Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Food play: A novel research methodology for visceral geographers and health researchers.

This paper reinforces the value of visceral geographic approaches to health research as a method 'beyond talking'. The paper establishes and sets out an integrative embodied multi-sensory research methodology - food play. Researchers across the social sciences and sciences are exploring the limits of logo and researcher centric research methods and exploring peoples sensory experience of themselves and the wider world using participatory, patient-centred, multi-sensory, visceral and biosocial geographic approaches. With reference to the growing interest in visceral approaches to research in geography, and sensory research in neurology, anthropology and embodied cognition in psychology, we argue that the presence and pungency of food uniquely animates research, and for our research, provided highly individualised insight into the lived experience of living long term with eating difficulties, allowing visceral difference to emerge and be expressed. We illustrate our approach with reference to a six-year research project, Resources for Living, co-produced with survivors of head and neck cancer and underpinned by a series of food play workshops to address post-treatment and chronic difficulties with food and eating.

Altered eating: a definition and framework for assessment and intervention.

BACKGROUND: Eating can be a significant challenge for cancer survivors; however, to date there is no systematic way of assessing and addressing food related quality of life in this group. The purpose of our study was to develop a framework for doing so. METHODS: Over the course of 6 years in participant-led food workshops, we worked alongside 25 head and neck cancer (HNC) survivors and their partners, employing video-reflexive ethnographic (VRE) methods. The current study reports on data from the two summative workshops of this series where we worked with participants to cohere the emergent themes. Video and transcripts were reviewed and coded with participants and stakeholders according to domains of life that were affected by food. Three of the authors, one of whom is both survivor and researcher, arrived at the consensus framework. RESULTS: Seven areas of life were identified as affecting, or being affected by, altered eating. Three were physiological: anatomical, functional and sensory. Two captured the cognitive and behavioural labour of eating. Social life and identity were altered. The foregoing had an enduring emotional impact. CONCLUSIONS: Altered eating has physical, emotional and social consequences. The altered eating framework provides a systematic way of exploring those consequences with individual survivors. This framework has the potential to improve both the assessment and treatment of altered eating, to benefit food-related quality of life.

A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

Swine (Sus scrofa) as a Model of Postinfarction Mitral Regurgitation and Techniques to Accommodate Its Effects during Surgical Repair.

Mitral regurgitation (MR) is a common heart-valve lesion after myocardial infarction in humans. Because it is considered a risk factor for accelerated heart failure and death, various surgical approaches and catheter-based devices to correct it are in development. Lack of a reproducible animal model of MR after myocardial infarction and reliable techniques to perform open-heart surgery in these diseased models led to the use of healthy animals to test new devices. Thus, most devices that are deemed safe in healthy animals have shown poor results in human efficacy studies, hampering progress in this area of research. Here we report our experience with a swine model of postinfarction MR, describe techniques to induce regurgitation and perform open-heart surgery in these diseased animals, and discuss our outcomes, complications, and solutions.

The Impact of Intimal Tear Location and Partial False Lumen Thrombosis in Acute Type B Aortic Dissection.

BACKGROUND: Partial false lumen (FL) thrombosis is a risk factor for long-term mortality in acute type B aortic dissection (ATBAD). This study investigates FL pressures in models of ATBAD with patent and partially thrombosed FL. METHODS: Twenty-five porcine aortas were used to create five models of ATBAD that were connected to a pulsatile flow loop. Models A through C had a patent FL with the following morphologies: model A, single proximal tear; model B, single distal tear; and model C, single proximal and single distal tear. Models D and E had a single proximal and a single distal tear, with partial FL thrombosis. Model D had FL occlusion of the proximal tear, and model D had FL occlusion of the distal tear. True lumen (TL) and FL pressures were measured at 90 to 150 mm Hg. RESULTS: In model A, FL pressures were 6 mm Hg higher than TL pressures (p < 0.01). In model B, FL pressures were 10 mm Hg lower than TL pressures (p ≤ 0.01). In model C, TL and FL pressures were equivalent. In model D, FL pressures were 40 mm Hg lower than TL pressures (p < 0.001). In model E, FL pressures were 10 mm Hg higher than TL pressures (p < 0.01). CONCLUSIONS: In a biologic model of ATBAD, the number, location, and FL thrombosis status determine FL pressure. In the setting of partial FL thrombosis, the FL pressure is reduced with proximal tear occlusion and increased with distal tear occlusion. Reduced FL pressure is related to retrograde flow.

Pre-clinical Experience with a Multi-Chordal Patch for Mitral Valve Repair.

Surgical repair of flail mitral valve leaflets with neochordoplasty has good outcomes, but implementing it in anterior and bi-leaflet leaflet repair is challenging. Placing and sizing individual neochordae is time consuming and error prone, with persistent localized flail if performed incorrectly. In this study, we report our pre-clinical experience with a novel multi-chordal patch for mitral valve repair. The device was designed based on human cadaver hearts, and laser cut from expanded polytetrafluoroethylene. The prototypes were tested in: (stage 1) ex vivo hearts with leaflet flail (N = 6), (stage 2) acute swine induced with flail (N = 6), and (stage 3) two chronic swine survived to 23 and 120 days (N = 2). A2 and P2 prolapse were successfully repaired with coaptation length restored to 8.1 ± 2.2mm after posterior repair and to 10.2 ± 1.3mm after anterior repair in ex vivo hearts. In vivo, trace regurgitation was seen after repair with excellent patch durability, healing, and endothelialization at euthanasia. A new device for easier mitral repair is reported, with good early pre-clinical outcomes.

Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study.

OBJECTIVE: To assess the risk of non-fatal ischemic stroke associated with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. METHODS: We performed a population-based case-control study. Patients were considered exposed if they were on treatment within a 30-day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. RESULTS: Two thousand eight hundred and eighty-eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in patients at high CV risk (OR = 0.94; 0.78-1.14). CONCLUSIONS: Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.

Temporal changes in interpapillary muscle dynamics as an active indicator of mitral valve and left ventricular interaction in ischemic mitral regurgitation.

BACKGROUND: Regional subpapillary myocardial hypokinesis may impair lateral reduction in the interpapillary muscle distance (IPMD) from diastole to systole, and adversely affect mitral valve geometry and tethering. OBJECTIVES: The goal of this study was to investigate the impact of impaired lateral shortening in the interpapillary muscle distance on mitral valve geometry and function in ischemic heart disease. METHODS: To quantify ventricular size/shape, regional myocardial contraction, lateral shortening of the IPMD, mitral valve geometry, and severity of mitral regurgitation, 67 patients with ischemic heart disease underwent cardiac magnetic resonance imaging, and a correlation analysis of measured parameters was performed. The impact of reduced IPMD shortening on mitral valve (dys)function was confirmed in swine and in a physiological computational mitral valve model. RESULTS: Lateral shortening of the IPMD from diastole to systole was severely reduced in patients with moderate/severe ischemic mitral regurgitation (9.6 ± 2.8 mm), but preserved in mild IMR (11.5 ± 3.4 mm). Left ventricular size and ejection fraction did not differ between the groups. In swine with subpapillary infarction and impaired IPMD, mitral regurgitation was evident within 1 week, compared to those pigs with a nonpapillary infarction and preserved IPMD. In the controlled computational valve model, IPMD had the maximal impact on regurgitation, and was exacerbated with additional annular dilation. CONCLUSIONS: By using cardiac magnetic resonance imaging in humans, we demonstrated that it is the impairment of lateral shortening between the papillary muscles, and not passive ventricular size, that governs the severity of mitral regurgitation. Loss of lateral shortening of IPMD tethers the leaflet edges and impairs their systolic closure, resulting in mitral regurgitation, even in small ventricles. Understanding the lateral dynamics of ventricular-valve interactions could aid the development of new repair techniques for ischemic mitral regurgitation.

First-grade cognitive abilities as long-term predictors of reading comprehension and disability status.

In a sample of 195 first graders selected for poor reading performance, the authors explored four cognitive predictors of later reading comprehension and reading disability (RD) status. In fall of first grade, the authors measured the children's phonological processing, rapid automatized naming (RAN), oral language comprehension, and nonverbal reasoning. Throughout first grade, they also modeled the students' reading progress by means of weekly Word Identification Fluency (WIF) tests to derive December and May intercepts. The authors assessed their reading comprehension in the spring of Grades 1-5. With the four cognitive variables and the WIF December intercept as predictors, 50.3% of the variance in fifth-grade reading comprehension was explained: 52.1% of this 50.3% was unique to the cognitive variables, 13.1% to the WIF December intercept, and 34.8% was shared. All five predictors were statistically significant. The same four cognitive variables with the May (rather than December) WIF intercept produced a model that explained 62.1% of the variance. Of this amount, the cognitive variables and May WIF intercept accounted for 34.5% and 27.7%, respectively; they shared 37.8%. All predictors in this model were statistically significant except RAN. Logistic regression analyses indicated that the accuracy with which the cognitive variables predicted end-of-fifth-grade RD status was 73.9%. The May WIF intercept contributed reliably to this prediction; the December WIF intercept did not. Results are discussed in terms of a role for cognitive abilities in identifying, classifying, and instructing students with severe reading problems.

Altered patterns of cortical activation in ALS patients during attention and cognitive response inhibition tasks.

Since amyotrophic lateral sclerosis (ALS) can be accompanied by executive dysfunction, it is hypothesised that ALS patients will have impaired performance on tests of cognitive inhibition. We predicted that ALS patients would show patterns of abnormal activation in extramotor regions when performing tests requiring the inhibition of prepotent responses (the Stroop effect) and the inhibition of prior negatively primed responses (the negative priming effect) when compared to healthy controls. Functional magnetic resonance imaging was used to measure activation during a sparse sequence block design paradigm investigating the Stroop and negative priming effects in 14 ALS patients and 8 healthy age- and IQ-matched controls. Behavioural measures of performance were collected. Both groups' reaction times (RTs) reflected the Stroop effect during scanning. The ALS and control groups did not differ significantly for any of the behavioural measures but did show significant differences in cerebral activation during both tasks. The ALS group showed increased activation predominantly in the left middle temporal gyrus (BA 20/21), left superior temporal gyrus (BA 22) and left anterior cingulate gyrus (BA 32). Neither group's RT data showed clear evidence of a negative priming effect. However the ALS group showed decreased activation, relative to controls, particularly in the left cingulate gyrus (BA 23/24), left precentral gyrus (BA 4/6) and left medial frontal gyrus (BA 6). Greater cerebral activation in the ALS group accompanying the performance of the Stroop effect and areas of decreased activation during the negative priming comparison suggest altered inhibitory processing in ALS, consistent with other evidence of executive dysfunction in ALS. The current findings require further exploration in a larger study.

Forensic palynology: why do it and how it works.

Forensic palynology has been a law enforcement tool for over 50 years. Forensic palynology is the application of pollen and spores in solving legal issues, either civil or criminal. Pollen and spores can be obtained from an extremely wide range of items, including bodies. Pollen and spores provide clues as to the source of the items and the characteristics of the environments from which the material on them is sourced. Their usefulness lies in a combination of their abundance, dispersal mechanisms, resistance to mechanical and chemical destruction, microscopic size, and morphology. Their often complex morphology allows identification to an individual parent plant taxon that can be related to a specific ecological habitat or a specific scene. Pollen and spore assemblages characterise different environments and scenes and can easily be picked up and transported away from scenes of interest without providing any visual clue to a suspect as to what has occurred. With so many publications and high-profile cases involving forensic palynology and environmental analysis now receiving publicity, the future of this branch of forensic science is assured. Furthermore, with the development of multi-disciplinary approaches to environmental analyses of crime scenes, far more detailed information is now available to law enforcement agencies, enabling them to determine with greater accuracy what may have happened during the commission of criminal activities.

The effect of noninvasive ventilation on ALS patients and their caregivers.

BACKGROUND: Noninvasive ventilation (NIV) reduces mortality and improves some aspects of quality of life (QoL) in ALS. However, concerns remain that progressive disability may negate these benefits and unnecessarily burden caregivers. METHODS: Thirty-nine patients requiring NIV were offered treatment. Twenty-six were established on NIV, but 13 declined or could not tolerate NIV. Fifteen patients without respiratory muscle weakness (RMW) but with similar ALS severity and age were studied in parallel. Caregivers of 21 NIV, 7 untreated, and 10 patients without RMW participated. Patients and caregivers had detailed QoL measurements for 12 months. NIV patients underwent cognitive testing before and after treatment. RESULTS: RMW correlated with lower QoL. The median survival of untreated patients (18 days; 95% CI 11 to 25 days) was shorter than for NIV patients (298 days; 95% CI 192 to 404 days) and non-RMW patients (370 days; 95% CI 278 to 462 days; log rank test [2 df] = 81, p = 0.00001). A wide range of QoL measures improved within 1 month of starting NIV, and improvements were maintained for 12 months. QoL of non-RMW patients declined as RMW progressed. Caregivers of NIV and non-RMW patients showed similar increases in burden, but NIV patient caregivers developed a deterioration in the Short Form-36 Vitality score. No improvements were found on measures of learning and recall in the NIV patients. CONCLUSIONS: Respiratory muscle weakness has a greater impact on quality of life (QoL) than overall ALS severity. Noninvasive ventilation (NIV) improves QoL despite ALS progression. NIV has no impact on most aspects of caregiver QoL and does not significantly increase caregiver burden or stress.

A molecular analysis of dietary diversity for three archaic Native Americans.

DNA was extracted from three fecal samples, more than 2,000 years old, from Hinds Cave, Texas. Amplification of human mtDNA sequences showed their affiliation with contemporary Native Americans, while sequences from pronghorn antelope, bighorn sheep, and cottontail rabbit allowed these animals to be identified as part of the diet of these individuals. Furthermore, amplification of chloroplast DNA sequences identified eight different plants as dietary elements. These archaic humans consumed 2-4 different animal species and 4-8 different plant species during a short time period. The success rate for retrieval of DNA from paleofeces is in strong contrast to that from skeletal remains where the success rate is generally low. Thus, human paleofecal remains represent a source of ancient DNA that significantly complements and may in some cases be superior to that from skeletal tissue.

A high uptake eye and foot screening service for an urban population.

AIMS: A community diabetes eye screening service using slit-lamp biomicroscopy and colour fundus photography was set up in 1993 at the Barnsley District General Hospital Diabetes Centre with a foot screening service being added in 1994. The service is available for all diabetic patients in the Barnsley health district (encompassing 220,000 people). After 4 1/2 years, a survey was carried out to establish the uptake of this service. METHODS: All diabetic patients on the local diabetes register were checked for attendance at the eye screening service or the Barnsley District General Hospital Eye Department. Questionnaires were sent to general practitioners to establish what screening was received by those attending neither of these services. RESULTS: More than 10% of patients were found to be incorrectly registered. Of the 4000 correctly registered diabetic patients, 62% were screened annually by this service and 25% were under the care of the Department of Ophthalmology. Half of the remaining 13% were screened at other hospitals or by opticians or general practitioners and the other half were either too old or ill to be screened or were non-compliant. CONCLUSIONS: This service has a high uptake, and is recommended for a circumscribed urban population.

Prevention of burn injuries to children involving nightwear.

The effectiveness of legislative intervention in the New Zealand market for children's nightclothes as an injury prevention strategy has been reassessed by examining those hospital admissions for the period 1980-8 (with emphasis on the 1985-8 period) in which clothing and/or nightclothes were involved. The profiles of the production of children's nightclothes (1977-86) and domestic heating (1984-8) were also examined. Ninety-five cases of burn injury discharges were identified (1985-8), and of those cases involving clothing 42% involved nightwear (49% 1981-4). Some of the 27% unspecified cases may have also involved nightwear (23%, 1981-4). A very strong linear downward trend for nightwear incidents was noted (chi 2 slope = 31.06, p less than 0.001). Forty-eight percent of cases involved children aged 1-6 years, and 68% involved pajamas. Stoves were the main specified ignition agent for nightclothes (36%). Open fires as a form of household heating decreased from 49% to 34% of households (1984-8). Estimated production of nightdresses in New Zealand also decreased (460,000 to 80,000 units, 1973-86). The pronounced decrease in injuries attributable to ignition of children's nightclothes is likely to be the result of mandatory controls on children's nightclothes, increased use of pyjamas, and a steady decrease in use of open fires and portable electric heaters. The typical injury event portrayed to the public of a girl in front of a heater or open fire needs to be corrected.

Further studies on histamine release from rat mast cells in vitro induced by peptides. Characteristics of a synthetic intermediate with potent releasing activity.

Previous studies on histamine release by corticotropin peptides and melittin peptides were extended, leading to the identification of a synthetic peptide intermediate, Lys(Z)-Arg(NO2)-Arg(NO2)OMe, (I) as an active non-cytolytic histamine releaser from rat mast cells. However, significant differences in the releasing capacity of optical isomers of this compound, and of Lys-Lys-Arg-ArgOMe [methyl ester of corticotropin-(15-18)-tetrapeptide; 'basic core'] were observed, with the L-forms being markedly more active. A study of various analogues of the tripeptide compound (I) indicated that the structural basis for mast-cell triggering by such peptidic agents was highly specific. The relevance of these observations to the immunologically induced histamine-release processes is discussed.

Flake tools stratified below paleo-Indian artifacts.

In northwest Missouri, Lithic stage flake tools struck from prepared cores have been excavated underlying a Paleo-Indian fluted point assemblage. These assemblages were in two different loesses of the last glaciation. Thermoluminescent analysis of stone tools dates the Paleo-Indian occupations at 8690 +/- 1000 B.C. and 12,855 +/- 1500 B.C.; the Lithic stage occupations must be older than 13,000 B.C. on the basis of geologic correlation, lithic analysis, and cultural stratigraphy.

The distribution of Nematospiroides dubius within the small intestine of laboratory mice.

Analyses of primary infections of Nematospiroides dubius in male and female laboratory mice show that on days 4--6 post-infection worms occupy up to 50% of the small intestine but as the age of the infection increases worm populations are highly aggregated in relation to the anterior sections of the small intestine. Individual worms are also shown to be aggregated with respect to each other. Between days 42 and 60 post-infection, although the pattern of distribution of N. dubius along the small intestine does not significantly change, survival of worms is influenced by both age and sex of ASH/CSI S.P.F. mice, reasons for which are discussed in the light of previous work on primary infections of N. dubius in other strains of laboratory mice.