Rochester, NY, United States
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Wychowski M.K.,Rochester General Hospital | Kouides P.A.,Roswell Park Cancer Institute
Annals of Pharmacotherapy | Year: 2012

Objective: To report a case of dabigatran-induced overanticoagulation in a patient who developed acute renal failure and to inform health care providers of the need for appropriate patient selection and periodic monitoring of renal function in the elderly. Case Summary: A 66-year-old woman treated with dabigatran for atrial fibrillation developed acute renal failure and upper gastrointestinal bleeding. She had been taking dabigatran 150 mg twice daily for 2 months, with intermittent renal insufficiency during the previous 6 months. On admission, laboratory values included serum creatinine 3.6 mg/dL, hematocrit 21%, and international normalized ratio greater than 10. She was treated with packed red blood cells, prothrombin complex concentrate, and multiple sessions of dialysis. There were no further bleeding events or additional transfusions for the remainder of the hospitalization. Her renal function never recovered and she remained hemodialysis-dependent. After a 47-day length of stay, she was transferred to a nursing home where she died 2 months later. Discussion: Renally eliminated drugs such as dabigatran place elderly patients at increased risk of drug accumulation and adverse drug events due to agerelated decline in renal function. In a recent case series, dabigatran toxicity in the elderly with renal impairment was described with 1 fatal outcome. Recent literature, including the package insert, advises intermittent monitoring of renal function in the elderly and those with moderate renal impairment. Consideration should also include the appropriateness of dabigatran therapy in patients with fluctuating renal function. In our patient, the Naranjo probability scale indicated a probable cause between the bleeding event and dabigatran use. Conclusions: Our case report, along with 2 other recent reports on dabigatran toxicity, illustrates the importance for appropriate patient selection and the need to periodically monitor renal function in elderly patients receiving dabigatran.


Keipp Talbot H.,Vanderbilt University | Falsey A.R.,Rochester General Hospital
Clinical Infectious Diseases | Year: 2010

Viral respiratory disease in older adults has been increasingly recognized as a significant cause of hospitalizations and death. Unfortunately, the recognition and diagnosis of infection due to many viral respiratory pathogens in older adults can be elusive because of atypical clinical presentations and the insensitivity of current laboratory diagnostic tests in this population. For influenza diagnosis, rapid antigen tests followed by viral culture (if antigen test results are negative), can be useful in older adults as long as clinicians are mindful of test limitations. Although specific, rapid antigen tests are insensitive in this population. Erroneous negative results may lead to delays in timely administration of antiviral treatment and institution of appropriate isolation precautions. The increasing availability of new, rapid, and sensitive molecular diagnostics, such as polymerase chain reaction testing, should provide more accurate and timely diagnoses of viral respiratory infections in older adults in the near future. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Pichichero M.E.,Rochester General Hospital
JAMA - Journal of the American Medical Association | Year: 2015

IMPORTANCE: Antimicrobial treatment reduces the symptoms of acute otitis media (AOM). The effect of antimicrobial treatment on the duration of middle ear effusion (MEE) and concomitant hearing impairment is not known. OBJECTIVE: To determine whether the antimicrobial treatment of AOM reduces the duration of MEE. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled trial involved a total of 84 children with AOM between 6 months and 15 years of age. Participants were recruited from September 14, 1999, to January 4, 2000; October 10, 2005, to December 16, 2005; and September 22, 2009, to June 4, 2012, from among children attending an AOM prevention trial and children visiting local outpatient clinics in Oulu, Finland. INTERVENTIONS: Children were randomly allocated to receive either 40mg/kg of amoxicillin-clavulanate or a placebo mixture per day for 7 days. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the time to the disappearance of MEE as defined by a normal tympanogram finding (A curve) from both ears on 2 consecutive measurement days. Parents performed daily tympanometry at home. The study physician performed tympanometry and otoscopy at study entry, after 3 and 7 days, and then weekly until both ears were healthy. The main secondary outcome measures were the time to normal otoscopy findings and the proportion of children without persistent MEE at 14 days and 2 months. RESULTS: Middle ear effusion disappeared 2.0 weeks (13.7 days) earlier (P = .02) in the antimicrobial group (mean time, 2.7 weeks; 95% CI, 1.7-3.7) than in the placebo group (4.7 weeks; 95% CI, 3.6-5.7). Normal otoscopy findings were observed 1.4 weeks sooner in the antimicrobial group than in the placebo group (P = .02).On day 14, 69% of children in the antimicrobial group and 38% in the placebo group had normal tympanometry findings (number needed to treat, 3.2; 95% CI, 2.0-10.5). On day 60, 2 children (5%) in the antimicrobial group and 10 children (24%) in the placebo group had persistent MEE (P = .01). CONCLUSIONS AND RELEVANCE: Antimicrobial treatment effectively reduced the duration of MEE and possible concomitant hearing impairment in children with AOM. Antimicrobial treatment also reduced the risk for persistent MEE. Copyright 2015 American Medical Association. All rights reserved.


Pichichero M.E.,Rochester General Hospital
Human Vaccines and Immunotherapeutics | Year: 2013

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vac-cinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. © 2013 Landes Bioscience.


Sterns R.H.,Rochester General Hospital
New England Journal of Medicine | Year: 2015

Human cells dwell in salt water. Their well-being depends on the ability of the body to regulate the salinity of extracellular fluids. By controlling water intake and excretion, the osmoregulatory system normally prevents the plasma sodium concentration from straying outside its normal range (135 to 142 mmol per liter). Failure of the system to regulate within this range exposes cells to hypotonic or hypertonic stress. This review considers the causes and consequences of an abnormal plasma sodium concentration and offers a framework for correcting it. © 2015 Massachusetts Medical Society.


Influenza-related illness is an enormous health burden in all age groups. Immunization remains the best method of prevention, yet despite the availability of a safe and effective vaccine, many individuals go unvaccinated each season. Intradermal (ID) vaccination represents an alternative approach to standard intramuscular (IM) vaccination and takes advantage of the immunologically active dermis capable of producing a robust immune response. Enhanced immunogenicity with ID vaccination compared with standard IM vaccination has been observed in several groups with a history of poor vaccine response rates, such as older adults and haemodialysis patients. In addition, these methods of delivery may increase acceptability in children and persons with needle phobias, thus addressing some of the present barriers to influenza immunization. © 2010 Elsevier Ltd.


Falsey A.R.,Rochester General Hospital
Infection and Drug Resistance | Year: 2012

Parainfuenza viruses (PIV) are common respiratory viruses that belong to the Paramyxoviridae family. PIV infection can lead to a wide variety of clinical syndromes ranging from mild upper respiratory illness to severe pneumonia. Severe disease can be seen in elderly or chronically ill persons and may be fatal in persons with compromised immune systems, particularly children with severe combined immunodefciency disease syndrome and hemato- pathic stem cell transplant recipients. At present, there are no licensed antiviral agents for the treatment of PIV infection. Aerosolized or systemic ribavirin in combination with intravenous gamma globulin has been reported in small, uncontrolled series and case reports of immuno- compromised patients. A number of agents show antiviral activity in vitro and in animals, but none are currently approved for human use. © 2012 Falsey, publisher and licensee Dove Medical Press Ltd.


Khan M.N.,Rochester General Hospital | Pichichero M.E.,Rochester General Hospital
Vaccine | Year: 2012

We evaluated the role of vaccine candidate surface proteins, PhtD and PhtE as antigens with functional importance for Streptococcus pneumoniae (pneumococci) in adherence to nasopharyngeal (D562) and lung (A549) epithelial cell lines. Comparing TIGR4 to PhtD and PhtE- isogenic mutants, a 40% (p= 0.001) and 42% (p= 0.002) drop in the number of epithelial cells with adherent pneumococci was observed to both cells lines with the mutants, as quantitated using flow cytometry. We expressed PhtD and PhtE on the surface of Escherichia coli and demonstrated that when PhtD and PhtE were surface expressed on E. coli, adherence increased to D562 and A549 cells, compared with the E. coli parent strain (p= 0.005, 0.013 for D562 and p= 0.034, p= 0.035 for A549). Using flow cytometry and confocal microscopy we found that pneumococci aggregated in the presence of human serum IgG, leading to a non-specific drop in adherence. Therefore IgG Fab fragments were prepared to study the functional role of PhtD and PhtE-specific Fabs in blocking adherence. The addition of 1 μg of IgG Fab from adult sera led to a 34% reduction (p= 0.002) and from children a 20% (p= 0.023) reduction in D562 epithelial cells with adherent pneumococci. In purified IgG from adult sera, the depletion of PhtD and PhtE specific Fab from total IgG Fab resulted in a significant increase in the number of D562 epithelial cells with adherent pneumococci (p= 0.005 for PhtD and p= 0.024 for PhtE). We conclude that antibody directed to PhtD and PhtE adhesins of pneumococci, if raised by vaccination, may function to prevent pneumococcal adherence to human airway epithelial cells. © 2012 Elsevier Ltd.


Pichichero M.E.,Rochester General Hospital
Pediatric Clinics of North America | Year: 2013

Acute otitis media (AOM) is diagnosed based on visualization of a full or bulging tympanic membrane with middle ear effusion. The distribution of bacteria causing AOM in North America under the influence of pneumococcal conjugate vaccination and antibiotic selection pressure has resulted in a predominance of β-lactamase-producing Haemophilus influenzae followed by penicillin-resistant Streptococcus pneumoniae. Although guidelines continue to endorse amoxicillin as the preferred treatment, amoxicillin/clavulanate in high dosage would be the preferred treatment based on the otopathogen mix currently. Antibiotic prophylaxis has fallen into disfavor as a preventative strategy for AOM recurrences. © 2013 Elsevier Inc.


Patent
Rochester General Hospital | Date: 2014-06-27

Disclosed are compositions and methods related to vaccination for AOM and children prone to AOM.

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