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.

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.

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.

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.

Ventricular arrhythmias and biventricular dysfunction after repair of tetralogy of Fallot.

To test the hypothesis that subclinical levels of ventricular dysfunction contribute to the development of ventricular arrhythmias after repair of tetralogy of Fallot, 38 postoperative patients were studied by radionuclide ventriculography and M-mode echocardiography. Eighteen patients (group I) had Lown grade 2 or greater ventricular arrhythmias on ambulatory electrocardiography or treadmill exercise, or both; 20 patients (group II) had no documented ventricular arrhythmias. Radionuclide ventriculograms were performed using technetium -99m-labeled red cells; ejection fractions were derived by computer from multigated images, with normal values being 45% for the right ventricle and 55% for the left ventricle. From M-mode echocardiography, right and left ventricular end-diastolic dimensions were expressed as a ratio, the highest normal value being 0.45. By radionuclide ventriculography, right ventricular ejection fraction was lower for group I (28 +/- 3%) than for group II (31 +/- 2%), but the difference was not significant (p less than 0.10). Left ventricular ejection fraction was significantly lower for group I than for group II (45 +/- 5% versus 55 +/- 3%, p less than 0.05). The echocardiographic right and left ventricular diastolic dimension ratio was elevated in all patients except two in group II; it was significantly greater in group I than in group II (0.84 +/- 0.06 versus 0.63 +/- 0.04, p less than 0.005). This study provides evidence for right ventricular dilation by M-mode echocardiography and for biventricular dysfunction by radionuclide ventriculography in patients who have undergone repair of tetralogy of Fallot.(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide augments the effects of captopril on nuclear studies in renovascular stenosis.

Captopril facilitates detection of unilateral renovascular hypertension by selectively reducing glomerular filtration rate in affected kidneys. To determine if volume depletion augments this response, we compared the effects of captopril, furosemide, and combined furosemide plus captopril on individual kidney computer-derived clearances of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and [131I]o-iodohippurate in two-kidney, one clip Goldblatt hypertensive rats and normal controls. In clipped kidneys, captopril reduced DTPA clearance significantly from baseline (from 0.31 +/- 0.02 to 0.19 +/- 0.04 ml/min/100 g; p less than 0.02) whereas furosemide alone had no effect (0.28 +/- 0.03 ml/min/100 g). Combined furosemide plus captopril further reduced clipped kidney DTPA clearance to a level significantly less than captopril alone (0.10 +/- 0.02 ml/min/100 g; p less than 0.02). Clipped kidney o-iodohippurate clearance was not changed from baseline by any treatment. In contralateral unclipped and normal kidneys, DTPA clearance did not decline from baseline following either captopril or furosemide plus captopril treatment. Since the dose of captopril used (3 mg/kg by intraperitoneal injection) did not reduce systolic blood pressure of hypertensive rats significantly, these changes probably reflect intrarenal rather than systemic hemodynamic effects of converting enzyme inhibition and are consistent with the hypothesis that captopril interferes with glomerular filtration in stenotic kidneys by reducing efferent arteriolar vascular resistance. Prior volume depletion accentuates the effect of captopril on stenotic kidney glomerular filtration rate, providing improved functional discrimination of stenotic kidneys from contralateral unclipped and normal kidneys. These results indicate that furosemide-induced volume depletion may increase the diagnostic sensitivity of captopril-enhanced 99mTc-DTPA renography in the detection of unilateral renovascular hypertension.

Orthostatic hypertension. Pathogenetic studies.

Among 1800 referred hypertensive patients, 181 had recumbent diastolic blood pressures (DBP) below 90 mm Hg and standing DBP above 90 mm Hg. Orthostatic increments in DBP were greater in these orthostatic hypertensive patients than in 181 persistently hypertensive patients and 134 normotensive subjects. In 12 patients with orthostatic hypertension, the orthostatic fall in cardiac output (27.3 +/- 2.9%, measured by a respiratory method) was double that in 8 normotensive subjects (13.3 +/- 3.7%, p less than 0.01). An inflated pressure suit over the pelvis and lower limbs prevented the excessive fall in cardiac output and significantly reduced (p less than 0.02) the excessive rise in standing DBP in orthostatic hypertensive patients. Gravitational pooling of blood in the legs and reduction of blood in the head was measured by external gamma counting of autologous erythrocytes labeled with sodium pertechnetate Tc 99m through ports in fixed positions over the leg and the temple. Orthostatic intravascular pooling was significantly greater (p less than 0.01) in orthostatic hypertensive subjects than in normotensive subjects, and the magnitudes of orthostatic pooling and orthostatic increases in DBP were closely correlated (r = +0.85). Plasma norepinephrine concentrations were similar in recumbency and after sustained handgrip exercise, but significantly greater (p less than 0.01) after 5 to 60 mins of standing in orthostatic hypertensive subjects than in normotensive subjects. Our results indicate that orthostatic hypertension is common and that its mechanism in representative patients involves excessive orthostatic blood pooling, which results in decreased venous return, decreased cardiac output, increased sympathetic stimulation (presumably through low-pressure cardiopulmonary receptors), and excessive arteriolar, but not venular, constriction.

Sustained pectin ingestion: effect on gastric emptying and glucose tolerance in non-insulin-dependent diabetic patients.

The effects of sustained pectin ingestion on gastric emptying, glucose tolerance, and hormone responses were studied in 12 stable, non-insulin-dependent (type 2) diabetic patients. Patients were placed on a 2400 kcal, low-fiber (3 g) diet for 2 wk, followed by 4 wk of an isocaloric diet supplemented with 20 g apple pectin/d. Gastric-emptying half-time, plasma glucose, glucagon, and human pancreatic polypeptide levels were determined. Gastric-emptying half-time was prolonged 43% (p less than 0.025) by pectin supplementation and returned to normal 3 d after its discontinuation. Fiber supplementation decreased the incremental area under the glucose tolerance curve from 34.8 +/- 3.0 to 27.9 +/- 3.2 mmol/L (p less than 0.01) but did not affect hormonal responses to a meal. Sustained pectin ingestion slowed the gastric-emptying rate and improved glucose tolerance; however, a direct relationship could not be demonstrated between changes in gastric emptying and changes in the incremental area under the glucose curve (r = 0.22).

Evaluation of plasma clearance by synthesis of continuous infusion: principles and use.

There is a technique of engineering analysis which can be described as "impulse synthesis" which uses the observational data of a system's response to a single sharp blow in order to predict its response to a steady force. This same technique has been applied to the calculation of in situ drug levels and for calculating plasma clearance values. The purpose of this paper is to elucidate the principles of this calculation technique and to critically assess its application to plasma clearance studies. We begin by tracing the history of the measurement of renal clearance of plasma. We then proceed to exposit the relevant principles of the synthesis technique. Finally, we report the results of our application of this technique to the analysis of simulated data in a manner intended to be of use to clinicians who might wish to consider employing the technique.

An adjustable zoom-made gain control for computerized gamma-camera systems.

Many nuclear medicine departments use a digital computer to process scintillation-camera images. For optimal use of the computer, there should be a means to amplify the position signals of each scintillation event by an appropriate amount before their conversion to digital form. What is needed is a series of calibrated gains from which the best value may be chosen. Many systems now in use do not provide such a selection. The circuitry described here provides an inexpensive solution to this problem. It may be inserted between the camera and the computer's analog-to-digital converters to provide the desired amplification. No internal modification of the computer or the camera is required.

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.

Ventilator-driven xenon ventilation studies.

A modification of a common commercial Xe-133 ventilation device is described for mechanically assisted ventilation imaging. The patient's standard ventilator serves as the power source controlling the ventilatory rate and volume during the xenon study, but the gases in the two systems are not intermixed. This avoids contamination of the ventilator with radioactive xenon. Supplemental oxygen and positive end-expiratory pressure (PEEP) are provided if needed. The system can be converted quickly for conventional studies with spontaneous respiration.

Evaluation of cyclosporine nephrotoxicity in rats with various renal radioactive agents.

The efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included [99mTc]DTPA, [131I]hippuran, [111In]lysozyme, [99mTc]glucoheptonate (GHA), [99mTc]dimercaptosuccinate (DMS) and [111In]aminated dextran (amdex). A small dose of [99mTc]- or [111In]DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another. There were statistically significant differences in the detectability of the renal functional impairment by plasma clearance, early and 2-hr renal uptake among the different agents. However, none was clearly superior to DTPA. This conclusion is consistent with previous studies which showed a parallel decline in glomerular filtration rate (GFR) and effective renal plasma flow in acute CyA toxicity probably due primarily to vasoconstriction.

Comparison of different radioactive agents for the detection of renovascular hypertension with captopril in a rat model.

In Goldblatt hypertension in rats produced by implanting a silver clip on the left renal artery, captopril induces a greater difference in the 1-min uptake of diethylenetriaminepentaacetic acid (DTPA) between the two kidneys than in baseline uptakes, similar to the experiences in unilateral renovascular hypertension in man. The combination of captopril and furosemide induces an even greater difference in renal uptakes than with captopril alone in this rat model. In paired experiments, DTPA complexes were used as a standard to compare the differences in renal uptake between the two kidneys after captopril-furosemide with other existing and potential renal radiodiagnostic agents. No statistically significant difference was found between DTPA, glucoheptonate, dimercaptosuccinic acid, aminated dextran, or lysozyme. However, the differences in renal uptake were significantly less with hippuran than with DTPA. Furosemide and captopril caused delayed renal retention of hippuran after one minute. This response appeared to be due to non-specific volume depletion because it occurred in both clipped and unclipped kidneys.

Detection of diffuse glomerular lesions in rats: I. Comparisons of conventional radioactive agents.

Conventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v. injection of puromycin aminonucleoside (PA) 9 days before the radionuclide studies, a model of spontaneous "minimal change" glomerulonephritis in humans. Computer-generated early renal uptake of [99mTc]DTPA or GHA correlated with the glomerular filtration rate (GFR) quantitated by biexponential plasma clearance of DTPA administered by single i.v. injection. The early renal uptake of hippuran and DMS correlated poorly with GFR as assessed by DTPA clearance. However, the 2-hr renal retention of DMS correlated well with the DTPA clearance. None of the parameters measured with [131I]hippuran correlated well with DTPA clearance, probably because of decreased protein plasma binding of hippuran secondary to hypoproteinemia in this experimental model. It was concluded that none of these agents was superior to labeled DTPA for the detection of glomerular damage in this experimental model.

Comparison of different radioactive renal agents in cisplatin-induced tubular toxicity in rats.

The efficacy of five different radiodiagnostic agents for detecting renal tubular dysfunction induced with cisplatin in rats was compared to controls. Diethylenetriaminepentaacetic acid (DTPA) labeled with 99mTc or 111In was administered simultaneously with each of the other four agents [99mTc]glucoheptonate, [99mTc]dimercaptosuccinic acid, [131I]hippuran and [111In]lysozyme) as a standard to normalize for differences in functional impairment from animal to animal from the same dose of cisplatin. The 2-hr plasma clearance and computer-generated 2- to 3-min uptake in the two kidneys with [99mTc]dimercaptosuccinic acid were significantly inferior to similar measurements with the other agents in differentiating abnormal from normal function. The 2-hr uptake of [99mTc]glucoheptonate and [111In]lysozyme proved of no value in this differentiation. The late renal retention of [99mTc]dimercaptosuccinic acid well separated the cisplatin from control rats, but the greatest difference was observed by the 2-hr uptakes of [131I]hippuran and DTPA.

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.

Diagnosis of angiotensinogenic hypertension: the complementary roles of renal scintigraphy and the saralasin infusion test.

A recently developed 1-day screening procedure for angiotensinogenic ("high-renin") hypertension is based on (A) a fall in blood pressure in response to intravenous infusion of the angiotensin antagonist, saralasin (P-113), and (B) peripheral venous renin assays by radioimmunoassay, in a sodium-depleted state. Out of 700 hypertensive patients screened by these tests, 160 had renal imaging performed with technetium-99m glucoheptonate and iodine-131 Hippuran. The P-113 infusion test proved superior to peripheral venous renin assays for the detection of angiotensinogenic hypertension. Positive infusion tests correlated well with renal vein renin assays. Frequently, however, both these tests were positive with bilateral renal disease and/or malignant hypertension. While renal imaging proved valuable in indicating which patients had a unilateral abnormality, it frequently could not distinguish unilateral renovascular disease from unilateral parenchymal disease unrelated to angiotensinogenic hypertension. Twenty-five patients in this series had arteriographic renal artery stenosis, of whom 3 had false negative P-113 infusion tests, 9 had negative peripheral renin assays, and 3 had no imaging abnormalities. This study indicates that scintigraphy is a useful procedure for the investigation of hypertensive patients when the initial P-113 infusion test is positive, or discordant with other findings. By imaging, angiotensinogenic hypertension due to bilateral renal disease can be distinguished from unilateral renovascular disease, and the site of the ischemic renal tissue can usually be identified.

Technetium-99m-methylene diphosphonate--a superior agent for skeletal imaging: comparison with other technetium complexes.

Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents.