Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: A multinational self-controlled case series in Europe

BACKGROUND: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1)pdm09 vaccination. METHODS: A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. RESULTS: Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1)pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1)pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2-5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7-2.8), which is the main finding. CONCLUSION: This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1)pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8). Based on the upper limits of the pooled estimate we can rule out with 95% certainty that the number of excess GBS cases after influenza A(H1N1)pdm09 vaccination would be more than 3 per million vaccinated

Laboratory Monitoring of Patients Treated with Antihypertensive Drugs and Newly Exposed to Non Steroidal Anti-Inflammatory Drugs: A Cohort Study

BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions

Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: A multinational self-controlled case series in Europe

Background: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk

Antiretroviral drug exposure in pregnancy and risk of congenital anomalies: a European case/non-case malformed study

PurposeAntiretroviral drugs are recommended during pregnancy to achieve HIV viral suppression and reduce mother-to-child transmission. Congenital anomaly signals were reported after fetal exposure to antiretroviral drugs in several studies warranting further investigation. We aimed to evaluate the risk of congenital anomalies after fetal exposure to antiretroviral drugs using the European congenital anomaly registry data.MethodsA case/non-case study was performed, using the EUROmediCAT central database. All the congenital anomalies, exposed to any antiretroviral drugs, were included from 1995 to 2019. We explored each signal identified from the literature for associations between congenital anomalies and specific antiretroviral exposures. We compared antiretroviral exposure between the signal anomalies (cases) and all other malformed registrations (controls). Reporting odds ratio (ROR) and their 95% confidence intervals were estimated and adjusted for registry and maternal age.ResultsBetween 1995 and 2019, 173 cases of congenital anomalies were observed after any exposure to antiretroviral drugs. The signal previously identified in the literature between congenital heart defects and exposure to zidovudine was confirmed in the main analysis (aROR 3.66 [1.63–8.23]). Other signals identified in the literature were not confirmed, although two cases of hypospadias and two cases of limb defects were reported after zidovudine and atazanavir exposure, respectively. The signal detection analysis did not reveal any new signal after applying the Bonferroni correction.ConclusionsOur study does not reveal new signals but confirms the previously identified signal between congenital heart defects and fetal exposure to zidovudine. The physio-pathological hypothesis induced by zidovudine exposure should be explored in future studies

The economic burden of asthma prior to death: a nationwide descriptive study

BackgroundIn addition to the clinical burden, asthma is responsible for a high economic burden. However, little is known about the economic burden of asthma prior to death.ObjectiveWe performed an economic analysis to describe the costs during 12 and 24 months prior to asthma death between 2013 and 2017 in France.MethodsAn observational cohort study was established using the French national health insurance database. Direct medical and non-medical costs, as well as costs related to absence from the workplace, were included in the analysis.ResultsIn total, 3,829 patients were included in the final analysis. Over 24 and 12 months prior to death, total medical costs per patient were €27,542 [26,545–28,641] and €16,815 [16,164–17,545], respectively. Total medical costs clearly increased over 24 months prior to death. Over 12 months prior to death, costs increased significantly according to age categories, with mean total costs of €8,592, €15,038, and €17,845, respectively, for the categories <18 years old, 18–75 years old, and 75+ years old (p < 0.0001). Over 12 months prior to death, costs were statistically higher in patients with a dispensation of six or more SABA canisters compared to those with a dispensation of five or less canisters (p < 0.0001). In multivariate analysis, comorbidities, hospital as location of death, and dispensation of 12 or more canisters of SABA per year are independent factors of the highest costs.ConclusionTo conclude, the economic burden of asthma death is high and increases with time, age, and SABA dispensation

Radiology

Background: A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose: To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods: In this secondary analysis, two prospectively collected independent stroke data sets (2012–2015 and 2017–2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1–3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion–related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results: Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58–80 years]; 207 men) and 173 (median age, 74 years [IQR, 65–82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P =.02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P =.004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P =.20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P =.01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P =.03). Conclusion: Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. © RSNA, 2022.Translational Research and Advanced Imaging Laborator

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Médicaments et vague de chaleur : approche pharmacoépidémiologique

La canicule de l'été 2003 a conduit à une surmortalité, en particulier chez les personnes de plus de 75 ans. Au cours de cet été, à partir des données de la Base Nationale de Pharmacovigilance (BNPV), nous avons caractérisé 68 cas d'effets indésirables médicamenteux possiblement liés à une chaleur excessive chez les plus de 70 ans. Il s'agissait principalement d'effets métaboliques, impliquant les diurétiques, les médicaments du système rénine-angiotensine-aldostérone, et les antidépresseurs sérotoninergiques. En 2006, lors d'une nouvelle vague de chaleur, les diurétiques étaient plus largement imputés, pour un nombre d'effet indésirables liés à la chaleur comparable. Nous avons ensuite réalisé prospectivement en 2007 l'étude multicentrique SIRIUS, afin de comparer les médicaments pris par les personnes hospitalisées pour une complication liée à la chaleur avec des médicaments pris par des témoins. Les cas prenaient un nombre plus important de médicaments, en particulier des neuroleptiques et des antalgiques, et présentaient plus souvent une fonction rénale altérée. Cette étude nous a permis de tester la faisabilité du protocole, réalisable en cas de nouvelle vague de chaleur dans les années ultérieuresAn exceptional heat wave occurred during august 2003 in France, leading to more than 14,800 deaths estimated. We characterized all 'serious' adverse drug reactions (ADR) occurred in patients older than 70 years between 1st July and 31st August 2003, recorded in the French PharmacoVigilance Database, and related to excessive heat (n=68). The most frequently ADRs were metabolic. Drugs more frequently involved were diuretics, angiotensin converting enzyme inhibitors, and antidepressants. During another summer with a heat wave in 2006, diuretics were more frequently involved, whereas the number of ADRs was similar. In 2007, we performed a multicentric case-control study in 3 university hospitals in France, to compare drugs taken by patients hospitalized for a 'serious' hyperthermia and/or dehydratation with controls. Cases took more drugs than controls (4.3 vs 3.9; p<0.001), particularly neuroleptic drugs (3.6% vs 0.5%; p=0.007), and presented more severe renal impairment. This pilot work could allow improving methodology of further studies on drugs during heat wave