COVID-19: using chest CT of major trauma patients to monitor and evaluate the second wave in London and the development of routine monitoring in practice.

AIM: To follow-up previous work evaluating incidental findings of COVID-19 signs on computed tomography (CT) images of major trauma patients to include the second wave prior to any major effects from vaccines. MATERIALS AND METHODS: The study population included all patients admitted following major trauma between 1 January 2020 and 28 February 2021 with CT including the lungs (n=1776). Major trauma patients admitted pre-COVID-19 from alternate months from January 2019 to November 2019 comprised a control group (n=837). The assessing radiologists were blinded to the time period and used double reading in consensus to determine if the patient had signs of COVID-19. Lung appearances were classified as no evidence of COVID-19, minor signs, or major signs. RESULTS: The method successfully tracked the second wave of the COVID-19 pandemic in London. The estimated population affected by the disease based on those with major signs was similar to estimates of the proportion of the population in London with antibodies (around 30% by end February 2021) and the total of major and minor signs produced a much higher figure of 68%, which may include all those with both antibody and just T-cell responses. CONCLUSIONS: Incidental findings on CT from major trauma patients may provide a novel and sensitive way of tracking the virus. It is recommended that all major trauma units include a simple question on signs of COVID-19 to provide an early warning system for further waves.

Valproate Reduces Delayed Brain Injury in a Rat Model of Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Spreading depolarizations (SDs) may contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). We tested whether SD-inhibitor valproate reduces brain injury in an SAH rat model with and without experimental SD induction. METHODS: Rats were randomized in a 2×2 design and pretreated with valproate (200 mg/kg) or vehicle for 4 weeks. SAH was induced by endovascular puncture of the right internal carotid bifurcation. One day post-SAH, brain tissue damage was measured with T2-weighted magnetic resonance imaging, followed by cortical application of 1 mol/L KCl (to induce SDs) or NaCl (no SDs). Magnetic resonance imaging was repeated on day 3 followed by histology to confirm neuronal death. Neurological function was measured with an inclined slope test. RESULTS: In the groups with KCl application, lesion growth between days 1 and 3 was 57±73 mm3 in the valproate-treated versus 237±232 mm3 in the vehicle-treated group. In the groups without SD induction, lesion growth in the valproate- and vehicle-treated groups was 8±20 mm3 versus 27±52 mm3. On fitting a 2-way analysis of variance model, we found a significant interaction effect between treatment and KCl/NaCl application of 161 mm3 (P=0.04). Number and duration of SDs, mortality, and neurological function were not statistically significantly different between groups. Lesion growth on magnetic resonance imaging correlated to histological infarct volume (Spearman's rho =0.83; P=0.0004), with areas of lesion growth exhibiting reduced neuronal death compared with primary lesions. CONCLUSIONS: In our rat SAH model, valproate treatment significantly reduced brain lesion growth after KCl application. Future studies are needed to confirm that this protective effect is based on SD inhibition.

Association between glycaemic control and common infections in people with Type 2 diabetes: a cohort study.

AIM: To investigate the impact of glycaemic control on infection incidence in people with Type 2 diabetes. METHODS: We compared infection rates during 2014 in people with Type 2 diabetes and people without diabetes in a large primary care cohort in the UK (the Royal College of General Practitioners Research and Surveillance Centre database). We performed multilevel logistic regression to investigate the impact of Type 2 diabetes on presentation with infection, and the effect of glycaemic control on presentation with upper respiratory tract infections, bronchitis, influenza-like illness, pneumonia, intestinal infectious diseases, herpes simplex, skin and soft tissue infections, urinary tract infections, and genital and perineal infections. People with Type 2 diabetes were stratified by good [HbA1c < 53 mmol/mol (< 7%)], moderate [HbA1c 53-69 mmol/mol (7-8.5%)] and poor [HbA1c > 69 mmol/mol (> 8.5%)] glycaemic control using their most recent HbA1c concentration. Infection incidence was adjusted for important sociodemographic factors and patient comorbidities. RESULTS: We identified 34 278 people with Type 2 diabetes and 613 052 people without diabetes for comparison. The incidence of infections was higher in people with Type 2 diabetes for all infections except herpes simplex. Worsening glycaemic control was associated with increased incidence of bronchitis, pneumonia, skin and soft tissue infections, urinary tract infections, and genital and perineal infections, but not with upper respiratory tract infections, influenza-like illness, intestinal infectious diseases or herpes simplex. CONCLUSIONS: Almost all infections analysed were more common in people with Type 2 diabetes. Infections that are most commonly of bacterial, fungal or yeast origin were more frequent in people with worse glycaemic control.

Sex Differences in Hemostatic Factors in Patients With Ischemic Stroke and the Relation With Migraine-A Systematic Review.

Background: Women are more affected by stroke than men. This might, in part, be explained by sex differences in stroke pathophysiology. The hemostasis system is influenced by sex hormones and associated with female risk factors for stroke, such as migraine. Aim: To systematically review possible sex differences in hemostatic related factors in patients with ischemic stroke in general, and the influence of migraine on these factors in women with ischemic stroke. Results: We included 24 studies with data on sex differences of hemostatic factors in 7247 patients with ischemic stroke (mean age 57-72 years, 27-57% women) and 25 hemostatic related factors. Levels of several factors were higher in women compared with men; FVII:C (116% ± 30% vs. 104% ± 30%), FXI (0.14 UI/mL higher in women), PAI-1 (125.35 ± 49.37 vs. 96.67 ± 38.90 ng/mL), D-dimer (1.25 ± 0.31 vs. 0.95 ± 0.24 µg/mL), and aPS (18.7% vs. 12.0% positive). In contrast, protein-S (86.2% ± 23.0% vs. 104.7% ± 19.8% antigen) and P-selectin (48.9 ± 14.4 vs. 79.1 ± 66.7 pg/mL) were higher in men. Most factors were investigated in single studies, at different time points after stroke, and in different stroke subtypes. Only one small study reported data on migraine and hemostatic factors in women with ischemic stroke. No differences in fibrinogen, D-dimer, t-PA, and PAI-1 levels were found between women with and without migraine. Conclusion: Our systematic review suggests that sex differences exist in the activation of the hemostatic system in ischemic stroke. Women seem to lean more toward increased levels of procoagulant factors whereas men exhibit increased levels of coagulation inhibitors. To obtain better insight in sex-related differences in hemostatic factors, additional studies are needed to confirm these findings with special attention for different stroke phases, stroke subtypes, and not in the least women specific risk factors, such as migraine.

Same-patient reproducibility of state entropy: a comparison of simultaneous bilateral measurements during general anesthesia.

BACKGROUND: State Entropy (SE) is an index of anesthetic depth similar to Bispectral Index (BIS). Both indices use a single-channel electroencephalogram, recorded from a unilaterally applied electrode on the forehead, as their input. Intrapatient reproducibility of BIS was questioned in a recent study in which simultaneous measurements from two electrodes applied to the same patient showed conflicting anesthetic depths. Our purpose was to determine whether SE results are similarly reproducible, even though their computation uses a different algorithm than BIS. In this study, we investigated the reproducibility of SE measurements simultaneously obtained from bilaterally applied electrodes in the same patient. METHODS: Entropy electrodes were applied bilaterally on 21 patients under general inhaled anesthesia. Simultaneous SE measurements from both electrodes were recorded every 10 s from each patient. Data were analyzed with Bland-Altman statistics. RESULTS: We obtained 14,379 pairs of SE measurements. Four percent of the individual measurements suggested conflicting anesthetic depth along with a numeric difference more than 10 points. Bias was not clinically significant (-0.3). Ninety-five percent limits of agreement were -11.7 and +11.6. CONCLUSIONS: SE showed a clinically significant degree of disagreement when probes were applied on both sides of the forehead in the same patient. Bland-Altman statistics showed better same-patient reproducibility in SE than did a similar study on BIS. Nevertheless, 4% of the simultaneously measured pairs of SE suggested different anesthetic depths and differed by more than 10 points. Caution is advised when using SE as a clinical index of anesthetic depth.

Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage.

Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T2-weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233 mm(3)) than in the no-SD group (29 ± 54 mm(3)) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.

Conductive hearing loss produces a reversible binaural hearing impairment.

Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7-15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90 degrees to the right, that was masked by two sources of broad-band noise. In one condition ("control"), both noise sources were 90 degrees right and, in the second condition ("bilateral"), one noise source was moved to 90 degrees left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

The effect of phenylephrine on the cornea.

Rabbit corneas were treated with three drops of phenylephrine hydrochloride with the epithelium intact or denuded. Corneal thickness was measured before and after drug treatment, and at various times after treatment the corneas were fixed for scanning and transmission electron microscopic observation. The results of this study show that phenylephrine caused a dramatic increase in corneal thickness (drug-induced edema) and cellular vacuolation within the keratocytes and endothelial cells in the corneas without the epithelium. Corneal thickness did not change and the ultrastructural changes were minimal following drug application in those corneas with the epithelium intact. Results of this study also suggest that phenylephrine has a cytotoxic effect on the corneal endothelium and keratocytes when used in corneas where the epithelium has been removed. In coreas with intact epithelium, the damage was less severe and limited to the epithelium.

Free-field binaural unmasking in ferrets.

Free-field detection by normal and monaural ferrets of a 500-Hz tone presented over 1 laterally placed loudspeaker and partially masked by narrow-band noise from 2 sources was studied at 2 angular separations of the noise sources (0 degree and 180 degrees). Monaural listening was achieved either by plugging 1 ear canal or removing 1 cochlea. Normal ferrets showed an improvement in detectability of the tone when there was a 180 degrees separation between the noise sources. This unmasking of the tone was abolished in both groups of monaural ferrets, suggesting that the unmasking was due to binaural processing. The development of an animal model demonstrating free-field binaural unmasking, in a species other than humans, will allow investigation into the functional consequences of experimental hearing loss.

Rapid development of the auditory brainstem response threshold in individual ferrets.

The development of the ferret auditory system was examined using the auditory brainstem response (ABR). Longitudinal recordings were obtained under short-acting anaesthesia from individual animals at 4-h or 24-h intervals. Particular attention was focused on the period from postnatal day (P) 26 to P32 when the ferret auditory system becomes functional. ABR thresholds to click stimuli presented in a free-field were found to decline precipitously within a 4-h period during the first 24 h following initial responsiveness. Latencies of waves I and IV of the ABR also declined significantly during this period, but the 'central conduction time' remained stable. A temporal correlation was observed between the time of the precipitous threshold decline and the time of opening of the external ear canal. No changes in cochlear anatomy were observed during this time. We suggest that the opening of the ear canal and/or the clearance of fluid from the middle ear explain the major change in threshold of hearing following onset of function.

Temporal non-linearities of the cochlear amplifier revealed by maximum length sequence stimulation.

OBJECTIVES: The objective of this study was to examine whether temporal non-linearities of the cochlear amplifier, as reflected by otoacoustic emissions (OAEs), exist and are distinct from any recording system non-linearities. METHODS: Maximum length sequence stimulation, at various stimulus rates, was used to evoke OAEs from normally hearing subjects. Recordings from a 2cc cavity were also made. The data were analyzed to obtain the linear response and estimates of the slices of the 2nd and 3rd order Volterra kernels. This provided a measure of two and 3 click non-linear temporal interactions, respectively. RESULTS: The results showed that temporal non-linearities of OAEs do exist, are stable and repeatable within individuals and have properties that differ from those shown by the conventional linear response. Whilst some of the non-linear response properties conformed to the expected pattern, of increasing amplitude with increase in stimulus rate, there are some areas in which they show an unpredicted complexity. CONCLUSIONS: Whilst system non-linearities could be found, there was no difficulty in distinguishing between the physiological and system non-linear components. New areas of research and application may result from the use of these new OAE responses.

Out-patient dietary management in the Prader-Willi syndrome.

Dietary adherence of eight children with the Prader-Willi syndrome was studied in the home environment. Weight changes were recorded at two-week intervals, and measured two-week dietary records were completed twice during the study by the parents of seven of the children. An eighth child was similarly followed for three months, and one dietary record was obtained. Calories, protein, fat, and carbohydrate contents were calculated, and related to recorded weight changes to determine which diets were most practical in controlling weight gain. Caloric requirements of children with the Prader-Willi syndrome appear to be much lower than those of healthy, active children of comparable ages. Age, degree of obesity, familial relationships, and probably, composition of the diet influenced the effectiveness of a given diet. Each family designed a diet which took into consideration the family's eating habits, as well as the needs of the Prader-Willi child. Frequent contact with the dietitian enabled each family to try new food preparation ideas. The effectiveness and acceptability of a low caloric, very low-carbohydrate diet should be tested over long periods in Prader-Willi children whose obesity is being managed in a non-institution setting.

Comparison of transient evoked otoacoustic emission thresholds recorded conventionally and using maximum length sequences.

Presenting clicks according to maximum length sequences (MLSs) enables transient evoked otoacoustic emissions (TEOAEs) to be recorded at very high stimulation rates. Despite a decrease in TEOAE amplitude, the very large number of responses obtainable at high rates means that both signal to noise ratio (SNR) and detection sensitivity increase as the click rate increases. This study characterises conventional and MLS TEOAEs near threshold for a group of normally hearing adults. Stimulus presentation rates of 40 clicks/s (conventional) and 5000 clicks/s (MLS) were used. Compared to conventional recordings, the MLS technique enabled smaller responses to be detected, when averaged for the same time and to the same SNR. TEOAE amplitude recorded at detection threshold for MLS responses was 13 dB lower than that recorded conventionally. For each individual, MLS recording also produced clear, repeatable responses at stimulus levels below the detection threshold for conventional TEOAEs. The click level at TEOAE threshold was 12 dB lower for MLS compared to conventional emissions. These results suggest that TEOAE thresholds are not absolute but strongly related to the detection sensitivity of the recording system and physiological noise. The initial growth rates and the shape of input/output functions were found to be similar for the two recording techniques.

Effect of olivocochlear bundle section on evoked otoacoustic emissions recorded using maximum length sequences.

Presenting clicks according to maximum length sequences (MLS) enables transient evoked otoacoustic emissions (TEOAE) to be recorded at very high stimulation rates. As the click rate is increased from 40 clicks/s up to a maximum rate of 5000 clicks/s there is a reduction in TEOAE amplitude that reaches an approximate asymptote at 1500 clicks/s. One hypothesis put forward to explain this MLS 'rate effect' is that ipsilateral efferent activity is involved. To test this hypothesis TEOAEs were recorded from both ears of five patients who had undergone a unilateral vestibular nerve section--a surgical procedure which also entails sectioning the olivocochlear bundle. TEOAEs were recorded conventionally at 40 clicks/s and using MLS stimulation at 5000 clicks/s. Increasing the rate from 40 to 5000 clicks/s was found to reduce the amplitude of the TEOAEs by equivalent amounts in ears ipsilateral and contralateral to a vestibular nerve section as well as in the ears of normal-hearing adults. Since an ear ipsilateral to a vestibular nerve section should have no efferent innervation the hypothesis that efferent activity is the major mechanism involved in the MLS rate effect is rejected. Instead, the possibility that intracochlear processes are the underlying mechanism will now be investigated.

Provision of counselling for the dying patient.

The majority of doctors and nurses clearly recognise their responsibility to provide palliative care to the dying patient, and also the need for effective communication, counselling and support for this group of patients. This paper explores some of the issues preventing patient and significant others from being referred to the counselling service at this stage, and demonstrates that the nursing staff feel both inadequate and ill prepared to deliver quality care to the dying patient and use avoidance as a coping mechanism.

Standards of palliative care in a renal care setting.

Palliative care has been described as the active total care of patients whose disease is not responsive to curative treatment. The principles of palliative care are applicable to patients living with non-malignant disease such as end stage renal failure. This paper describes the development of standards of palliative care in a renal care setting. It emphasises the need for a multidisciplinary basis for palliative care and specifies standards of practice in six core areas: Assessment and Referral, Pain and Symptom Control, Communication and giving information, Sexuality, Spirituality and Bereavement.