Defective Viral Genomes May Indicate Greater Flu Virus Severity

MedicalResearch.com Interview with:
Ana Falcón
Department of Molecular and Cellular Biology
National Center for Biotechnology
Spanish National Research Council (CNB-CSIC)
Madrid, Spain

MedicalResearch.com: What is the background for this study?

Response: Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the elderly and patients with certain medical conditions. Infection of apparently healthy individuals nonetheless accounts for many severe disease cases and deaths, suggesting that viruses with increased pathogenicity co-circulate with pandemic or epidemic viruses.

IAV virulence and pathogenesis are dependent on complex, multigenic mechanisms involving the viral genetic characteristics, the host conditions, the virus-host interactions, and the host response to the infection. Influenza virus pathogenicity has been studied in depth for many years, and several amino acid changes have been identified as virulence determinants, however, a general pathogenicity determinant has not been characterized.

A proportion of influenza virus particles have defective genome RNAs (Defective Viral Genomes-DVGs) due to internal deletions of viral segments. The DVGs have the 3’ and 5’ ends of the parental RNA segments, and most have a single, large central deletion that generates viral RNAs of 180–1000 nucleotides. The presence of DVGs potentiates the host response in cultured cells and in animal models and leads to attenuated infection, possibly through recognition of double-stranded RNA by receptors that activate antiviral signaling cascades.

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Pandemic Flu May Increase Risk of Type 1 Diabetes In Genetically Predisposed Patients

MedicalResearch.com Interview with:
Paz Lopez-Doriga Ruiz MD, PhD candidate Norwegian Institute of Public Health Department of Non Communicable Diseases OsloPaz Lopez-Doriga Ruiz MD, PhD candidate

Norwegian Institute of Public Health
Department of Non Communicable Diseases
Oslo 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Some case reports have linked pandemic influenza to the development of type 1 diabetes. Other studies have suggested that also respiratory infections may contribute to type 1 diabetes risk.

 Our findings supports a suggested role of respiratory infections in the etiology of type 1 diabetes and influenza virus could be a contributing factor to the development of clinical diabetes, due to stress and inflammation in predisposed individuals.

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New Rapid Flu Tests Are Simple, Fast and Accurate

MedicalResearch.com Interview with:

Jesse Papenburg, MD MSc FRCPC FRQS Clinical Research Scholar Assistant Professor of Pediatrics, McGill University Div. of Pediatric Infectious Diseases, Dept. of Microbiology Montreal Children’s Hospital Montreal, QC

Dr. Papenburg

Jesse Papenburg, MD MSc FRCPC
FRQS Clinical Research Scholar
Assistant Professor of Pediatrics, McGill University
Div. of Pediatric Infectious Diseases, Dept. of Microbiology
Montreal Children’s Hospital
Montreal, QC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Influenza viruses cause yearly epidemics of acute respiratory illness affecting 5 to 30 percent of the population. Diagnosing influenza on the basis of only clinical symptoms is difficult because its manifestations vary and are nonspecific. Reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard for flu diagnosis, but these tests must be sent to a laboratory and have turnaround times that extend beyond the clinical encounter. Rapid and accurate diagnosis of influenza has the potential to improve patient outcomes and decrease health care costs.

Since 2011, two novel classes of rapid influenza diagnostic assays i.e., with results available in <30 minutes, have been commercialized with claims of improved sensitivities based on technological improvements: 1) automated immunochromatographic antigen detection tests (digital immunoassays, DIAs) and 2) rapid nucleic acid amplification tests (NAATs).

Our systematic review and meta-analysis synthesized the available evidence and compared the diagnostic accuracy of commercially available rapid tests for the detection of influenza A and B infection:

  • Overall, the rapid tests displayed very high specificities (≥98%). Physicians can therefore diagnose influenza with confidence on the basis of a positive RIDT, DIA, or rapid NAAT result.
  • The pooled sensitivities for DIAs (80.0% for influenza A and 76.8% for influenza B) and rapid NAATs (91.6% for influenza A and 95.4% for influenza B) are markedly higher than those for RIDTs (54.4% for influenza A and 53.2% for influenza B).

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Nasal Spray Flu Vaccine Ineffective and Not Recommended

MedicalResearch.com Interview with:

Michael Jackson  PhD, MPH Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network

Dr. Jackson

Michael Jackson  PhD, MPH
Kaiser Permanente Washington Health Research Institute (KPWHRI) principal investigator for the United States Influenza Vaccine Effectiveness Network 

MedicalResearch.com: What is the background for this study?

  • Response: Each year, Kaiser Permanente Washington is one of five sites across the country that participate in the United States Influenza Vaccine Effectiveness Network. The Network reports its early interim results in the MMWRand presents additional interim results to the Advisory Committee on Immunization Practices (ACIP)This New England Journal of Medicine publication is an update of those interim results.
  • The findings in this New England Journal of Medicine are special because prior randomized controlled trials indicated that the nasal spray vaccine (FluMist)—also called live attenuated influenza vaccine (LAIV)—would work well to protect children and teens from the flu, whereas in actual practice we found that the flu shot worked much better, particularly against the predominant strain, A(H1N1)pdm09.
  • The nasal spray vaccine was first seen to be less effective for young children than the flu shot in 2013-2014 for the A(H1N1)pdm09 virus strain. In response, the A(H1N1)pdm09 virus strain used in the nasal spray vaccine was changed for the 2015-2016 influenza season. The 2016/17 season was the first since 2015-2016 to be dominated by the A(H1N1)pdm09 virus, making this our first opportunity to evaluate the updated nasal spray vaccine.
  • The Influenza Vaccine Effectiveness Network evaluated the impact of this change as part of our estimates of influenza vaccine effectiveness in 2015-2016. Preliminary findings from this study were presented to the ACIP in June 2016, which led to the nasal spray vaccine not being recommended in 2016-2017 in the US, although the nasal spray vaccine remains licensed in the US. In 2016-2017, the LAIV A(H1N1)pdm09 vaccine strain was unchanged from 2015-2016.

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Dissolvable Microneedle Patches Can Be Vaccination Game Changer

MedicalResearch.com Interview with:
Dr Nadine G Rouphael MD
Associate Professor of Medicine, Emory University
Director of the VTEU and HIPC networks at the
Hope Clinic of the Emory Vaccine Center
Decatur GA 30030, USA

MedicalResearch.com: What is the background for this new technology and study? What are the main findings?

Response: Different groups including a group of researchers at Georgia Tech have been working on the microneedle technology for more than 20 years. The dissolvable microneedle patches are already used in several cosmetic products and drugs. However, vaccination with microneedle patches has been studied mostly in animals.

Our phase 1 trial published this week in The Lancet showed that vaccination with the microneedle patches was safe, with no related serious adverse events reported. Local skin reactions to the patches were mostly mild itching and faint redness that lasted two to three days. No new chronic medical illnesses or influenza-like illnesses were reported with either the patch or the injection groups. Antibody responses generated by the vaccine, as measured through analysis of blood samples, were similar in the groups vaccinated using patches and those receiving intramuscular injection, and these immune responses were still present after six months. When asked after immunization, more than 70 percent of patch recipients reported they would prefer patch vaccination over injection or intranasal vaccination for future vaccinations.

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Efficacy of Recombinant Flu Vaccine in Adults 50 Years of Age or Older 

MedicalResearch.com Interview with:

Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT 

Dr. Dunkle

Lisa M. Dunkle, M.D.
Chief Medical Officer
Protein Sciences Corporation
1000 Research Parkway
Meriden, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one.

These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future.

The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.”

Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases

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Study Finds No Link Between First Trimester Influenza Vaccination and Major Structural Birth Defects

MedicalResearch.com Interview with:

Dr. Elyse Olshen Kharbanda, MD MPH HealthPartners Institute Minneapolis, MN

Dr. Kharbanda

Dr. Elyse Olshen Kharbanda, MD MPH

HealthPartners Institute
Minneapolis, MN

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women who get the flu are at an increased risk for severe illness. To protect pregnant women, the Advisory Committee on Immunization Practices recommends women receive inactivated influenza vaccine (IIV) during any trimester of their pregnancy.

This study used data from the Vaccine Safety Datalink to evaluate if there was an increased risk for selected major structural birth defects for infants whose mothers received IIV in the first trimester of pregnancy versus infants who were unexposed to IIV. Among over 425,000 live births, including 52,856 whose mothers received IIV during first trimester, we evaluated risks for major structural birth defects.  In this large observational study, we did not observe increased risks for major structural birth defects in offspring following first trimester maternal inactivated influenza vaccine exposure.

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Flu Treatment With Neuraminidase Inhibitors During Pregnancy Not Linked To Birth Defects

MedicalResearch.com Interview with:

Dr. Sophie Graner Department of Women's and Childrens Health Karolinska Institute, Stockholm, Sweden

Dr. Graner

Dr. Sophie Graner
Department of Women’s and Childrens Health
Karolinska Institute, Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations.
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First Childhood Exposure Determines How Sick You Get From Flu As Adult

MedicalResearch.com Interview with:
Katelyn M. Gostic and
Monique Ambrose

Department of Ecology and Evolutionary Biology
University of California
Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Monique Ambrose: Influenza pandemics pose a serious, recurrent threat to human public health. One of the most probable sources of future pandemic influenza viruses is the pool of influenza A virus (IAV) subtypes that currently circulate in non-human animals. It has traditionally been thought that the human population is immunologically naïve and unprotected against these unfamiliar subtypes. However, our work suggests that an individual ‘imprints’ to the influenza A virus (IAV) encountered in early childhood in such a way that they retain protection against severe disease if they later encounter a novel IAV subtype that belongs to the same genetic group as their first exposure.

Our research looked at human cases of H5N1 and H7N9, two avian IAV subtypes of global concern, to investigate what factors most strongly predicted risk of severe disease. The most striking explanatory factor was childhood IAV imprinting: our results suggest that individuals who had childhood imprinting on an IAV in the same genetic group as the avian IAV they encountered later in life experienced 75% protection against severe disease and 80% protection against death.

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Many Children With Asthma Still Not Receiving Flu Vaccine

MedicalResearch.com Interview with:

Deepa Patadia, MD Wexner Medical Center The Ohio State University

Dr. Deepa Patadia

Deepa Patadia, MD
Wexner Medical Center
The Ohio State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Influenza vaccination is recommended every autumn for all children 6 months of age and older. It is particularly important for children with asthma, who are at high risk of hospitalization or severe illness if they contract influenza infection. The rates of influenza vaccination in children with asthma have not previously been well studied, but Healthy People 2020 has set a target goal to vaccinate 70% of all children for influenza. We found that rates of vaccination in our large primary care population was much lower than the target rate, with less than 50% of all children receiving the vaccine each year over a 5 year period; however rates were higher in children with asthma, albeit still only at 55%.

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Live Nasal and Injectable Flu Vaccines Had Similar Effectiveness in Pediatric Study

MedicalResearch.com Interview with:

Dr. Mark Loeb BSc (McGill), MD (McGill), MSc (McMaster), FRCPC Professor, Department of Pathology and Molecular Medicine Joint Member, Dept of Clinical Epidemiology & Biostatistics Division Director, Infectious Diseases, McMaster University

Dr. Mark Loeb

Dr. Mark Loeb
BSc (McGill), MD (McGill), MSc (McMaster), FRCPC
Professor, Department of Pathology and Molecular Medicine
Joint Member, Dept of Clinical Epidemiology & Biostatistics
Division Director, Infectious Diseases, McMaster University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is that in the U.S, the Advisory Committee on Immunization Practices (ACIP), the committee that advises the CDC on vaccination policy, decided this June not to recommend LAIV (nasal live vaccine) for children. This is because of non-randomized studies conducted in the U.S suggesting that the vaccine was ineffective. This was an unprecedented decision in influenza vaccine policy making for children.

Our study, a randomized, blinded, controlled trial, which is the most rigorous type of study design, conducted over 3 years (2012-13, 2013-2014, 2014-2015 influenza seasons), showed in fact very similar protection for children and their communities for the live and inactivated vaccines. We conducted the study in the Hutterite community of Western Canada which allowed us to compare the effect of the vaccines in entire communities. That is, we were able to study the direct effect and the indirect effect of these vaccines.

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Flu Vaccination During Pregnancy Protects Mother and Infant

MedicalResearch.com Interview with:

Marta C. Nunes, PhD DST/NRF:Vaccine Preventable Diseases Respiratory and Meningeal Pathogens Research Unit University of Witwatersrand Chris Hani Baragwanath Academic Hospital Soweto, South Africa

Dr. Marta Nunes

Marta C. Nunes, PhD
DST/NRF:Vaccine Preventable Diseases
Respiratory and Meningeal Pathogens Research Unit
University of Witwatersrand
Chris Hani Baragwanath Academic Hospital
Soweto, South Africa

MedicalResearch.com: What is the background for this study?

Response: Young infants are at increased risk for influenza infection and hospitalizations associated with influenza infection. While active annual influenza vaccination is the most efficient mode for the prevention of influenza infection, current vaccines are poorly immunogenic and not licensed for use in infants

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Flu Vaccination During Pregnancy Protects Both Mother and Baby

MedicalResearch.com Interview with:

Julie H. Shakib, DO, MS, MPH Assistant Professor of Pediatrics | University of Utah Medical Director | Well Baby and Intermediate Nursery Salt Lake City

Dr. Julie Shakib

Julie H. Shakib, DO, MS, MPH
Assistant Professor of Pediatrics | University of Utah
Medical Director | Well Baby and Intermediate Nursery
Salt Lake City 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Shakib: Immunization against influenza in the first six months of life is ineffective  due to an immature immune response. Passive protection via maternal immunization offers an alternative but only a few studies have evaluated the efficacy of this immunization strategy. We found that in infants born to women immunized against influenza during pregnancy, the risk of laboratory-confirmed influenza and influenza-related hospitalization were reduced by 70% and 81% in their first 6 months of life, respectively.This large study provides more evidence that when women are immunized against influenza during pregnancy, their infants are much less likely to be diagnosed with influenza in their first 6 months.

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Morning Flu Vaccinations May Be More Effective

MedicalResearch.com Interview with:

Dr Anna C. Phillips PhD CPsychol AFBPsS Reader in Behavioural Medicine School of Sport, Exercise & Rehabilitation Sciences University of Birmingham Edgbaston Birmingham

Dr. Anna Phillips

Dr Anna C. Phillips PhD CPsychol AFBPsS
Reader in Behavioural Medicine
School of Sport, Exercise & Rehabilitation Sciences
University of Birmingham
Edgbaston Birmingham

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Phillips: We know that various factors can affect the response to vaccination and that older adults have a poorer response than younger people, i.e. they produce fewer antibodies.  We also know that many immune messengers and important hormones have daily rhythms in their levels and wanted to test whether the antibody response to vaccination might also be affected by time of day.  We randomised surgeries to giving morning or afternoon vaccinations and tested before and one month after the vaccination for levels of antibodies.

Two of the three flu strains (viruses) contained in the vaccine showed a higher antibody response in the morning than in the afternoon, up to 4 x higher to one of the strains (A/California) and 1.5 x higher to the B strain. None of the potential mechanisms we measured (immune messengers, hormones) seemed to be driving this effect.

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Hospital Stays Provide Opportunity to Vaccinate High Risk Patients

MedicalResearch.com Interview with:

Sara Y. Tartof, PhD, MPH Kaiser Permanente Southern California Department of Research & Evaluation

Dr. Sarah Tartoff

Sara Y. Tartof, PhD, MPH
Kaiser Permanente Southern California Department of Research & Evaluation

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Tartof: The flu is a highly contagious respiratory infection that can cause serious complications, hospitalizations and, in some cases, even death. Some people, such as older adults, young children and people with certain health conditions, are at high risk for serious complications. In addition to recommending annual flu vaccination for people 6 months of age and older, the Centers for Disease Control and Prevention recommends that hospitalized patients who are eligible receive the flu vaccine before discharge.

Historically, inpatient rates of vaccination have been low. There has been concern among surgeons that vaccinating patients while they are in the hospital can contribute to increased risk of vaccine-related fever or muscle pain, which might be incorrectly attributed to surgical complications. However, there have been no data to support that concern. The objective of this study was to provide clinical evidence that would either substantiate or refute concerns about the safety of perioperative vaccination.

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Flu Infection Raises Risk of New Onset Atrial fibrillation

MedicalResearch.com Interview with:
Tze-Fan Chao MD PhD
Division of Cardiology, Department of Medicine
Taipei Veterans General Hospital
Institute of Clinical Medicine, and Cardiovascular Research Center
National Yang-Ming University, Taipei, Taiwan
Su-Jung Chen MD
Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital,
Institute of Public Health and School of Medicine, National Yang-Ming University
Taipei, Taiwan

MedicalResearch: What is the background for this study? What are the main findings?

Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, accounting for frequent hospitalizations, hemodynamic abnormalities, and thromboembolic events. Although the detailed mechanism of the occurrence of Atrial fibrillation remains unclear, systemic inflammation and sympathetic nervous system have been demonstrated to play an important role in the pathogenesis of AF. Flu (influenza infection) is a common disease which could happen to everyone in the daily life. It could cause significant morbidity and mortality, and is a serious human health concern worldwide. Previous studies have shown that influenza infection not only results in the productions of pro-inflammatory cytokines, but also activates the sympathetic nervous system, which are all related to the occurrence of  Atrial fibrillation. Therefore, we hypothesized that influenza infection could be a risk factor of new-onset AF. We also tested the hypothesis that influenza vaccination, a useful way to reduce the risk of influenza infection, could decrease the risk of AF.

In this large scale nationwide case-control study, a total of 11,374 patients with newly diagnosed  Atrial fibrillation were identified from the Taiwan National Health Insurance Research Database. On the same date of enrollment, 4 control patients (without AF) with matched age and sex were selected to be the control group for each study patient. The relationship between AF and influenza infection/vaccination 1 year before the enrollment was analyzed. The results showed that influenza infection was associated with an 18% increased risk of AF, and the risk could be easily reduced through influenza vaccination.

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Pregnant Women With Flu At High Risk of Serious Illness and Complications

Ikwo Oboho, MD, ScMLCDR, United States Public Health Service Medical Epidemiologist, Centers for Disease Control and PreventionPriority Populations Treatment Team| HIV Care & Treatment Branch | Division of Global HIV/TB Atlanta, GA 30333

Dr. Ikwo Oboho

MedicalResearch.com Interview with:
Ikwo Oboho, MD, ScMLCDR

United States Public Health Service
Medical Epidemiologist, Centers for Disease Control and PreventionPriority Populations Treatment Team| HIV Care & Treatment Branch | Division of Global HIV/TB
Atlanta, GA 30333

MedicalResearch.com: What is the background for this study?

Dr. Oboho: ·Pregnant women with flu are at high risk of serious illness and complications, including death.

The study is based on data gathered from a nationwide flu surveillance network that includes 14 states. The analysis focused on pregnant women hospitalized with laboratory-confirmed flu over four recent flu seasons, from 2010 to 2014.

MedicalResearch.com: What are the main findings? 

Dr. Oboho: ·       During the study period, 865 pregnant women were hospitalized with flu. Sixty-three of these patients, or about 7 percent, had severe illness.

  • After adjusting for underlying medical conditions, vaccination status, and pregnancy trimester, we found that early treatment with the antiviral drug oseltamivir was associated with a shorter hospital stay.
  • Among pregnant women with severe flu illness who were treated early with oseltamivir — within two days of the start of symptoms — the median length of stay was about five days shorter compared to hospitalized pregnant women with severe flu illness who were treated later
  • Pregnant women who were hospitalized with severe cases of flu illness were half as likely to have been vaccinated as women with non-severe illness.

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When Not Mandatory, Many Resident Physicians Did Not Get Flu Vaccine

Mubdiul Ali Imtiaz, MD Department of Internal Medicine Rutgers University, New Jersey Medical School Newark, NJ 07103.

Dr.  Mubdiul Ali Imtiaz

MedicalResearch.com Interview with:
Mubdiul Ali Imtiaz, MD

Department of Internal Medicine
Rutgers University, New Jersey Medical School
Newark, NJ 07103

Medical Research: What is the background for this study?

Response: Resident physicians (RPs) were defined to be all individuals enrolled in a graduate medical education training program in a healthcare setting. There were 611 resident physicians enrolled in 47 post-graduate residency and fellowship programs at RU-NJMS during the 2013-2014 academic year. Influenza immunization was strongly recommended, but not mandatory for Resident physicians during 2013-2014. A link to the online survey using a standardized, anonymous, self-administered questionnaire was emailed by the program-chiefs to their respective RPs to collect demographic characteristics, influenza immunization status during the 2013-2014 and the previous season, and reasons for non-vaccination.

Medical Research: What are the main findings?

Response: The overall self-reported immunization rate of  Resident physicians in 2013-2014 was 76.7%. The immunization rate did not differ by the location of medical school attended (P= 0.55) or sex (P= 0.69). Among the respondents, 95.8% had influenza vaccination in the past and 83.1% received influenza vaccine during 2012-2013 flu season. History of influenza vaccination ever and in 2012-2013 were both significantly associated with receiving the vaccine during the 2013-2014 season (P<0.01 for both). The most common reason for not being vaccinated (38.6%) was “lack of time to get immunized” (see Figure 1). The most common cited motivating factors to be vaccinated during the next influenza season among the NVRPs were “making vaccinations in the workplace at convenient locations and times” (43.2%), “availability of mobile flu vaccination carts in hospital floors” (40.9%), and “establishing mandatory flu vaccination for employment” (36.4%).

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No Evidence That Tylenol Beneficial in Flu Infections

MedicalResearch.com Interview with:
Dr. Irene Braithwaite
Deputy Director
Medical Research Institute of New Zealand
Wellington NZ

Medical Research: What is the background for this study? What are the main findings?

Dr. Braithwaite: We know from animal models that the reduction of fever is associated with an increased risk of dying from influenza. We also know that some influenza viruses cannot replicate well in the human febrile range (38 to 40 Celsius). Yet, guidelines on the management of community acquired influenza infection in humans is to rest, maintain hydration and to take antipyretics such as paracetamol on the basis that this may help and is unlikely to cause harm. We undertook this study to see whether using regular paracetamol during influenza infection might be harmful, as it may allow the influenza virus to replicate more readily, and increase and/or prolong symptoms.

To the best of our knowledge, this is the first randomised controlled trial comparing the effects of regular paracetamol (1gram four times daily for five days) versus placebo in human adults infected with influenza. We found that there was no difference in influenza viral loads, temperature or influenza symptoms between the regular paracetamol group and placebo group.

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Statins May Dampen Efficacy of Flu Vaccination

Saad Omer MBBS MPH PhD Associate Professor Emory Vaccine Center Associate Professor Global Health and Epidemiology Rollins School of Public Health Emory University

Dr. Saad Omer

MedicalResearch.com Interview with:
Saad Omer MBBS MPH PhD

Associate Professor Emory Vaccine Center
Associate Professor Global Health and Epidemiology
Rollins School of Public Health
Emory University

MedicalResearch: Can you give us a little background on this study?

Dr. Omer: My background is in global health, epidemiology and pediatrics and I have been fortunate to conduct field and clinical vaccine trials in a number of countries and with multiple infectious diseases including influenza, polio, measles and pneumococcal vaccines.

We were familiar with the data on investigating the potential effects of statins on other infections i.e. sepsis and community acquire pneumonia including

Dr. Vandermeer’s study in 2012 suggesting that “statin use may be associated with reduced mortality in patients hospitalized with influenza”.

Statins have lipid-lowering effects but they also exhibit anti-inflammatory and immunomodulatory properties. For lack of a better image, I think of statins as acting like a ‘big hammer made of Jell-O’: they have a broad, small dampening effect on immune response (as opposed to a narrow or deep effect).

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Flu Vaccines Prevent Over Half of Hospitalizations For Influenza Pneumonia

Carlos G. Grijalva, MD MPH Associate Professor Department of Health Policy Vanderbilt University Medical Center Nashville, TN 37212MedicalResearch.com Interview with:
Carlos G. Grijalva, MD MPH
Associate Professor
Department of Health Policy
Vanderbilt University Medical Center
Nashville, TN 37212 

Medical Research: What is the background for this study?

Dr. Grijalva: Influenza is an important cause of disease. Every year influenza causes more than 200,000 hospitalizations in the US. The most effective strategy to prevent influenza infections is vaccination. Several studies have shown that influenza vaccines can prevent fever or respiratory symptoms caused by influenza. However, whether influenza vaccines can prevent more serious complications of influenza such as pneumonia, remains unclear

This was a multicenter collaboration between academic institutions and the centers for disease control and prevention. We used data from the Etiology of Pneumonia in the community or EPIC study, a large prospective study of hospitalizations for pneumonia conducted between 2010 and 2012. The EPIC study enrolled patients from Chicago, IL, Salt Lake City, UT, and Memphis and Nashville, TN. The main goal of the EPIC study was to determine the causes of pneumonia in children and adults hospitalized with pneumonia.

Medical Research:? What are the main findings?

Dr. Grijalva: We conducted a case-control study using data from EPIC. Our study included more than 2700 patients hospitalized for pneumonia, including both children and adults. Approximately 6% of these patients had influenza pneumonia and were identified as cases. Other patients hospitalized for pneumonia that was not caused by influenza were the controls. We compared the history of influenza vaccination between cases and controls. We found that influenza vaccination was associated with a reduced risk of influenza pneumonia that required hospitalization. The estimated vaccine effectiveness was 57%. This means that about 57% of hospitalizations due to influenza-associated pneumonia could be prevented through influenza vaccination.

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All Health Care Workers Should Receive Flu Vaccination Every Year

MedicalResearch.com Interview with:
Carla L. Black PhD Immunization Services Division National Center for Immunization and Respiratory Diseases CDC
Carla L. Black PhD
Immunization Services Division
National Center for Immunization and Respiratory Diseases
CDC 

Medical Research: What is the background for this study? What are the main findings?

Dr. Black: The Advisory Committee on Immunization Practices (ACIP) recommends that all health-care personnel (HCP) be vaccinated annually against influenza. Vaccination of health-care personnel can reduce influenza-related morbidity and mortality among HCP and their patients. Overall, 77.3% of HCP reported receiving an influenza vaccination in the 2014-15 season, similar to the 75.2% coverage among HCP reported in the 2013-14 season. Coverage was highest among  health-care personnel working in hospitals (90.4%) and lowest among HCP working in long-term care (LTC) settings (63.9%).

Flu vaccination coverage was highest in settings with employer flu vaccination requirements and promotion of flu vaccination. Vaccination coverage was 96% among HCP with an employer requirement for vaccination. Among HCP without an employer requirement for vaccination, vaccination coverage was higher for HCP working in settings where vaccination was offered on-site at no cost for one day (73.6%) or multiple days (83.9%) compared with  health-care personnel  working in settings where vaccination was promoted but not offered on-site (59.5%) or not promoted in any manner (44.0%).

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High Dose Flu Vaccine In Elderly Reduced Overall Health Care Costs

Dr Ayman Chit PhD Sanofi Pasteur Swiftwater, PA 18370MedicalResearch.com Interview with:
Dr Ayman Chit PhD

Sanofi Pasteur
Swiftwater, PA 18370

Medical Research: What is the background for this study? What are the main findings?

Dr. Chit: Our analysis used data from a large-scale, multi-center efficacy trial, in which a higher-dose split-virus inactivated influenza vaccine (IIV-HD, Fluzone® High-Dose vaccine, Sanofi Pasteur) was compared to a standard-dose split-virus inactivated influenza vaccine (IIV-SD, Fluzone vaccine, Sanofi Pasteur) in persons 65 years of age and older.  These data were supplemented with US healthcare cost data.

In the efficacy trial, a total of 31,989 adults 65 years of age and older were randomly assigned in a 1:1 ratio to receive either IIV-HD or IIV-SD and followed for six to eight months post-vaccination for the occurrence of influenza, serious adverse events, and medical encounters. Healthcare utilization (HCU) data were captured for all participants through a surveillance program that covered each influenza season, including the following events occurring within 30 days after any respiratory illness: use of prescription and non-prescription medications (limited to antipyretics/analgesics/non-steroidal anti-inflammatory drugs, antivirals and antibiotics), emergency room visits, non-routine or urgent care visits, and hospitalizations. In addition, all hospitalizations were captured for participants for the entire duration of the study.

The primary results from the efficacy trial were published in The New England Journal of Medicine, which reported that IIV-HD was 24.2% (95% confidence interval [CI], 9.7% to 36.5%) more effective in preventing laboratory-confirmed influenza-like illness compared to IIV-SD.1 In the current supplemental analysis of the trial, we used US healthcare cost data to evaluate economic impacts of using IIV-HD compared to IIV-SD within the efficacy trial participants. In this analysis, total healthcare payer costs (the combined costs of study vaccine, prescription drugs, emergency room visits, non-routine and urgent-care visits, and hospital admissions) were about $116 less per person.

  1. DiazGranados et al, NEJM, 2014;14;371(7):635-45 

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Elders Also Benefit When Young Adults Get Flu Vaccine

Dr. Glen Taksler, PhD Medicine Institute Cleveland Clinic Main CampusMedicalResearch.com Interview with:
Dr. Glen Taksler, PhD
Medicine Institute
Cleveland Clinic Main Campus

Medical Research: What is the background for this study? What are the main findings?

Dr. Taksler: Although young, healthy adults who develop influenza are usually able to recover, they may spread the flu to other people in the community who have a higher risk of hospitalization or other serious complications. These higher-risk people have a limited ability to protect themselves from influenza, because flu vaccines are less effective in the elderly and in people with weakened immune systems.

To better understand whether young, healthy adults could help the community-at-large by getting a flu vaccine, we looked at data on more than 3 million Medicare beneficiaries across 8 influenza seasons.

We found that the elderly had 21% lower odds of developing influenza if they lived in areas where more nonelderly adults (people aged 18-64 years old) got a flu vaccine.

Importantly, we found these benefits even in elderly adults who obtained an influenza vaccine, perhaps because flu vaccines are less effective in the elderly.  This means that elderly adults who were proactive to try to prevent influenza still benefited from communitywide vaccination.

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Flu Vaccine Less Effective This Year Because Flu Virus Acquired A Mutation

Scott E. Hensley, Ph.D. Assistant Professor Wistar Institute Philadelphia, PA 1910MedicalResearch.com Interview with:
Scott E. Hensley, Ph.D.
Assistant Professor
Wistar Institute
Philadelphia, PA 1910

 

Medical Research: What is the background for this study? What are the main findings?

Response: Previous studies documented that the the 2014-2015 H3N2 flu vaccine strain was antigenically distinct compared to most recent H3N2 flu strains.  Recent H3N2 strains possess several mutation and it was previously unknown which of these mutations contributed to the 2014-2015 vaccine mismatch.  We used a reverse-genetic engineering approach to identify specific viral mutations that contributed to the 2014-2015 vaccine mismatch.

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Commuter Patterns Can Help Predict Influenza Spread

MedicalResearch.com Interview with:
Brooke Bozick

Ph.D. Candidate
Population Biology, Ecology, & Evolution Program
Emory University

MedicalResearch: What is the background for this study?

Response: Previous research at the global scale has shown that air travel is important for the spread of disease. For example, much work has focused on the recent Ebola epidemic in Africa, identifying where this disease emerged and then using air travel networks to predict the path of spread from there.

At a more local scale, other modes of transportation may be more important to structuring pathogen populations. We were interested in investigating seasonal influenza in the United States. Previous research has shown that once the winter influenza epidemic starts, it spreads very rapidly across the continental states, suggesting that the US may act as one large, well-mixed population. Previous work using genetic data to look for spatial structure at this scale didn’t identify any patterns. However, these studies used geographic proximity to define the distance between states; we wanted to see whether similar patterns existed at this spatial scale if we instead used movement data as a proxy for the distance between locations. Commuter movements have previously been shown to correlate with influenza timing and spread based on influenza-like-illness and mortality data.

MedicalResearch: What are the main findings?

Response: We found that spatial structure is detectable within the US. We used data on the genetic distance between sequences collected from different states and compared that to different measures of ‘distance’ between states—geographic proximity, the daily number of people flying between states and the daily number of commuters traveling between states using ground transportation—to see whether any correlations were present. Further, we did this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes have different epidemiological properties, so there was reason to believe that the observed patterns might differ depending on subtype.

We found that some correlations were present for all the distance metrics studied, but that they were observed a greater proportion of the time when looking at commuter movements, and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast to coast, any signature of spatial structure is likely obscured before we have a chance to observe it.

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High-Dose Flu Vaccine Prevented More Influenza Infections In Elderly Than Standard Dose

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD MedicalResearch.com Interview with:
Dr Richard Forshee PhD

Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research
U.S. Food and Drug Administration

Silver Spring, MD
On behalf of the study authors

Medical Research: What is the background for this study? What are the main findings?

Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken.  The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group.  The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients.

In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness.  This pathway reduces the time it takes for needed medical products to become available to the public.  Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease.

As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease.

A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older.  The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose.

Additional background about this study: “Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis” is available at:

http://dx.doi.org/10.1016/S1473-3099(14)71087-4

A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at:

http://dx.doi.org/10.1016/S1473-3099(15)70020-4 Continue reading

Text Message Improves Pediatric Flu Vaccination Rates

Melissa Stockwell, MD, MPH, FAAP Florence Irving Assistant Professor of Pediatrics and Population and Family Health Columbia University - College of Physicians & Surgeons and Mailman School of Public Health Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac) Co-Director, Primary Care Clinician Research Fellowship in Community Health New York, NY 10032MedicalResearch.com Interview with:
Melissa Stockwell, MD, MPH, FAAP

Florence Irving Assistant Professor of Pediatrics and Population and Family Health, Columbia University – College of Physicians & Surgeons and Mailman School of Public Health
Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac);
Co-Director, Primary Care Clinician Research Fellowship in Community Health

Medical Research: What is the background for this study? What are the main findings?

Response:  Influenza can be a very serious disease and is more than just a bad cold.  Some children who are 6 months through 8 years need two doses of the influenza vaccine in a season depending on if and when they received previous influenza vaccine doses. We know that only about half of these families who want to vaccinate their children against the flu and get the first dose, come back to get the second dose.
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Researchers Aim To Make Influenza Vaccine More Effective For High Risk Patients

Adrian Egli, MD PhD Research Group leader Infection Biology Laboratory Department of Biomedicine University of Basel and University Hospital Basel Basel, SwitzerlandMedicalResearch.com Interview with:
Adrian Egli, MD PhD Research Group leader
Infection Biology Laboratory
Department of Biomedicine
University of Basel and University Hospital Basel
Basel, Switzerland

Medical Research: What is the background for this study? What are the main findings?

Dr. Egli: Infections with influenza viruses are associated with a high morbidity and mortality. In particular, people with a weak immune system are at danger for more severe complications. This includes elderly people, pregnant women, patients after transplantation, patients with HIV infection, chronic diseases such as diabetes and many more. In these high-risk groups, annual vaccination is clearly recommended.

However, due to the immunsuppressive condition the immune response to the influenza vaccine is often reduced. The seroconversion rate – a 4-fold antibody titer increase upon vaccination – is one of the key markers for a successful vaccination. In young adults the seroconversion rate is normally >85%; however, in patients with immunosuppression, this can be lower than 40%. Improving vaccine efficacy is one of the key focuses of my research group. We try to understand, how to improve vaccines and better protect the people at the highest risks for influenza-associated complications.

In this study, we could show that an important cytokine, called Interferon lambda, is clearly associated with the vaccine induced antibody response upon influenza vaccination. We could show that genetic polymorphisms, in one of the Interferon lambda gene family (IFNL3), are modulating the expression of this gene. This strongly affects the cross talk between the innate and adaptive immune response in the context of vaccination. We observed that, the more Interferon lambda is present, the lower the antibody response is. People with a lower expression of Interferon lambda had a significant higher response to the vaccine. Therefore, we developed substances to block the effect of Interferon lambda. We could show in vitro, that due to the Interferon lambda blockade, the antibody production was improved.

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Flu Vaccination May Be Effective Even When Circulating Strain Different From Vaccine

MedicalResearch.com Interview with:
Maryam Darvishian MSc
Department of Epidemiology, University Medical Center Groningen,
Unit of PharmacoEpidemiology and PharmacoEconomics (PE2),
Department of Pharmacy, University of Groningen,
and 
Prof Edwin R van den Heuvel
Department of Epidemiology, University Medical Center Groningen,
University of Groningen, Groningen, Netherlands
Department of Mathematics and Computer Science,
Eindhoven University of Technology, Eindhoven, Netherlands

Medical Research: What is the background for this study?

Reply: In most developed countries, seasonal influenza vaccine is the standard care for elderly people, but there exists still discussions on whether vaccination is effective. Conducting RCT is not considered ethical and thus the main body of evidence comes from observational studies. Unfortunately, these studies (e.g. cohort studies) are susceptible to different sources of biases especially selection bias which makes it difficult to judge the effectiveness. In recent years test-negative design (TND) studies has been designed. It is a special type of case-control study which would limit the bias, due to similar health care-seeking behavior in cases and controls. The current study is a meta-analysis of TND case-control studies. It is the first meta-analysis of this type of studies and also the first meta-analysis that combined 35 studies for estimation of influenza vaccine effectiveness. More specifically, the meta-analysis assesses the influenza vaccine effectiveness against laboratory-confirmed influenza (LCI) among the elderly population. Continue reading

Flu Season Linked To Increase in Acute Aortic Dissection

MedicalResearch.com Interview with:
Harleen Sandhu, MD MPH
Senior Researcher
University of Texas Health Science Center at Houston

Medical Research: What is the background for this study? What are the main findings?

Dr. Sandhu: Previous studies have shown a correlation between seasonal variations and occurrence of acute aortic dissection, however, reasons for such associations are unknown. Seasonal flu activity has been associated with the occurrence of cardiovascular diseases such as acute myocardial infarction in the past. This led us to verify this seasonal correlation in our experience with acute aortic dissection patients and to further investigate if its incidence was associated with flu activity. Our results confirmed the seasonal variation in acute aortic dissection as well as demonstrated a positive correlation with seasonal flu activity.

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Flu Mutations Led To More Disease Among Middle-Aged Adults

Scott E. Hensley, Ph.D. Assistant Professor, The Wistar Institute Philadelphia, PA 19104MedicalResearch.com Interview with
Scott E. Hensley, Ph.D.
Assistant Professor, The Wistar Institute
Philadelphia, PA 19104

 

Medical Research: What are the main findings of the study?

Dr. Hensley: We found that H1N1 viruses recently acquired a mutation that abrogates binding of influenza antibodies that are present in a large number of middle-aged adults.  We propose that this mutation lead to increased disease among middle-aged adults during the 2013-2014 influenza season.
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Prior Bird Flu Vaccination Offers Some Protection Against Newer Strains

Robert B Belshe, MD  Division of Infectious Diseases, Allergy & Immunology Saint Louis University School of MedicineMedicalResearch.com Interview with:
Robert B Belshe, MD 
Division of Infectious Diseases, Allergy & Immunology
Saint Louis University School of Medicine

 

Medical Research: What are the main findings of the study?

Response: A vaccine that protects against an old strain of avian flu primes the immune system to mount a rapid response when a vaccine designed to protect against a related but different and new strain of avian flu is given a year later, according to Saint Louis University research findings reported in JAMA.

In addition, when combined with an adjuvant, which is a chemical that stimulates the immune system to produce more antibodies, a lower dose of the new avian flu vaccine worked better in triggering an immune response than a stronger dose without adjuvant. That means the amount of vaccine against a new strain of bird flu can be stretched to protect more people if an adjuvant is added.

Both findings represent important strategies researchers can continue to study to fight new strains of bird flu that people previously have not been exposed to, and consequently can rapidly turn into a pandemic outbreak and public health emergency, said Robert Belshe, M.D., professor of infectious diseases, allergy and immunology at Saint Louis University and the lead author of the article, which appeared in the Oct. 8, 2014 issue of JAMA.

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Mandatory Flu Shots For Health Care Workers Boosts Vaccination Rates

Allison Weinmann  MBBS, FRACP Senior Staff, Division Infectious Diseases Director HFHS Immunization Team Medical Director Infection Control and Prevention, West Bloomfield Hospital Henry Ford Health System Clinical Assistant Professor, Wayne State University Detroit, Mi 48202MedicalResearch.com Interview with:
Allison Weinmann  MBBS, FRACP
Senior Staff, Division Infectious Diseases
Director HFHS Immunization Team
Medical Director Infection Control and Prevention, West Bloomfield Hospital
Henry Ford Health System
Clinical Assistant Professor, Wayne State University
Detroit, Mi 48202

Medical Research: What are the main findings of this study?

Dr. Weinmann: The main findings included:

  • Mandatory influenza immunization for health care workers without allowing optional opt-out (and only allowing for documented medical or religious exemption) successfully raised our immunization uptake among all our employees to over 99% sustainable for the last 2 years which we consider a very important patient safety initiative.
  • Less than 2% of workers met a medical or religious exemption.
  • A prior optional opt out with mask wearing was problematic for staff and patients and did not reach our goal of close to 100% immunization uptake.

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Fluzone High-Dose Vaccine Found More Effective Than Standard-Dose Vaccine

David P. Greenberg, M.D. Vice President, Scientific & Medical Affairs, and Chief Medical Officer Sanofi Pasteur US.MedicalResearch.com Interview with:
David P. Greenberg, M.D.
Vice President, Scientific & Medical Affairs, and Chief Medical Officer
Sanofi Pasteur US.

 

Medical Research: What are the main findings of the study?

Dr. Greenberg: The New England Journal of Medicine published positive results from a randomized, double-blind, large-scale, multi-center efficacy trial, which found that Fluzone® High-Dose (Influenza Vaccine) was more efficacious in preventing influenza illness (“the flu”) in adults 65 years of age and older compared to standard-dose Fluzone vaccine. Fluzone High-Dose vaccine was found to be 24.2 percent (95% CI, 9.7 to 36.5) more effective in preventing influenza relative to standard-dose Fluzone vaccine for the primary endpoint (laboratory-confirmed influenza associated with typical clinical symptoms occurring at least 14 days post-vaccination caused by any viral type or subtype). In other words, investigators determined that participants in the Fluzone High-Dose vaccine group were less likely to get the flu than those in the standard-dose Fluzone vaccine group. The study safety data were consistent with previous Fluzone High-Dose vaccine studies.

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Promising New Influenza Drug Reduces Flu Symptoms and Viral Shedding

MedicalResearch.com Interview with:
Prof. Jean-Francois Rossignol, FRSC, FRCPath
Romark Laboratories, LC

MedicalResearch: What are the main findings of the study?

Prof. Rossignol: Nitazoxanide, a new orally administered drug in development for treating influenza, reduced the duration of symptoms of uncomplicated influenza compared to a placebo. The drug also reduced viral shedding. Side effects were similar for the drug and placebo treatment arms. The study was designed and conducted in compliance with FDA guidelines for studying new drugs for influenza.
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Flu Vaccination During Pregnancy and Infant Outcomes

MedicalResearch Interview:
Dr Nicoline van der Maas MD
Epidemiologist
National Institute for Public Health and the Environment
Centre for Infectious Disease Control
Epidemiology and Surveillance
The Netherlands

MedicalResearch: What are the main findings of the study?

Dr. van der Maas: The main finding, presented at the ESPID, is that we found no difference in growth, development and infection related contact rates with the general practitioner after the first year of life between infants of unvaccinated mothers and infants of mothers, vaccinated with an adjuvanted Influenza A (H1N1) vaccine during the second and third trimester of pregnancy.

The offer of a H1N1 vaccination to pregnant women in their second and third trimester did not have a negative impact on infants’ health during the first year of life.

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Maternal Influenza and Offspring Bipolar Disorder

MedicalResearch.com Interview with:
Alan S. Brown, M.D., M.P.H. Professor of Clinical Psychiatry and Clinical Epidemiology College of Physicians and Surgeons of Columbia University Director Unit in Birth Cohort Studies Division of Epidemiology New York State Psychiatric Institute New York, NY 10032Alan S. Brown, M.D., M.P.H.
Professor of Clinical Psychiatry and Clinical Epidemiology College of Physicians and Surgeons of Columbia University Director
Unit in Birth Cohort Studies Division of Epidemiology New York State Psychiatric Institute
New York, NY

MedicalResearch.com: What are the main findings of the study?

Dr. Brown: We found that a mother’s exposure to influenza during pregnancy, documented by antibodies in her serum, increased the risk of bipolar disorder with psychotic symptoms in her offspring.  We did not show a relationship between influenza and bipolar disorder not accompanied by psychosis.
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Increased Risk of Flu-Like Illnesses After Well-Child Visits

Philip M. Polgreen, MD, MPH. Associate Professor of Internal Medicine - Infectious Diseases University of Iowa Carver College of MedicineMedicalResearch.com Interview with:
Philip M. Polgreen, MD, MPH.
Associate Professor of Internal Medicine – Infectious Diseases
University of Iowa Carver College of Medicine

MedicalResearch.com: What are the main findings of the study?

Dr. Polgreen: In this paper, to determine if well-child visits are associated with increased risk for subsequent influenza-like-illness visits, we used a large database that tracks healthcare expenditures of families over time. Controlling for other factors such as the presence of other children, insurance and demographics, we found that well-child visits were a risk factor for subsequent influenza-like-illness within the next two weeks for a patient or for a family member. The estimated probability of a subsequent influenza-like illness visit was increased by 3.2 percentage points for those with well-child visit. We estimated that this additional risk translates to over 700,000 cases of influenza-like-illness per year in the United States. Total costs (lost wages, medical costs, etc.) for these infections could amount to $500 million annually.
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Severe Flu Associated with Younger Age, Lack of Vaccination

Dr Cameron Wolfe MBBS(Hons), MPH Assistant Professor of Medicine Clinical / Transplant Infectious Diseases Duke University Medical CenterMedicalResearch.com Interview with:
Dr Cameron Wolfe MBBS(Hons), MPH
Assistant Professor of Medicine
Clinical / Transplant Infectious Diseases
Duke University Medical Center


MedicalResearch.com: What are the main findings of the study?

Dr. Wolfe: The major findings of the study were that at least in our center, there was a significant burden of critical illness due to H1N1 influenza infection.  The average age of the patients admitted to the hospital was just 28yrs, consistent with the younger patient age in 2009 when H1N1 emerged.  Most critically, we also observed a significantly lower rate of influenza vaccine uptake in patients admitted to the Intensive Care Units at our center.
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Flu: Vaccine For Prevention in Children

Ghassan Dbaibo, M.D., FAAP Professor and Vice-Chair for Research and Faculty Development Department of Pediatrics and Adolescent Medicine Head, Division of Pediatric Infectious Diseases Director, Center for Infectious Diseases Research Professor, Department of Biochemistry and Molecular Genetics American University of Beirut Beirut, LebanonMedicalResearch.com Interview with:
Ghassan Dbaibo, M.D., FAAP
Professor and Vice-Chair for Research and Faculty Development
Department of Pediatrics and Adolescent Medicine
Head, Division of Pediatric Infectious Diseases
Director, Center for Infectious Diseases Research
Professor, Department of Biochemistry and Molecular Genetics
American University of Beirut Beirut, Lebanon

MedicalResearch.com: What are the main findings of the study?

Dr. Dbaibo:

  • 55% efficacy (95% CI 39–67%) for prevention of all influenza
  • These results are comparable with other estimates of efficacy and effectiveness for trivalent inactivated flu vaccines in this age group
  •  73% efficacy (97.5% CI 47–86%) for prevention of moderate-to-severe influenza
  • By preventing moderate-to-severe influenza, vaccination prevented the most clinically consequential outcomes of infection, reducing hospitalisations by 75% and medical visits by 69%.
  • Seroprotection rates of more than 95% for each of the four influenza strains in the vaccine
  • An acceptable safety and reactogenicity profile
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Flu: Media Reporting and Competing Interests

MedicalResearch.com with:
Dr Kate Mandeville MD MPH Clinical Research Fellow, London School of Hygiene and Tropical MedicineDr Kate Mandeville MD MPH
Clinical Research Fellow, London School of Hygiene and Tropical Medicine

 


MedicalResearch.com: What is the background for your study?

Dr. Mandeville: The UK spent nearly one billion pounds on pharmaceutical drugs during the swine flu pandemic, including vaccine and antiviral drugs. After the swine flu pandemic, it was revealed that some scientists on the World Health Organization’s advisory committee had links with the pharmaceutical industry. Scientists often provide commentary for journalists on emerging health risks and we set out to see whether scientists commentating on swine flu were also more likely to have links to pharmaceutical companies. We analysed UK newspaper coverage of the swine flu pandemic between April and July 2009. This was the period in which the UK government was making decisions on how best to respond to the emerging pandemic, including providing the public with vaccine and antiviral drugs. We looked for how often scientists were quoted in articles on the pandemic from a wide range of newspapers. We then examined these comments in more detail to see if scientists made an assessment of the risk to the public from swine flu, and compared these against assessments made by official agencies like the Department of Health. We also judged whether the scientists promoted or rejected the use of vaccines or antiviral drugs. For each scientist, we then looked for links with the pharmaceutical industry – or what we formally call competing interests – from a variety of sources, including scientific papers and the internet.

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Flu and Pediatric Deaths

MedicalResearch.com Interview with:
Karen K. Wong, MD MPH
Community Interventions for Infection Control Unit
Division of Global Migration & Quarantine
Centers for Disease Control and Prevention

MedicalResearch.com: What are the main findings of the study?

Dr. Wong: There were 830 pediatric influenza-associated deaths reported to CDC during the 2004–2005 through 2011–2012 seasons; deaths occurred in children of all ages, and 43% had no high-risk medical conditions. Of children 6 months of age or older whose vaccination status was known, only 16% had been fully vaccinated with seasonal influenza vaccine.
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Study showed Flu vaccines for nursing home workers effective in reducing outbreaks

Eurekalert Sept 12 2011

Higher flu vaccination rates for health care personnel can dramatically reduce the threat of flu outbreak among nursing home residents, according to a study published in the October issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

The study, which focused on nursing homes in New Mexico, found that when a facility had between 51 and 75 percent of its health care personnel with direct patient care vaccinated, the chances of a flu outbreak in that facility went down by 87 percent.

“The Centers for Disease Control and Prevention have long recommended that health care personnel in nursing homes get vaccinated against the flu, but we didn’t know just how much help these recommendations might be in reducing flu outbreaks among residents,” said Aaron Wendelboe of the University of Oklahoma, the lead author of the study. “We found strong evidence to support the CDC’s recommendation that to protect residents of nursing homes, health care personnel should be vaccinated annually.”

In association with the New Mexico Department of Health, Wendelboe and his team surveyed influenza rates at the state’s 75 long-term care facilities during the 2006-2007 and 2007-2008 flu seasons. They then looked for correlations between vaccination rates at each facility and whether there was an influenza outbreak.

While increased vaccination of direct care healthcare workers was associated with fewer flu outbreaks, the study found that vaccination rates among residents did not discourage outbreaks. In fact, higher resident vaccination was correlated with a higher probability of an outbreak. That result was unexpected and hard to explain, the researchers say. “While the explanation is likely multi-factorial, we suspect a large factor is that facilities with high resident vaccination rates may over-rely on the direct protection bestowed by vaccinating the residents and under-value the indirect protection bestowed by vaccinating employees,” Wendelboe and his team write.

Despite recommendations by the CDC and the Society for Healthcare Epidemiology of America, vaccination rates among U.S. healthcare workers still hover under 65 percent.

“That vaccinating health care personnel provided more protection to residents than vaccinating residents themselves underscores the importance of these recommendations,” Wendelboe said.

 

Why Influenza B Virus Exclusively Infects Humans

NEW BRUNSWICK, N.J. – Researchers at Rutgers University and the University of Texas at Austin have reported a discovery that could help scientists develop drugs to fight seasonal influenza epidemics caused by the common influenza B strain.

Their discovery also helps explain how influenza B is limited to humans, and why it cannot be as virulent as A strains that incorporate new genes from influenza viruses that infect other species. The devastating flu pandemic of 1918, the pandemics of 1968 and 1977, and the avian influenza that emerged in the middle of the last decade were caused by influenza A viruses. Understanding features of influenza B virus that limit it to humans will help scientists better understand how influenza A strains are able to cross species.

The researchers have determined the three-dimensional structure of a complex between an influenza B virus protein and one of its human protein targets, resulting in suppression of the cell’s natural defenses to the infection and paving the way for the virus to replicate efficiently.

“Our study shows the basis by which non-structural protein 1 of influenza B, or NS1B, binds to a human host protein, immobilizing it to prevent it from fighting the virus,” said Gaetano Montelione, a lead author and professor of biochemistry and molecular biology, School of Arts and Sciences, at Rutgers. That human protein, known as interferon-stimulated gene 15 protein or ISG15, is an essential part of the defense mechanism that human cells use to protect themselves from viral infections. Chemicals that block the binding of NS1B to ISG15 may have antiviral potential against influenza B virus.

The study, led by professors Montelione and Robert Krug at the University of Texas at Austin, also reveals why NS1B cannot bind ISG15 molecules in other species, such as dogs or mice. Only human and non-human primate ISG15 proteins have a unique molecular sequence in a small part of the protein that makes it possible to bind to the NS1B protein. So far, influenza B virus has been found only in humans.

“The three-dimensional structure of the NS1B-ISG15 complex, which we determined using X-ray crystallography, has given us a clear understanding of the molecular basis for this species specificity,” said Krug, professor and chair of molecular genetics and microbiology.

“Flu infections continue to be a major health problem, with more effective drugs critically needed to treat infected individuals and control potential pandemics,” said Aaron Shatkin, director of the Center for Advanced Biotechnology and Medicine (CABM) at Rutgers and an eminent virologist. “This discovery opens new possibilities for achieving these very important goals.”

Participating in the study from Rutgers were Rongjin Guan, Li-Ching Ma and Brendan Amer, who along with Montelione are members of CABM and the Northeast Structural Genomics Consortium. They were joined by Paul Leonard of the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, who is also a member of CABM and the Howard Hughes Medical Institute. Participating from the University of Texas at Austin were Haripriya Sridharan and Chen Zhao, who along with Krug are also members of the university’s Institute for Cellular and Molecular Biology.

Montelione is the Jerome and Lorraine Aresty Chair in Cancer Research at Rutgers, an endowed chair established to support Montelione’s research efforts in the general area of cancer biology research. Significantly, some of the human proteins that are targets of the influenza virus’s defense mechanisms, like ISG15, are also important in cancer biology. Krug is a Fellow of the Mr. And Mrs. Corbin J. Robertson, Sr. Regents Chair in Molecular Biology at the University of Texas at Austin.

The work was supported by grants from the Protein Structure Initiative (PSI-Biology) Program of the National Institutes of Health and its National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Disease, and the Howard Hughes Medical Institute.