Publications by authors named "Guliz Erdem"

48 Publications

Tinea faciei caused by Trichophyton benhamiae in a child.

Pediatr Dermatol 2020 Dec 18. Epub 2020 Dec 18.

Division of Pediatric Infectious Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

Tinea faciei is a common pediatric skin disease, most often caused by fungi of the genus Trichophyton. T benhamiae has been recently reclassified as a distinct species and is recognized as an emerging zoonotic dermatophyte with a wide range of possible infectious reservoirs worldwide. We present a previously healthy 7-year-old child presenting with unusual inflammatory facial plaques due to T benhamiae, confirmed by mass spectroscopy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.14486DOI Listing
December 2020

Cerebrospinal Fluid Analysis for Viruses by Metagenomic Next-Generation Sequencing in Pediatric Encephalitis: Not Yet Ready for Prime Time?

J Child Neurol 2020 Nov 18:883073820972232. Epub 2020 Nov 18.

Division of Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA.

Background: Metagenomic next-generation sequencing offers an unbiased approach to identifying viral pathogens in cerebrospinal fluid of patients with meningoencephalitis of unknown etiology.

Methods: In an 11-month case series, we investigated the use of cerebrospinal fluid metagenomic next-generation sequencing to diagnose viral infections among pediatric hospitalized patients presenting with encephalitis or meningoencephalitis of unknown etiology. Cerebrospinal fluid from patients with known enterovirus meningitis were included as positive controls. Cerebrospinal fluid from patients with primary intracranial hypertension were included to serve as controls without known infections.

Results: Cerebrospinal fluid metagenomic next-generation sequencing was performed for 37 patients. Among 27 patients with encephalitis or meningoencephalitis, 4 were later diagnosed with viral encephalitis, 6 had non-central nervous system infections with central nervous system manifestations, 6 had no positive diagnostic tests, and 11 were found to have a noninfectious diagnosis. Metagenomic next-generation sequencing identified West Nile virus (WNV) in the cerebrospinal fluid of 1 immunocompromised patient. Among the 4 patients with known enterovirus meningitis, metagenomic next-generation sequencing correctly identified enteroviruses and characterized the viral genotype. No viral sequences were detected in the cerebrospinal fluid of patients with primary intracranial hypertension. Metagenomic next-generation sequencing also identified sequences of nonpathogenic torque Teno virus in cerebrospinal fluid specimens from 13 patients.

Conclusions: Our results showed viral detection by cerebrospinal fluid metagenomic next-generation sequencing only in 1 immunocompromised patient and did not offer a diagnostic advantage over conventional testing. Viral phylogenetic characterization by metagenomic next-generation sequencing could be used in epidemiologic investigations of some viral pathogens, such as enteroviruses. The finding of torque Teno viruses in cerebrospinal fluid by metagenomic next-generation sequencing is of unknown significance but may merit further exploration for a possible association with noninfectious central nervous system disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0883073820972232DOI Listing
November 2020

Pediatric Inpatient Problem List Review and Accuracy Improvement.

Hosp Pediatr 2020 Nov 13;10(11):941-948. Epub 2020 Oct 13.

Nationwide Children's Hospital, Columbus, Ohio; and.

Background And Objectives: The problem list (PL) is a meaningful use-incentivized criterion for electronic health record documentation. Inconsistent use or inaccuracy of the PL can create communication gaps among providers, potentially leading to diagnostic delays and serious safety events. The objective of the study was to increase the rate of PL review by attending physicians for inpatients discharged from hospital pediatrics and infectious disease services from a baseline of 70% to 80% by June 2018 and to sustain the rate for 6 months. The secondary aim was to improve PL accuracy by decreasing the rate of duplicate codes and red code diagnoses that should resolve before discharge from a baseline of 12% and 11%, respectively, to 5% and sustaining the rate for 6 months.

Methods: A quality improvement team used the Institute for Healthcare Improvement Model for Improvement. We tracked duplicate codes and red codes as surrogate markers of PL quality. Rates of PL review and PL quality were analyzed monthly via statistical process control charts (p-charts) with 3-σ control limits to identify special cause variation.

Results: PL review improved from a baseline of 70% to 90%, and the change was sustained for 1 year. PL quality improved as duplicate codes at the time of discharge decreased from 12% to 6% and as red codes decreased from a baseline of 11% to 6%.

Conclusions: The PL is an important communication tool that is underused. By engaging and educating stakeholders, incentivizing compliance, standardizing PL management, leveraging electronic health record enhancements, and providing physician feedback, we improved PL meaningful use and quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/hpeds.2020-0059DOI Listing
November 2020

Year-Round, Routine Testing of Multiple Body Site Specimens for Human Parechovirus in Young Febrile Infants.

J Pediatr 2021 Feb 9;229:216-222.e2. Epub 2020 Oct 9.

Division of Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH.

Objectives: To test our hypothesis that routine year-round testing of specimens from multiple body sites and genotyping of detected virus would describe seasonal changes, increase diagnostic yield, and provide a better definition of clinical manifestations of human parechovirus (PeV-A) infections in young febrile infants.

Study Design: PeV-A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was incorporated in routine evaluation of infants aged ≤60 days hospitalized at Nationwide Children's Hospital for fever and/or suspected sepsis-like syndrome beginning in July 2013. We reviewed electronic medical records of infants who tested positive for PeV-A between July 2013 and September 2016. Genotyping was performed with specific type 3 RT-PCR and sequencing.

Results: Of 1475 infants evaluated, 130 (9%) tested positive for PeV-A in 1 or more sites: 100 (77%) in blood, 84 (65%) in a nonsterile site, and 53 (41%) in cerebrospinal fluid (CSF). Five infants (4%) were CSF-only positive, 31 (24%) were blood-only positive, and 20 (15%) were nonsterile site-only positive. PeV-A3 was the most common type (85%) and the only type detected in CSF. Although the majority (79%) of infections were diagnosed between July and December, PeV-A was detected year-round. The median age at detection was 29 days. Fever (96%), fussiness (75%), and lymphopenia (56%) were common. Among infants with PeV-A-positive CSF, 77% had no CSF pleocytosis. The median duration of hospitalization was 41 hours. Four infants had bacterial coinfections diagnosed within 24 hours of admission; 40 infants had viral coinfections.

Conclusions: Although most frequent in summer and fall, PeV-A infections were encountered in every calendar month within the 3-year period of study. More than one-half of patients had PeV-A detected at more than 1 body site. Coinfections were common. PeV-A3 was the most common type identified and the only type detected in the CSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546655PMC
February 2021

Manifestations of Toxic Shock Syndrome in Children, Columbus, Ohio, USA, 2010-2017.

Emerg Infect Dis 2020 06;26(6):1077-1083

Data are limited on the incidence and management of streptococcal toxic shock syndrome (TSS) and nonstreptococcal TSS in children. We aimed to define the clinical patterns of TSS at Nationwide Children's Hospital in Ohio as they relate to published criteria, diagnostic decisions, and treatment options. Through retrospective chart reviews, we identified 58 patients with TSS (27 streptococcal, 31 nonstreptococcal) during January 2010-September 2017. We observed clinical and laboratory findings that are not part of TSS criteria, such as pyuria in streptococcal TSS (50% of patients) and pulmonary involvement (85%) and coagulopathy (92%) in nonstreptococcal TSS patients. Recommended treatment with clindamycin and intravenous immunoglobulin was delayed in streptococcal TSS patients without rash (3.37 days vs. 0.87 days in patients with rash), leading to prolonged hospitalization and complications. Incorporation of additional TSS signs and symptoms would be helpful in TSS diagnosis and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2606.190783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258457PMC
June 2020

Decreasing the Duration of Discharge Antibiotic Treatment Following Inpatient Skin and Soft Tissue Abscess Drainage.

Pediatr Qual Saf 2020 Mar-Apr;5(2):e257. Epub 2020 Feb 15.

Section of Infectious Diseases, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio.

Introduction: Skin and soft tissue abscesses do not require prolonged systemic antimicrobial treatment following drainage. We aimed to decrease the duration of discharge antibiotic treatment to less than 5 days following inpatient incision and drainage of uncomplicated abscesses.

Methods: A new treatment protocol that defined uncomplicated abscesses, as well as inclusion and exclusion criteria, was created to monitor the accurate duration of prescribed therapy at discharge. We implemented a treatment algorithm that takes into account the epidemiologic changes in microbial etiologies and the presence of systemic findings for patients after surgical incision and drainage. We used control charts to assess the impact of the interventions.

Results: Four hundred and eighteen patients were discharged following abscess drainage from our inpatient infectious diseases unit in 2016. The patients were 3 months to 21 years of age. Only 72 (17%) patients had prescribed discharge antibiotic treatment courses that were less than 5 days [range 0-31 days, median 8 days (IQR 6, 9)], and the average prescribed course at discharge was 8.6 days. During the study period, we significantly decreased the average duration of discharge antibiotics to 7.3 days in all patients ( = 0.0016, 95% CI: -2.1036 to -0.4964, difference of means -1.3). The discharge treatment duration of patients with uncomplicated abscess was shorter at 4.7 days [range 0-9 days, median 5 days, (IQR 3, 5)]. Prescription compliance to less than 5 days treatment course at discharge increased from the baseline of 17% to 42% overall.

Conclusions: Standardizing definitions of uncomplicated skin and soft tissue abscesses was critical to the success of this project. In addition to possible improved treatment adherence and decreased side effects, our protocol led to decreased patient care costs with no documented changes in readmission rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/pq9.0000000000000257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190260PMC
February 2020

Eosinophilic Pneumonia and Lymphadenopathy Associated With Vaping and Tetrahydrocannabinol Use.

Pediatrics 2020 04;145(4)

Divisions of Pulmonary Medicine.

Idiopathic acute eosinophilic pneumonia is a rare and potentially life-threatening condition that is defined by bilateral pulmonary infiltrates and fever in the presence of pulmonary eosinophilia. It often presents acutely in previously healthy individuals and can be difficult to distinguish from infectious pneumonia. Although the exact etiology of idiopathic acute eosinophilic pneumonia remains unknown, an acute hypersensitivity reaction to an inhaled antigen is suggested, which is further supported by recent public health risks of vaping (electronic cigarette) use and the development of lung disease. In this case, a patient with a year-long history of vaping in conjunction with tetrahydrocannabinol cartridge use who was diagnosed with idiopathic acute eosinophilic pneumonia with associated bilateral hilar lymphadenopathy is described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2019-3007DOI Listing
April 2020

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial.

Lancet 2019 12 10;394(10216):2263-2270. Epub 2019 Dec 10.

Norwich Medical School, University of East Anglia, Norfolk, Norwich, UK; Cardiology Department, Norfolk and Norwich University Hospital, Norwich, UK. Electronic address:

Background: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.

Methods: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.

Findings: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.

Interpretation: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications.

Funding: British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)32518-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934233PMC
December 2019

The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease.

Contemp Clin Trials 2019 04 3;79:98-103. Epub 2019 Mar 3.

Harbor-UCLA Medical Center, 1124 W. Carson St., Torrance, CA, 90509, United States.

Background: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10-20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients.

Objectives: The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience.

Methods: The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5-18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm.

Conclusion: This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2019.02.008DOI Listing
April 2019

Multiple sites PCR testing for enteroviruses in young febrile infants.

Lancet Infect Dis 2019 03;19(3):239-240

Division of Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, USA; The Ohio State University, College of Medicine, Columbus, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(19)30042-8DOI Listing
March 2019

Pneumococcal colonization among tracheostomy tube dependent children.

PLoS One 2018 19;13(10):e0206305. Epub 2018 Oct 19.

College of Medicine, The Ohio State University, and Nationwide Children's Hospital, Columbus, Ohio, United States of America.

Streptococcus pneumoniae colonization is a precursor to pneumococcal disease. Although children with a tracheostomy have an increased risk of pneumococcal pneumonia, the pneumococci colonizing their lower airways remain largely uncharacterized. We sought to compare lower respiratory tract isolates colonizing tracheostomy patients and a convenience sample of isolates from individuals intubated for acute conditions. We collected pneumococcal isolates from the lower respiratory tract of 27 patients with a tracheostomy and 42 patients intubated for acute conditions. We compared the penicillin susceptibility, rates of co-colonization, genetic background, and serotype of isolates colonizing these patient populations. Isolates from both groups showed high genetic diversity. Forty multi-locus sequence types and 20 serotypes were identified. There was no significant difference in serotype distribution, co-colonization rates, vaccine coverage, or non-susceptibility to penicillin among pneumococcal isolates from the two groups. Colonization of the lower airways with non-vaccine serotypes 15B/C, 23B and 35B was noted for the first time in patients with tracheostomies and supports recently observed increases in nasopharyngeal colonization and disease due to these serotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206305PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195293PMC
April 2019

Enlarging verrucous plaques in a teenager.

Pediatr Dermatol 2018 Sep;35(5):671-672

Division of Pediatric Dermatology, Nationwide Children's Hospital and College of Medicine, The Ohio State University, Columbus, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pde.13506DOI Listing
September 2018

Clinical and Radiologic Manifestations of Bone Infection in Children with Cat Scratch Disease.

J Pediatr 2018 10 2;201:274-280.e12. Epub 2018 Jul 2.

Pediatrics, Nationwide Children's Hospital, Columbus, OH; The Ohio State University College of Medicine, Columbus, OH.

We identified 13 patients with cat scratch (Bartonella henselae) bone infection among those admitted to a large tertiary care children's hospital over a 12-year period. The median age was 7 years and the median time from onset of illness to diagnosis was 10 days. Multifocal osteomyelitis involving spine and pelvis was common; no patient had a lytic bone lesion. Median treatment duration was 28 days (IQR, 24.5 days). Despite significant variations in treatment duration and antimicrobial therapy choices, all patients showed improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.05.033DOI Listing
October 2018

No Evidence of Human Leukocyte Antigen Gene Association With Rheumatic Fever Among Children in Samoa.

J Pediatric Infect Dis Soc 2015 Mar 16;4(1):71-3. Epub 2014 Jul 16.

Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu.

Human leukocyte antigens (HLAs) have been implicated in rheumatic fever pathogenesis. This pilot whole genome association study compares genotypes of Samoan children with rheumatic fever to unaffected siblings and unrelated healthy controls. No risk-related genotypes were associated with HLA genes. Thirteen Regions of Interest were identified as candidates for further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/pit064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965876PMC
March 2015

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

Am Heart J 2015 May 12;169(5):605-12. Epub 2015 Feb 12.

Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, UK.

Rationale: A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial.

Design: A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2015.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441104PMC
May 2015

Anomalous origin and interarterial course of right coronary artery associated with angina and proven ischemia.

Int J Angiol 2014 Dec;23(4):271-4

Department of Radiology, Sonomed Imaging Center, Istanbul, Turkey.

Clinical significance of coronary arteries with anomalous origin and/or course is highly heterogeneous. Anomalies with the origin from the opposite sinus and interarterial course can be associated with angina, syncope, and sudden cardiac death. However, there are no clear guidelines for diagnosis and treatment of such cases. We present the case of a young lady who presented with typical angina, and later proved to have an anomalous right coronary artery (RCA) originating from the left sinus of Valsalva coursing between the aorta and pulmonary artery. This was associated with demonstrable stress ischemia with nuclear perfusion scan. The patient underwent surgery with a bypass graft to the anomalous RCA with complete relief of her angina.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0033-1349165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244247PMC
December 2014

Progressive rash and fever in an infant.

Clin Pediatr (Phila) 2015 Mar 19;54(3):293-5. Epub 2014 Aug 19.

Nationwide Children's Hospital, Infectious Diseases, Columbus, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0009922814547567DOI Listing
March 2015

A prospective, randomized, placebo-controlled, double-blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol.

Trials 2013 Dec 1;14:408. Epub 2013 Dec 1.

The Heart Hospital, University College London Hospitals NHS Foundation Trust, 16-18 Westmoreland Street, London W1G 8PH, UK.

Background: Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS. Preclinical, neonatal, and pediatric studies have indicated that angiotensin receptor blockers (ARBs) may reduce the rate of aortic dilatation. This trial will investigate the effects of irbesartan on aortic dilatation in Marfan syndrome.

Methods/design: The Aortic Irbesartan Marfan Study (AIMS) is an investigator-led, prospective, randomized, placebo-controlled, double-blind, phase III, multicenter trial. Currently, 26 centers in the UK will recruit 490 clinically confirmed MFS patients (aged ≥6 to ≤40 years) using the revised Ghent diagnostic criteria. Patients will be randomized to irbesartan or placebo. Aortic root dilatation will be measured by transthoracic echocardiography at baseline and annually thereafter. The primary outcome is the absolute change in aortic root diameter per year measured by echocardiography. The follow-up period will be a minimum of 36 months with an expected mean follow-up period of 48 months.

Discussion: This is the first clinical trial to evaluate the ARB irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS. Not only will this provide useful information on the safety and efficacy of ARBs in MFS, it will also provide a rationale basis for potentially lifesaving therapy for MFS patients.

Trial Registration: ISRCTN, 90011794.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1745-6215-14-408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220813PMC
December 2013

Severe hypokalemia probably associated with sertraline use.

Ann Pharmacother 2014 Feb 19;48(2):297-300. Epub 2013 Nov 19.

Gaziosmanpasa Hospital, Istanbul, Turkey.

Objective: To report a case of ventricular fibrillation caused by severe hypokalemia probably associated with sertraline use.

Case Summary: A 48-year-old male patient experienced ventricular fibrillation and cardiac arrest 2 hours after an uneventful coronary angiography procedure, which revealed normal, unobstructed coronary arteries. Blood chemistry was immediately obtained, revealing a very low potassium (K+) level of 2.44 mEq/L. Other blood electrolytes, including magnesium, ECG, and corrected QT intervals, were all within normal limits. A thorough search for an etiology of hypokalemia, including adrenal gland causes, herbal product consumption, and toxic exposure, did not reveal any identifiable cause. This led us to consider the only drug he was on--sertraline 50 mg per day--as the possible culprit.

Discussion: There has been no clear identification of severe hypokalemia associated with sertraline use in the literature. However, there have been a considerable number of self-reported cases of hypokalemia in patients on sertraline therapy. Scoring according to the Naranjo adverse drug reaction scale revealed a probable relationship between severe hypokalemia and sertraline use in our patient. No clear pathogenic mechanism for the effect of sertraline on serum K equilibrium is known. However, considering the number of self-reported incidences and this case report, the effect of sertraline on serum K levels warrants consideration.

Conclusions: This is the first documented case report of severe hypokalemia probably associated with sertraline use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1060028013512789DOI Listing
February 2014

Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design.

Syst Rev 2013 Jan 18;2. Epub 2013 Jan 18.

Clinical Trials and Evaluation Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK.

Unlabelled: The Beta-Blockers in Heart Failure Collaborative Group (BB-HF) was formed to obtain and analyze individual patient data from the major randomized controlled trials of beta-blockers in heart failure. Even though beta-blockers are an established treatment for heart failure, uptake is still sub-optimal. Further, the balance of efficacy and safety remains uncertain for common groups including older persons, women, those with impaired renal function and diabetes. Our aim is to provide clinicians with a thorough and definitive evidence-based assessment of these agents. We have identified 11 large randomized trials of beta-blockers versus placebo in heart failure and plan to meta-analyze the data on an individual patient level. In total, these trials have enrolled 18,630 patients. Uniquely, the BB-HF group has secured access to the individual data for all of these trials, with the participation of key investigators and pharmaceutical companies.Our principal objectives include deriving an overall estimate of efficacy for all-cause mortality and cardiovascular hospitalization. Importantly, we propose a statistically-robust sub-group assessment according to age, gender, diabetes and other key factors; analyses which are only achievable using an individual patient data meta-analysis. Further, we aim to provide an assessment of economic benefit and develop a risk model for the prognosis of patients with chronic heart failure.This paper outlines inclusion criteria, search strategies, outcome measures and planned statistical analyses.

Trial Registration:

Clinical Trial Registration Information: http://clinicaltrials.gov/ct2/show/NCT00832442.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2046-4053-2-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564787PMC
January 2013

Rates and causes of death from non-ST elevation acute coronary syndromes: ten year follow-up of the PRAIS-UK registry.

Int J Cardiol 2013 Sep 6;168(1):490-4. Epub 2012 Nov 6.

Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust, Imperial College London, United Kingdom.

Background: Long term nationally representative mortality rates following acute coronary syndrome (ACS) admissions are lacking beyond 5 years. We report rates and causes of mortality at approximately 10 years from PRAIS-UK.

Methods: PRAIS-UK was a prospective registry of 1046 non-ST-elevation ACS admissions to 56 UK hospitals between 1998 and 1999. 493 patients surviving to 6 months were consented to long term follow-up. We identified deaths and causes (ICD codes) via the UK central death register and examined the influence of baseline characteristics and early revascularisation procedures. A modified GRACE risk score was constructed to determine the association of baseline score with long term risk of death.

Results: The mean age was 66 years and 40% were women. After a median follow-up of 11.6 years (IQR 6.3-11.9), 46% (225) of patients had died with 55% being classified as cardiovascular. In a multivariate analysis, the following variables were associated with higher mortality (hazard ratio [HR] and 95% confidence intervals [CI]): age (10 years increase) 2.14 (1.87 to 2.45), ST depression or bundle branch block (compared to normal ECG) 1.68 (1.06 to 2.67), and history of heart failure (compared to no HF) 1.81 (1.28 to 2.56). The HR for risk of death in patients who received a revascularisation procedure (versus those who did not) in the first 6 months was 0.41 (0.24 to 0.69). The mean adapted GRACE score was 99.3 ± 26.4, associated with approximately 50% mortality at 10 years.

Conclusions: Non-ST elevation ACS is associated with about 50% mortality over 10 years that may be improved by early revascularisation. Well designed long-term registries can provide key data to determine prognosis and burden of disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2012.09.160DOI Listing
September 2013

How should I treat an ostial thrombotic occlusion of the right coronary artery in the setting of an acute myocardial infarction?

EuroIntervention 2012 Jun;8(2):282-9

Department of Cardiology, Gaziosmanpasa Hospital, Istanbul, Turkey.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJV8I2A43DOI Listing
June 2012

Calcineurin inhibitor treatment of intravenous immunoglobulin-resistant Kawasaki disease.

J Pediatr 2012 Sep 6;161(3):506-512.e1. Epub 2012 Apr 6.

Department of Pediatrics, University of California at San Diego and Rady Children's Hospital, La Jolla, CA, USA.

Objective: To describe the clinical course and outcome of 10 patients with Kawasaki disease (KD) treated with a calcineurin inhibitor after failing to respond to multiple therapies.

Study Design: Demographic and clinical data were prospectively collected using standardized case report forms. T-cell phenotypes were determined by flow cytometry, and KD risk alleles in ITPKC (rs28493229), CASP3 (rs72689236), and FCGR2A (rs1801274) were genotyped.

Results: Intravenous followed by oral therapy with cyclosporine (CSA) or oral tacrolimus was well tolerated and resulted in defervescence and resolution of inflammation in all 10 patients. There were no serious adverse events, and a standardized treatment protocol was developed based on our experiences with this patient population. Analysis of T-cell phenotype by flow cytometry in 2 subjects showed a decrease in circulating activated CD8(+) and CD4(+) T effector memory cells after treatment with CSA. However, suppression of regulatory T-cells was not seen, suggesting targeting of specific, proinflammatory T-cell compartments by CSA.

Conclusion: Treatment of refractory KD with a calcineurin inhibitor appears to be a safe and effective approach that achieves rapid control of inflammation associated with clinical improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2012.02.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613150PMC
September 2012

Assessing bleeding risk in acute coronary syndromes.

Rev Esp Cardiol (Engl Ed) 2012 Jan 5;65(1):4-6. Epub 2011 Nov 5.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.recesp.2011.08.005DOI Listing
January 2012

Motile ciliary microorganisms in peritoneal fluid.

Diagn Cytopathol 2011 Aug 9;39(8):606-7. Epub 2010 Nov 9.

Department of Pediatrics, Alberta Health Services, Alberta, Canada.

We report a patient with chronic renal failure and ciliocytophthoria or "detached ciliary tufts" identified from her peritoneal fluid. The recognition of these rare structures is critical to avoid misdiagnosing a presumed protozoan infection and embarking on further costly investigations and unnecessary treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dc.21505DOI Listing
August 2011

Emergence of erythromycin- and clindamycin-resistant Streptococcus pyogenes emm 90 strains in Hawaii.

J Clin Microbiol 2011 Jan 10;49(1):439-41. Epub 2010 Nov 10.

Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, Honolulu, Hawaii 96826, USA.

We identified 12 erythromycin- and clindamycin-resistant emm 90 group A streptococcus (GAS) isolates during a retrospective invasive disease survey in Hawaii. A comparison with 20 type-matched isolates showed all resistant isolates to be emm 90.4b with the constitutive or inducible macrolide-lincosamide-streptogramin B resistance phenotype (cMLS(B) or iMLS(B)). All isolates had the same pulsed-field gel electrophoresis (PFGE) pattern, suggesting clonal spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.02208-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020461PMC
January 2011

Priming the immune system for heart disease: a perspective on group A streptococci.

J Infect Dis 2010 Oct;202(7):1059-67

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

Although immune responses against group A streptococci and the heart have been correlated with antibodies and T cell responses against cardiac myosin, there is no unifying hypothesis about carditis caused globally by many different serotypes. Our study identified disease-specific epitopes of human cardiac myosin in the development of rheumatic carditis in humans. We found that immune responses to cardiac myosin were similar in rheumatic carditis among a small sample of worldwide populations, in which immunoglobulin G targeted human cardiac myosin epitopes in the S2 subfragment hinge region within S2 peptides containing amino acid residues 842-992 and 1164-1272. An analysis of rheumatic carditis in a Pacific Islander family confirmed the presence of potential rheumatogenic epitopes in the S2 region of human cardiac myosin. Our report suggests that cardiac myosin epitopes in rheumatic carditis target the S2 region of cardiac myosin and are similar among populations with rheumatic carditis worldwide, regardless of the infecting group A streptococcal M serotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1086/656214DOI Listing
October 2010

An insert in the covS gene distinguishes a pharyngeal and a blood isolate of Streptococcus pyogenes found in the same individual.

Microbiology (Reading) 2010 Oct 15;156(Pt 10):3085-3095. Epub 2010 Jul 15.

University of Hawai'i, John A. Burns School of Medicine, Department of Tropical Medicine, Medical Microbiology and Pharmacology, Honolulu, HI, USA.

Expression of the extensive arsenal of virulence factors by Streptococcus pyogenes is controlled by many regulators, of which CovRS is one of the best characterized and can influence ∼15 % of the genome. Animal models have established that mutants of covRS arise spontaneously in vivo resulting in highly invasive organisms. We analysed a pharyngeal and a blood isolate of S. pyogenes recovered from the same individual 13 days apart. The two isolates varied in many phenotypic properties including SpeB production, which were reflected in transcriptomic analyses. PFGE, multilocus sequence typing and partial sequencing of some key genes failed to show any differences except for an 11 bp insert in the covS gene in the blood isolate which caused a premature termination of transcription. Complementation of a fully functional covS gene into the blood isolate resulted in high expression of CovS and expression of speB. These results, showing a pharyngeal and a blood isolate from a single individual differing by a simple insertion, provide evidence for the model that regulatory gene mutations allow S. pyogenes to invade different niches in the body.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/mic.0.042614-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068697PMC
October 2010

Community-acquired Staphylococcus aureus pneumonia among hospitalized children in Hawaii.

Pediatr Pulmonol 2010 Sep;45(9):898-905

Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96826, USA.

Summary Background: Invasive community acquired (CA) Staphylococcus aureus (SA) disease has been endemically observed in Hawaiian children. We wanted to evaluate the clinical, laboratory findings, and outcomes of methicillin-resistant SA (MRSA) and methicillin-susceptible SA (MSSA) associated pneumonia admissions.

Methods: We performed retrospective chart reviews of 38 culture proven SA pneumonia patients admitted to a pediatric tertiary medical center in Hawaii between January 1996 to December 2007.

Results: Twenty-six patients (68%) had MRSA and 12 patients (32%) had MSSA infection. The mean age of MRSA patients was 2.8 and 6.7 years for MSSA patients (P < 0.05). Pacific Islander and Native Hawaiian patients were affected disproportionately compared to non-Pacific Islander and Hawaiian groups (P < 0.0001). Demographic data, days of fever, tachypnea, hypoxia, and length of stay (LOS) were not significantly different between MRSA and MSSA infected patients. The mean LOS was 26.2 days (range 6-138 days); mean length of fever was 12.4 days. Seventy five percent (15 of 20) of patients who required intubation had MRSA. Twenty-one of the 29 (72%) total patients with pleural effusions had MRSA infection and all required chest tube placements. Two (5%) patients died; both had MRSA infection.

Conclusions: Younger Pacific Islander/Native Hawaiian children were affected disproportionately and had MRSA infection more frequently. MRSA infected patients appeared to have severe disease with frequent chest tube placement, intubation, and fatality. Overall, both MRSA and MSSA pneumonia resulted in prolonged hospitalization, multiple complications, and significant healthcare costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.21269DOI Listing
September 2010

What goes into a major acute coronary syndrome trial and what will future trials look like?

Curr Cardiol Rep 2010 Jul;12(4):348-55

Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.

Acute coronary syndromes (ACS) are common and carry a high risk of death and serious complications. Over the past three decades, the international cardiology community has collaborated in numerous large, well-designed randomized trials evaluating promising new treatments leading to important improvements in care for patients with ACS. Industry has funded most of the ACS trials of new pharmacologic treatments, but there are many independently funded trials evaluating treatment strategies such as percutaneous coronary intervention. Improvements in ACS care have led to challenges in demonstrating the efficacy of new treatments and many current trials are comparing one active treatment against another, although new paradigms including anti-inflammatory treatments and stem cell infusions are being tested against placebo. Developing new drugs for ACS is a very expensive process with many trials not showing any benefit, and much of this expense is related to the cost of large multicenter phase 3 trials. Reducing the administrative burden and associated costs of ACS trials is an important immediate goal if the strong tradition of large collaborative trials is to continue, as well as the need for health care providers to engage more actively in the clinical research process and support large multinational independently funded trials. We discuss methodologic issues of ACS trials with recent examples and provide some perspectives for the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11886-010-0119-4DOI Listing
July 2010