We aimed to determine the frequency of dehydration, risk factors, and associations with outcomes at hospital discharge after stroke.
We linked clinical data from stroke patients in 2 prospective ...hospital registers with routine blood urea and creatinine results. Dehydration was defined by a blood urea-to-creatinine ratio >80.
Of 2591 patients registered, 1606 (62%) were dehydrated at some point during their admission. Independent risk factors for dehydration included older age, female gender, total anterior circulation syndrome, and prescribed diuretics (all P<0.001). Patients with dehydration were significantly more likely be dead or dependent at hospital discharge than those without (χ(2)=170.5; degrees of freedom=2; P<0.0001).
Dehydration is common and associated with poor outcomes. Further work is required to establish if these associations are causal and if preventing or treating dehydration improves outcomes.
Aim The aim of this study was to review systematically the prevalence of headache and migraine in children and adolescents and to study the influence of sex, age, and region of residence on the ...epidemiology.
Method We systematically searched the literature in electronic databases to cover the period between 1 January 1990 and 31 December 2007. We assessed and included population‐based studies on epidemiology of headache and migraine in children and adolescents if they fulfilled the following criteria: (1) reporting on unselected childhood population; (2) reliable methods of data collection using a questionnaire or face‐to‐face interviews; (3) using the International Headache Society’s (IHS) criteria (1988 or 2004) for the diagnosis of migraine; and (4) provision of sufficient and explicit data for analysis. We used Excel, Stata, and Confidence Interval Analysis software.
Results We identified and analysed 50 population‐based studies reporting the prevalence of headache and/or migraine in children and adolescents (<20y). The estimated prevalence of headache over periods between 1 month and lifetime in children and adolescents is 58.4% (95% confidence interval CI 58.1–58.8). Females are more likely to have headache than males (odds ratio OR 1.53, 95% CI 1.48–1.6). The prevalence of migraine over periods between 6 months and lifetime is 7.7% (95% CI 7.6–7.8). Females are more likely than males to have migraine (OR 1.67, 95% CI 1.60–1.75). Regional differences in prevalence of migraine, though statistically significant, may not be of clinical significance. The change in the IHS’s criteria for the diagnosis of migraine was not associated with any significant change in the prevalence of migraine.
Interpretation This study confirms the global high prevalence of headache and migraine in children and adolescents. Sex, age, and regional differences are evident.
There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent ...innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log
/day (p = 0.04). We hence need a larger trial to confirm our findings.
Background
Abdominal aortic aneurysm (AAA) rupture is a common cause of sudden death. Pre-emptive elective surgical repair can prevent aneurysm rupture and be life-saving. Ultrasmall ...superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation using magnetic resonance imaging (MRI) in patients with AAAs. For this reason, USPIO-enhanced MRI represents a promising new technique that could improve risk prediction and better guide surgical intervention.
Objectives
To assess whether or not USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes in patients with AAAs.
Design
A prospective multicentre open-label observational cohort study.
Setting
Three secondary and tertiary care hospitals in Scotland.
Participants
Patients (
n
= 342) aged > 40 years with a maximum anteroposterior AAA diameter of ≥ 40 mm confirmed by abdominal ultrasonography, and under ultrasonographic surveillance as part of routine clinical care.
Interventions
USPIO-enhanced MRI of AAA.
Main outcome measures
The primary end point was the composite of aneurysm rupture or repair. Secondary outcomes included rate of aneurysm growth, all-cause mortality and aneurysm-related mortality.
Results
Participants (85% male, aged 73.1 ± 7.2 years) had a baseline aneurysm diameter of 49.6 ± 7.7 mm, and USPIO enhancement was identified in 146 participants (42.7%), absent in 191 participants (55.8%) and indeterminate in 5 participants (1.5%). During follow-up (1005 ± 280 days), there were 17 AAA ruptures (5.0%), 126 AAA repairs (36.8%) and 48 deaths (14.0%). Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1 ± 2.5 vs. 2.5 ± 2.4 mm/year;
p
= 0.0424), although this was not independent of current smoking habits (
p
= 0.1993). The primary end point (aneurysm rupture or repair) occurred more frequently in participants with USPIO enhancement 69/146 (47.3%) vs. 68/191 (35.6%), difference 11.7%, 95% confidence interval 1.1% to 22.2%;
p
= 0.0308: this was similar for each component of rupture (6.8% vs. 3.7%;
p
= 0.1857) or repair (41.8% vs. 32.5%;
p
= 0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (
p
= 0.0275). Baseline AAA diameter (
p
< 0.0001) and current smoking habits (
p
= 0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (
c
-statistic 0.7935 to 0.7936).
Conclusions
USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with AAAs, and predicts the rate of aneurysm growth and clinical outcome. USPIO-enhanced MRI does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Larger trials are now needed to explore the prediction of emergent aneurysm events to establish the added benefit of USPIO-enhanced MRI. Comparative outcome studies should determine whether or not using other imaging biomarkers that track alternative disease processes have better predictive capability than USPIO-enhanced MRI.
Trial registration
Current Controlled Trials ISRCTN76413758.
Funding
This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.
High-risk human papillomavirus causes cervical cancer. Vaccines have been developed that significantly reduce the incidence of preinvasive and invasive disease. This population-based observational ...study used linked screening, immunization, and cancer registry data from Scotland to assess the influence of age, number of doses, and deprivation on the incidence of invasive disease following administration of the bivalent vaccine.
Data for women born between January 1, 1988, and June 5, 1996, were extracted from the Scottish cervical cancer screening system in July 2020 and linked to cancer registry, immunization, and deprivation data. Incidence of invasive cervical cancer per 100 000 person-years and vaccine effectiveness were correlated with vaccination status, age at vaccination, and deprivation; Kaplan Meier curves were calculated.
No cases of invasive cancer were recorded in women immunized at 12 or 13 years of age irrespective of the number of doses. Women vaccinated at 14 to 22 years of age and given 3 doses of the bivalent vaccine showed a significant reduction in incidence compared with all unvaccinated women (3.2/100 000 95% confidence interval (CI) = 2.1 to 4.6 vs 8.4 95% CI = 7.2 to 9.6). Unadjusted incidence was significantly higher in women from most deprived (Scottish Index of Multiple Deprivation 1) than least deprived (Scottish Index of Multiple Deprivation 5) areas (10.1/100 000 95% CI = 7.8 to 12.8 vs 3.9 95% CI = 2.6 to 5.7). Women from the most deprived areas showed a significant reduction in incidence following 3 doses of vaccine (13.1/100 000 95% CI = 9.95 to 16.9 vs 2.29 95% CI = 0.62 to 5.86).
Our findings confirm that the bivalent vaccine prevents the development of invasive cervical cancer and that even 1 or 2 doses 1 month apart confer benefit if given at 12-13 years of age. At older ages, 3 doses are required for statistically significant vaccine effectiveness. Women from more deprived areas benefit more from vaccination than those from less deprived areas.
Optimization of technical parameters that influence the performance of human papillomavirus (HPV) testing on self-taken samples is important. Here, the authors assessed the impact of resuspension ...volume on the detection of HPV using four validated HPV assays. Two self-sampling devices, FLOQSwabs
and Evalyn
Brushes, were inoculated with dilutions of HPV-16-positive cell line, then resuspended in various volumes of ThinPrep. The influence of vortexing during resuspension was also assessed. At target concentrations around the assay cutoff, larger volumes led to decreased HPV detection. Interestingly, the effect(s) of vortexing differed by the self-sampling device. Resuspension in 5 ml or less may maximize the detection of HPV sequences. Using a proxy of clinical material, the current observations underline the importance of optimizing preanalytical laboratory processes to support high-quality HPV testing of self-samples.
Two commonly used sampling devices, FLOQSwab
and Evalyn
Brush, were used alongside four clinically validated HPV detection assays, Anyplex™ II HPV 28, Aptima HPV, Alinity m HR HPV and cobas
8800 HPV. The sampling device was submerged into suspensions of an HPV-16-containing cell line (1–2 copies of HPV-16 per cell) at known concentrations, and then resuspended in various volumes of ThinPrep. Cellular concentrations ranged from 10
cells/ml to 10
cells/ml, and resuspension volumes were either 3 ml, 5 ml, 10 ml or 20 ml, to reflect the range of volumes found in the literature. The impact of using a vortex at the time of resuspension was also assessed.
•Seizure detection multimodal novel algorithm using photoplethysmography has been clinically evaluated with pre-specified cut off points.•Phase 3 prospective real time clinical trial, with ...synchronised EEG videotelemetry for multicentre paediatric and adult cohorts.•False Alarm Rate (24 h FAR) 4.5, Median 1.0, standard deviation 7.8, 320 min between false alarms, 0.187/h.•Seizure detection latency (median heart rate change) from seizure onset to detection time 58 s (31, 90).
Undetected and prolonged epileptic seizures can result in hypoxic brain damage or death and occur most often when the victim is in bed alone or unsupervised. Sudden unexpected death in epilepsy may not always be preventable but it is believed that timely assistance with rescue medication and body re-positioning may overcome respiratory compromise in some cases. A novel algorithm based on a real time moving 9 s epoch, calculating 25 % percentage heart rate change and/or an oxygen saturation trigger level of <85 % was developed using photoplethysmography and incorporated into a prototype data storage device.
The algorithm was clinically evaluated in this multicentre trial in the detection of clinically significant epileptic seizures. A range of epileptic seizures and normal physiological events were recorded and classified by reference standard EEG Videotelemetry and time-synchronised event data recorded by the prototype device incorporating the pre-specified cut-off points prospectively and retrospective analysis of all events.
119 participants who were attending electroencephalographic (EEG) videotelemetry as part of their clinical management of their epilepsy consented to take part in the trial. 683 epileptic seizures (77 clinically significant seizures) and 2648 normal physiological events were captured. When using pre-specified cut-off point 25 % heart rate change and/or oxygen desaturation <85 % on the basis of one/other, the device showed a sensitivity of 87 % for detecting clinically significant seizures. False Alarm Rate 4.5 (24 h FAR), detection latency of 58 s using heart rate percentage change.
The results indicate that the novel algorithm can be used in detecting clinically significant seizures.
Cre recombinase (Cre)‐mediated targeted insertion of a transgene is a powerful technique that can be used to tailor genomes. When combined with somatic cell nuclear transfer it could offer an ...efficient way to generate transgenic livestock with site‐specific genetic modifications that are free of antibiotic selection markers. We have engineered primary bovine fibroblasts to contain a chromosomal acceptor site with incompatible loxP/lox2272 sites for Cre‐mediated cassette exchange and show for the first time that Cre‐mediated targeting can be applied in these acceptor cells. Molecular characterization of the resulting cell clones revealed Cre‐mediated transgene insertion efficiencies of up to 98% when antibiotic selection was used to identify transgene containing cell clones. Most clonal lines also contained random insertions of the targeting and Cre expression plasmids with only about 10% of the clones being exclusively modified by the intended targeted insertion. This targeting efficiency was sufficient to enable the isolation of correctly targeted clones without the help of antibiotic selection. Therefore, this recombinase‐mediated insertion strategy has the potential to produce transgenic cattle from antibiotic selection marker‐free somatic cells with transgenes inserted into proven genomic loci ensuring reliable expression levels.
Human papillomavirus (HPV) molecular testing targets either the late gene L1 or early genes E6 and/or E7. Loss of L1 during integration is suggested to compromise sensitivity in samples associated ...with cancer, however, clear evidence for this is lacking. Our aim is to address this by performing a head-to-head comparison between assays targeting L1 vs E6/E7, using a series of high-grade and invasive disease samples within different biological matrices and anatomical sites.
We obtained 298 samples comprising of liquid-based cytology and biopsies of cervical cancer and cervical intraepithelial neoplasia grade 3, in addition to biopsies of penile and oropharyngeal cancers. Two commercially available HPV primary screening assays and two assays with extended genotyping were applied to the sample set targeting L1 (Abbott RealTime HR HPV Assay and Optiplex HPV Genotyping Test) and E6/E7 genes (Xpert HPV Test and EuroArray HPV Test).
Agreement for high-risk HPV (hrHPV) for all samples types between the screening assays is over 88% and over 96% for the two genotyping assays. For HPV 16 agreement is over 90% for both screening and genotyping assays. Kappa statistics show good to very good agreement between the screening and genotyping assays for hrHPV and HPV 16.
Analysis of the valid results from our data indicates that L1 and E6/E7 targeting assays show similar performance for detection of hrHPV in high grade cervical lesions and cancers of cervix, penis and oropharynx.
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