Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

Vaccine patterns among patients diagnosed with Guillain-Barré Syndrome and matched counterparts in a Medicare supplemental population, 2000-2020.

Some vaccines have a small risk of Guillain-Barré Syndrome (GBS), a rare autoimmune disorder characterized by paralysis if untreated. The CDC's Advisory Committee on Immunization Practices (ACIP) guidelines do not consider GBS a precaution for future vaccines unless GBS developed within six weeks after a tetanus-toxoid-containing vaccine or influenza vaccine. Our goal was to describe vaccine patterns before and after GBS diagnosis. We matched each of 709 patients diagnosed with GBS from 2002 to 2020 with Medicare supplemental insurance to 10 counterparts without GBS (1:10) on age and sex. Propensity score-based weighting balanced covariates between groups, and we estimated weighted mean cumulative counts (wMCC) of vaccines/person before and after GBS diagnosis. Among patients with GBS, 7% were diagnosed within 42 days after a vaccine. Prior to GBS diagnosis, the wMCC of vaccines per person was similar between GBS cases and matched counterparts, but after two years of follow-up, GBS patients received 21 fewer vaccines/100 people than counterparts (wMCC difference -0.21 vaccines/person, 95% CI -0.24 to -0.18); GBS patients received 16 vaccines/100 people while matched counterparts received 36/100. Vaccine use was reduced following GBS diagnosis despite no ACIP precaution for most (93%) patients in this study. The observed drop in vaccines after GBS diagnosis indicates a disconnect between clinical practice and current recommendations.

Patient-related healthcare costs for diarrhoea, Guillain Barré syndrome and invasive non-typhoidal salmonellosis in Gondar, Ethiopia, 2020.

BACKGROUND: Globally, foodborne diseases result in a significant disease burden with low- and middle-income countries disproportionately affected. Estimates of healthcare costs related to foodborne disease can aid decision makers to take action to mitigate risks and prevent illness. However, only limited data on the African continent are available, especially related to more severe sequelae. We provide estimates of direct and indirect (non)-medical costs of patients with diarrhoea, Guillain-Barré syndrome (GBS), and invasive non-typhoidal salmonellosis (iNTS) in three healthcare facilities in Gondar, Ethiopia. METHODS: We used healthcare data from patient records, interviews with family caregivers and 2020 healthcare resource unit costs. Descriptive statistical analysis was performed. For diarrhoea, differences in mean and median transformed costs between healthcare facilities and etiologies (Campylobacter spp., enterotoxigenic Escherichia coli, non-typhoidal Salmonella enterica) were analysed with ANOVA and chi squared tests. Contribution of healthcare facility, dehydration severity, sex, age and living area to transformed costs was identified with linear regression. Results are in 2020 USD per patient. To extrapolate to national level, 2017 national incidence estimates were used. RESULTS: Mean direct medical costs were 8.96 USD for diarrhoea (health centre 6.50 USD, specialised hospital 9.53 USD, private clinic 10.56 USD), 267.70 USD for GBS, and 47.79 USD for iNTS. Differences in costs between diarrhoea patients were mainly associated with healthcare facility. Most costs did not differ between etiologies. Total costs of a diarrhoea patient in the specialised hospital were 67 USD, or 8% of gross national income per capita. For direct medical plus transport costs of a GBS and iNTS patient in the specialised hospital, this was 33% and 8%, respectively. Of the 83.9 million USD estimated national non-typhoidal Salmonella enterica related cost, 12.2% was due to iNTS, and of 187.8 million USD related to Campylobacter spp., 0.2% was due to GBS. CONCLUSION: Direct medical costs per patient due to GBS and iNTS were 30 respectively five times those due to diarrhoea. Costs of a patient with diarrhoea, GBS or iNTS can be a substantial part of a household's income. More severe sequalae can add substantially to cost-of-illness of foodborne hazards causing diarrheal disease.

Assessment of neurological sequelae and new-onset symptoms in the long-term follow-up of paediatric Guillain-Barre syndrome: A longitudinal study from India.

BACKGROUND: Guillain-Barre syndrome (GBS) is the commonest cause of acute flaccid paralysis in children. There is a paucity of studies that assess the long-term outcome of paediatric GBS. AIM: To assess the frequency of neurological sequelae and the new-onset symptoms in the long-term follow-up of paediatric GBS and to identify the risk factors associated with them. METHODS: This longitudinal study involved 78 children with GBS treated between January 2015 and 2021. The parents of those children were contacted to visit the hospital for a detailed neurological examination and to look for new-onset symptoms after the initial treatment for GBS. RESULTS: Of the 78 children, acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, and acute motor-sensory axonal neuropathy variants were observed in 30 (38.5%), 27 (34.6%) and 11 (14.1%) children, respectively. The median (interquartile range (IQR)) duration of follow-up was 3 (2, 4.5) years. The median (IQR) time to independent ambulation was 30 (13.5, 105) days. The neurological sequelae were found in 22 (28.2%) children. GBS disability score at admission (odds ratio (OR) = 4.6; 95% confidence interval (CI): 1.1-19.8; P = 0.04) and axonal variant of GBS (OR = 4.1; 95% CI: 1.5-20.8; P = 0.04) were found to be independent predictors of neurologic sequelae. A total of 28 children experienced new-onset symptoms after GBS, with frequent falls while running and fatigue being the predominant symptoms. Those children with demyelinating variant achieved independent ambulation earlier than the axonal group on survival analysis (log-rank P value = 0.04). CONCLUSION: The presence of neurological sequelae and new-onset symptoms were found in 28.2 and 35% of the GBS children, respectively. High GBS disability score at admission and axonal variant of GBS were independent predictors of neurological sequelae. Knowledge about these would help in devising a plan for rehabilitation.

A Broad Safety Assessment of the Recombinant Herpes Zoster Vaccine.

The recombinant herpes zoster vaccine (RZV), approved as a 2-dose series in the United States in October 2017, has proven highly effective and generally safe. However, a small risk of Guillain-Barré syndrome after vaccination was identified after approval, and questions remain about other possible adverse events. This data-mining study assessed RZV safety in the United States using the self-controlled tree-temporal scan statistic, scanning data on thousands of diagnoses recorded during follow-up to detect any statistically unusual temporal clustering of cases within a large hierarchy of diagnoses. IBM MarketScan data on commercially insured persons at least 50 years of age receiving RZV between January 1, 2018, and May 5, 2020, were used, including 56 days of follow-up; 1,014,329 doses were included. Statistically significant clustering was found within a few days of vaccination for unspecified adverse effects, complications, or reactions to immunization or other medical substances/care; fever; unspecified allergy; syncope/collapse; cellulitis; myalgia; and dizziness/giddiness. These findings are consistent with the known safety profile of this and other injected vaccines. No cluster of Guillain-Barré syndrome was detected, possibly due to insufficient sample size. This signal-detection method has now been applied to 5 vaccines, with consistently plausible results, and seems a promising addition to vaccine-safety evaluation methods.

Catastrophic health expenditure in patients with Guillain Barre syndrome: Retrospective study.

INTRODUCTION: Catastrophic health expenditure (CHE) is a reliable measure of the financial unpreparedness of the studied population to meet unexpected health issues. The alarming proportion of patients who incur CHE in the wake of an acute neurological illness like Guillain Barre Syndrome (GBS) is of serious concern in a country like India where a large majority of households are uninsured. METHODOLOGY: Medical records of patients diagnosed with at a tertiary care centre in Delhi were analysed retrospectively to determine the rate of CHE. Clinical details and other contributory variables were also recorded. RESULTS: 53 patients with a median age of 29 years (10.5-46.5) were included in the study. Tow- third of patients were less than 40 years of age and 58.5% were male. 90.6% of patients incurred CHE with a median amount INR 273 300 spent out of pocket. CONCLUSION: The enormous magnitude of financial distress and crisis emerging out of an acute neurological illness needs to be addressed with urgency to prevent impoverishment of already weakened households.

Costs of Guillain-Barré Syndrome in the Brazilian Federal District: the patients' perspective.

BACKGROUND: Although rare, Guillain-Barré Syndrome (GBS) has a high economic burden, with consequences for families and society. This study aimed to estimate the total cost of GBS, per individual and per variant of the disease, as well as its effect on household income, from the perspective of patients. METHODS: This was a cost-of-illness study from the perspective of patients and their families, with a time horizon from disease onset to 6 mo after discharge. The total cost of GBS was estimated by bottom-up microcosting, considering direct and indirect costs. RESULTS: The median cost of GBS per individual was US$1635.5, with direct costs accounting for 64.3% of this amount. Among the variants analyzed, acute motor sensory axonal neuropathy (US$4660.1) and acute inflammatory demyelinating polyneuropathy (US$2017.0) exhibited the highest costs compared with acute motor axonal neuropathy (US$1635.5) and Miller Fisher Syndrome (US$1464.8). The costs involved compromise more than 20% of the household income of 22 (47.8%) patients. CONCLUSIONS: This study demonstrated how costly GBS can be. It is hoped that decision-makers will analyze these results with a view to improving the structure of healthcare services.

Risk of Guillain-Barré syndrome following herpes zoster, United States, 2010-2018.

Epidemiologic data regarding the risk of Guillain-Barré syndrome (GBS) following herpes zoster (HZ) are limited. We conducted a self-controlled case series analysis using two large national data sources to evaluate the risk of GBS following HZ among U.S. adults. We analyzed medical claims from the IBM® MarketScan® Commercial Claims and Encounters (persons 18-64 years during 2010-2018) and Centers for Medicare and Medicaid Services Medicare (persons ≥65 years during 2014-2018) databases. HZ cases were defined as persons with an outpatient claim with a primary or secondary ICD-9 or ICD-10 diagnostic code for HZ. GBS cases were defined as persons with an inpatient claim with a principle diagnostic code for GBS and an associated procedural code. We compared the rates of GBS following HZ in the 1-42-day risk window versus primary (100-365-day) or secondary (43-99-day) control windows. We identified 489,516 persons 18-64 years of age and 650,229 persons ≥65 years of age with HZ, among whom 11 and 41, respectively, developed GBS 1-365 days following HZ. The risk of GBS following HZ was increased during the risk window as compared to the primary control window for both groups, with a rate ratio of 6.3 (95% CI, 1.8-21.9) for those 18-64 years and 4.1 (95% CI, 1.9-8.7) for those ≥65 years. This study provides new and methodologically rigorous epidemiologic support for an association between HZ and GBS, and useful context regarding the benefits versus potential risks of zoster vaccination.

Risk of Guillain-Barré Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries.

Importance: Guillain-Barré syndrome can be reported after vaccination. This study assesses the risk of Guillain-Barré syndrome after administration of recombinant zoster vaccine (RZV or Shingrix), which is administered in 2 doses 2 to 6 months apart. Objective: Use Medicare claims data to evaluate risk of developing Guillain-Barré syndrome following vaccination with zoster vaccine. Design, Setting, and Participants: This case series cohort study included 849 397 RZV-vaccinated and 1 817 099 zoster vaccine live (ZVL or Zostavax)-vaccinated beneficiaries aged 65 years or older. Self-controlled analyses included events identified from 2 113 758 eligible RZV-vaccinated beneficiaries 65 years or older. We compared the relative risk of Guillain-Barré syndrome after RZV vs ZVL, followed by claims-based and medical record-based self-controlled case series analyses to assess risk of Guillain-Barré syndrome during a postvaccination risk window (days 1-42) compared with a control window (days 43-183). In self-controlled analyses, RZV vaccinees were observed from October 1, 2017, to February 29, 2020. Patients were identified in the inpatient, outpatient procedural (including emergency department), and office settings using Medicare administrative data. Exposures: Vaccination with RZV or ZVL vaccines. Main Outcomes and Measures: Guillain-Barré syndrome was identified in Medicare administrative claims data, and cases were assessed through medical record review using the Brighton Collaboration case definition. Results: Amongst those who received RZV vaccinees, the mean age was 74.8 years at first dose, and 58% were women, whereas among those who received the ZVL vaccine, the mean age was 74.3 years, and 60% were women. In the cohort analysis we detected an increase in risk of Guillain-Barré syndrome among RZV vaccinees compared with ZVL vaccinees (rate ratio [RR], 2.34; 95% CI, 1.01-5.41; P = .047). In the self-controlled analyses, we observed 24 and 20 cases during the risk and control period, respectively. Our claims-based analysis identified an increased risk in the risk window compared with the control window (RR, 2.84; 95% CI, 1.53-5.27; P = .001), with an attributable risk of 3 per million RZV doses (95% CI, 0.62-5.64). Our medical record-based analysis confirmed this increased risk (RR, 4.96; 95% CI, 1.43-17.27; P = .01). Conclusions and Relevance: Findings of this case series cohort study indicate a slightly increased risk of Guillain-Barré syndrome during the 42 days following RZV vaccination in the Medicare population, with approximately 3 excess Guillain-Barré syndrome cases per million vaccinations. Clinicians and patients should be aware of this risk, while considering the benefit of decreasing the risk of herpes zoster and its complications through an efficacious vaccine, as risk-benefit balance remains in favor of vaccination.

Global, regional, and national burden of Guillain-Barré syndrome and its underlying causes from 1990 to 2019.

BACKGROUND: This article presents the first detailed analysis of the prevalence and disability burden of Guillain-Barré syndrome (GBS) from 1990 to 2019 by cause, age, sex, and Socio-demographic Index (SDI) in 204 countries and territories. METHODS: Data from the Global Burden of Diseases Study (GBD) 2019 were used. GBD 2019 modelled the prevalence of GBS using hospital and claims data. Years lived with disability (YLDs) were estimated as the product of the GBS prevalence and the disability weight. This article also reported proportions in the age-standardised prevalence rate that were due to six underlying causes of GBS. RESULTS: In 2019, there were 150,095 [95% uncertainty intervals (UI) 119,924 to 188,309] total cases of GBS worldwide, which resulted in 44,407 (95% UI 28,016 to 64,777) YLDs. Globally, there was a 6.4% (95% UI 3.6 to 9.5) increase in the age-standardised prevalence of GBS per 100,000 population between 1990 and 2019. High-income Asia Pacific [1.9 (95% UI: 1.5 to 2.4)] and East Asia [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardised prevalence rates (per 100,000), respectively, in 2019. Nationally, Japan [6.4 (95% UI: 5.3 to 7.7)] and China [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardised prevalence rates (per 100,000). The age-standardised burden of GBS increased with increasing age and was higher in males in all age groups. Furthermore, the age-standardised prevalence of GBS (per 100,000) had a positive association with the level of development, as measured by SDI, although this association was not strong. Upper respiratory infections and unknown causes accounted for the highest proportions of underlying causes. CONCLUSIONS: Globally, the prevalence of GBS continues to increase. Geographical differences and strategies aimed at preventing infectious diseases should be considered in future health policy planning and decision-making processes. This study had several limitations, such as using the same disability weight for all causes and a reliance on hospital- and self-reported data, which should be addressed in future research.

Sensitivity of Guillain-Barre Syndrome Surveillance in the Brazilian Federal District, using the Capture-Recapture Method.

INTRODUCTION: Guillain-Barre Syndrome (GBS) is an acute immune-mediated polyneuropathy that compromises the peripheral and cranial nerves. It is characterized by rapid-onset paresthesia accompanied by progressive weakness in the lower extremities followed by symmetric ascending paralysis. METHODOLOGY: assessment of sensitivity to detect GBS between March 2017 and May 2019 in a public referral hospital, using the capture-recapture method based on the Chapman estimator and comparing three GBS data sources: the hospital-based sentinel surveillance system (VSBH), Human Immunoglobulin Dispensing Records System (RDIH), and Hospital Information System (SIH). RESULTS: A total of 259 possible cases were identified (captured). Of these, 58 were confirmed and most resided in the Federal District. The VSBH showed the greatest sensitivity in case identification. The temporal distribution of cases showed periods with no cases identified, and more were registered during the rainy season from October to May, when high temperatures also occur. CONCLUSIONS: Increased circulation of arboviruses and gastrointestinal infections during the rainy season may explain the greater concentration of GBS cases. It is important to note that one-third of the cases identified in the different data sources do not converge, demonstrating that no single surveillance system is 100% effective. The severity and possible increase in cases related to GBS demonstrates the need for an improved surveillance system capable of monitoring and following-up cases involving neurological syndromes, regardless of the event preceding infection.

Guillain-Barré syndrome in low-income and middle-income countries: challenges and prospects.

The epidemiology, clinical characteristics, management and outcome of Guillain-Barré syndrome (GBS) differ between low-income and middle-income countries (LMIC) and high-income countries (HIC). At present, limited data are available on GBS in LMIC and the true incidence of GBS in many LMIC remains unknown. Increased understanding of GBS in LMIC is needed because poor hygiene and high exposure to infections render populations in LMIC vulnerable to GBS outbreaks. Furthermore, insufficient diagnostic and health-care facilities in LMIC contribute to delayed diagnosis in patients with severe presentations of GBS. In addition, the lack of national clinical guidelines and absence of affordable, effective treatments contribute to worse outcomes and higher mortality in LMIC than HIC. Systematic population-based surveillance studies, cohort and case-control studies are required to understand the incidence and risk factors for GBS. Novel, targeted and cost-effective treatment strategies need to be developed in the context of health system challenges in LMIC. To ensure integrative rehabilitation services in LMIC, existing prognostic models must be validated, and responsive outcome measures that are cross-culturally applicable must be developed. Therefore, fundamental and applied research to improve the clinical management of GBS in LMIC should become a critical focus of future research programmes.

Burden of Disease of Guillain-Barré Syndrome in Brazil before and during the Zika virus epidemic 2014-2016.

OBJECTIVE: To estimate the burden of disease of Guillain-Barré syndrome (GBS) in Brazil in 2014, 1 year before the Zika virus epidemic, and in 2015 and 2016 during the epidemic. METHODS: The burden of disease of GBS was estimated using the summary measure of population health: Disability Adjusted Life Years (DALY), that combines both mortality (Years of Life Lost YLLs) and morbidity (Years Lived with Disability) components. The study population was composed of GBS hospitalised cases and deaths from the information systems of the Brazilian Unified Health System. RESULTS: The GBS incidence rate in 2014, 2015 and 2016 was 0.74, 0.96, 1.02/100 000 respectively, and the mortality rate in the same period was 0.08, 0.009 and 0.11/100 000 habitants. The DALYs calculated using the point estimate of GBS disability weight and its values of the confidence interval (0.198 and 0.414) were 5725.90 (5711.79-5742.89) in 2014, 6054.61 (6035.57-6077.54) in 2015 and 7588.49 (7570.20-7610.51) in 2016. The DALYs were high among the male population and in age groups between 20 and 50 years. CONCLUSIONS: The increase in DALYs in the years 2015 and 2016 compared to 2014 probably resulted from the introduction of ZIKV in Brazil, reinforcing the importance of investments in the prevention of ZIKV infection and in the care of GBS patients.

OBJECTIF: Estimer la charge de morbidité du syndrome de Guillain-Barré (SGB) au Brésil en 2014, un an avant l'épidémie du virus Zika (ZIKV) et en 2015 et 2016 pendant l'épidémie. MÉTHODES: La charge de la maladie du SGB a été estimée à l'aide de la mesure récapitulative de la santé de la population: années de vie ajustées en fonction de l'incapacité (AVCI), qui combine à la fois les composantes de la mortalité (années de vie perdues AVP) et de la morbidité (années vécues avec une incapacité). La population de l'étude était composée de cas hospitalisés du SGB et de décès provenant des systèmes d'information du système de santé unifié brésilien. RÉSULTATS: Le taux d'incidence du SGB en 2014, 2015 et 2016 était de 0,74 ; 0,96 et 1,02/100.000 respectivement et le taux de mortalité au cours de la même période était de 0,08 ; 0,009 et 0,11/100.000 habitants. Les AVCI calculées à l'aide des points d'estimation du poids de l'incapacité du SGB et de ses valeurs de l'intervalle de confiance (0,198 et 0,414) étaient de 5.725,90 (5.711,79-5.742,89) en 2014 ; 6.054,61 (6.035,57-6.077,54) en 2015 et 7.588,49 (7.570,20 - 7.610,51) en 2016. Les AVCI étaient élevés parmi la population masculine et dans les groupes d'âge entre 20 et 50 ans. CONCLUSIONS: L'augmentation des AVCI en 2015 et 2016 par rapport à 2014 résulte probablement de l'introduction du ZIKV au Brésil, renforçant l'importance des investissements dans la prévention de l'infection par le ZIKV et dans la prise en charge des patients atteints de SGB.

Zika and dengue but not chikungunya are associated with Guillain-Barré syndrome in Mexico: A case-control study.

Background Zika, dengue and chikungunya viruses (ZIKV, CHIKV and DENV) are temporally associated with neurological diseases, such as Guillain-Barré syndrome (GBS). Because these three arboviruses coexist in Mexico, the frequency and severity of GBS could theoretically increase. This study aims to determine the association between these arboviruses and GBS in a Mexican population and to establish the clinical characteristics of the patients, including the severity of the infection. A case-control study was conducted (2016/07/01-2018/06/30) in Instituto Mexicano del Seguro Social (Mexican Social Security Institute) hospitals, using serum and urine samples that were collected to determine exposure to ZIKV, DENV, CHIKV by RT-qPCR and serology (IgM). For the categorical variables analysis, Pearson's χ2 or Fisher exact tests were used, and the Mann-Whitney U test for continuous variables. To determine the association of GBS and viral infection diagnosis through laboratory and symptomatology before admission, we calculated the odds ratio (OR) and 95% confidence intervals (95%CI) using a 2x2 contingency table. A p-value ≤ 0.05 was considered as significant. Ninety-seven GBS cases and 184 controls were included. The association of GBS with ZIKV acute infection (OR, 8.04; 95% CI, 0.89-73.01, p = 0.047), as well as laboratory evidence of ZIKV infection (OR, 16.45; 95% CI, 2.03-133.56; p = 0.001) or Flavivirus (ZIKV and DENV) infection (OR, 6.35; 95% CI, 1.99-20.28; p = 0.001) was observed. Cases of GBS associated with ZIKV demonstrated a greater impairment of functional status and a higher percentage of mechanical ventilation. According to laboratory results, an association between ZIKV or ZIKV and DENV infection in patients with GBS was found. Cases of GBS associated with ZIKV exhibited a more severe clinical picture. Cases with co-infection were not found.

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

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.

Incidence of Campylobacter-Associated Guillain-Barré Syndrome Estimated from Health Insurance Data.

Guillain-Barré syndrome (GBS) is sometimes preceded by Campylobacter infection. We estimated the cumulative incidence of Campylobacter-associated GBS in the United States using a retrospective cohort design. We identified a cohort of patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code of "intestinal infection due to Campylobacter" (008.43) using MarketScan Research Databases for 2004-2013. Campylobacter patients with an encounter for "acute infective polyneuritis" (AIP; ICD-9-CM 357.0) were identified. Patients with an inpatient encounter having AIP as the principal diagnosis were considered probable GBS cases. Patients with probable GBS ≤8 weeks after the Campylobacter encounter were considered probable Campylobacter-associated GBS cases. For comparison, we repeated this analysis for patients with "other Salmonella infections" (ICD-9-CM: 003). Among 9315 Campylobacter patients, 16 met the case definition for probable GBS. Two were hospitalized with probable GBS ≤8 weeks after the encounter listing a Campylobacter diagnosis (9 and 54 days) and were considered probable cases of Campylobacter-associated GBS; this results in an estimated cumulative incidence of 21.5 per 100,000 Campylobacter patients (95% confidence interval [CI]: 3.7-86.6), or 5% of all estimated GBS cases. The remaining 14 patients were diagnosed with probable GBS on the same encounter (n = 12) or 1-3 days (n = 2), before the encounter listing the Campylobacter diagnosis. Including these cases increased the cumulative incidence to 172 per 100,000 Campylobacter cases (95% CI: 101.7-285.5), 41% of estimated GBS cases. This study, using a method not previously applied to United States data, supports other data that Campylobacter is an important contributor to GBS, accounting for at least 5% and possibly as many as 41% of all GBS cases. These data can be used to inform estimates of the burden of Campylobacter infections, including economic cost.

Guillain-Barré syndrome and antecedent cytomegalovirus infection, USA 2009-2015.

OBJECTIVE: To describe incidence and clinical characteristics of cases of Guillain-Barré syndrome (GBS) in the USA during 2009-2015, and characteristics of GBS cases with antecedent cytomegalovirus (CMV) infection among persons with employer-sponsored insurance. METHODS: We analyzed medical claims from IBM Watson MarketScan® databases. GBS patients were defined as enrollees with an inpatient claim with GBS as the principal diagnosis code, based on ICD-9 or ICD-10, and ≥ 1 claim for lumbar puncture or EMG/nerve conduction study. We assessed intensive care unit (ICU) hospitalization, intubation, dysautonomia, and death. We also assessed selected infectious illness within 60 days prior to the first GBS-coded inpatient claim. RESULTS: We identified 3486 GBS patients; annual incidence was 1.0-1.2/100,000 persons during 2009-2015. GBS incidence was higher in males (1.2/100,000) than in females (0.9/100,000) (p = 0.006) and increased with age, from 0.4/100,000 in persons 0-17 years old to 2.1/100,000 in persons ≥ 65 years old (p < 0.001). Half of GBS patients were hospitalized in the ICU, 8% were intubated, 2% developed dysautonomia, and 1% died. Half had a claim for antecedent illness, but only 125 (3.5%) had a claim for specific infectious pathogens. The mean age among 18 GBS patients with antecedent CMV infection was 39 years versus 47 years among those without antecedent  CMV infection (p = 0.038). CONCLUSIONS: Incidence of GBS using a large national claims database was comparable to that reported in the literature, but cases appeared to be less severe. Half of GBS patients reported prior infectious illness, but only a minority had a specific pathogen identified.

Surveillance for Guillain-Barré syndrome after 2015-2016 and 2016-2017 influenza vaccination of Medicare beneficiaries.

BACKGROUND: Guillain-Barré syndrome (GBS) is a serious acute demyelinating disease, an increased risk of which was found after the 1976 swine flu vaccinations. The U.S. Food and Drug Administration, in collaboration with the Centers for Medicare & Medicaid Services, has been conducting active surveillance for GBS after influenza vaccinations of Medicare Fee-For-Service beneficiaries since 2009. METHODS: We conducted active surveillance for GBS claims in the 2015-2016 and 2016-2017 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT) to monitor for signals of GBS risk. We performed self-controlled risk interval (SCRI) analyses at the end of both seasons, including chart confirmation in the 2015-2016 season, to estimate the odds ratio of GBS risk. We used 1-42 and 8-21 days post-vaccination as primary and secondary risk windows, respectively, and 43-84 days post-vaccination as the control window. RESULTS: Over 13 million beneficiaries were vaccinated in each season. USPRT found a low magnitude signal for GBS in both seasons. SCRI analyses did not find excess GBS risk following any influenza vaccine for days 1-42 post-vaccination in either season. In the 2015-2016 season, for the 8-21 day window, our chart-confirmation showed an attributable GBS risk of 0.87 (95% CI: 0.16, 1.49) and 1.68 (95% CI: 0.69, 2.41) cases per million vaccinees after all seasonal and high dose (HD) vaccines, respectively, an elevated GBS risk for beneficiaries aged ≥75 years following all seasonal vaccines (OR: 2.25; 95% CI: 1.15, 4.39) and HD vaccine (OR: 3.67, 95% CI: 1.52, 8.85), and an elevated GBS risk for males who received seasonal vaccines (OR: 2.18; 95% CI: 1.15, 4.15) and HD vaccine (OR: 3.33; 95% CI: 1.35, 8.20). The finding of elevated GBS risk with advancing age and in males is consistent with literature; however, a distinction between HD and SD was a new finding. In the 2016-17 season, for the 8-21 day window, attributed cases showed an attributable GBS risk of 0.87 (95% CI: 0.03, 1.61) and 1.11 (95% CI: 0.00, 2.01) cases per million vaccinees after all seasonal and HD vaccines, respectively. We found no excess GBS risk for standard dose vaccines in the 8-21 day window in either season. CONCLUSIONS: Our primary analysis finding of no excess GBS risk during both seasons was reassuring. The slightly elevated GBS risk, although in the expected range, in the 8-21 day window after all seasonal and high dose vaccines, but not after standard dose vaccines is hypothesis-generating because the difference may be due to vaccine factors such as antigen amount or strains in various seasons or due to host factors.