Effects of BNT162b2 mRNA vaccine on COVID-19 infection and hospitalisation amongst older people: matched case control study for England.

BACKGROUND: The BNT162b2 mRNA vaccine has been shown to be effective at preventing serious COVID-19 events in clinical trials. There is less evidence on effectiveness in real-world settings, especially for older people. Here, we aimed to estimate vaccine effectiveness in the context of the rapid NHS mass-vaccination programme in England, exploiting age-based vaccination eligibility thresholds to minimise and correct for selection bias. METHODS: We studied 170,226 individuals between the ages of 80 and 83 years from community settings outside care homes who received one dose of BNT162b2 mRNA between the 15 and 20 December 2020 and were scheduled a second dose 21 days later. We matched these vaccine recipients to slightly younger (aged 76-79 years) persons not yet eligible to receive the vaccine on gender, area of residence, area deprivation, health status, living arrangements, acute illness, and history of seasonal flu vaccination. We compared their rates of COVID-19 positivity and hospitalisation in the subsequent 45 days. We adjusted for the increasing concentration of COVID-19 positivity in the control population caused by the requirement to have no COVID-19 symptoms prior to vaccination. RESULTS: Emergency hospital admissions were 51.0% (95% confidence interval 19.9 to 69.5%) lower and positive COVID-19 tests were 55.2% (40.8 to 66.8%) lower for vaccinated individuals compared to matched controls 21 to 27 days after first vaccination. Emergency admissions were 75.6% (52.8 to 87.6%) lower, and positive COVID-19 tests were 70.1% (55.1 to 80.1%) lower 35 to 41 days after first vaccination when 79% of participants had received a second dose within 26 days of their first dose. CONCLUSIONS: Receipt of the BNT162b2 mRNA vaccine is effective at reducing COVID-19 hospitalisations and infections. The nationwide vaccination of older adults in England with the BNT162b2 mRNA vaccine reduced the burden of COVID-19.

Effects of BNT162b2 mRNA vaccine on Covid-19 infection and hospitalisation among older people: matched case control study for England

BackgroundThe BNT162b2 mRNA vaccine has been shown to be effective at preventing serious Covid-19 events in clinical trials. There is less evidence on effectiveness in real-world settings, especially for older people. The rapid roll-out of the NHS vaccination programme in England based on age thresholds offers an opportunity to make unbiased comparisons of outcomes between vaccinated and unvaccinated populations. Methods and FindingsWe matched older (aged 80-83 years) vaccine recipients with younger (aged 76-79 years) persons not yet eligible to receive the vaccine on gender, area of residence, area deprivation, health status, living arrangements, acute illness, and history of seasonal flu vaccination. We also adjusted for the over-representation of Covid-19 positive individuals in the control population because eligibility for vaccination required no Covid-19 symptoms in the previous two weeks. The study population included 170,226 individuals between the ages of 80 and 83 years from community settings outside care homes who received one dose of BNT162b2 mRNA between the 15th and 20th December 2020 and were scheduled a second dose 21 days later. We found emergency hospital admissions were 51.0% (95% confidence interval: 19.9% to 69.5%) lower and positive Covid-19 tests were 55.2% (40.8% to 66.8%) lower for vaccinated individuals compared to matched controls 21 to 27 days after first vaccination. Emergency admissions were 75.6% (52.8% to 87.6%) lower and positive Covid-19 tests were 70.1% (55.1% to 80.1%) lower 35 to 41 days after first vaccination when 79% of participants had received a second dose within 26 days of their first dose. ConclusionsReceipt of the BNT162b2 mRNA vaccine is effective at reducing Covid-19 hospitalisations and infections. The nationwide vaccination of older adults in England with the BNT162b2 mRNA vaccine reduced the burden of Covid-19.

A Pilot Study Investigating a Novel Non-Linear Measure of Eyes Open versus Eyes Closed EEG Synchronization in People with Alzheimer's Disease and Healthy Controls

BACKGROUND: The incidence of Alzheimer disease (AD) is increasing with the ageing population. The development of low cost non-invasive diagnostic aids for AD is a research priority. This pilot study investigated whether an approach based on a novel dynamic quantitative parametric EEG method could detect abnormalities in people with AD. METHODS: 20 patients with probable AD, 20 matched healthy controls (HC) and 4 patients with probable fronto temporal dementia (FTD) were included. All had detailed neuropsychology along with structural, resting state fMRI and EEG. EEG data were analyzed using the Error Reduction Ratio-causality (ERR-causality) test that can capture both linear and nonlinear interactions between different EEG recording areas. The 95% confidence intervals of EEG levels of bi-centroparietal synchronization were estimated for eyes open (EO) and eyes closed (EC) states. RESULTS: In the EC state, AD patients and HC had very similar levels of bi-centro parietal synchronization; but in the EO resting state, patients with AD had significantly higher levels of synchronization (AD = 0.44; interquartile range (IQR) 0.41 vs. HC = 0.15; IQR 0.17, p < 0.0001). The EO/EC synchronization ratio, a measure of the dynamic changes between the two states, also showed significant differences between these two groups (AD ratio 0.78 versus HC ratio 0.37 p < 0.0001). EO synchronization was also significantly different between AD and FTD (FTD = 0.075; IQR 0.03, p < 0.0001). However, the EO/EC ratio was not informative in the FTD group due to very low levels of synchronization in both states (EO and EC). CONCLUSION: In this pilot work, resting state quantitative EEG shows significant differences between healthy controls and patients with AD. This approach has the potential to develop into a useful non-invasive and economical diagnostic aid in AD.

The effects of focused attention training on the duration of novice drivers' glances inside the vehicle.

Several studies have documented that the failure of drivers to attend to the forward roadway for a period lasting longer than 2-3 s is a major cause of highway crashes. Moreover, several studies have demonstrated that novice drivers are more likely to glance away from the roadway than the experienced drivers for extended periods when attempting to do a task inside the vehicle. The present study examines the efficacy of a PC-based training programme (FOrward Concentration and Attention Learning, FOCAL) designed to teach novice drivers not to glance away forthese extended periods of time. A FOCAL-trained group was compared with a placebo-trained group in an on-road test, and the FOCAL-trained group made significantly fewer glances away from the roadway that were more than 2 s than the placebo-trained group. Other measures indicated an advantage for the FOCAL-trained group as well. Statement of relevance: Distracted driving is increasingly a problem, as cell phones, navigation systems, and other in-vehicle devices are introduced into the cabin of the automobile. A training programme is described that has beentested on the open road and can reduce the behaviours that lead to crashes caused by the distracted driving.

Evidence for the mechanisms of zinc uptake by rice using isotope fractionation.

In an earlier study, we found that rice (Oryza sativa) grown in nutrient solution well-supplied with Zn preferentially took up light (64)Zn over (66)Zn, probably as a result of kinetic fractionation in membrane transport processes. Here, we measure isotope fractionation by rice in a submerged Zn-deficient soil with and without Zn fertilizer. We grew the same genotype as in the nutrient solution study plus low-Zn tolerant and intolerant lines from a recombinant inbred population. In contrast to the nutrient solution, in soil with Zn fertilizer we found little or heavy isotopic enrichment in the plants relative to plant-available Zn in the soil, and in soil without Zn fertilizer we found consistently heavy enrichment, particularly in the low-Zn tolerant line. These observations are only explicable by complexation of Zn by a complexing agent released from the roots and uptake of the complexed Zn by specific root transporters. We show with a mathematical model that, for realistic rates of secretion of the phytosiderophore deoxymugineic acid (DMA) by rice, and realistic parameters for the Zn-solubilizing effect of DMA in soil, solubilization and uptake by this mechanism is necessary and sufficient to account for the measured Zn uptake and the differences between genotypes.

An EM algorithm for estimating SPECT emission and transmission parameters from emissions data only.

A maximum-likelihood (ML) expectation-maximization (EM) algorithm (called EM-IntraSPECT) is presented for simultaneously estimating single photon emission computed tomography (SPECT) emission and attenuation parameters from emission data alone. The algorithm uses the activity within the patient as transmission tomography sources, with which attenuation coefficients can be estimated. For this initial study, EM-IntraSPECT was tested on computer-simulated attenuation and emission maps representing a simplified human thorax as well as on SPECT data obtained from a physical phantom. Two evaluations were performed. First, to corroborate the idea of reconstructing attenuation parameters from emission data, attenuation parameters (mu) were estimated with the emission intensities (lambda) fixed at their true values. Accurate reconstructions of attenuation parameters were obtained. Second, emission parameters lambda and attenuation parameters mu were simultaneously estimated from the emission data alone. In this case there was crosstalk between estimates of lambda and mu and final estimates of lambda and mu depended on initial values. Estimates degraded significantly as the support extended out farther from the body, and an explanation for this is proposed. In the EM-IntraSPECT reconstructed attenuation images, the lungs, spine, and soft tissue were readily distinguished and had approximately correct shapes and sizes. As compared with standard EM reconstruction assuming a fix uniform attenuation map, EM-IntraSPECT provided more uniform estimates of cardiac activity in the physical phantom study and in the simulation study with tight support, but less uniform estimates with a broad support. The new EM algorithm derived here has additional applications, including reconstructing emission and transmission projection data under a unified statistical model.

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Transmission maximum-likelihood reconstruction with ordered subsets for cone beam CT.

An iterative algorithm is presented for accelerated reconstruction of cone beam transmission CT data (CBCT). CBCT supplies an attenuation map for SPECT attenuation compensation and anatomical correlation. Iterative algorithms are necessary to reduce truncation artifacts and 3D reconstruction artifacts. An existing transmission maximum-likelihood algorithm (TRML) is accurate but the reconstruction time is too long. The new algorithm is a modified EM algorithm, based on ordered subsets (OSEM). OSEM was evaluated in comparison to TRML using a thorax phantom and a 3D Defrise phantom. A wide range of image measures were evaluated, including spatial resolution, noise, log likelihood, region quantification, truncation artifact removal, and 3D artifact removal. For appropriate subset size, OSEM produced essentially the same image as TRML, but required only one-tenth as many iterations. Thus, adequate images were available in two to four iterations (20-30 min on a SPARC 2 workstation). Further, OSEM still approximately maximizes likelihood: divergence occurs only for very high (and clinically irrelevant) iterations. Ordered subsets are likely to be useful in other geometries (fan and parallel) and for emission CT as well. Therefore, with ordered subsets, high-quality iterative reconstruction is now available in clinically practical reconstructions times.

Fluoridation in Anglesey 1993: a clinical study of dental caries in 5-year-old children who had experienced sub-optimal fluoridation.

Several studies since the commencement of fluoridation in 1955 have demonstrated over 50% reduction in mean dmft for 5-year-old Anglesey children in comparison with local control groups. From 1987 fluoridation became intermittent and in 1991 it was terminated. In the present study, carried out in 1993, the total number of children examined was 725 (88.4% of the entire population of 5-year-old school children), of whom 498 had continually resided in specific water distribution zones. The mean dmft for the entire number examined was 2.01 (SD = 3.27). For those who had experienced fluoridation during approximately 35% of their lives (n = 230) it was 1.81 (SD = 2.86) and for those who had experienced fluoridation for less than 10% of their lives (n = 268) it was 2.28 (SD = 3.48). In 1987/88, the last year of optimal fluoridation, the mean dmft of Anglesey 5-year-old children was 0.80 (SD = 1.43) and for those resident on the non-fluoridated Gwynedd mainland it was 2.26 (SD = 3.17). The study demonstrates the serious consequences for dental health when fluoridation is withdrawn and how difficult it will be to reach dental health targets in North Wales without fluoridation.

Dissociation of bone mineral density from age-related decreases in insulin-like growth factor-I and its binding proteins in the male rat.

We evaluated the possibility that age-related decreases in circulating and/or bone-associated insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) were associated with the development of osteopenia in 8-, 16-, and 24-month-old specific pathogen-free Brown Norway/Fischer 344 male rats. We measured bone mineral densities (BMD) of femurs by dual-energy x-ray absorptiometry. IGFs and IGFBPs were extracted from bone and separated by molecular exclusion HPLC before quantitation by specific radioligand assays. BMD did not change significantly between 8 and 24 months of age. IGF-I levels decreased by about 30% between 8 and 24 months in both serum and bone. Similarly, both circulating and bone-derived IGFBPs also declined (30% and 60%, respectively) with age. Thus, maintenance of femoral BMD throughout most of the adult rat life span was dissociated from the age-related decline in circulating and bone-associated IGF-I and IGFBPs.

Inflammatory myofibroblastic tumor in children.

The authors presented the cases of two children with inflammatory myofibroblastic (IMF) tumor and reviewed the literature to facilitate the preoperative recognition, delineate the clinical features, and describe the natural history of this entity. The first child had IMF tumor arising from the mesentery of the small intestine. He presented with an abdominal mass associated with severe inflammatory response manifested by fever, impaired growth, thrombocytosis, and microcytic, hypochromic anemia. After surgical resection, his fever resolved and his growth rate and the laboratory abnormalities normalized. Five months after initial diagnosis, the fever, anemia, and thrombocytosis recurred along with two tumors arising from the omentum and the abdominal soft tissue. After the second surgery, he remains free of recurrent disease for 30 months. The second child presented with a lung mass that was radiologically indistinguishable from pulmonary sequestration. After surgical resection, she remains free of recurrent disease for 18 months. IMF tumor should be considered in any solid tumor that occurs in association with a chronic inflammatory response. IMF tumor should also be considered in the differential diagnosis of pulmonary sequestration.

Phantom study of breast tissue attenuation in myocardial imaging.

The attenuation of photons by the breasts and other soft tissue overlying the chest may decrease the diagnostic accuracy of SPECT myocardial imaging. In this experiment, we measured the attenuation distortion of myocardial polar maps using a thorax phantom with a cardiac insert and added breast tissue. The distortion was measured using a regional semiquantitative analysis. Attenuation compensation was performed using a conebeam radionuclide CT attenuation map. Breast tissue attenuation created apparent "defects" in the polar map, where the intensity was reduced by up to 35% relative to the most intense region. However, the size, location and severity of the reduction depended on cardiac insert orientation and breast placement. For the geometries studied, apparent "defects" were observed in the anterior wall, the apex, the inferior wall and basal regions. These results suggest that attenuation artifacts may occur in almost any location. However, the attenuation compensation nearly eliminated the apparent defects and improved polar map symmetry. After compensation, the variations between regions were generally 5% or less. Therefore, we expect that attenuation compensation will improve diagnostic accuracy in myocardial imaging in female patients and in males with excessive musculature or soft tissue. Without such compensation, diagnosis may be compromised.

The clinical comparison of Oxoid Signal with Bactec blood culture systems for the detection of streptococcal and anaerobic bacteraemias.

Blood cultures were taken from 47 patients 1-2 min after dental extraction. These samples were tested by the radiometric Bactec 460 and Oxoid Signal systems for the detection of streptococcal and anaerobic bacteraemias. Streptococci were isolated from 19 (40%) patients and anaerobes from 15 (32%). In this study the Oxoid Signal system was significantly better for isolating oral anaerobes than the Bactec system; five isolates were obtained with the Bactec system and 14 with the Signal system. There was no significant difference in the isolation of streptococci between these two systems (Bactec 14, Oxoid Signal 10). The contamination rate was 4.1% for Bactec and 7.5% for the Oxoid Signal system.

Fluoridation in Anglesey: a clinical study of dental caries in mothers at term.

A study of dental caries was carried out involving 1537 mothers who attended St David's Hospital, Gwynedd, between July 1986 and July 1987 for their confinement. The study was 'blind' in respect of residence. The mean DMFT value for mothers with continuous residence in the non-fluoridated Gwynedd mainland was 13.6 and the mean DMFT value for mothers living in the Anglesey Health Unit who had consumed fluoridated mains water from birth was 30% lower at 9.5 (P less than 0.0001). The confidence interval for the difference between means was 3.4-4.9. The samples from the two areas showed no significant differences in social class and age group structures. The percentage of Anglesey mothers with DMFT exceeding 15 was less than one-sixth of that for mainland mothers and the percentage of those with DMFT less than 6 was three times greater. The mean DMFS value for occlusal sites in premolars was 3.9 for mainland Gwynedd and for Anglesey 52% less at 1.9 (P less than 0.0001) with a confidence interval of 1.6-2.4. For smooth surface sites in posterior teeth, the difference was not as pronounced, with a mean DMFS value for mainland of 20.3 and for Anglesey 42% less at 11.8 (P less than 0.0001) with a confidence interval of 7.5-9.6. The results showed that child-bearing women continued to enjoy important benefits from water fluoridation into their early thirties.

Arterial embolisation of a facial haemangioma.

Non-invasive investigations in the diagnosis of highly vascular lesions are without doubt a sound principle. A case is presented however, in which the clinical diagnosis of a haemangioma was confirmed by ultrasound and magnetic resonance imaging (MRI) but required further investigation by angiography to facilitate treatment. Embolisation is a well established technique available in most large radiology departments, but may not be well known by general dental practitioners.

Persistent pain inhibits contralateral somatosensory cortical activity in humans.

To assess cortical activity during pain perception, regional cerebral blood flow (rCBF) studies were done in humans using single photon emission computed tomography (SPECT) with the radiotracer Tc99m-HMPAO and magnetic resonance imaging localization. Normalized SPECT data were analyzed by region of interest and change distribution. Contralateral somatosensory rCBF was decreased when the digits of the hand were immersed in a hot water bath for 3 min which was rated as moderately painful (persistent pain). No decrease was observed when the hand was immersed in tepid water (control). In contrast, cortical rCBF was increased during vibratory and sensorimotor tasks, in the contralateral somatosensory and sensorimotor areas, respectively. These results indicate that pain perception in man is associated with somatosensory cortical inhibition.

Imaging of the human torso using cone-beam transmission CT implemented on a rotating gamma camera.

Radionuclide transmission CT generated on a rotating gamma camera can improve SPECT imaging by providing attenuation maps for attenuation compensation and for anatomical correlation. This paper demonstrates the feasibility and high quality of cone-beam transmission CT (CB-CT) of human subjects, in comparison to conventional parallel-ray CT, and evaluates some possible imaging protocols. Two CB-CT implementation modes, with a cone-beam collimator and without any collimator, were evaluated. Three human subjects of different dimensions were imaged. For the two smaller subjects, the CB-CT images were dramatically superior, in terms of noise and resolution, to those obtained with a parallel-ray geometry. The image noise was less by a factor of 6. CB-CT linear attenuation coefficients were found to be in close agreement with published values for various tissues. For the largest subject, image truncation produced a ring artifact at the edge, but inside the artifact, the image quality was still very good. Cone-beam images obtained without any collimator were acceptable, but photon scatter degraded the image contrast.

Cone-beam transmission computed tomography for nonuniform attenuation compensation of SPECT images.

This paper develops and tests cone-beam transmission computed tomography (CB-CT) for attenuation compensation of SPECT images. CB-CT was implemented on a rotating gamma camera with a point source (1-2 mCi) of 99mTc, and a light-weight aluminum source holder. A cone-beam collimator may be used but is not required. Since the point source is either located at the collimator focal point, or the camera is uncollimated, CB-CT has excellent sensitivity (at least 150 times that of a parallel-hole, high-resolution collimator). The predicted resolution is equal to the intrinsic gamma camera resolution (3-4 mm), which is much higher than for a high-resolution, parallel-hole collimator (10-20 mm). In the present study, CB-CT provided low noise, high-resolution attenuation maps for use in a nonuniform attenuation-weighted backprojection algorithm. The attenuation compensation accuracy was tested using basic geometries of line sources and nonuniform density models. For the appropriate scaling of the attenuation map, the attenuation compensation was accurate and removed the SPECT image distortion associated with nonuniform attenuation. Attenuation maps acquired either with cone beam collimator or without any collimator were both successful. Using CB-CT, SPECT can thus be made much more accurate without adding unduly to the imaging time, complexity, or cost.