Comparison of alpha-spending plans for near #realtime #monitoring for #GBS after #influenza #vaccination during the 2010/11 influenza season (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2020 Jan 10. pii: S0264-410X(19)31674-3. doi: 10.1016/j.vaccine.2019.12.032. [Epub ahead of print]

Comparison of alpha-spending plans for near real-time monitoring for Guillain-Barré after influenza vaccination during the 2010/11 influenza season.

Sandhu SK1, Hua W2, MaCurdy TE3, Franks RL4, Avagyan A4, Chillarige Y4, Wernecke M4, Kelman J5, Ball R2.

Author information: 1 Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: sukhminder.sandhu@fda.hhs.gov. 2 Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. 3 Stanford University, Stanford, CA, USA; Acumen LLC, Burlingame, CA, USA. 4 Acumen LLC, Burlingame, CA, USA. 5 Centers for Medicare and Medicaid Services, Washington, DC, USA.

 

Abstract

BACKGROUND:

Near real-time surveillance of the influenza vaccine, which is administered to a large proportion of the US population every year, is essential to ensure safety of the vaccine. For efficient near real-time surveillance, it is key to select appropriate parameters such as monitoring start date, number of interim tests and a scheme for spending a pre-defined total alpha across the entire influenza season. Guillain-Barré Syndrome, shown to be associated with the 1976 influenza vaccine, is used to evaluate how choices of these parameters can affect whether or not a signal is detected and the time to signal. FDA has been monitoring for the risk of GBS after influenza vaccination for every influenza season since 2008.

METHODS:

Using Medicare administrative data and the Updating Sequential Probability Ratio Test methodology to account for claims delay, we evaluated a number of different alpha-spending plans by varying several parameters.

RESULTS:

For relative risks of 5 or greater, almost all alpha-spending plans have 100% power; however, for relative risks of 1.5 or lower, the constant and O’Brien-Fleming plans have increasingly more power. For RRs of 1.5 and greater, the Pocock plan signals earliest but would not signal at a RR of 1.25, as observed in prior influenza seasons. There were no remarkable differences across the different plans in regards to monitoring start dates defined by the number of vaccinations; reducing the number of interim tests improves performance only marginally.

CONCLUSIONS:

A constant alpha-spending plan appears to be robust, in terms of power and time to detect a signal, across a range of these parameters, including alternate monitoring start dates based on either cumulative vaccinations or GBS claims observed, frequency of monitoring, hypothetical relative risks, and vaccine uptake patterns.

Published by Elsevier Ltd.

KEYWORDS: Alpha-spending; Guillain-Barré Syndrome; Immunization; Influenza; Sequential test; Vaccine

PMID: 31932134 DOI: 10.1016/j.vaccine.2019.12.032

Keywords: Drugs safety; Seasonal Influenza; Vaccines; GBS.

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#Zika virus #infection causes temporary #paralysis in adult mice with motor #neuron synaptic retraction and evidence for proximal peripheral #neuropathy (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Dec 20;9(1):19531. doi: 10.1038/s41598-019-55717-3.

Zika virus infection causes temporary paralysis in adult mice with motor neuron synaptic retraction and evidence for proximal peripheral neuropathy.

Morrey JD1, Oliveira ALR2, Wang H3, Zukor K3, de Castro MV2, Siddharthan V3.

Author information: 1 Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322-5600, United States of America. john.morrey@usu.edu. 2 Institute of Biology, University of Campinas, Campinas, SP, Brazil. 3 Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, Utah, 84322-5600, United States of America.

 

Abstract

Clinical evidence is mounting that Zika virus can contribute to Guillain-Barré syndrome which causes temporary paralysis, yet the mechanism is unknown. We investigated the mechanism of temporary acute flaccid paralysis caused by Zika virus infection in aged interferon αβ-receptor knockout mice used for their susceptibility to infection. Twenty-five to thirty-five percent of mice infected subcutaneously with Zika virus developed motor deficits including acute flaccid paralysis that peaked 8-10 days after viral challenge. These mice recovered within a week. Despite Zika virus infection in the spinal cord, motor neurons were not destroyed. We examined ultrastructures of motor neurons and synapses by transmission electron microscopy. The percent coverage of motor neurons by boutons was reduced by 20%; more specifically, flattened-vesicle boutons were reduced by 46%, and were normalized in recovering mice. Using electromyographic procedures employed in people to help diagnose Guillain-Barré syndrome, we determined that nerve conduction velocities between the sciatic notch and the gastrocnemius muscle were unchanged in paralyzed mice. However, F-wave latencies were increased in paralyzed mice, which suggests that neuropathy may exist between the sciatic notch to the nerve rootlets. Reversible synaptic retraction may be a previously unrecognized cofactor along with peripheral neuropathy for the development of Guillain-Barré syndrome during Zika virus outbreaks.

PMID: 31862897 DOI: 10.1038/s41598-019-55717-3

Keywords: Zika Virus; GBS; Neurology; Animal models.

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#Diagnosis and #Treatment of #GBS During The #Zika Virus #Epidemic In #Brazil: A National Survey Study (J Periph Nerv Syst., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Peripher Nerv Syst. 2019 Nov 20. doi: 10.1111/jns.12358. [Epub ahead of print]

Diagnosis and Treatment of Guillain-Barré Syndrome During The Zika Virus Epidemic In Brazil: A National Survey Study.

Leonhard SE1, Conde RM2, de Assis Aquino Gondim F3, Jacobs BC1,4.

Author information: 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands. 2 Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil. 3 Department of Internal Medicine, Neurology Division, Federal University of Ceará, Fortaleza, CE, Brazil. 4 Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.

 

Abstract

BACKGROUND AND AIMS:

The Zika virus (ZIKV) epidemic in Brazil in 2015-2016 was followed by an increase in the incidence of patients with Guillain-Barré syndrome (GBS). With this national survey study, we aimed to gain a better understanding of how neurologists in Brazil are currently diagnosing and treating patients with GBS, and how this increase in incidence has impacted the management of the disease.

METHODS:

The questionnaire consisted of 52 questions covering: personal profile of the neurologist, practice of managing GBS during and outside of the ZIKV epidemic, and limitations in managing GBS. All 3264 neurologists that were member of the Brazilian Academy of Neurology at the time of the study were invited to participate.

RESULTS:

The questionnaire was fully answered by 171 (5%) neurologists. Sixty-one percent of neurologists noticed an increase in patients with GBS during the ZIKV epidemic, and 30% experienced an increase in problems in managing GBS during this time. The most important limitations in the diagnosis and management of GBS included the availability of nerve conduction studies (NCS), beds in the Intensive Care Unit (ICU) and referral to rehabilitation centers. Most neurologists did not use a protocol for treating patients with GBS and the treatment practice varied.

INTERPRETATION:

Increasing availability of NCS and beds in the ICU and rehabilitation centers, and the implementation of (inter)national guidelines, are critical in supporting Brazilian neurologist in their management of GBS, and are especially important in preparing for future outbreaks.

This article is protected by copyright. All rights reserved.

KEYWORDS: Guillain-Barré syndrome; Zika virus; clinical practice; management; survey

PMID: 31746070 DOI: 10.1111/jns.12358

Keywords: Zika Virus; GBS; Neurology; Brazil.

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Antecedent #infections in #GBS: a single-center, prospective study (Ann Clin Transl Neurol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Ann Clin Transl Neurol. 2019 Nov 12. doi: 10.1002/acn3.50946. [Epub ahead of print]

Antecedent infections in Guillain-Barré syndrome: a single-center, prospective study.

Hao Y1, Wang W1, Jacobs BC2, Qiao B1, Chen M3, Liu D1, Feng X1, Wang Y1,4.

Author information: 1 Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China. 2 Department of Neurology and Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands. 3 Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, Hunan Province, China. 4 Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.

 

Abstract

OBJECTIVE:

To investigate the spectrum of antecedent infections in Chinese patients with Guillain-Barré syndrome (GBS) and analyze the infections-related clinical phenotypes locally.

METHODS:

A prospective case-control study of 150 patients diagnosed with GBS and age- and sex-matched neurological and healthy controls was performed to investigate recent infections of 14 pathogens serologically and collect the clinical data during a follow-up of 12 months.

RESULTS:

In total, 53% of patients with GBS had a positive serology for recent infection, including Campylobacter jejuni (27%), influenza A (17%) and B (16%), hepatitis A virus (5%), dengue virus (3%), cytomegalovirus (3%), Epstein-Barr virus (3%), Mycoplasma pneumoniae (2%), herpes simplex virus (2%), varicella-zoster virus (1%), and rubella virus (1%). Serology for infections of hepatitis E virus, Haemophilus influenzae, and Zika virus was negative. There was a higher frequency of C. jejuni, influenza A, influenza B, and hepatitis A virus infections in GBS patients than both the neurological and healthy controls. C. jejuni infection was more frequent in younger GBS patients and was associated with antibodies against GM1, GalNAc-GD1a, and GM1:galactocerebroside complex. Influenza B infection was associated with a pure motor form of GBS.

INTERPRETATION:

C. jejuni, influenza A, influenza B, and hepatitis A virus serve as the most common cause of antecedent infections in GBS locally. Influenza B-related GBS may represent a pure motor phenotype. Differences in the infectious spectrum worldwide may contribute to the geographical clinical heterogeneity of GBS.

© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

PMID: 31714025 DOI: 10.1002/acn3.50946

Keywords: GBS; Neurology; Hepatitis A; Seasonal Influenza.

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Second #IVIg course in #GBS with poor #prognosis: the non-randomised ISID study (J Neurol Neurosurg Psychiatry, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Neurol Neurosurg Psychiatry. 2019 Oct 5. pii: jnnp-2019-321496. doi: 10.1136/jnnp-2019-321496. [Epub ahead of print]

Second IVIg course in Guillain-Barré syndrome with poor prognosis: the non-randomised ISID study.

Verboon C1, van den Berg B1, Cornblath DR2, Venema E1,3, Gorson KC4, Lunn MP5, Lingsma H3, Van den Bergh P6, Harbo T7, Bateman K8, Pereon Y9, Sindrup SH10, Kusunoki S11, Miller J12, Islam Z13, Hartung HP14, Chavada G15, Jacobs BC1,16, Hughes RAC17, van Doorn PA18; IGOS Consortium.

Author information: 1 Department of Neurology, Erasmus MC, Rotterdam, The Netherlands. 2 Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA. 3 Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. 4 Department of Neurology, St. Elizabeth’s Medical Center, Boston, Massachusetts, USA. 5 Department of Neurology, National Hospital for Neurology and Neurosurgery, London, UK. 6 Department of Neurology, University Clinic St. Luc, Leuven, Belgium. 7 Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 8 Department of Neurology, University of Cape Town, Cape Town, South Africa. 9 Department of Clinical Neurophysiology, Reference Centre for NMD, Nantes University Hospital, Nantes, France. 10 Department of Neurology, Odense University Hospital, Odense, Denmark. 11 Department of Neurology, Kindai University Faculty of Medicine, Osaka, Japan. 12 Department of Neurology, Royal Victoria Infirmary, Newcastle, UK. 13 Department of Laboratory Sciences and Services Division, The International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. 14 Department of Neurology, Heinrich Heine University, Düsseldorf, Germany. 15 Department of Neurology, University of Glasgow, Glasgow, UK. 16 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. 17 MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK. 18 Department of Neurology, Erasmus MC, Rotterdam, The Netherlands p.a.vandoorn@erasmusmc.nl.

 

Abstract

OBJECTIVE:

To compare disease course in patients with Guillain-Barré syndrome (GBS) with a poor prognosis who were treated with one or with two intravenous immunoglobulin (IVIg) courses.

METHODS:

From the International GBS Outcome Study, we selected patients whose modified Erasmus GBS Outcome Score at week 1 predicted a poor prognosis. We compared those treated with one IVIg course to those treated with two IVIg courses. The primary endpoint, the GBS disability scale at 4 weeks, was assessed with multivariable ordinal regression.

RESULTS:

Of 237 eligible patients, 199 patients received a single IVIg course. Twenty patients received an ‘early’ second IVIg course (1-2 weeks after start of the first IVIg course) and 18 patients a ‘late’ second IVIg course (2-4 weeks after start of IVIg). At baseline and 1 week, those receiving two IVIg courses were more disabled than those receiving one course. Compared with the one course group, the adjusted OR for a better GBS disability score at 4 weeks was 0.70 (95%CI 0.16 to 3.04) for the early group and 0.66 (95%CI 0.18 to 2.50) for the late group. The secondary endpoints were not in favour of a second IVIg course.

CONCLUSIONS:

This observational study did not show better outcomes after a second IVIg course in GBS with poor prognosis. The study was limited by small numbers and baseline imbalances. Lack of improvement was likely an incentive to start a second IVIg course. A prospective randomised trial is needed to evaluate whether a second IVIg course improves outcome in GBS.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

KEYWORDS: Guillain-Barré syndrome; poor prognosis; second IVIg course; treatment

PMID: 31586949 DOI: 10.1136/jnnp-2019-321496

Keywords: GBS; Immunoglobulins.

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Do #Vaccines Trigger #Neurological Diseases? Epidemiological Evaluation of Vaccination and Neurological Diseases Using Examples of #MS, #GBS and #Narcolepsy (CNS Drugs., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

CNS Drugs. 2019 Oct 1. doi: 10.1007/s40263-019-00670-y. [Epub ahead of print]

Do Vaccines Trigger Neurological Diseases? Epidemiological Evaluation of Vaccination and Neurological Diseases Using Examples of Multiple Sclerosis, Guillain-Barré Syndrome and Narcolepsy.

Stowe J1, Andrews N2, Miller E3.

Author information: 1 Immunisation and Countermeasures, Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK. Julia.stowe@phe.gov.uk. 2 Statistics and Modelling Economics Unit, Public Health England, London, NW9 5EQ, UK. 3 Immunisation and Countermeasures, Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK.

 

Abstract

This article evaluates the epidemiological evidence for a relationship between vaccination and neurological disease, specifically multiple sclerosis, Guillain-Barré syndrome and narcolepsy. The statistical methods used to test vaccine safety hypotheses are described and the merits of different study designs evaluated; these include the cohort, case-control, case-coverage and the self-controlled case-series methods. For multiple sclerosis, the evidence does not support the hypothesized relationship with hepatitis B vaccine. For Guillain-Barré syndrome, the evidence suggests a small elevated risk after influenza vaccines, though considerably lower than after natural influenza infection, with no elevated risk after human papilloma virus vaccine. For narcolepsy, there is strong evidence of a causal association with one adjuvanted vaccine used in the 2009/10 influenza pandemic. Rapid investigation of vaccine safety concerns, however biologically implausible, is essential to maintain public and professional confidence in vaccination programmes.

PMID: 31576507 DOI: 10.1007/s40263-019-00670-y

Keywords: Drugs safety; Vaccines; GBS; Narcolepsy; Neurology.

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Adverse events following #adenovirus type 4 and type 7 #vaccine, live, oral in the Vaccine Adverse Event Reporting System (#VAERS), #USA, October 2011-July 2018 (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2019 Sep 20. pii: S0264-410X(19)31188-0. doi: 10.1016/j.vaccine.2019.08.087. [Epub ahead of print]

Adverse events following adenovirus type 4 and type 7 vaccine, live, oral in the Vaccine Adverse Event Reporting System (VAERS), United States, October 2011-July 2018.

McNeil MM1, Paradowska-Stankiewicz I2, Miller ER2, Marquez PL2, Seshadri S3, Collins LC Jr3, Cano MV2.

Author information: 1 Immunization Safety Office, Division of Healthcare Quality Promotion (DHQP), National Center for Zoonotic and Emerging Infectious Diseases (NCZEID), Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA. Electronic address: mmm2@cdc.gov. 2 Immunization Safety Office, Division of Healthcare Quality Promotion (DHQP), National Center for Zoonotic and Emerging Infectious Diseases (NCZEID), Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA. 3 Immunization Healthcare Division, Public Health Division, Defense Health Agency, Falls Church, VA 22042, USA.

 

Abstract

BACKGROUND:

In March 2011, the U.S. Food and Drug Administration licensed adenovirus type 4 and type 7 vaccine, live, oral (Barr Labs, Inc.) (adenovirus vaccine) for use in military personnel 17 through 50 years of age. The vaccine was first universally administered to U.S. military recruits in October 2011. We investigated adverse event (AE) reports following the adenovirus vaccine submitted to the Vaccine Adverse Event Reporting System (VAERS).

METHODS:

We searched the VAERS database for U.S. reports among persons who received adenovirus vaccine during October 2011 through July 2018 including participants in a military observational study. We reviewed all serious reports and accompanying medical records. We compared the proportion of serious reports in a proxy military recruit population and reviewed all reports of suspected allergic reactions following adenovirus vaccination.

RESULTS:

During the analytic period, VAERS received 100 reports following adenovirus vaccination; 39 (39%) were classified as serious and of these, 17 (44%) were from the observational study. One death was reported. Males accounted for 72% of reports. Median age of vaccinees was 19 years (range 17-32). The most frequently reported serious AEs were Guillain Barré syndrome (GBS) (n = 12) and anaphylaxis (n = 8); of these, two GBS and all the anaphylaxis reports were reported in the observational study. Reports documented concurrent receipt of multiple other vaccines (95%) and penicillin G (IM Pen G) or other antibiotics (50%).

CONCLUSIONS:

The reporting rate for serious AEs was higher than with other vaccines administered in the comparison military recruit population (39% vs 18%); however, we identified no unexpected or concerning pattern of adenovirus vaccine AEs. Co-administration of vaccines and IM Pen G was commonly reported in this military population. These exposures may have contributed to the GBS and anaphylaxis outcomes observed with the adenovirus vaccine. Future adenovirus vaccine safety studies in a population without these co-administrations would be helpful in clarifying the vaccine’s safety profile.

Published by Elsevier Ltd.

KEYWORDS: Adenovirus vaccine; Adverse event; Epidemiology; Hereditary Neuropathy with Liability to Pressure Palsy; Surveillance; Vaccine safety

PMID: 31548014 DOI: 10.1016/j.vaccine.2019.08.087

Keywords: Adenovirus; Vaccines; Drugs Safety; GSB; USA.

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