A count of 3 neonatal morbidities (bronchopulmonary dysplasia, brain injury, and severe retinopathy of prematurity) strongly predict the risk of death or neurosensory impairment in extremely low ...birth weight infants who survive to 36 weeks' postmenstrual age. Neonatal infection has also been linked with later impairment. We examined whether the addition of infection to the count of 3 neonatal morbidities further improves the prediction of poor outcome.
We studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in Preterms and survived to 36 weeks' postmenstrual age. Culture-proven sepsis, meningitis, and stage II or III necrotizing enterocolitis were recorded prospectively. We investigated the incremental prognostic importance of neonatal infection by adding terms for the different types of infection to a logistic model that already contained terms for the count of bronchopulmonary dysplasia, brain injury, and severe retinopathy. Poor outcome at 18 months of age was death or survival with 1 or more of the following: cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness.
There were 414 (44%) infants with at least 1 episode of infection or necrotizing enterocolitis. Meningitis and the presence of any type of infection added independent prognostic information to the morbidity-count model. The odds ratio associated with infection or necrotizing enterocolitis in this model was 50% smaller than the odds ratio associated with each count of the other 3 neonatal morbidities. Meningitis was rare and occurred in 22 (2.3%) of 944 infants.
In this cohort of extremely low birth weight infants who survived to 36 weeks' postmenstrual age, neonatal infection increased the risk of a late death or survival with neurosensory impairment. However, infection was a weaker predictor of poor outcome than bronchopulmonary dysplasia, brain injury, and severe retinopathy.
Nematode parasites infect approximately 1.5 billion people globally and are a significant public health concern. There is an accepted need for new, more effective anthelmintic drugs. Nicotinic ...acetylcholine receptors on parasite nerve and somatic muscle are targets of the cholinomimetic anthelmintics, while glutamate-gated chloride channels in the pharynx of the nematode are affected by the avermectins. Here we describe a novel nicotinic acetylcholine receptor on the nematode pharynx that is a potential new drug target. This homomeric receptor is comprised of five non-α EAT-2 subunits and is not sensitive to existing cholinomimetic anthelmintics. We found that EAT-18, a novel auxiliary subunit protein, is essential for functional expression of the receptor. EAT-18 directly interacts with the mature receptor, and different homologs alter the pharmacological properties. Thus we have described not only a novel potential drug target but also a new type of obligate auxiliary protein for nAChRs.
Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, ...risk, and cost, it is important to understand these tests' comparative effectiveness.
The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs. the annual fecal immunochemical test (FIT) in 50,000 average risk individuals. CONFIRM examines whether screening colonoscopy will be superior to a FIT-based screening program in the prevention of CRC mortality measured over 10 years. Eligible individuals 50-75 years of age and due for CRC screening are recruited from 46 Veterans Affairs (VA) medical centers. Participants are randomized to either colonoscopy or annual FIT. Results of colonoscopy are managed as per usual care and study participants are assessed for complications. Participants testing FIT positive are referred for colonoscopy. Participants are surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC. The primary endpoint is CRC mortality. The secondary endpoints are (1) CRC incidence (2) complications of screening colonoscopy, and (3) the association between colonoscopists' characteristics and neoplasia detection, complications and post-colonoscopy CRC. CONFIRM leverages several key characteristics of the VA's integrated healthcare system, including a shared medical record with national databases, electronic CRC screening reminders, and a robust national research infrastructure with experience in conducting large-scale clinical trials. When completed, CONFIRM will be the largest intervention trial conducted within the VA (ClinicalTrials.gov identifier: NCT01239082).
ACC/AHA Task Force Members Jonathan L. Halperin, MD, FACC, FAHA, Chair Glenn N. Levine, MD, FACC, FAHA, Chair-Elect Jeffrey L. Anderson, MD, FACC, FAHA, Immediate Past Chair¶ Nancy M. Albert, PhD, ...RN, FAHA¶ Sana M. Al-Khatib, MD, MHS, FACC, FAHA Kim K. Birtcher, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC Joaquin E. Cigarroa, MD, FACC Lesley H. Curtis, PhD, FAHA Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Samuel Gidding, MD, FAHA Mark A. Hlatky, MD, FACC John Ikonomidis, MD, PhD, FAHA Jose Joglar, MD, FACC, FAHA Richard J. Kovacs, MD, FACC, FAHA¶ E. Magnus Ohman, MD, FACC¶ Susan J. Pressler, PhD, RN, FAHA Frank W. Sellke, MD, FACC, FAHA¶ Win-Kuang Shen, MD, FACC, FAHA¶ Duminda N. Wijeysundera, MD, PhD Table of Contents Preamblee29 Introductione31 Methodology and Evidence Reviewe31 Organization of the GWCe31 Document Review and Approvale31 Scope of the Guidelinee31 General Principlese32 Mechanisms and Definitionse32 Epidemiology, Demographics, and Public Health Impacte32 Evaluation of the Patient With Suspected or Documented SVTe34 Clinical Presentation and Differential Diagnosis on the Basis of Symptomse34 Evaluation of the ECGe36 Principles of Medical Therapye40 Acute Treatment: Recommendationse41 Ongoing Management: Recommendationse43 Basic Principles of Electrophysiological Study, Mapping, and Ablatione45 Mapping With Multiple and Roving Electrodese45 Tools to Facilitate Ablation, Including 3-Dimensional Electroanatomic Mappinge45 Mapping and Ablation With No or Minimal Radiatione45 Ablation Energy Sourcese46 Sinus Tachyarrhythmiase46 Physiological Sinus Tachycardiae46 Inappropriate Sinus Tachycardiae46 Acute Treatmente46 Ongoing Management: Recommendationse53 Nonsinus Focal Atrial Tachycardia and MATe54 Focal Atrial Tachycardiae54 Acute Treatment: Recommendationse56 Ongoing Management: Recommendationse58 Multifocal Atrial Tachycardiae58 Acute Treatment: Recommendatione59 Ongoing Management: Recommendationse59 Atrioventricular Nodal Reentrant Tachycardiae60 Acute Treatment: Recommendationse61 Ongoing Management: Recommendationse63 Manifest and Concealed Accessory Pathwayse64 Management of Patients With Symptomatic Manifest or Concealed Accessory Pathwayse66 Acute Treatment: Recommendationse66 Ongoing Management: Recommendationse68 Management of Asymptomatic Pre-Excitatione69 PICOTS Critical Questionse69 Asymptomatic Patients With Pre-Excitation: Recommendationse71 Risk Stratification of Symptomatic Patients With Manifest Accessory Pathways: Recommendationse72 Atrial Fluttere72 Cavotricuspid Isthmus-Dependent Atrial Fluttere72 Non-Isthmus-Dependent Atrial Flutterse74 Acute Treatment: Recommendationse76 Ongoing Management: Recommendationse78 Junctional Tachycardiae80 Acute Treatment: Recommendationse81 Ongoing Management: Recommendationse81 Special Populationse82 Pediatricse82 Patients With Adult Congenital Heart Diseasee83 Clinical Featurese83 Acute Treatment: Recommendationse85 Ongoing Management: Recommendationse87 Pregnancye90 Acute Treatment: Recommendationse90 Ongoing Management: Recommendationse91 SVT in Older Populationse92 Acute Treatment and Ongoing Management: Recommendatione92 Quality-of-Life Considerationse93 Cost-Effectivenesse93 Shared Decision Makinge93 Evidence Gaps and Future Research Needse94 Referencese95 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)e108 Appendix 2 Reviewer Relationships With Industry and Other Entities (Relevant)e110 Appendix 3 Abbreviationse115 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health.
Freeze and breakup dates of ice on lakes and rivers provide consistent evidence of later freezing and earlier breakup around the Northern Hemisphere from 1846 to 1995. Over these 150 years, changes ...in freeze dates averaged 5.8 days per 100 years later, and changes in breakup dates averaged 6.5 days per 100 years earlier; these translate to increasing air temperatures of about 1.2°C per 100 years. Interannual variability in both freeze and breakup dates has increased since 1950. A few longer time series reveal reduced ice cover (a warming trend) beginning as early as the 16th century, with increasing rates of change after about 1850.
Background: Recent public attention on drinking water supplies in the aftermath of waterborne infection outbreaks in Walkerton and North Battleford raises questions about safety. We analyzed ...information on waterborne outbreaks occurring between 1974 and 2001 in order to identify apparent trends, review the current status of monitoring and reporting, and gain a better understanding of the impact of drinking water quality on public health and disease burden. Methods: Data from outbreak investigations, published and unpublished, were categorized by the type of drinking water provider and were assessed to be definitely, probably or possibly waterborne in nature. Results: The final data set consisted of 288 outbreaks of disease linked to a drinking water source. There were 99 outbreaks in public water systems, 138 outbreaks in semi-public systems and 51 outbreaks in private systems. The main known causative agents of waterborne disease outbreaks were (in descending frequency of occurrence) Giardia, Campylobacter, Cryptosporidium, Norwalk-like viruses, Salmonella and hepatitis A virus. Summary: We found that severe weather, close proximity to animal populations, treatment system malfunctions, poor maintenance and treatment practices were associated with the reported disease outbreaks resulting from drinking water supplies. However, issues related to the accuracy, co-ordination, compatibility and detail of data exist. A systematic and coordinated national surveillance system for comparison purposes, trend identification and policy development is needed so that future waterborne disease outbreaks can be avoided. Introduction : Les éclosions récentes d'infections d'origine hydrique à Walkerton et à North Battleford ont galvanisé l'attention publique sur la qualité des réserves d'eau potable. Nous avons analysé des renseignements sur les éclosions d'origine hydrique ayant eu lieu au Canada entre 1974 et 2001 afin de dégager des tendances, de réexaminer le niveau de déclaration et d'accroître notre compréhension de l'impact de la qualité de l'eau potable sur le fardeau des maladies d'origine hydrique à l'échelle nationale. Méthode : Nous avons rassemblé des données d'enquêtes sur des éclosions d'origine hydrique à partir de sources publiées et non publiées recueillies auprès de professionnels de la santé publique au Canada. Nous avons catégorisé les données selon le type de service d'eau potable (public ou non). En tenant compte de la valeur probante des données disponibles, nous avons aussi catégorisé les éclosions selon notre certitude d'une origine hydrique (possible, probable ou certaine). Résultats : En tout, 288 éclosions de maladies ont été reliées à une source d'eau potable. Il y a eu 99 éclosions associées aux systèmes publics d'eau, 138 aux systèmes parapublics, et 51 aux systèmes privés. Les causes infectieuses connues (en ordre de fréquence) étaient Giardia, Campylobacter, Cryptosporidium, les norovirus, Salmonella et le virus de l'hépatite A. Discussion : Nous avons constaté que les conditions météorologiques, la proximité de populations animales, le mauvais fonctionnement du système de traitement et les carences dans les pratiques de traitement ou d'entretien étaient associés aux éclosions provenant de réserves d'eau potable. Notre recherche soulève plusieurs questions rattachées à l'exactitude, à la comparabilité, au niveau de détail et à la coordination des données. Un système de surveillance national, systématique et coordonné permettrait de mieux dégager des tendances et d'effectuer des comparaisons d'une province ou d'un territoire à l'autre, et appuierait l'élaboration d'interventions visant à alléger le fardeau des maladies d'origine hydrique.
Delivering high quality genomics-informed care to patients requires accurate test results whose clinical implications are understood. While other actors, including state agencies, professional ...organizations, and clinicians, are involved, this article focuses on the extent to which the federal agencies that play the most prominent roles — the Centers for Medicare and Medicaid Services enforcing CLIA and the FDA — effectively ensure that these elements are met and concludes by suggesting possible ways to improve their oversight of genomic testing.
Chemical substances from theses are not widely accessible as searchable machine-readable formats. In this article, we describe our workflow for extracting, registering, and sharing chemical ...substances from the University of Alabama theses to enhance discovery. In total, 73 theses were selected for the project, resulting in about 3,000 substances registered using the IUPAC International Chemical Identifier and deposited in PubChem as either structure-data files or Simplified Molecular-Input Line-Entry System notations. In addition to substances being deposited in PubChem, an archive copy was also deposited in the University of Alabama Institutional Repository. The PubChem records for the substance depositions include the full bibliographic reference and link to the thesis full text or thesis metadata when the full text is not yet available. Excluding mixtures, we found that 40% of the shared substances were new to PubChem at the time of deposition. We conclude this article with a detailed discussion about our experiences, challenges, and recommendations for librarians and curators engaged in sharing chemical substance data from theses and similar documents.
The histopathology of the inner ear in a patient with hearing loss caused by the p.L114P COCH mutation and its correlation with the clinical phenotype are presented. To date, 23 COCH mutations ...causative of DFNA9 autosomal dominant sensorineural hearing loss and vestibular disorder have been reported, and the histopathology of the human inner ear has been described in 4 of these. The p.L114P COCH mutation was first described in a Korean family. We have identified the same mutation in a family of non-Asian ancestry in the USA, and the temporal bone histopathology and clinical findings are presented herein. The histopathology found in the inner ear was similar to that shown in the 4 other COCH mutations and included degeneration of the spiral ligament with deposition of an eosinophilic acellular material, which was also found in the distal osseous spiral lamina, at the base of the spiral limbus, and in mesenchymal tissue at the base of the vestibular neuroepithelium. This is the first description of human otopathology of the COCH p.L114P mutation. In addition, it is the only case with otopathology characterization in an individual with any COCH mutation and residual hearing, thus allowing assessment of primary histopathological events in DFNA9, before progression to more profound hearing loss. A quantitative cytologic analysis of atrophy in this specimen and immunostaining using anti-neurofilament and anti-myelin protein zero antibodies confirmed that the principal histopathologic correlate of hearing loss was degeneration of the dendritic fibers of spiral ganglion cells in the osseous spiral lamina. The implications for cochlear implantation in this disorder are discussed.
This article reviews controlled research on treatments for childhood externalizing behavior disorders. The review is organized around 2 subsets of such disorders: disruptive behavior disorders (i.e., ...conduct disorder, oppositional defiant disorder) and attention-deficit/hyperactivity disorder (ADHD). The review was based on a literature review of nonresidential treatments for youths ages 6-12. The pool of studies for this age group was limited, but results suggest positive outcomes for a variety of interventions (particularly parent training and community-based interventions for disruptive behavior disorders and medication for ADHD). The review also highlights the need for additional research examining effectiveness of treatments for this age range and strategies to enhance the implementation of effective practices.
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