69% for apremilast and 59% for methotrexate in the first year of treatment. Apremilast-treated patients had a higher risk of discontinuation than methotrexate-treated patients when considering the study population as a whole (hazard ratio 1·28, 95% confidence interval 1·23-1·34) or in a propensity-score-matched analysis (hazard ratio 1·34, 95% confidence interval 1·27-1·41; P < 0·001). CONCLUSIONS: Our real-world data suggest that in the first year of treatment, the discontinuation rate was significantly higher for apremilast-treated patients than for methotrexate-treated patients, regardless of the previous therapeutic lines received. What's already known about this topic? Psoriasis is a common chronic, relapse-remitting, inflammatory skin disease associated with severe psychosocial impact. Apremilast, a phosphodiesterase 4 inhibitor, is one of the most recently commercialized psoriasis drugs. Little is known about the long-term clinical effectiveness of apremilast. What does this study add? The discontinuation rate at 1 year for apremilast was 69%, compared with 58% for methotrexate, in a nationwide population-based cohort including 14 147 nonselected adult patients with psoriasis. Patients in the apremilast cohort had a higher risk of discontinuation than patients in the methotrexate cohort using propensity-score matching, including potentially relevant individual risk factors such as age, sex, comorbidities and psoriatic arthritis, and regardless of the previous therapeutic lines received. In daily practice, physicians should take these results into account when choosing between methotrexate and apremilast as a first-line systemic therapy.

From the hierarchical organization of the central nervous system to the hierarchical aspects of biocodes.

The quite recent (at least on the evolutionary time scale) emergence of nervous systems in complex organisms enabled the living beings to build a wide-ranging model of the external world in order to predict and evaluate the outcomes of their actions. Such a process likely represents a real coding activity, since, by proper handling of information, it generates a mapping between the external environment and internal cerebral activity patterns. The patterns of neural activity that correspond to the final maps, however, emerge from the holistic assembly of a multilevel functional organization. Nerve tissue components, indeed, appear organized in compartments, also called functional modules (FM), that contain system components and circuits of different miniaturizations not only arranged to work together either in parallel or in series but also nested within each other. At least three levels can be recognized in a functional module and it is possible to point out that such a hierarchical organization of the brain circuits could be mirrored by a corresponding hierarchical organization of biocodes. This feature can also suggest the hypothesis that the same logic could operate also at system level to integrate FM into functional brain areas and to associate areas to generate the final map used by humans to image the external world and to imagine untestable worlds.

Value of a national administrative database to guide public decisions: From the système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France.

In 1999, French legislators asked health insurance funds to develop a système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) [national health insurance information system] in order to more precisely determine and evaluate health care utilization and health care expenditure of beneficiaries. These data, based on almost 66 million inhabitants in 2015, have already been the subject of numerous international publications on various topics: prevalence and incidence of diseases, patient care pathways, health status and health care utilization of specific populations, real-life use of drugs, assessment of adverse effects of drugs or other health care procedures, monitoring of national health insurance expenditure, etc. SNIIRAM comprises individual information on the sociodemographic and medical characteristics of beneficiaries and all hospital care and office medicine reimbursements, coded according to various systems. Access to data is controlled by permissions dependent on the type of data requested or used, their temporality and the researcher's status. In general, data can be analyzed by accredited agencies over a period covering the last three years plus the current year, and specific requests can be submitted to extract data over longer periods. A 1/97th random sample of SNIIRAM, the échantillon généraliste des bénéficiaires (EGB), representative of the national population of health insurance beneficiaries, was composed in 2005 to allow 20-year follow-up with facilitated access for medical research. The EGB is an open cohort, which includes new beneficiaries and newborn infants. SNIIRAM has continued to grow and extend to become, in 2016, the cornerstone of the future système national des données de santé (SNDS) [national health data system], which will gradually integrate new information (causes of death, social and medical data and complementary health insurance). In parallel, the modalities of data access and protection systems have also evolved. This article describes the SNIIRAM data warehouse and its transformation into SNDS, the data collected, the tools developed in order to facilitate data analysis, the limitations encountered, and changing access permissions.

[Identification of neurodegenerative diseases in administrative databases in France: A systematic review of the literature]. / Identification des maladies neurodégénératives dans les bases de données médicoadministratives en France : revue systématique de la littérature.

BACKGROUND: Given the health, social and economic burden of neurodegenerative diseases (ND), the development of epidemiologic studies is required. Administrative databases, such as the French national health insurance database (SNIIRAM) could represent an opportunity for researchers. ND could be presumed from drug reimbursement data, hospital stays or registration of a chronic condition. The aim of this study was to describe, in French administrative databases, algorithms used to identify Alzheimer's disease and associated disorders (ADAD), Parkinson's disease and associated disorders (PDAD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). METHODS: A systematic literature review was performed in Medline and gray literature through December 31th, 2015. French studies focusing on ADAD, PDAD, MS or ALS as a primary health outcome, conducted among one of the SNIIRAM data sources (outpatient reimbursements, chronic condition registration, hospital discharge) were included. RESULTS: Thirty-four studies were included (ADAD, n=18, PDAD, n=9, MS, n=4, ALS, n=3), leading to 36 algorithms. For each studied ND, there was an important variability in the algorithms, concerning (i) the type of criteria used (administrative database versus multi-source systems); (ii) the number of criteria used; (iii) the definition used for each criteria. The extent and level of drug exposure highly varied. Identification through hospitalizations showed variations in terms of type of stay (short stay, long-term stay, psychiatric ward…), extent of diagnosis codes used, diagnosis type (principal, related, associated diagnosis) and period used. A validation study was conducted for 2 out of 36 algorithms (PDAD), and criteria completeness was estimated for 3 algorithms (MS, ALS). CONCLUSION: Despite the increase in ND identification among French administrative databases, few algorithms have been validated. Validation studies should be encouraged.

Interventions for raising breast cancer awareness in women.

BACKGROUND: Breast cancer continues to be the most commonly diagnosed cancer in women globally. Early detection, diagnosis and treatment of breast cancer are key to better outcomes. Since many women will discover a breast cancer symptom themselves, it is important that they are breast cancer aware i.e. have the knowledge, skills and confidence to detect breast changes and present promptly to a healthcare professional. OBJECTIVES: To assess the effectiveness of interventions for raising breast cancer awareness in women. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register (searched 25 January 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 27 January 2016), MEDLINE OvidSP (2008 to 27 January 2016), Embase (Embase.com, 2008 to 27 January 2016), the World Health Organization's International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (searched 27 Feburary 2016). We also searched the reference lists of identified articles and reviews and the grey literature for conference proceedings and published abstracts. No language restriction was applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) focusing on interventions for raising women's breast cancer awareness i.e. knowledge of potential breast cancer symptoms/changes and the confidence to look at and feel their breasts, using any means of delivery, i.e. one-to-one/group/mass media campaign(s). DATA COLLECTION AND ANALYSIS: Two authors selected studies, independently extracted data and assessed risk of bias. We reported the odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous outcomes and mean difference (MD) and standard deviation (SD) for continuous outcomes. Since it was not possible to combine data from included studies due to their heterogeneity, we present a narrative synthesis. We assessed the quality of evidence using GRADE methods. MAIN RESULTS: We included two RCTs involving 997 women: one RCT (867 women) randomised women to receive either a written booklet and usual care (intervention group 1), a written booklet and usual care plus a verbal interaction with a radiographer or research psychologist (intervention group 2) or usual care (control group); and the second RCT (130 women) randomised women to either an educational programme (three sessions of 60 to 90 minutes) or no intervention (control group). Knowledge of breast cancer symptomsIn the first study, knowledge of non-lump symptoms increased in intervention group 1 compared to the control group at two years postintervention, but not significantly (OR 1.1, 95% CI 0.7 to 1.6; P = 0.66; 449 women; moderate-quality evidence). Similarly, at two years postintervention, knowledge of symptoms increased in the intervention group 2 compared to the control group but not significantly (OR 1.4, 95% CI 0.9 to 2.1; P = 0.11; 434 women; moderate-quality evidence). In the second study, women's awareness of breast cancer symptoms had increased one month post intervention in the educational group (MD 3.45, SD 5.11; 65 women; low-quality evidence) compared to the control group (MD -0.68, SD 5.93; 65 women; P < 0.001), where there was a decrease in awareness. Knowledge of age-related riskIn the first study, women's knowledge of age-related risk of breast cancer increased, but not significantly, in intervention group 1 compared to control at two years postintervention (OR 1.8; 95% CI 0.9 to 3.5; P < 0.08; 447 women; moderate-quality evidence). Women's knowledge of risk increased significantly in intervention group 2 compared to control at two years postintervention (OR 4.8, 95% CI 2.6 to 9.0; P < 0.001; 431 women; moderate-quality evidence). In the second study, women's perceived susceptibility (how at risk they considered themselves) to breast cancer had increased significantly one month post intervention in the educational group (MD 1.31, SD 3.57; 65 women; low-quality evidence) compared to the control group (MD -0.55, SD 3.31; 65 women; P = 0.005), where a decrease in perceived susceptibility was noted. Frequency of Breast CheckingIn the first study, no significant change was noted for intervention group 1 compared to control at two years postintervention (OR 1.1, 95% CI 0.8 to 1.6; P = 0.54; 457 women; moderate-quality evidence). Monthly breast checking increased, but not significantly, in intervention group 2 compared to control at two years postintervention (OR 1.3, 95% CI 0.9 to 1.9; P = 0.14; 445 women; moderate-quality evidence). In the second study, women's breast cancer preventive behaviours increased significantly one month post intervention in the educational group (MD 1.21, SD 2.54; 65 women; low-quality evidence) compared to the control group (MD 0.15, SD 2.94; 65 women; P < 0.045). Breast Cancer AwarenessWomen's overall breast cancer awareness did not change in intervention group 1 compared to control at two years postintervention (OR 1.8, 95% CI 0.6 to 5.30; P = 0.32; 435 women; moderate-quality evidence) while overall awareness increased in the intervention group 2 compared to control at two years postintervention (OR 8.1, 95% CI 2.7 to 25.0; P < 0.001; 420 women; moderate-quality evidence). In the second study, there was a significant increase in scores on the Health Belief Model (that included the constructs of awareness and perceived susceptibility) at one month postintervention in the educational group (mean 1.21, SD 2.54; 65 women) compared to the control group (mean 0.15, SD 2.94; 65 women; P = 0.045).Neither study reported outcomes relating to motivation to check their breasts, confidence to seek help, time from breast symptom discovery to presentation to a healthcare professional, intentions to seek help, quality of life, adverse effects of the interventions, stages of breast cancer, survival estimates or breast cancer mortality rates. AUTHORS' CONCLUSIONS: Based on the results of two RCTs, a brief intervention has the potential to increase women's breast cancer awareness. However, findings of this review should be interpreted with caution, as GRADE assessment identified moderate-quality evidence in only one of the two studies reviewed. In addition, the included trials were heterogeneous in terms of the interventions, population studied and outcomes measured. Therefore, current evidence cannot be generalised to the wider context. Further studies including larger samples, validated outcome measures and longitudinal approaches are warranted.

ASSESSMENT OF ADVERSE DRUG REACTIONS AS CARDIOVASCULAR RISK FACTORS.

UNLABELLED: A wide range of pharmaceutical substances can induce side-effects expressed as cardiovascular changes or events, adding to other risk factors or worsening preexisting cardiovascular diseases. AIM: Continuous study focused on iatrogenic conditions representing cardiovascular risk factors. METHODS: We developed a descriptive study of patients admitted to the Iasi Vth Internal Medicine and Geriatrics-Gerontology Clinic between 1998-2013, focusing on iatrogenic conditions representing cardiovascular risk factors. RESULTS: We have diagnosed 81 cases of drug-induced hypertension, and 43 patients with hypertensive crises; 72 cases of iatrogenic hyperglycemia; 36 cases of drug-induced hyperuricemia; 50 cases of drug-induced dyslipidemias; and 17 cases of iatrogenic obesity. These iatrogenic diseases were more common in women and the elderly. Twenty-eight patients have developed simultaneous adverse drug reactions induced by the same drug and manifest as different cardiovascular risk factors. CONCLUSIONS: Cardiovascular risk factors can be induced to a significant extent by chronic drug administration. Some medications (e.g., NSAIDs, corticoids, beta-blockers, diuretics, contraceptives) can act on the same patient by multiple pathogenic links. The adverse drug reactions can be cardiovascular risk factors that persist in time, or can be removed (by discontinuing the administration of the implicated drug). The highest importance of their acknowledgment relies on the possibility of their prevention through carefully balancing the benefits and the risk of each new medication.

Segmentação de candidatos a nódulo pulmonar baseado em tomografia computadorizada / Segmentation of pulmonary nodule candidates based on computed tomography

O presente trabalho apresenta uma metodologia para segmentação automática de candidatos a nódulos pulmonares solitários usando Autômato Celular. A detecção precoce de nódulos pulmonares solitários que podem vir a se tornar câncer é essencial para sobrevida dos pacientes. Para auxiliar os especialistas na identificação desses nódulos estão sendo desenvolvidos sistemas auxiliados por computadores que visam automatizar os trabalhos de detecção e classificação. A etapa de segmentação desempenha um papel fundamental na detecção automática de nódulos pulmonares, pois permite separar os elementos de imagem em regiões que apresentam a mesma propriedade ou característica. A metodologia utilizada nessa pesquisa inclui aquisição das imagens, eliminação de ruídos, segmentação do parênquima pulmonar e segmentação dos candidatos a nódulos pulmonares solitários. Os testes foram realizados utilizando conjunto de imagens da base LIDC-IDRI, contendo 739 nódulos. Os resultados mostram uma sensibilidade de 95,66% dos nódulos considerados.

The present work presents a methodology for automatic segmentation of pulmonary solitary nodules candidates using cellular automaton. Early detection of pulmonary solitary nodules that may become cancer is essential for survival of patients. To assist the experts in the identification of these nodules are being developed computer aided systems that aim to automate the work of detection and classification. The segmentation stage plays a key role in automatic detection of lung nodules, as it allows separating the image elements in regions, which have the same property or characteristic. The methodology used in the article includes acquisition of images, noise elimination, pulmonary parenchyma segmentation and segmentation of pulmonary solitary nodules candidates. The tests were conducted using set of images of the LIDC-IDRI base, containing 739 nodules. The test results show a sensitivity of 95.66% of the nodules.

Individual differences in reading aloud: a mega-study, item effects, and some models.

Normal individual differences are rarely considered in the modelling of visual word recognition--with item response time effects and neuropsychological disorders being given more emphasis--but such individual differences can inform and test accounts of the processes of reading. We thus had 100 participants read aloud words selected to assess theoretically important item response time effects on an individual basis. Using two major models of reading aloud--DRC and CDP+--we estimated numerical parameters to best model each individual's response times to see if this would allow the models to capture the effects, individual differences in them and the correlations among these individual differences. It did not. We therefore created an alternative model, the DRC-FC, which successfully captured more of the correlations among individual differences, by modifying the locus of the frequency effect. Overall, our analyses indicate that (i) even after accounting for individual differences in general speed, several other individual difference in reading remain significant; and (ii) these individual differences provide critical tests of models of reading aloud. The database thus offers a set of important constraints for future modelling of visual word recognition, and is a step towards integrating such models with other knowledge about individual differences in reading.

The unexplained nature of reading.

The effects of properties of words on their reading aloud response times (RTs) are 1 major source of evidence about the reading process. The precision with which such RTs could potentially be predicted by word properties is critical to evaluate our understanding of reading but is often underestimated due to contamination from individual differences. We estimated this precision without such contamination individually for 4 people who each read 2,820 words 50 times each. These estimates were compared to the precision achieved by a 31-variable regression model that outperforms current cognitive models on variance-explained criteria. Most (around 2/3) of the meaningful (non-first-phoneme, non-noise) word-level variance remained unexplained by this model. Considerable empirical and theoretical-computational effort has been expended on this area of psychology, but the high level of systematic variance remaining unexplained suggests doubts regarding contemporary accounts of the details of the mechanisms of reading at the level of the word. Future assessment of models can take advantage of the availability of our precise participant-level database.

Using the Language Environment Analysis (LENA) system in preschool classrooms with children with autism spectrum disorders.

This study describes the language environment of preschool programs serving children with autism spectrum disorders (ASDs) and examines relationships between child characteristics and an automated measure of adult and child language in the classroom. The Language Environment Analysis (LENA) system was used with 40 children with ASD to collect data on adult and child language. Standardized assessments were administered to obtain language, cognitive, and autism severity scores for participants. With a mean of over 5 hours of recording across two days several months apart, there was a mean of 3.6 child vocalizations per minute, 1.0 conversational turns (in which either the adult or child respond to the other within 5 seconds) per minute, and 29.2 adult words per minute. Two of the three LENA variables were significantly correlated with language age-equivalents. Cognitive age-equivalents were also significantly correlated with two LENA variables. Autism Diagnostic Observation Schedule severity scores and LENA variables were not significantly correlated. Implications for using the LENA system with children with ASD in the school environment are discussed.

Hospital clinicians' information behaviour and attitudes towards the 'Clinical Informationist': an Irish survey.

BACKGROUND: Hospital clinicians are increasingly expected to practice evidence-based medicine (EBM) in order to minimize medical errors and ensure quality patient care, but experience obstacles to information-seeking. The introduction of a Clinical Informationist (CI) is explored as a possible solution. AIMS: This paper investigates the self-perceived information needs, behaviour and skill levels of clinicians in two Irish public hospitals. It also explores clinicians' perceptions and attitudes to the introduction of a CI into their clinical teams. METHODS: A questionnaire survey approach was utilised for this study, with 22 clinicians in two hospitals. Data analysis was conducted using descriptive statistics. RESULTS: Analysis showed that clinicians experience diverse information needs for patient care, and that barriers such as time constraints and insufficient access to resources hinder their information-seeking. Findings also showed that clinicians struggle to fit information-seeking into their working day, regularly seeking to answer patient-related queries outside of working hours. Attitudes towards the concept of a CI were predominantly positive. CONCLUSION: This paper highlights the factors that characterise and limit hospital clinicians' information-seeking, and suggests the CI as a potentially useful addition to the clinical team, to help them to resolve their information needs for patient care.

Urotensin II receptor and acetylcholine release from mouse cervical spinal cord nerve terminals.

Accumulating evidence indicate that the neuropeptide urotensin II and urotensin II receptors are expressed in subsets of mammal spinal motoneurons. In fact, a role for the peptide in the regulation of motoneuron function at neuromuscular junction has been suggested, while roles for urotensin II at central synapses in spinal cord have never been addressed. We found that urotensin II receptors were closely associated with cholinergic terminals apposed to a subset of motoneuron and non-motoneuron cell bodies in the ventral horn of the adult mouse cervical spinal cord; urotensin II receptor was also expressed on non-cholinergic nerve terminals. In particular, urotensin II receptor appeared associated with both large cholinergic C-boutons and standard cholinergic terminals contacting some motoneuron perikarya. Cholinergic nerve terminals from mouse cervical spinal cord were equipped with functional presynaptic urotensin II receptors linked to excitation of acetylcholine release. In fact, functional experiments conducted on cervical spinal synaptosomes demonstrated a urotensin II evoked calcium-dependent increase in [(3)H]acetylcholine release pharmacologically verified as consistent with activation of urotensin II receptors. In spinal cord these actions would facilitate cholinergic transmission. These data indicate that, in addition to its role at the neuromuscular junction, urotensin II may control motor function through the modulation of motoneuron activity within the spinal cord.

Prohemostatic therapy: the rise and fall of aprotinin.

Aprotinin has been used clinically to enhance hemostasis for decades and was approved in the United States by the Food and Drug Administration in 1993 to reduce the transfusion requirement during coronary artery bypass surgery. Marketing of aprotinin ceased recently when observational studies and a randomized clinical trial reported increased cardiovascular toxicity in patients receiving this drug. The importance of prohemostatic therapy is reviewed in light of new information on long-term deleterious effects of blood transfusion, including increased risk of cardiovascular disease, malignancy, and infection possibly attributable to delivery of a load of red cell-derived redox-active iron. Weaknesses in design of clinical trials that failed to control adequately for such alternative mechanisms of toxicity complicate interpretation of risks versus benefits in clinical trials of aprotinin given to reduce transfusion requirement in the acute surgical setting. Properties and applications of aprotinin that may not have received sufficient attention in the decision to remove this drug from the therapeutic armamentarium are reviewed. Potential application of prohemostatic drugs, including aprotinin to special populations at risk for operative blood loss requiring transfusion, is illustrated by the description of nine patients with coagulopathies whose operative bleeding was managed effectively with aprotinin. This drug may remain safe and effective in patients at risk of bleeding with surgery. Beneficial effects of aprotinin seemingly unrelated to its prohemostatic properties, especially its apparent striking antineoplastic effects, warrant further study.

Extubation versus tracheostomy in withdrawal of treatment-ethical, clinical, and legal perspectives.

The provision of life-sustaining ventilation, such as tracheostomy to critically ill patients, is commonly performed. However, the utilization of tracheostomy or extubation after a withdrawal of treatment decision is debated. There is a dearth of practical information available to aid clinical decision making because withdrawal of treatment is a challenging scenario for all concerned. This is further complicated by medicolegal and ethical considerations. Care of the "hopelessly ill" patient should be based on daily evaluation and comfort making it impossible to fit into general algorithms. Although respect for autonomy is important in healthcare, it is limited for patients in an unconscious state. Beneficence remains the basis for withdrawing treatment in futile cases and underpins the "doctrine of double effect." This article presents a relevant clinical case of hypoxic brain injury where a question of withdrawal of treatment arose and examines the ethical, clinical, and medicolegal considerations inherent in such cases, including beneficence, nonmaleficence, and the "sanctity of life doctrine." In addition, the considerations of prognosis for recovery, patient autonomy, patient quality of life, and patient family involvement, which are central to decision making, are addressed. The varying legal frameworks that exist internationally regarding treatment withdrawal are also described. Good ethics needs sound facts, and despite the lack of legal foundation in several countries, withdrawal of treatment remains practiced, and the principles described within this article aim to aid clinician decision making during such complex and multifaceted end-of-life decisions.