Acquired hemophilia as the cause of life-threatening hemorrhage in a 94-year-old man: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acquired factor VIII deficiency is a rare entity that can lead to severe and life-threatening bleeding. We describe a case of severe bleeding from the tongue secondary to acquired hemophilia and discuss treatment options, including aminocaproic acid and recombinant factor VIII, which have not been widely reported in the literature for the management of such patients.</p> <p>Case presentation</p> <p>A 94-year-old Caucasian man presented to our institution with diffuse bruising and extensive bleeding from the tongue secondary to mechanical trauma. He had no prior history of bleeding and his medical history was unremarkable except for dementia and hypertension. Coagulation studies revealed a prolonged activated partial thromboplastin time and a mixing study was consistent with the presence of an inhibitor. Quantitative assays revealed a reduced level of factor VIII activity (1%) and the presence of a factor VIII inhibitor, measured at seven Bethesda units, in the serum. Oral prednisone therapy (60mg/day) was given. He also received intravenous aminocaproic acid and human concentrate of factor VIII (Humate-P) and topical anti-thrombolytic agents (100 units of topical thrombin cream). His hospital course was prolonged because of persistent bleeding and the development of profuse melena. He required eight units of packed red blood cells for transfusion. Hospitalization was also complicated by bradycardia of unclear etiology, which started after infusion of aminocaproic acid. His activated partial thromboplastin time gradually normalized. He was discharged to a rehabilitation facility three weeks later with improving symptoms, stable hematocrit and resolving bruises.</p> <p>Conclusions</p> <p>Clinicians should suspect a diagnosis of acquired hemophilia in older patients with unexplained persistent and profound bleeding from uncommon soft tissues, including the tongue. Use of factor VIII (Humate-P) and aminocaproic acid can be useful in this coagulopathy but clinicians should be aware of possible life-threatening side effects in older patients, including bradycardia.</p

Protocol for a multicentre randomised controlled trial of STeroid Administration Routes For Idiopathic Sudden sensorineural Hearing loss:The STARFISH trial

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model

Changing Preferences for Survival After Hospitalization With Advanced Heart Failure

ObjectivesThis study was designed to analyze how patient preferences for survival versus quality-of-life change after hospitalization with advanced heart failure (HF).BackgroundAlthough patient-centered care is a priority, little is known about preferences to trade length of life for quality among hospitalized patients with advanced HF, and it is not known how those preferences change after hospitalization.MethodsThe time trade-off utility, symptom scores, and 6-min walk distance were measured in 287 patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheter Effectiveness) trial at hospitalization and again during 6 months after therapy to relieve congestion.ResultsWillingness to trade was bimodal. At baseline, the median trade for better quality was 3 months' survival time, with a modest relation to symptom severity. Preference for survival time was stable for most patients, but increase after discharge occurred in 98 of 145 (68%) patients initially willing to trade survival time, and was more common with symptom improvement and after therapy guided by pulmonary artery catheters (p = 0.034). Adjusting days alive after hospital discharge for patients' survival preference reduced overall days by 24%, with the largest reduction among patients dying early after discharge (p = 0.0015).ConclusionsPreferences remain in favor of survival for many patients despite advanced HF symptoms, but increase further after hospitalization. The bimodal distribution and the stability of patient preference limit utility as a trial end point, but support its relevance in design of care for an individual patient

Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.

Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce

Risk governance in organizations

Dieses Buch dokumentiert 10 Jahre Risk-Governance-Forschung an der Universität Siegen. In 50 Beiträgen reflektieren Forscher und Praktiker Risk Governance vor dem Hintergrund ihrer eigenen Forschungen und/oder Erfahrungen und geben jeweils einen Entwicklungsimpuls für die Zukunft der Risk Governance. Das Buch zeigt die große Bandbreite und Tiefe des Forschungsgebietes auf und diskutiert Grundannahmen, Implementierungsfragen, die Rolle der Risk Governance als Transformationsmotor, ihre Wirkung in den verschiedenen betrieblichen Funktionen, Entwicklungsperspektiven und den Beitrag der Risk Governance zu einer nachhaltigen Ausrichtung von Unternehmen.This book documents 10 years of risk governance research at the University of Siegen. In 50 contributions, researchers and practitioners reflect on risk governance against the background of their own research and/or experience and provide a development impetus for the future of risk governance. The book shows the wide range and depth of the research field and discusses basic assumptions, implementation issues, the role of risk governance as transformation engine, its impact in the various operational functions, development perspectives, and the contribution of risk governance to a sustainable orientation of companies

Physician privacy concerns when disclosing patient data for public health purposes during a pandemic influenza outbreak

Background: Privacy concerns by providers have been a barrier to disclosing patient information for public health\ud purposes. This is the case even for mandated notifiable disease reporting. In the context of a pandemic it has been\ud argued that the public good should supersede an individual’s right to privacy. The precise nature of these provider\ud privacy concerns, and whether they are diluted in the context of a pandemic are not known. Our objective was to\ud understand the privacy barriers which could potentially influence family physicians’ reporting of patient-level\ud surveillance data to public health agencies during the Fall 2009 pandemic H1N1 influenza outbreak.\ud Methods: Thirty seven family doctors participated in a series of five focus groups between October 29-31 2009.\ud They also completed a survey about the data they were willing to disclose to public health units. Descriptive\ud statistics were used to summarize the amount of patient detail the participants were willing to disclose, factors that\ud would facilitate data disclosure, and the consensus on those factors. The analysis of the qualitative data was based\ud on grounded theory.\ud Results: The family doctors were reluctant to disclose patient data to public health units. This was due to concerns\ud about the extent to which public health agencies are dependable to protect health information (trusting beliefs),\ud and the possibility of loss due to disclosing health information (risk beliefs). We identified six specific actions that\ud public health units can take which would affect these beliefs, and potentially increase the willingness to disclose\ud patient information for public health purposes.\ud Conclusions: The uncertainty surrounding a pandemic of a new strain of influenza has not changed the privacy\ud concerns of physicians about disclosing patient data. It is important to address these concerns to ensure reliable\ud reporting during future outbreaks.University of Ottawa Open Access Author Fun

An Individual Participant Data Meta-analysis: Behavioral Treatments for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Objective: Behavioral interventions are well established treatments for children with attention-deficit/hyperactivity disorder (ADHD). However, insight into moderators of treatment outcome is limited.Method: We conducted an individual participant data meta-analysis [IPDMA], including data of randomized controlled behavioral intervention trials for individuals with ADHD[less than]18 years. Outcomes were symptoms of ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD) and impairment. Moderators investigated were symptoms and impairment severity, medication use, age, IQ, sex, socioeconomic status, and single parenthood. Results: For raters most proximal to treatment, small to medium sized effects of behavioral interventions were found for symptoms of ADHD, inattention, hyperactivity/impulsivity (HI), ODD and CD, and impairment. Blinded outcomes were only available for small preschool subsamples and limited measures. CD symptoms and/or diagnosis moderated outcome on ADHD, HI, ODD, and CD symptoms. Single parenthood moderated ODD outcome, ADHD severity moderated impairment outcome. Higher baseline CD or ADHD symptoms, a CD diagnosis, and single parenthood were related to worsening of symptoms in the untreated, but not in the treated group, indicating a protective rather than an ameliorative effect of behavioral interventions for these children.Conclusion: Behavioral treatments are effective for reducing ADHD symptoms, behavioral problems, and impairment as reported by raters most proximal to treatment. Those with severe CD or ADHD symptoms, a CD diagnosis, or single parents, should be prioritized for treatment, as they may evidence worsening of symptoms in the absence of intervention

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM 2.5), nitrogen dioxide (NO 2), black carbon (BC), and ozone (O 3), as well as 8 PM 2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM 2.5 (hazard ratio per 5 µg/m 3: 1.25; 95% confidence interval: 1.01-1.55), NO 2 (1.13; 0.95-1.34 per 10 µg/m 3), and BC (1.12; 0.94-1.34 per 0.5 × 10 -5m -1), and a negative association with O 3 (0.74; 0.58-0.94 per 10 µg/m 3). Associations of PM 2.5, NO 2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM 2.5 remained robust when adjusted for NO 2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO 2 or BC attenuated to null. O 3 associations remained negative, but no longer statistically significant in models with PM 2.5. We detected suggestive positive associations with the potassium component of PM 2.5. CONCLUSION: Long-term exposure to PM 2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC