National Guideline Clearinghouse | Guidelines for field triage of injured patients. Recommendations of the National Expert Panel on Field Triage, 2011.

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National Guideline Clearinghouse | Guidelines for field triage of injured patients. Recommendations of the National Expert Panel on Field Triage, 2011.

Guideline Title

Guidelines for field triage of injured patients. Recommendations of the National Expert Panel on Field Triage, 2011.

 

 

Bibliographic Source(s)

Sasser SM, Hunt RC, Faul M, Sugerman D, Pearson WS, Dulski T, Wald MM, Jurkovich GJ, Newgard CD, Lerner EB, Cooper A, Wang SC, Henry MC, Salomone JP, Galli RL, Centers for Disease Control and Prevention (CDC). Guidelines for field triage of injured patients: recommendations of the National Expert Panel on Field Triage, 2011. MMWR Recomm Rep 2012 Jan 13;61(RR-1):1-20. [87 references] PubMed

 

 

Guideline Status

This is the current release of the guideline.
This guideline updates a previous version: Sasser SM, Hunt RC, Sullivent EE, Wald MM, Mitchko J, Jurkovich GJ, Henry MC, Salomone JP, Wang SC, Galli RL, Cooper A, Brown LH, Sattin RW, National Expert Panel on Field Triage, Centers for Disease Control and Prevention. Guidelines for field triage of injured patients. Recommendations of the National Expert Panel on Field Triage. MMWR Recomm Rep 2009 Jan 23;58(RR-1):1-35. [160 references]

MMWR Recomm Rep. 2012 Jan 13;61(RR-1):1-20.

Guidelines for field triage of injured patients: recommendations of the National Expert Panel on Field Triage, 2011.

Sasser SM, Hunt RC, Faul M, Sugerman D, Pearson WS, Dulski T, Wald MM, Jurkovich GJ, Newgard CD, Lerner EB; Centers for Disease Control and Prevention (CDC).

Source

Division of Injury Response, National Center for Injury Prevention and Control, CDC, Atlanta, Georgia 30341-3717, USA.

Abstract

In the United States, injury is the leading cause of death for persons aged 1-44 years. In 2008, approximately 30 million injuries were serious enough to require the injured person to visit a hospital emergency department (ED); 5.4 million (18%) of these injured patients were transported by Emergency Medical Services (EMS). On arrival at the scene of an injury, the EMS provider must determine the severity of injury, initiate management of the patient’s injuries, and decide the most appropriate destination hospital for the individual patient. These destination decisions are made through a process known as “field triage,” which involves an assessment not only of the physiology and anatomy of injury but also of the mechanism of the injury and special patient and system considerations. Since 1986, the American College of Surgeons Committee on Trauma (ACS-COT) has provided guidance for the field triage process through its “Field Triage Decision Scheme.” This guidance was updated with each version of the decision scheme (published in 1986, 1990, 1993, and 1999). In 2005, CDC, with financial support from the National Highway Traffic Safety Administration, collaborated with ACS-COT to convene the initial meetings of the National Expert Panel on Field Triage (the Panel) to revise the decision scheme; the revised version was published in 2006 by ACS-COT (American College of Surgeons. Resources for the optimal care of the injured patient: 2006. Chicago, IL: American College of Surgeons; 2006). In 2009, CDC published a detailed description of the scientific rationale for revising the field triage criteria (CDC. Guidelines for field triage of injured patients: recommendations of the National Expert Panel on Field Triage. MMWR 2009;58[No. RR-1]). In 2011, CDC reconvened the Panel to review the 2006 Guidelines in the context of recently published literature, assess the experiences of states and local communities working to implement the Guidelines, and recommend any needed changes or modifications to the Guidelines. This report describes the dissemination and impact of the 2006 Guidelines; outlines the methodology used by the Panel for its 2011 review; explains the revisions and modifications to the physiologic, anatomic, mechanism-of-injury, and special considerations criteria; updates the schematic of the 2006 Guidelines; and provides the rationale used by the Panel for these changes. This report is intended to help prehospital-care providers in their daily duties recognize individual injured patients who are most likely to benefit from specialized trauma center resources and is not intended as a mass casualty or disaster triage tool. The Panel anticipates a review of these Guidelines approximately every 5 years.

PMID:

22237112

[PubMed - indexed for MEDLINE]

Free full text

Guidelines for field triage of injured patie… [MMWR Recomm Rep. 2012] – PubMed – NCBI

Press Announcements > FDA: Over-the-counter asthma inhalers containing chloroflouorocarbons (CFCs) will no longer be made or sold after Dec. 31, 2011

The U.S. Food and Drug Administration says users of epinephrine inhalers containing chlorofluorocarbons (CFCs) should plan now to get a prescription for a replacement product because these inhalers will not be made or sold after Dec. 31, 2011.
Epinephrine inhalers, marketed by Armstrong Pharmaceutical Inc. as Primatene Mist, are the only FDA-approved inhalers for the temporary relief of occasional symptoms of mild asthma that are sold over-the-counter in retail stores without a prescription. The product uses CFCs to propel the medicine out of the inhaler so that consumers can breathe it into their lungs.
However, Primatene Mist will no longer be available by year’s end because no CFC-containing epinephrine inhalers can be made or sold after Dec. 31, 2011, to comply with obligations made under the Montreal Protocol on Substances that Deplete the Ozone Layer. This is an international agreement signed by the United States, in which countries agreed to phase-out substances that deplete the ozone layer, including CFCs, after certain dates.

For more information please visit: CFCsL:
Press Announcements > FDA: Over-the-counter asthma inhalers containing chloroflouorocarbons (CFCs) will no longer be made or sold after Dec. 31, 2011

NIH study finds omalizumab relieves seasonal asthma attacks in youth, Wednesday, March 16, 2011 News Release - National Institutes of Health (NIH)

Wednesday, March 16, 2011
5 p.m. EDT Contact:
Julie Wu
wujuli@niaid.nih.gov
301-02-1663

NIH study finds omalizumab relieves seasonal asthma attacks in youth
Symptoms reduced in children and young people with moderate to severe disease

A drug that targets the antibody immunoglobulin E (IgE), a key player in asthma, nearly eliminated seasonal increases in asthma attacks and decreased asthma symptoms among young people living in inner city environments, a clinical trial sponsored by the National Institutes of Health has found.

The findings will appear in the March 17 issue of the New England Journal of Medicine.

This investigational use of the drug omalizumab, sold under the brand name Xolair, was conducted in eight U.S. cities by the Inner City Asthma Consortium (ICAC), a nationwide clinical trials network supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. Additional support for this research was provided by the NIH National Center for Research Resources and Novartis Pharmaceuticals Corporation.

“We know that treatment based on NIH asthma guidelines is generally effective in managing the disease, but many patients still experience asthma attacks requiring visits to emergency rooms and hospitalizations,” says NIAID Director Anthony S. Fauci, M.D. “The results of this study are extremely promising because they show that the addition of omalizumab to the NIH guidelines-based therapy for asthma offers improved asthma control and the potential to decrease the burden of this chronic disease in children and adolescents.”

In the United States, asthma affects approximately 18 million adults and 7 million children under the age of 18. Symptoms include wheezing, coughing, chest tightness and shortness of breath, any of which can be provoked by viral infections, allergens and air pollution. The number of asthma attacks rises in the spring and fall seasons when more allergens are in the air and the occurrence of respiratory viruses increases.

The study enrolled 419 children and youths, ages 6 to 20 years old, diagnosed with moderate to severe allergic asthma lasting more than one year. The children came from Boston, Chicago, Cleveland, Dallas, Denver, New York City, Tucson, Ariz. and Washington, D.C. Nearly all were minorities, including African-Americans (60 percent) and Hispanics (37 percent).

The primary goal of the study was to determine if adding omalizumab to NIH guidelines-based asthma therapy reduced the number of days that participants experienced any asthma-related symptoms. Another aim was to find out if the addition of omalizumab could also reduce the number of severe asthma attacks.

In addition to standard therapy, half of the participants were assigned at random to receive omalizumab, and the other half a placebo. Drug or placebo was delivered via an injection under the skin every two to four weeks over the 60-week period of study.

As the trial proceeded, participants returned to the clinic every three months for evaluation of their symptoms. As needed, their non-trial medications were adjusted according to the NIH asthma treatment guidelines.

At the end of the study, the investigators found that, overall, children and adolescents who received omalizumab had a 25 percent reduction in days with symptoms and a 30 percent reduction in asthma attacks compared with those who received placebo. Those who received omalizumab also had a 75 percent reduction in hospitalizations. Importantly, the spring and fall increases in asthma attacks that were seen in the participants receiving placebo were almost eliminated in those participants receiving omalizumab.

“The spike in asthma attacks in the fall, which is associated with colds and other viral airway infections, disappeared in the kids in the omalizumab group,” says William Busse, M.D., the principal investigator of ICAC and professor of medicine at the University of Wisconsin-Madison. “Because the drug specifically targets IgE, which is the antibody responsible for allergies, our observations show the possible interplay between allergies, respiratory viruses and IgE in provoking asthma attacks.”

Children and adolescents who responded the best to omalizumab had positive skin tests for cockroach allergy and high levels of cockroach allergen in their homes. In previous work by NIAID-supported researchers, the combination of cockroach allergy and exposure to cockroaches was found to be an important cause of asthma-related illness and hospitalization.

Omalizumab is a humanized monoclonal antibody, a pure form of a single protein, custom-made for use in humans, which binds to and blocks the activity of IgE, an important molecule in allergy. When allergens bind to IgE on the surface of certain immune cells, these cells release substances that cause allergic reactions. In the airways, these substances trigger the muscles to contract, trapping air inside the lungs and causing difficulty breathing.

“We continue searching for therapeutic strategies to reduce the enormous burden of asthma. Following on the findings reported here, ICAC studies now under way will help us to determine if adding omalizumab only during the period before fall seasonal asthma symptoms occur, rather than throughout the year, results in the same successful disease management,” says Daniel Rotrosen, M.D., director of NIAID’s Division of Allergy, Immunology and Transplantation, which oversees the ICAC program.

Omalizumab is approved in the United States for patients ages 12 and older with moderate to severe persistent allergic asthma. The drug is jointly developed by Genentech Inc., a member of the Roche group, under an agreement with Novartis Pharma AG. Patients who are interested in adding omalizumab to their current asthma treatment should speak with their health care professional. For more information about omalizumab, visit www.xolair.com.

The NIH Guidelines for the Diagnosis and Management of Asthma can be viewed or downloaded at www.nhlbi.nih.gov/guidelines/asthma/.

The National Center for Research Resources (NCRR), a part of NIH, provides laboratory scientists and clinical researchers with the resources and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR supports all aspects of translational and clinical research, connecting researchers, patients and communities across the nation. For more information, visit www.ncrr.nih.gov.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference: WW Busse et al. A randomized trial to evaluate the impact of the addition of omalizumab to guidelines based therapy of inner-city children and adolescents with asthma. New England Journal of Medicine. DOI: 10.1056/NEJMoa1009705 (2011).
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NIH study finds omalizumab relieves seasonal asthma attacks in youth, Wednesday, March 16, 2011 News Release – National Institutes of Health (NIH)

Genome-Wide Association Studies of Alcohol Depende... [Curr Psychiatry Rep. 2011] - PubMed result

Curr Psychiatry Rep. 2011 Jan 21. [Epub ahead of print]

Genome-Wide Association Studies of Alcohol Dependence and Substance Use Disorders.
Treutlein J, Rietschel M.

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim (CIMH), University of Heidelberg, J5, 68159, Mannheim, Germany,

jens.treutlein@zi-mannheim.de.

Abstract

Genome-wide association studies (GWAS) currently represent the most systematic approach to genetic research into complex disorders. They can detect associations of common variants in genomic regions in the absence of an a priori assumption. Most of the GWAS of addiction performed to date have focused on alcohol dependence or smoking behavior. Four GWAS of alcohol dependence have been published thus far, and only two single nucleotide polymorphisms have received modest support of replication in a subsequent study. Many more GWAS have been conducted for smoking behavior. One large, single GWAS and meta-analyses of the phenotype “smoking quantity” have generated convincing evidence for the contribution of variants in genes for cholinergic nicotinic receptor subunits. This article focuses on GWAS of alcohol addiction and provides an overview of GWAS of other substance abuse disorders.

PMID: 21253885 [PubMed - as supplied by publisher]
Genome-Wide Association Studies of Alcohol Depende… [Curr Psychiatry Rep. 2011] – PubMed result

Canadian Expert Group consensus recommendations: ... [Curr Oncol. 2011] - PubMed - NCBI

Curr Oncol. 2011 Aug;18(4):e180-4.

Canadian Expert Group consensus recommendations: KRAS testing in colorectal cancer.

Aubin F, Gill S, Burkes R, Colwell B, Kamel-Reid S, Koski S, Pollett A, Samson B, Tehfe M, Wong R, Young S, Soulières D.

Source

Centre Hospitalier de l’Université de Montréal, Montreal, QC.

Abstract

Monoclonal antibodies against the epidermal growth factor receptor (anti-egfr) when used in the treatment of metastatic colorectal cancer are associated with improved survival. Patients whose tumours harbor a KRAS mutation in codon 12 or 13 have been shown not to benefit from anti-egfr antibodies. The importance of KRAS mutation status in the management of patients with metastatic colorectal cancer has led to the elaboration of Canadian consensus recommendations on KRAS testing, with the aim of standardizing practice across Canada and reconciling testing access with the clinical demand for testing. The present guidelines were developed at a Canadian consensus meeting held in Montreal in April 2010. The best available evidence and expertise were used to develop recommendations for various aspects of KRAS testing, including indications and timing for testing, sample requirements, recommendations for reporting requirements, and acceptable turnaround times.

PMID:

21874108

[PubMed - in process]

PMCID: PMC3149550

Canadian Expert Group consensus recommendations: … [Curr Oncol. 2011] – PubMed – NCBI

Influenza B Viruses with Mutation in the Neuraminidase Active Site, North Carolina, USA, 2010–11 - Vol. 17 No. 11 - November 2011 - Emerging Infectious Disease journal - CDC

Volume 17, Number 11—November 2011

Dispatch

Influenza B Viruses with Mutation in the Neuraminidase Active Site, North Carolina, USA, 2010–11

Article Contents

• The Study


• Conclusions


• Acknowledgments


• References


• Figure


• Table 1


• Table 2


• Suggested Citation

Katrina Sleeman, Tiffany G. Sheu, Zack Moore, Susan Kilpatrick, Shikha Garg, Alicia M. Fry, and Larisa V. Gubareva 

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (K. Sleeman, T.G. Sheu, S. Garg, A.M. Fry, L.V. Gubareva); Battelle, Atlanta (T.G. Sheu); North Carolina Department of Health and Human Services, Raleigh, North Carolina, USA (Z. Moore, S. Kilpatrick)

Suggested citation for this article

Abstract

Oseltamivir is 1 of 2 antiviral medications available for the treatment of influenza B virus infections. We describe and characterize a cluster of influenza B viruses circulating in North Carolina with a mutation in the neuraminidase active site that may reduce susceptibility to oseltamivir and the investigational drug peramivir but not to zanamivir.

Influenza B viruses are responsible for sporadic seasonal influenza illness and can be associated with severe illness and death. In the United States, there are 2 classes of antiviral drugs licensed by the Food and Drug Administration for treatment of influenza infections. The adamantanes are ineffective against influenza B viruses, which limits the available antiviral options to 2 neuraminidase inhibitors (NAIs), inhaled zanamivir and oral oseltamivir. Influenza B viruses seem to have reduced susceptibility to NAIs compared with influenza A viruses on the basis of neuraminidase inhibition (NAI) assays (1,2). Furthermore, in clinical studies, changes conferring either resistance or reduced susceptibility to NAIs have been identified in the neuraminidase (NA) of influenza B viruses isolated from patients after treatment (3–6). Although the use of an antiviral agent can lead to the development of drug resistance, influenza B viruses with a reduced NAI susceptibility have also been recovered from patients with no history of exposure (5,7–10). It is therefore plausible that such mutations may be naturally occurring within the NA of influenza B viruses.

The Study

During routine influenza antiviral susceptibility surveillance, an influenza B virus, B/North Carolina/11/2010, with reduced susceptibility to oseltamivir and the investigational NAI peramivir was detected by using the fluorescent NAI assay based on IC₅₀ values (amount of NAI required to inhibit 50% of viral NA activity). According to the current algorithm, viruses with elevated IC₅₀ values, when compared with a drug-susceptible control reference virus, are further investigated by using either conventional sequencing or pyrosequencing. Sequence analysis for the NA gene of B/North Carolina/11/2010 showed a novel substitution, present as a mixed population, of isoleucine (I) to valine (V) at position 221 (B NA numbering corresponds to 222 in N2 NA amino acid numbering). A substitution of I to threonine (T) at 221 has previously been associated with reduced susceptibility to NAIs in influenza B viruses (1,5,9). Moreover, reduced susceptibility to oseltamivir has been reported in viruses with variation at the corresponding residue (223, N1 NA numbering) in the pandemic (H1N1) 2009 virus (11,12) and in influenza A/H5N1 (13) and A/H3N2 viruses (14).
Subsequent fluorescent NAI testing of isolates recovered during surveillance showed a cluster of 14 influenza B viruses from North Carolina with elevated oseltamivir IC₅₀ values compared with reference wild-type influenza B, wild-type pandemic (H1N1) 2009, and wild-type A(H3N2) viruses; a similar trend was observed for peramivir IC₅₀ values (Table 1). When comparing the pandemic (H1N1) 2009 virus with the oseltamivir-resistance conferring H275Y substitution and an influenza A (H3N2) virus with the oseltamivir-resistance conferring E119V substitution, the North Carolina B viruses showed intermediate susceptibility (Table 1). The influenza B virus carrying the R152K substitution was resistant to all NAIs compared with the influenza B viruses with I221V (Table 1). In the chemiluminescent NAI assay, the oseltamivir IC₅₀ values for the I221V variants were greater than that for the E119V influenza A (H3N2) virus variant, which has been associated with oseltamivir resistance (Table 1) (15). Pyrosequencing analysis showed I221V as well as wild-type (I221) in the propagated viruses used in the NAI assays. The presence of wild-type variants is likely to reduce IC₅₀ values.

A total of 258 influenza B virus isolates from domestic and foreign laboratories submitted to the Centers for Disease Control and Prevention for routine surveillance were screened for the I221V substitution by using single-nucleotide polymorphism (SNP) pyrosequencing analysis (10). All viruses were wild type at this position, with the exception of the 14 viruses from North Carolina with reduced susceptibility in the NAI assay (Table 2). All 14 viruses were collected from patients in North Carolina during November 2010 through February 2011.

Because some susceptibility-altering NA mutations have been shown to arise from virus propagation in tissue culture (15), pyrosequencing analysis at position 221 in available matching clinical specimens was performed to rule out cell culture selection. The I221V substitution was identified in the 9 available matching clinical specimens (Table 2). Notably, most of the clinical specimens contained higher percentages of the V221 variant compared with the matching virus isolates, which may indicate a potential selective pressure for the wild-type variant (I221) in cell culture.
An epidemiologic investigation and enhanced surveillance was initiated in cooperation with the North Carolina Department of Health and Human Services. Of 220 patients with influenza B virus infections in North Carolina during November 2010 through March 2011, specimens from 209 patients underwent pyrosequencing analysis. Specimens from 45 (22%) patients from 13 counties contained the I221V mutation based on SNP pyrosequencing analysis; patient median age was 12 years (range 6 months–60 years). Among 199 patients with available antiviral treatment information, specifically for oseltamivir use, none had documented exposure to the virus before specimen collection. This finding may indicate that influenza B viruses carrying the I221V mutation are co-circulating with wild-type influenza B viruses in North Carolina.

Conclusions

Although the NA change I221V has been seen among the N1 NA subtype of influenza A viruses (1,13), such a change has not been reported in influenza B viruses. Amino acid 221 is known to be a highly conserved residue of the NA enzyme active site. To date, all influenza B viruses with the I221V substitution appear to be limited geographically; however, monitoring is ongoing. Although oseltamivir IC₅₀ values obtained with the influenza B viruses carrying the I221V substitution are similar to those seen with influenza A(H3N2) viruses carrying the oseltamivir-resistance conferring substitution E119V (Table 1), the clinical significance of the altered susceptibility associated with I221V in influenza B viruses is unknown at this time and warrants further investigation. Furthermore, such variant-dependent elevated IC₅₀ values highlight the need for establishing a correlation between laboratory-determined IC₅₀ values and clinical resistance.

Figure

Figure. Phylogenetic analysis of A) hemagglutinin and B) neuraminidase genes of Victoria lineage type B influenza viruses (n = 89). Red indicates the 2010−2011 Northern Hemisphere vaccine strain; blue indicates the cluster…

Phylogenetic analysis of the hemagglutinin gene of the North Carolina B viruses carrying the I221V change in the NA is consistent with the B Victoria lineage (Figure, panel A). Similarly, phylogenetic analysis of the NA gene demonstrated that the North Carolina B viruses with the I221V change also belong to the B Victoria lineage and form a cluster because of the I221V substitution (Figure, panel B). As of March 2011, of the 438 influenza B viruses isolated in the United States, 94% were antigenically characterized as B/Brisbane/60/2008-like (B-Victoria lineage) (www.cdc.gov/flu/weekly). The cluster of North Carolina influenza B viruses carrying the I221V mutation antigenically matched the current influenza B component of the seasonal influenza vaccine. Data collected from an ongoing epidemiologic and clinical correlation study will be the subject of a more detailed future report.

Dr Sleeman is an associate service fellow in the Molecular Epidemiology Team of the Influenza Division at the Centers for Disease Control and Prevention in Atlanta, Georgia. Her research interests are negative-strand RNA viruses and antiviral drugs, with a particular emphasis on influenza viruses and antiviral drug resistance.

Acknowledgments

We thank all collaborators in the World Health Organization Global Influenza Surveillance Network, including the National Influenza Centers, for submission of isolates. We also thank members of the Molecular Epidemiology Team, the Virus Reference Team, and the Sequencing Group of the Influenza Division at the Centers for Disease Control and Prevention for contributions with this project.

References

1. Monto  AS, McKimm-Breschkin  JL, Macken  C, Hampson  AW, Hay  A, Klimov  A, Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother. 2006;50:2395–402. DOIPubMed


2. Carr  S, Ilyushina  NA, Franks  J, Adderson  EE, Caniza  M, Govorkova  EA, Oseltamivir-resistant influenza A and B viruses pre- and post-viral therapy in children and young adults with cancer. Pediatr Infect Dis J. 2011;30:284–8. DOIPubMed


3. Kawai  N, Ikematsu  H, Iwaki  N, Maeda  T, Satoh  I, Hirotsu  N, A comparison of the effectiveness of oseltamivir for the treatment of influenza A and influenza B: a Japanese multicenter study of the 2003–2004 and 2004–2005 influenza seasons. Clin Infect Dis. 2006;43:439–44. DOIPubMed


4. Gubareva  LV, Matrosovich  MN, Brenner  MK, Bethell  RC, Webster  RG. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis. 1998;178:1257–62. DOIPubMed


5. Hatakeyama  S, Sugaya  N, Ito  M, Yamazaki  M, Ichikawa  M, Kimura  K, Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. JAMA. 2007;297:1435–42. DOIPubMed


6. Sugaya  N, Tamura  D, Yamazaki  M, Ichikawa  M, Kawakami  C, Kawaoka  Y, Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza infection in children. Clin Infect Dis. 2008;47:339–45. DOIPubMed


7. Hurt  AC, Kimm-Breschkin  JL, McDonald  M, Barr  IG, Komadina  N, Hampson  AW. Identification of a human influenza type B strain with reduced sensitivity to neuraminidase inhibitor drugs. Virus Res. 2004;103:205–11. DOIPubMed


8. Hurt  AC, Iannello  P, Jachno  K, Komadina  N, Hampson  AW, Barr  IG, Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient. Antimicrob Agents Chemother. 2006;50:1872–4. DOIPubMed


9. Sheu  TG, Deyde  VM, Okomo-Adhiambo  M, Garten  RJ, Xu  X, Bright  RA, Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother. 2008;52:3284–92. DOIPubMed


10. Sheu  TG, Deyde  VM, Garten  RJ, Klimov  AI, Gubareva  LV. Detection of antiviral resistance and genetic lineage markers in influenza B virus neuraminidase using pyrosequencing. Antiviral Res. 2010;85:354–60. DOIPubMed


11. Nguyen  HT, Fry  AM, Loveless  PA, Klimov  AI, Gubareva  LV. Recovery of a multidrug-resistant strain of pandemic influenza A 2009 (H1N1) virus carrying a dual H275Y/I223R mutation from a child after prolonged treatment with oseltamivir. Clin Infect Dis. 2010;51:983–4. DOIPubMed


12. van der Vries  E, Stelma  FF, Boucher  CAB. Emergence of a multidrug-resistant pandemic influenza A(H1N1) virus. N Engl J Med. 2010;363:1381–2. DOIPubMed


13. Hurt  AC, Holien  JK, Barr  IG. In vitro generation of neuraminidase inhibitor resistance in A(H5N1) influenza viruses. Antimicrob Agents Chemother. 2009;53:4433–40. DOIPubMed


14. Baz  M, Abed  Y, McDonald  J, Boivin  G. Characterization of a multidrug-resistant influenza A/H3N2 virus shed during 1 year by an immunocompromised child. Clin Infect Dis. 2006;43:1555–61. DOIPubMed


15. Okomo-Adhiambo  M, Demmler-Harrison  GJ, Deyde  VM, Sheu  TG, Xu  X, Klimov  AI, Detection of E119V and E119I mutations in influenza A (H3N2) viruses isolated from an immunocompromised patient: challenges in diagnosis of oseltamivir resistance. Antimicrob Agents Chemother. 2010;54:1834–41. DOIPubMed

Figure

• Figure. Phylogenetic analysis of A) hemagglutinin and B) neuraminidase genes of Victoria lineage type B influenza viruses (n = 89). Red indicates the 2010−2011 Northern Hemisphere vaccine strain; blue indicates the…

Tables

• Table 1. Comparison of influenza virus susceptibility, North Carolina, USA, 2010−11 influenza seasons


• Table 2. Percentage composition of isoleucine and valine at position 221 in the neuraminidase of virus isolates and clinical specimens with reduced susceptibility to oseltamivir and peramivir, North Carolina, USA, 2010−11 influenza season…

Suggested citation for this article: Sleeman K, Sheu TG, Moore Z, Kilpatrick S, Garg S, Fry AM, et al. Influenza B viruses with mutation in the neuraminidase active site, North Carolina, USA, 2010−11. Emerg Infect Dis [serial on the Internet]. 2011 Nov [date cited]. http://dx.doi.org/10.3201/eid1711.110787

DOI: 10.3201/eid1711.110787

Influenza B Viruses with Mutation in the Neuraminidase Active Site, North Carolina, USA, 2010–11 – Vol. 17 No. 11 – November 2011 – Emerging Infectious Disease journal – CDC

The Pharmacogenetic Rescue of Side-Lined Anticance... [Ann Pharmacother. 2011] - PubMed result

Ann Pharmacother. 2011 Feb 8. [Epub ahead of print]

The Pharmacogenetic Rescue of Side-Lined Anticancer Drugs to the Front-Line: Gefitinib as a Case Example (February).
Li-Wan-Po A, Farndon PA, Kobayashi S, Mitsudomi T, Potter VA.

National Genetics Education and Development Centre, Morris House, c/o Birmingham Women’s Hospital, Edgbaston, Birmingham, England.

Abstract

OBJECTIVE: To illustrate the increasing importance of pharmacogenetics in drug development and clinical practice through a critical analysis of the validation and licensing of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, as a treatment for non-small cell lung cancer (NSCLC).

DATA SOURCES: Journal articles and the “grey” literature were identified through a systematic search of MEDLINE (to June 2010) and the Web sites of the major drug regulators. References identified through the reference lists of major published reviews of gefitinib and Erb receptors, including EGFR, were also reviewed.

STUDY SELECTION AND DATA EXTRACTION: A broad appraisal of the titles and abstracts of articles on gefitinib and tyrosine kinase inhibitors in lung cancer was undertaken to identify pertinent concepts and relevant publications for further analysis. Articles deemed particularly relevant were retrieved for detailed appraisal. Dossiers on the licensing of gefitinib from the Food and Drug Administration Web site and major published reviews were retrieved. Relevant pharmacogenetic issues were identified and the clinical studies addressing these were evaluated.

DATA SYNTHESIS: Initial promising trial data for gefitinib in NSCLC led to its conditional marketing approval. When the drug’s efficacy was not confirmed in a pivotal Phase 3 trial, its prescribing was restricted. Subsequent discovery of activating mutations in the tyrosine kinase domain of EGFR led to further retrospective and prospective evaluation of the drug in patients with those mutations. The new evidence was sufficiently robust to persuade the drug regulators to license the drug as first-line treatment for patients with locally advanced or metastatic NSCLC who test positive for those mutations.

CONCLUSIONS: Pharmacogenetic evidence has played a key role in rescuing gefitinib for front-line treatment of NSCLC. This case-example portends what will be increasingly likely scenarios in the regulation and clinical validation of targeted drug therapies.

PMID: 21304034 [PubMed - as supplied by publisher]

The Pharmacogenetic Rescue of Side-Lined Anticance… [Ann Pharmacother. 2011] – PubMed result

NIH statement on Food Allergy Awareness Week 2011—May 8–14, May 2, 2011 News Release - National Institutes of Health (NIH)

For Immediate Release
Monday, May 2, 2011 Contact:
NIAID Office of Communications
National Institute of Allergy and Infectious Diseases Home Page
301-402-1663

NIH statement on Food Allergy Awareness Week 2011—May 8–14
Daniel Rotrosen, M.D., and Anthony S. Fauci, M.D.
National Institute of Allergy and Infectious Diseases
National Institutes of Health

We observe Food Allergy Awareness Week this year acknowledging those who live every day with the concern that their exposure to certain foods may have the potential to trigger a life-threatening allergic reaction. The Centers for Disease Control and Prevention estimates that food allergy affects 5 percent of children under the age of 5 and 4 percent of older children in the United States. Scientists believe that the percentage of adults with food allergy is similar to that observed in older children. Until we can better understand why food allergy develops in one person and not another, and find out how to prevent and possibly cure food allergy, research and education are two of the best tools to help people living with this disorder.

In this regard, we at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, were gratified to work with 34 professional organizations, patient advocacy groups and federal agencies to develop new national guidelines for the diagnosis and management of food allergy, published in December 2010. The Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel [Food Allergy Clinical Practice Guidelines] reflect long-awaited agreement across medical specialties about what food allergy is and how to diagnose and treat it. This summer, NIAID will publish a summary of the key points for patients.

The most common food allergens affecting Americans are milk, egg, peanut, tree nuts, soy, wheat, fish and crustacean shellfish. Currently, there is no way to prevent or cure food allergy. Food-allergic people must avoid certain foods and constantly guard against accidental exposures to hidden food allergens. Available medications can treat symptoms — which range from itching to a life-threatening drop in blood pressure — but only after the allergic reaction to food occurs.

Food Allergy Awareness Week was established in 1997 by the Food Allergy and Anaphylaxis Network (FAAN), a patient and family advocacy and education organization. This year, the Food Allergy Initiative, another advocacy group, joins FAAN in recognizing the commemorative week. Both FAAN and FAI participated in the development of the food allergy guidelines.

As the lead NIH institute for food allergy research, NIAID supports basic research and clinical studies to better understand the causes of food allergy and develop new preventions and treatments. Many of these efforts focus on how the immune systems of people with food allergy might be modified to eliminate their allergic reactions to food. Other studies are examining food allergy-associated allergic diseases, such as eosinophilic esophagitis, a condition that occurs when eosinophils (a type of immune cell associated with allergic reactions) accumulate in the esophagus, and are studying how genes, the environment and other allergic diseases may affect the development, persistence and severity of food allergy.

In 2010, NIAID renewed funding for two programs in food allergy research: the Consortium for Food Allergy Research (CoFAR) and Exploratory Investigations in Food Allergy. CoFAR conducts laboratory and clinical studies to test promising immune interventions to prevent and treat the condition and to determine the role of genetic and environmental factors in causing food allergy. Currently CoFAR is evaluating possible ways to treat people with food allergies, such as peanut allergy, by exposing them to the food allergen delivered as a liquid placed under the tongue, as a suppository or as part of a specialized skin patch. Exploratory Investigations in Food Allergy, which started in 2008 and is co-funded by FAAN and FAI, supports projects to improve understanding of food allergy. Approximately 29 grants have been awarded through this initiative, 90 percent of which fund investigators new to the field of food allergy research.

During Food Allergy Awareness Week, we recognize the people who live with food allergy, and we thank the patients and families who have given their time to participate in food allergy clinical trials. Their involvement in clinical research has contributed to the development of improved ways to prevent and treat this condition so that all people affected by food allergy can enjoy a better quality of life.

For more information about food allergy, visit NIAID’s Food Allergy Web portal: Food Allergy.

Dr. Fauci is Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland. Dr. Daniel Rotrosen is Director of the Division of Allergy, Immunology and Transplantation at NIAID.

Media inquiries can be directed to the NIAID Office of Communications at 301-402-1663, niaidnews@niaid.nih.gov.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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NIH statement on Food Allergy Awareness Week 2011—May 8–14, May 2, 2011 News Release – National Institutes of Health (NIH)

Food Allergy Clinical Practice Guidelines:
Food Allergy Clinical Practice Guidelines

What"s new in non-small cell lung cancer for patho... [Pathology. 2011] - PubMed result

Pathology. 2011 Feb;43(2):103-15.
What’s new in non-small cell lung cancer for pathologists: the importance of accurate subtyping, EGFR mutations and ALK rearrangements.

Cooper WA, O’toole S, Boyer M, Horvath L, Mahar A.

*Tissue Pathology and Diagnostic Oncology, Australia †Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, Australia ‡Discipline of Pathology, School of Medicine, University of Western Sydney, Sydney, Australia §Garvan Institute of Medical Research, Darlinghurst, Australia ||Sydney Medical School, University of Sydney, Sydney, Australia ¶St Vincent’s Clinical School, University of New South Wales, Sydney, Australia.

Abstract

In the past, the only critical point of distinction in the pathological diagnosis of lung cancer was between small cell and non-small cell lung cancer (NSCLC). The emergence of new targeted therapies and clinical trials demonstrating differing efficacy and toxicity of treatments according to specific histological subtypes of NSCLC, has resulted in an increasing need for improvements in pathological diagnosis. Accurate distinction between adenocarcinoma and squamous cell carcinoma is now critical as histological subtyping has the potential to influence clinical decision making and impact on patient outcome. While morphological criteria remain the most important feature to distinguish NSCLC subtypes, use of mucin and immunohistochemical stains (TTF-1, p63 and CK5/6) can be of assistance in difficult small biopsy cases. With the emergence of selective kinase inhibitors targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), there is a corresponding need to identify the subset of NSCLCs harbouring specific genetic mutations associated with sensitivity to these agents, almost all of which are found in adenocarcinomas. In this review, the importance of accurately subtyping NSCLC is discussed, along with a suggested approach for distinguishing histological subtypes in small biopsy specimens. The significance of EGFR and ALK mutations in NSCLC and the impact of these genotypes on pathology and clinical practice are also reviewed.

PMID: 21233671 [PubMed - in process]
What’s new in non-small cell lung cancer for patho… [Pathology. 2011] – PubMed result

Genome-Wide Association Studies: Is there a Genoty... [Curr Pharm Des. 2011] - PubMed result

Curr Pharm Des. 2011 Feb 28. [Epub ahead of print]

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?
Abbatecola AM, Oliveri F, Corsonello A, Antonicelli R, Corica F, Lattanzio F.

Italian National Research Center on Aging (INRCA), Scientific Direction, Ancona, Italy. angela_abbatecola@libero.it.

Abstract
There is a dramatic increase in the number of elderly persons on a worldwide scale with an increase in chronic comorbidities, especially type 2 diabetes (T2DM) and dementia. Although cognitive faculties commonly deteriorate in non-diabetic persons as they age, several studies have concluded that diabetes is uniquely associated with cognitive decline and is associated with a two-fold risk of Alzheimer’s Disease (AD). Studies have also suggested that good glycemic has shown to improve cognitive status, however whether the use of specific anti-diabetic oral agents may play an additional role in controlling against cognitive deterioration is unknown. In addition, excitotoxicity from the overstimulation of glutamate receptors is considered a major cause of neuron death in AD and statins may be promising agents for protecting against memory loss. Possible pathophysiologic mechanisms common to both T2DM and AD are glucose toxicity and a direct effect of insulin on amyloid metabolism. In fact, AD and T2DM have comparable pathological features in the islet and brain (amyloid derived from amyloid β protein (β-amyloid) in the brain in AD and islet amyloid derived from islet amyloid polypeptide in the pancreas in T2DM). Evidence is growing linking precursors of amyloid deposition in the brain and pancreas to the pathogenesis of AD and T2DM, respectively. Indeed, the need to identify agents capable of correcting such pathological features may in turn significantly protect against the accumulation of β-amyloid in the brain, known to interfere with correct cognitive function. Cholesterol may also be directly involved in β-amyloid aggregation: abnormal oxidative metabolites such as cholesterol-derived aldehydes can modify β-amyloid, firstly promoting Schiff base formation, then accelerating the early stages of amyloidogenesis. At the moment, genome-wide association studies (GWAS) have begun to elucidate the genetic architecture of chronic diseases including, T2DM and AD. Thus, one of the challenges for a successful GWAS in the future will be to identify a genotype in older persons with T2DM for good drug response, which in turn may protect against cognitive decline and AD. The literature has suggested that the use of insulin sensitizers and statins are correlated with a lower rate of cognitive decline in older persons. In this paper, we will explore recent findings regarding diverse single nucleotide polymorphisms from GWAS on T2DM, AD and both. We will also shed light on future pathways, as the basis of improving drug and diagnostics development for a better integration of genetic studies for precise drug-development focusing on the role of genetic variation in maintaining metabolic control and cognitive performance.

PMID: 21352095 [PubMed - as supplied by publisher]

Genome-Wide Association Studies: Is there a Genoty… [Curr Pharm Des. 2011] – PubMed result