Background rates of adverse events of special interest for COVID-19 vaccines: A multinational Global Vaccine Data Network (GVDN) analysis.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring. METHODS: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios. RESULTS: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19. CONCLUSION: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

Low-cost 3D-printed anthropomorphic cardiac phantom, for computed tomography automatic left ventricle segmentation and volumetry - A pilot study.

INTRODUCTION: Accurate cardiac left ventricle (LV) delineation is essential to CT-derived left ventricular ejection fraction (LVEF). To evaluate dose-reduction potential, an anatomically accurate heart phantom, with realistic X-ray attenuation is required. We demonstrated and tested a custom-made phantom using 3D-printing, and examined the influence of image noise on automatically measured LV volumes METHODS: A single coronary CT angiography (CCTA) dataset was segmented and converted to Standard Tessellation Language (STL) mesh, using open-source software. A 3D-printed model, with hollow left heart chambers, was printed and cavities filled with gelatinized contrast media. This was CT-scanned in an anthropomorphic chest phantom, at different exposure conditions. LV and "myocardium" noise and attenuation was measured. LV volume was automatically measured using two different methods. We calculated Spearmans' correlation of LV volume with noise and contrast-noise ratio respectively om 486 scans of the phantom. Source images were compared to one phantom series with similar parameters. This was done using Dice coefficient on LV short-axis segmentations. RESULTS: Phantom "Myocardium" and LV attenuation was comparable to measurements on source images. Automatic volume measurement succeeded, with mean volume deviation to patient images less than 2 ml. There was a moderate correlation of volume with CNR, and strong correlation of volume with image noise. With papillary muscles included in LV volume, the correlation was positive, but negative when excluded. Variation of volumes was lowest at 90-100 kVp for both methods in the 486 repeat scans. The Dice coefficient was 0.87, indicating high overlap between the single phantom series and source scan. Cost of 3D-printer and materials was 400 and 30 Euro respectively. CONCLUSION: Both anatomically and radiologically the phantom mimicked the source scans closely. LV volumetry was reliably performed with automatic algorithms. IMPLICATIONS FOR PRACTICE: Patient-specific cardiac phantoms may be produced at minimal cost and can potentially be used for other anatomies and pathologies. This enables radiographic phantom studies without need for dedicated 3D-labs or expensive commercial phantoms.

Design of a 3D printed coronary artery model for CT optimization.

INTRODUCTION: To design a custom phantom of the coronary arteries to optimize CT coronary angiography (CCTA) protocols. METHODS: Characteristics of the left and right coronary arteries (mean Hounsfield Unit (HU) values and diameters) were collected from consecutive CCTA examinations (n = 43). Four different materials (two mixtures of glycerine, gelatine and water, pig hearts, Ecoflex™ silicone) were scanned inside a Lungman phantom using the CCTA protocol to find the closest model to in vivo data. A 3D printed model of the coronary artery tree was created using CCTA data by exporting a CT volume rendering into Autodesk Meshmixer™ software. The model was placed in an acid bath for 5 h, then covered in Ecoflex™, which was removed after drying. Both the Ecoflex™ and pig heart were later filled with a mixture of contrast (Visipaque 320 mg I/ml), NaCl and gelatin and scanned with different levels of tube current and iterative reconstruction (ASiR-V). Objective (HU, noise and size (vessel diameter) and subjective analysis were performed on all scans. RESULTS: The gelatine mixtures had HU values of 130 and 129, Ecoflex™ 65 and the pig heart 56. At the different mA/ASiR-V levels the contrast filled Ecoflex™ had a mean HU 318 ± 4, noise 47±7HU and diameter of 4.4 mm. The pig heart had a mean HU of 209 ± 5, noise 38±4HU and a diameter of 4.4 mm. With increasing iterative reconstruction level the visualisation of the pig heart arteries decreased so no measurements could be performed. CONCLUSION: The use of a 3D printed model of the arteries and casting with the Ecoflex™ silicone is the most suitable solution for a custom-designed phantom. IMPLICATIONS FOR PRACTICE: Custom designed phantoms using 3D printing technology enable cost effective optimisation of CT protocols.

3D virtual reality simulation in radiography education: The students' experience.

INTRODUCTION: Simulation forms a key element of undergraduate Radiography education as it enables students to develop their clinical skills in a safe environment. In this study, an immersive three-dimensional (3D) virtual radiography simulation tool was piloted in an undergraduate Radiography curriculum and user feedback retrieved. METHODS: The 3D virtual simulation tool by Virtual Medical Coaching Ltd was introduced to first year radiography students (n = 105). This technology guided students through a comprehensive process of learning anatomy, radiographic positioning and pathology. Students then X-rayed a virtual patient in the VR suite using HTC Vive Pro™ headsets and hand controllers. Instant feedback was provided. An online survey was later disseminated to students to gather user feedback. Thematic and descriptive statistical analyses were applied. RESULTS: A response rate of 79% (n = 83) was achieved. Most respondents (58%) reported enjoying VR simulation, whilst some felt indifferent towards it (27%). Ninety-four percent would recommend this tool to other students. The mean length of time it took for students to feel comfortable using the technology was 60 min (10-240 min). Most respondents (58%) desired more VR access. Students attributed enhanced confidence in the areas of beam collimation (75%), anatomical marker placement (63%), centring of the X-ray tube (64%) and exposure parameter selection (56%) to their VR practice. Many students (55%) advocated the use of VR in formative or low stakes assessments. Issues flagged included technical glitches, inability to palpate patient and lack of constructive feedback. CONCLUSION: Student feedback indicates that 3D virtual radiography simulation is a valuable pedagogical tool in radiography education IMPLICATIONS FOR PRACTICE: 3D immersive VR simulation is perceived by radiography students to be a valuable learning resource. VR needs to be strategically implemented into curricula to maximise its benefits.

CTSim: Changing teaching practice in radiography with simulation.

INTRODUCTION: Simulation offers radiography students the possibility to experiment with Computed Tomography (CT) in a way not possible in clinical practice. The aim of this work was to test a newly developed simulator 'CTSim' for effectiveness in teaching and learning. METHODS: The simulator was tested in two phases. The first phase used a test-retest methodology with two groups, a group that experienced a Simulation based learning intervention and one which did not. The second phase subsequently tested for changes when the same intervention was introduced as part of an existing CT training module. RESULTS: Phase 1 demonstrated statistically significant improvement of mean scores from 58% to 68% (P < .05) for students who experienced the intervention against no change in scores for the control group. Phase 2 saw mean scores improve statistically significantly in a teaching module from 66% to 73% (P < .05) following the application of the intervention as an active learning component. CONCLUSION: The use of the CTSim simulator had a demonstrable effect on student learning when used as an active learning component in CT teaching. IMPLICATIONS FOR PRACTICE: Simulation tools have a place in enhancing teaching and learning in terms of effectiveness and also introduce variety in the medium by which this is done.

The risk of Kawasaki disease after pneumococcal conjugate & meningococcal B vaccine in England: A self-controlled case-series analysis.

Kawasaki disease (KD) is an uncommon condition occasionally reported after childhood vaccination. Admissions with a KD-compatible diagnosis identified from a national database in England were linked to immunisation records to investigate the risk after pneumococcal conjugate (PCV) or meningococcal B (MenB) vaccines. Both are given at 2/4/12 months of age but were introduced sequentially, allowing their effects to be separately assessed. A total of 553 linked admissions in 512 individuals were validated as KD. The relative incidence (RI) within 28 days of PCV doses 1 or 2 measured by the self-controlled case-series method was 0.62 (95% confidence interval (CI) 0.38-1.00) with a significantly decreased risk after dose 3 (RI 0.30 (95% CI 0.11-0.77)). For MenB vaccine, the RI after doses 1 or 2 was 1.03 (95% CI 0.51-2.05) and 0.64 (95% CI 0.08-5.26) after dose 3. This study shows no evidence of an increased risk of KD after either vaccine.

Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing.

Mechanical stretch of cardiac muscle modulates action potential propagation velocity, causing potentially arrhythmogenic conduction slowing. The mechanisms by which stretch alters cardiac conduction remain unknown, but previous studies suggest that stretch can affect the conformation of caveolae in myocytes and other cell types. We tested the hypothesis that slowing of action potential conduction due to cardiac myocyte stretch is dependent on caveolae. Cardiac action potential propagation velocities, measured by optical mapping in isolated mouse hearts and in micropatterned mouse cardiomyocyte cultures, decreased reversibly with volume loading or stretch, respectively (by 19±5% and 26±4%). Stretch-dependent conduction slowing was not altered by stretch-activated channel blockade with gadolinium or by GsMTx-4 peptide, but was inhibited when caveolae were disrupted via genetic deletion of caveolin-3 (Cav3 KO) or membrane cholesterol depletion by methyl-ß-cyclodextrin. In wild-type mouse hearts, stretch coincided with recruitment of caveolae to the sarcolemma, as observed by electron microscopy. In myocytes from wild-type but not Cav3 KO mice, stretch significantly increased cell membrane capacitance (by 98±64%), electrical time constant (by 285±149%), and lipid recruitment to the bilayer (by 84±39%). Recruitment of caveolae to the sarcolemma during physiologic cardiomyocyte stretch slows ventricular action potential propagation by increasing cell membrane capacitance.

Pandemic A/H1N1 2009 influenza vaccination, preceding infections and clinical findings in UK children with Guillain-Barré syndrome.

OBJECTIVE: To record clinical findings in all new cases of Guillain-Barré syndrome (GBS) or Fisher syndrome (FS) in UK children in the 2 years following September 2009 and determine the proportion temporally associated with recent infections, pandemic H1N1 (2009) strain influenza vaccination or seasonal influenza vaccination. DESIGN: A prospective UK-wide epidemiological study using the British Paediatric Surveillance Unit system. PATIENTS: Children aged 16 years or less meeting the Brighton Collaboration criteria for GBS or FS. RESULTS: 112 children with GBS (66 boys and 46 girls) and 3 boys with FS were identified in 2 years. All but one recovered sufficiently to go home. The annual UK incidence rate of GBS in patients less than 15 years old was 0.45/100 000, similar to other countries. There was evidence of infection in the 3 months preceding onset in 92/112 GBS and 3/3 FS cases. Of those living in England, 7 cases received pandemic A/H1N1 2009 influenza vaccination before GBS symptom onset (3/7 were within 6 months including 1 within 3 months); 2 children received 2010/2011 seasonal influenza vaccination within 6 months of GBS onset. The numbers vaccinated were not significantly greater than expected by chance. CONCLUSIONS: The outcome for childhood GBS and FS after 6 months was better than reported in adults. Most UK GBS and FS cases had infections in the preceding 3 months. When considering the children living in England, there was no significantly increased risk of GBS after pandemic A/H1N1 2009 influenza vaccination or 2010/2011 seasonal influenza vaccination.

Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United Kingdom.

Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were withdrawn in the United Kingdom in 1992 following demonstration of an increased risk of aseptic meningitis 15-35 days after vaccination. Following introduction of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom) in 1998, active surveillance of aseptic meningitis and convulsion was established to evaluate the risk associated with the new vaccine. No laboratory-confirmed cases of mumps meningitis were detected among children aged 12-23 months after administration of 1.6 million doses of Priorix (upper 95% confidence limit of risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No cases of aseptic meningitis were detected among children aged 12-23 months, who had received over 99,000 doses of Priorix (upper 95% confidence limit of risk: 1:27,000), in a regional database of hospital-admitted cases. This compares with an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence of convulsion was found in the 6- to 11-day period after receipt of Priorix (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with the known effects of the measles component of MMR vaccine-but not in the 15- to 35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as occurred with Urabe-containing vaccines. This study demonstrates the power of active postmarketing surveillance to identify or exclude events too rare to be detected in prelicensure trials.

No evidence of an association between MMR vaccine and gait disturbance.

BACKGROUND: MMR vaccine has been reported to cause gait disturbance, and this possible association has been claimed to support the MMR-causes-autism theory. AIMS: To determine whether any association between gait disturbance and MMR vaccination exceeds the age related background rate of gait disturbance, using record linkage and self control case series analyses. METHODS: MMR vaccination records were linked to hospital admission and general practitioner attendance data. An increased rate of gait problems with onset in various intervals in the 60 day period after MMR vaccination was looked for in children aged 12 to <24 months. RESULTS: No evidence of an increased rate of hospital admission or general practice consultations for gait disturbance was found in the putative post-vaccination risk periods. CONCLUSIONS: This study provides no evidence for a causal association between MMR and gait disturbance.

Prevalence of autism and parentally reported triggers in a north east London population.

BACKGROUND: The recorded prevalence of autistic spectrum disorders has risen over recent decades. Measles, mumps and rubella (MMR) vaccine has been blamed, by causing a "new variant" form of "regressive autism" associated with "autistic enterocolitis". AIMS: To estimate the prevalence of autism and to assess any changes in parental perception regarding the onset or causes of autism. METHODS AND RESULTS: A total of 567 children with autistic spectrum disorder in five districts in north east London were identified, born 1979-98. Reported autism, excluding the 94 cases of Asperger's syndrome, increased by year of birth until 1992, since when prevalence has plateaued. This flattening off persisted after allowing for expected delay in diagnosis in more recent birth cohorts. The age at diagnosis of autistic spectrum disorder was estimated to have decreased per five year period since 1983, by 8.7% for childhood autism and by 11.0% for atypical autism. There was some evidence that MMR was more likely to be mentioned as a trigger after August 1997 than before. CONCLUSIONS: The prevalence of autism, which was apparently rising from 1979 to 1992, reached a plateau from 1992 to 1996 at a rate of some 2.6 per 1000 live births. This levelling off, together with the reducing age at diagnosis, suggests that the earlier recorded rise in prevalence was not a real increase but was likely due to factors such as increased recognition, a greater willingness on the part of educationalists and families to accept the diagnostic label, and better recording systems. The proportion of parents attributing their child's autism to MMR appears to have increased since August 1997.

Differential effects of intraspecific interactions on the striatal dopamine system in social and non-social voles.

We used in vivo microdialysis to examine the responses to intraspecific social interactions in the striatal dopamine systems of females of two vole species displaying vastly different social structures. Both highly social prairie voles and asocial meadow voles had similar increases in extracellular dopamine associated with mating. There was a species-specific effect of social condition on extracellular dihydroxyphenylacetic acid (DOPAC). Exposure to a conspecific male significantly decreased extracellular DOPAC in female prairie voles isolated for approximately 18 h during surgical recovery. Such decrease in DOPAC was not seen if females experienced continued isolation or if they were housed with a sibling during surgical recovery. No changes in extracellular DOPAC were seen in meadow voles after manipulations of social environment. Together, our data indicate that mating-associated dopamine release is independent from mating systems. However, species-specific patterns of extracellular DOPAC suggest that social isolation may be a more stressful stimulus for the social prairie vole than for the asocial meadow vole.

Recall bias, MMR, and autism.

Parents of autistic children with regressive symptoms who were diagnosed after the publicity alleging a link with measles, mumps, and rubella (MMR) vaccine tended to recall the onset as shortly after MMR more often than parents of similar children who were diagnosed prior to the publicity. This is consistent with the recall bias expected under such circumstances.

Addiction medicine in organ tansplantation.

Allocation of organs for transplant has created medical, ethical, and economic concerns at a time when availability of all organs is extremely limited. Although transplantation is the final treatment for many diseases, it is not available to everyone. Patients' use of alcohol and other drugs has become a controversial and debated issue in the transplant community. Compliance is important for all transplant recipients, but it becomes even more important in patients whose drug or alcohol use has caused their organ disease. The issue of addiction appears to be more critical with transplant patients because of the potential for noncompliance, which may lead to graft loss. Local, regional, and national regulations have also affected the allocation of organs. At The Cleveland Clinic Foundation, a chemical dependency transplant team was formed in response to criteria of the Ohio Solid Organ Transplantation Consortium for transplant patients with addictive disorders. The assessment, treatment, and monitoring of these patients requires specific expertise; a prominent role on transplant teams for specialists in addiction has resulted. The purpose of this article is to describe the responsibilities of the chemical dependency transplant team, the scope of the referral and evaluation process, and the team's appropriate roles with patients and transplant professionals.

Idiopathic thrombocytopenic purpura and MMR vaccine.

A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.

Does oral polio vaccine cause intussusception in infants? Evidence from a sequence of three self-controlled cases series studies in the United Kingdom.

BACKGROUND: The use of live oral poliomyelitis vaccine (OPV) has led to the elimination of poliomyelitis disease in many countries since licensure in 1960. The discovery of an increased risk of an intestinal obstruction known as intussusception following live rotavirus vaccination raised questions about the possibility of a link between live OPV and intussusception. METHODS: Three self-controlled case-series studies were carried out. The first was exploratory and included 218 intussusception episodes from hospital admissions data linked to vaccination records in the Thames region. The two subsequent studies, which used further hospital admissions data and the General Practice Research Database (GPRD) included 107 and 198 episodes respectively and were used to test hypotheses generated in the first study. RESULTS: In the exploratory study risk periods of up to 6 weeks after each dose were examined. The only period with some evidence of an increased risk was the 14-27-day period after the third dose (relative incidence (RI) = 1.97, p = 0.011). The second hospital admissions study and the GPRD study showed no evidence of an increased relative incidence in any putative risk period and did not confirm the increased risk in the 14-27-day period after dose 3 with a combined RI of 1.03. CONCLUSIONS: The sequence of studies does not support the hypothesis that OPV causes intussusception. The increased RI in the first study may be explained as a chance finding due to the number of risk periods examined and highlights the need for caution when looking at many risk periods without an a priori hypothesis.

Approaching a consensus: psychosocial support services for solid organ transplantation programs.

BACKGROUND: Solid organ transplantation has become an accepted treatment for individuals with end-stage organ dysfunction. Criteria are being developed in the United States to determine medical eligibility for transplant candidates and competencies for transplant centers and physicians. To date, similar criteria for psychosocial services have not been developed. DESIGN AND SETTING: We queried participants in a specialty psychosocial transplant meeting to determine their views of which psychosocial services are essential to the comprehensive care of transplant patients in the United States. RESULTS: There was broad based multidisciplinary support for proactive pretransplant screening to discern individual psychosocial needs; focused pretransplant interventions to improve candidacy and future compliance; and posttransplant programs that address psychosocial, rehabilitation, and financial issues. CONCLUSION: Among psychosocial providers of solid organ transplantation services, there is support for expanding routine screening and support services to individuals who are candidates for and undergo solid organ transplantation.