Seizures

Seizures are common in intensive care patients generally. Cardiac surgery or post-cardiac arrest patients are at particular risk of brain injury. Seizures are an important and potentially reversible cause of prolonged unconsciousness as well as being associated with poorer ICU outcome, although the latter may be multifactorial. Cerebral metabolic rate is greatly increased during seizure activity that may lead to energetic crisis and neuronal injury. Non-convulsive seizures are particularly common in ICU patients and are therefore under-recognised. Electroencephalography (EEG) is therefore an essential ICU investigation the diagnosis of seizures, epileptiform activity and for distinguishing these from other disorders of consciousness, which may have characteristic EEG signatures. Continuous EEG is particularly sensitive for clinically occult seizures and is also helpful for managing seizures refractory to simple treatment. However EEG requires specific expertise to perform and interpret which can be a barrier to its use

Mass Spectrometric Methods for Distinguishing Structural Isomers of Glutathione Conjugates of Estrone and Estradiol 11Presented in part at the 45th ASMS Conference, Palm Springs, CA, June 1997.

AbstractCollisionally activated decompositions (CAD) of [M+H]+ ions from two sets (estrone and estradiol) of three isomeric glutathione (GSH) conjugates were studied by using five tandem mass spectrometric methods: (1) low energy (LE) CAD in an ion trap, (2) LE CAD in a triple quadrupole, (3) electrospray ionization (ESI)-source CAD in a tandem four sector, (4) high energy (HE) CAD of both ESI-produced and fast-atom bombardment (FAB)-produced ions in a tandem four-sector mass spectrometer, and (5) metastable-ion decompositions of FAB-produced ions. Four types of fragment ions are produced. The first type, formed from cleavage of the peptide backbone, gives rise to modified b2, modified y2, y2, and b1 ions. These fragments are observed with all the methods and show that the catechol estrogen attachment is at the cysteine moiety of the GSH. Internal fragment ions are the second type, and they also support that the modification is at cysteine. The third type involves fragmentation of the C–S bond to give an ion containing the steroid bonded to the sulfur. The fourth type of fragment ion is similar to the third but involves oxidation of the steroid ring and reduction of the GSH moiety; it is the most isomer specific of the four. The isomer-specific ions are of relatively low abundance in the product-ion spectra taken on the triple quadrupole and ion trap, but their abundances can be improved by increasing the collision energy. ESI source-CAD and the HE-CAD spectra of the isomers are the most distinctive because abundant product ions of all four types are seen in a single spectrum

The limiting behavior of solutions to p-Laplacian problems with convection and exponential terms

We consider, for $a,l\geq1,$ $b,s,\alpha>0,$ and $p>q\geq1,$ the homogeneous Dirichlet problem for the equation $-\Delta_{p}u=\lambda u^{q-1}+\beta u^{a-1}\left\vert \nabla u\right\vert ^{b}+mt^{l-1}e^{\alpha t^{s}}$ in a smooth bounded domain $\Omega\subset\mathbb{R}^{N}.$ We prove that under certain setting of the parameters $\lambda,$ $\beta$ and $m$ the problem admits at least one positive solution. Using this result we prove that if $\lambda,\beta>0$ are arbitrarily fixed and $m$ is sufficiently small, then the problem has a positive solution $u_{p},$ for all $p$ sufficiently large. In addition, we show that $u_{p}$ converges uniformly to the distance function to the boundary of $\Omega,$ as $p\rightarrow\infty.$ This convergence result is new for nonlinearities involving a convection term.Comment: 18 page

Prehospital determinants of successful resuscitation after traumatic and non-traumatic out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is prevalent in the UK. Reported survival is lower than in countries with comparable healthcare systems; a better understanding of outcome determinants may identify areas for improvement. METHODS: An analysis of 9109 OHCA attended in East of England between 1 January 2015 and 31 July 2017. Univariate descriptives and multivariable analysis were used to understand the determinants of survival for non-traumatic cardiac arrest (NTCA) and traumatic cardiac arrest (TCA). Two Utstein outcome variables were used: survival to hospital admission and hospital discharge. RESULTS: The incidence of OHCA was 55.1 per 100 000 population/year. The overall survival to hospital admission was 27.6% (95% CI 26.7% to 28.6%) and the overall survival to discharge was 7.9% (95% CI 7.3% to 8.5%). Survival to hospital admission and survival to hospital discharge were both greater in the NTCA group compared with the TCA group: 27.9% vs 19.3% p=0.001, and 8.0% vs 3.8% p=0.012 respectively.Determinants of NTCA and TCA survival were different, and varied according to the outcome examined. In NTCA, bystander cardiopulmonary resuscitation (CPR) was associated with survival at discharge but not at admission, and the likelihood of bystander CPR was dependent on geographical socioeconomic status. An air ambulance was associated with increased survival to both hospital admission and discharge in NTCA, but only with survival to admission in TCA. CONCLUSION: NTCA and TCA are clinically distinct entities with different predictors for outcome-future OHCA reports should aim to separate arrest aetiologies. Determinants of survival to hospital admission and discharge differ in a way that likely reflects the determinants of neurological injury. Bystander CPR public engagement may be best focused in more deprived areas

Assessment of post-operative pain in children: who knows best?

Pain assessment in children can be extremely challenging. Most professional bodies recommend that parents or carers should be involved with their child's pain assessment; but the evidence that parents can accurately report pain on behalf of their children is mixed. Our objective was to examine whether there were differences in post-operative pain score ratings between the child, nurse and parent or carer after surgery. Cognitively intact children aged four upwards, undergoing all surgical procedures, whose parents were present in the post-anaesthetic recovery unit (PACU), were studied. Thirty-three children were included in the study. The numerical rating scale was used to rate the child's pain by the child, nurse and parent on arrival to the PACU and prior to discharge. We found strong correlations between children's, nurses' and parent's pain scores on admission and discharge from PACU. The intraclass correlation coefficient of pain scores reported by children, nurses and parents was 0.94 (95% confidence intervals 0.91-0.96, P<0.0001). In cognitively intact children, it is adequate to manage pain based upon the assessment of children's and nurses' pain scores alone. The numerical rating scale appeared to be suitable for younger children. Whilst there are benefits of parents being present in recovery, it is not essential for optimizing the assessment of pain

Urine Biomarkers of Risk in the Molecular Etiology of Breast Cancer

Endogenous estrogens can be bio-activated to endogenous carcinogens via formation of estrogen quinones. Estrogen-3,4-quinones react with DNA to form mutagenic depurinating estrogen-DNA adducts. The carcinogenicity of endogenous estrogens is related to unbalanced estrogen metabolism leading to excess estrogen quinones and formation of depurinating DNA adducts. The present studies were initiated to confirm that relatively high levels of depurinating estrogen-DNA adducts are present in women at high risk for breast cancer or diagnosed with the disease. These adducts may be biomarkers for early detection of breast cancer risk. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry to analyze urine samples from 40 healthy control women, 40 high-risk women and 40 women with newly diagnosed breast cancer. Estrogen metabolism was shifted from protective methoxylation and conjugation pathways in healthy control women towards activating pathways leading to formation of depurinating DNA adducts in women at high risk or with breast cancer. These results support the hypothesis that breast cancer is initiated by mutations derived from depurination of estrogen-DNA adducts. Therefore, relative levels of depurinating estrogen-DNA adducts could become biomarkers for early detection of breast cancer risk and aid in determining preventive strategies

Development and Validation of an Electronic Postoperative Morbidity Score.

BACKGROUND: Electronic health records are being adopted due to numerous potential benefits. This requires the development of objective metrics to characterize morbidity, comparable to studies performed in centers without an electronic health record. We outline the development of an electronic version of the postoperative morbidity score for integration into our electronic health record. METHODS: Twohundred and three frail patients who underwent elective surgery were reviewed. We retrospectively defined postoperative morbidity score on postoperative day 3. We also recorded potential electronic surrogates for morbidities that could not be easily extracted in an objective format. We compared discriminative capability (area under the receiver operator curve) for patients having prolonged length of stay or complex discharge requirements. RESULTS: One hundred thirty-nine patients (68%) had morbidity in ≥1 postoperative morbidity score domain. Initial electronic surrogates were overly sensitive, identifying 173 patients (84%) as having morbidity. We refined our definitions using backward logistic regression against "gold-standard" postoperative morbidity score. The final electronic postoperative morbidity score differed from the initial version in its definition of cardiac and neurological morbidity. There was no significant difference in the discriminative capability between electronic postoperative morbidity score and postoperative morbidity score for either outcome (area under the receiver operator curve: 0.66 vs 0.66 for complex discharge requirement, area under the receiver operator curve: 0.66 vs 0.67 for a prolonged length of stay; P> .05 for both). Patients with postoperative morbidity score or electronic postoperative morbidity score-defined morbidity on day 3 had increased risk of prolonged length of stay (P < .001 for both). CONCLUSIONS: We present a variant of postoperative morbidity score based on objective electronic metrics. Discriminative performance appeared comparable to gold-standard definitions for discharge outcomes. Electronic postoperative morbidity score may allow characterization of morbidity within our electronic health record, but further study is required to assess external validity