An evidence-based approach to provide essential and desirable components to develop surveys on Sudden Unexpected Death in Epilepsy (SUDEP) for doctors: A focused review.

Sudden Unexpected Death in Epilepsy (SUDEP) is a major concern for people with epilepsy, their families, their care givers, and medical professionals. There is inconsistency in the SUDEP counselling doctors provide, compared to what is recommended in clinical guidelines. Numerous national and international surveys have highlighted how epilepsy professionals, usually doctors, deliver SUDEP risk counselling, particularly, when they deliver it and to whom. These surveys help understand the unmet need, develop suitable strategies, and raise awareness among clinicians with the eventual goal to reduce SUDEPs. However, there is no standardised survey or essential set of questions identified that can be used to evaluate SUDEP counselling practice globally. This focused review analyses the content of all published SUDEP counselling surveys for medical professionals (n=16) to date covering over 4000 doctors across over 30 countries and five continents. It identifies 36 question themes across three topics. The questions are then reviewed by an expert focus group of SUDEP communication experts including three doctors, an expert statistician and SUDEP Action, an UK based charity specialising in epilepsy deaths with a pre-set criterion. The review and focus group provide ten essential questions that should be included in all future surveys inquiring on SUDEP counselling. They could be used to evaluate current practice and compare findings over time, between services, across countries and between professional groups. They are provided as a template to download and use. The review also explores if there is a continued need in future for similar surveys to justify this activity.

The impact of COVID-19 on epilepsy care: Perspectives from UK healthcare workers.

The COVID-19 pandemic has created an immense pressure on healthcare providers, resulting in a shift to remote consultations and the redeployment of healthcare workers (HCWs). We present survey data from the United Kingdom (UK) HCWs to outline how changes in healthcare provision impact clinicians' wellbeing and ability to provide adequate care. We designed an online survey to gather the experiences of HCWs providing care to people with epilepsy. We received seventy-nine responses from UK-based HCWs, of whom 43% reported an impact on their mental health. Changes to service delivery have resulted in 71% of clinicians performing > 75% of their consultations remotely. Diagnosing and treating epilepsy has changed, with a fifth of respondents being significantly less confident in diagnosing epilepsy. Ultimately, these results show that COVID-19 has had an overall negative impact on HCWs and their ability to provide epilepsy care. These results must be considered when reorganizing health services to ensure optimal outcomes for people with epilepsy.

Decreasing the risk of sudden unexpected death in epilepsy: structured communication of risk factors for premature mortality in people with epilepsy.

BACKGROUND AND PURPOSE: Good practice guidelines highlight the importance of making people with epilepsy aware of the risk of premature mortality in epilepsy particularly due to sudden unexpected death in epilepsy (SUDEP). The SUDEP and Seizure Safety Checklist ('Checklist') is a structured risk communication tool used in UK clinics. It is not known if sharing structured information on risk factors allows individuals to reduce SUDEP and premature mortality risks. The aim of this study was to ascertain if the introduction of the Checklist in epilepsy clinics led to individual risk reduction. METHODS: The Checklist was administered to 130 consecutive people with epilepsy attending a specialized epilepsy neurology clinic and 129 attending an epilepsy intellectual disability (ID) clinic within a 4-month period. At baseline, no attendees at the neurology clinic had received formal risk advice, whereas all those attending the ID clinic had received formal risk advice on multiple occasions for 6 years. The Checklist was readministered 1 year later to each group and scores were compared with baseline and between groups. RESULTS: Of 12 risk factors considered, there was an overall reduction in mean risk score for the general (P = 0.0049) but not for the ID (P = 0.322) population. Subanalysis of the 25% of people at most risk in both populations showed that both sets had a significant reduction in risk scores (P < 0.001). CONCLUSION: Structured discussion results in behavioural change that reduces individual risk factors. This impact seems to be higher in those who are at current higher risk. It is important that clinicians share risk information with individuals as a matter of public health and health promotion.

Amine-terminated nanoparticle films: pattern deposition by a simple nanostencilling technique and stability studies under X-ray irradiation.

Thin films made up of arrays of amine-terminated silicon nanoparticles (NH2-SiNPs) synthesized by a new evaporation technique have been formed by employing TEM grids as nanostencils. FTIR imaging illustrates the feasibility of the method in nanoscale device fabrication applications. Micro-mapping over areas of the nanoparticle material allows the surface chemistry to be examined. FTIR imaging shows trace amounts of oxide confined to the NP surfaces. Thicker films formed by dropcasting allowed the nanoparticle behaviour to be studied under conditions of extended exposure to 150 eV photons radiation by X-ray photoelectron spectroscopy (XPS). The XPS spectrum was monitored over the Si2p region and the initial peak at 100.53 eV was observed to shift to higher binding energies as irradiation progressed which is indicative of charge trapping within the film. This result has potential consequences for applications where NH2-SiNPs are used in X-ray environments such as in bioimaging where the increasing charge buildup is related to enhanced cytotoxicity.

Diverse populations of intrinsic cholinergic interneurons in the mouse olfactory bulb.

Cholinergic activities affect olfactory bulb (OB) information processing and associated learning and memory. However, the presence of intrinsic cholinergic interneurons in the OB remains controversial. As a result, morphological and functional properties of these cells are largely undetermined. We characterized cholinergic interneurons using transgenic mice that selectively mark choline acetyltransferase (ChAT)-expressing cells and immunolabeling. We found a significant number of intrinsic cholinergic interneurons in the OB. These interneurons reside primarily in the glomerular layer (GL) and external plexiform layer (EPL) and exhibit diverse distribution patterns of nerve processes, indicating functional heterogeneity. Further, we found these neurons express ChAT and vesicular acetylcholine transporter (VAChT), but do not immunoreact to glutamatergic, GABAergic or dopaminergic markers and are distinct from calretinin-expressing interneurons. Interestingly, the cholinergic population partially overlaps with the calbindin D28K-expressing interneuron population, revealing the neurotransmitter identity of this sub-population. Additionally, we quantitatively determined the density of VAChT labeled cholinergic nerve fibers in various layers of the OB, as well as the intensity of VAChT immunoreactivity within the GL, suggesting primary sites of cholinergic actions. Taken together, our results provide clear evidence showing the presence of a significant number of cholinergic interneurons and that these morphologically and distributionally diverse interneurons make up complex local cholinergic networks in the OB. Thus, our results suggest that olfactory information processing is modulated by dual cholinergic systems of local interneuron networks and centrifugal projections.

Structure of a human lysosomal sulfatase.

BACKGROUND: . Sulfatases catalyze the hydrolysis of sulfuric acid esters from a wide variety of substrates including glycosaminoglycans, glycolipids and steroids. There is sufficient common sequence similarity within the class of sulfatase enzymes to indicate that they have a common structure. Deficiencies of specific lysosomal sulfatases that are involved in the degradation of glycosamino-glycans lead to rare inherited clinical disorders termed mucopolysaccharidoses. In sufferers of multiple sulfatase deficiency, all sulfatases are inactive because an essential post-translational modification of a specific active-site cysteine residue to oxo-alanine does not occur. Studies of this disorder have contributed to location and characterization of the sulfatase active site. To understand the catalytic mechanism of sulfatases, and ultimately the determinants of their substrate specificities, we have determined the structure of N-acetylgalactosamine-4-sulfatase. RESULTS: . The crystal structure of the enzyme has been solved and refined at 2.5 resolution using data recorded at both 123K and 273K. The structure has two domains, the larger of which belongs to the alpha/beta class of proteins and contains the active site. The enzyme active site in the crystals contains several hitherto undescribed features. The active-site cysteine residue, Cys91, is found as the sulfate derivative of the aldehyde species, oxo-alanine. The sulfate is bound to a previously undetected metal ion, which we have identified as calcium. The structure of a vanadate-inhibited form of the enzyme has also been solved, and this structure shows that vanadate has replaced sulfate in the active site and that the vanadate is covalently linked to the protein. Preliminary data is presented for crystals soaked in the monosaccharide N-acetylgalactosamine, the structure of which forms a product complex of the enzyme. CONCLUSIONS: . The structure of N-acetylgalactosamine-4-sulfatase reveals that residues conserved amongst the sulfatase family are involved in stabilizing the calcium ion and the sulfate ester in the active site. This suggests an archetypal fold for the family of sulfatases. A catalytic role is proposed for the post-translationally modified highly conserved cysteine residue. Despite a lack of any previously detectable sequence similarity to any protein of known structure, the large sulfatase domain that contains the active site closely resembles that of alkaline phosphatase: the calcium ion in sulfatase superposes on one of the zinc ions in alkaline phosphatase and the sulfate ester of Cys91 superposes on the phosphate ion found in the active site of alkaline phosphatase.

Crystallization and preliminary characterization of human recombinant N-acetylgalactosamine-4-sulfatase.

Crystals of human recombinant N-acetylgalactosamine-4-sulfatase have been grown using vapour diffusion. The protein contains approximately 13%(w/w) carbohydrate. The crystals belong to the tetragonal space group P4(1)2(1)2 or its enantiomorph P4(3)2(1)2 with a = b = 108.0 and c = 145.5 A. The crystals diffract to 2.7 A resolution.

Pregnancy outcome and infant development following gestational cocaine use by social cocaine users in Toronto, Canada.

To determine the effect of first trimester cocaine use on pregnancy outcome we conducted a prospective cohort study of 30 women admitting to social cocaine use (SCU) during early pregnancy, 20 users of cannabis during the first trimester and 30 matched recreational drug-free control subjects. The groups were of similar age, marital status, and obstetric history and were predominantly white. They were of similar socioeconomic status (SES), however the spouses of the cocaine users were of significantly lower SES than those of both control groups (p less than 0.005). The number of years of education of the cocaine users and the fathers of the SCU-exposed fetuses was significantly lower than that of the recreational drug-free control subjects (p = 0.004), however, female IQ was similar among the three groups (109.1 +/- 12.4 cocaine; 109.1 +/- 25.2 cannabis; 114.1 +/- 11.7 drug-free). Alcohol and cigarette use was greater among the cocaine users than among subjects of the recreational drug-free control group (p less than 0.025). Cocaine and the associated lifestyle were not associated with any adverse obstetric or neonatal endpoint (pregnancy weight gain, incidence of delivery complications, gestational age, birth weight, Apgar scores, and rates of major and minor malformations). There were no differences between groups in attaining developmental milestones. Mental and motor scores on the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales were identical among the three groups, studied at a mean of 19.7 months of age. We conclude that outcome of pregnancy of social cocaine users and subsequent infant physical and cognitive development are within normal limits at 1.6 years of age.

The prognostic value of computed tomography of the brain in asphyxiated premature infants.

Computed tomography brain scans were done during the first two weeks of life in 145 asphyxiated or apneic newborn infants with birth weights less than 1,500 gm. Sixty-two survived and were assessed neurodevelopmentally at 18 months from the term date. Follow-up CT scans were done at six months post term. There were major neurodevelopmental defects in 15 children, minor defects in 10, and no gross abnormalities in 37. The neonatal CT scans showed germinal layer hemorrhage in 45 (73%) of the survivors and was combined with ventricular bleeding in 29 cases (47%). Areas of hypodensity of brain tissue were present in all neonatal CT and were extensive in 84%. Ventricular dilatation occurred in 31%. There was a significant relationship between hydrocephalus and CT findings of IVH and dilated ventricles, but no relationship between outcome at 18 months and any other features of the neonatal CT. Only four of 56 CT scans done at six months post term were normal. Dilatation of the ventricles and subarachnoid spaces was common but was not related to subsequent neurodevelopmental status.

Is intensive care justified for infants weighing less than 801 gm at birth?

During 1974-1977, 158 infants of birth weights less than 801 gm were referred from outlying hospitals. The survival rate was 25% for the whole group and 35% for those weighing 700 to 800 gm. Many were in a poor condition on arrival. One hundred and nineteen died. The most common causes of death were intracranial hemorrhage (39), RDS (26), and infection (13). Thirty-seven of the 39 survivors were followed until 18 months postterm. Growth failure was common--57% were below the third percentile in weight, 37% in length, and 17% in head circumference. Three had retrolental fibroplasia. Five children (14%) had major neurologic sequelae. Eight were severely handicapped with a Bayley score of less than 70 and ten were moderately handicapped with a Bayley score between 70 and 84, resulting in a neurodevelopmental handicap rate of 49%. Significant factors correlating with survival and intact outcome were birth weight greater than or equal to 700 gm, gestation greater than or equal to 26 weeks, the absence of asphyxia, and good condition on arrival at the NICU. There was no intact survival below 700 gm birth weight. The handicap rate of survivors between 700 and 800 gm was only 39%. Although intensive care in a referral unit may not be justified for those less than 700 gm, every effort should be made in the care of those 700 to 800 gm.

The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy.

Prospective follow-up studies were done on 62 term infants who were treated as neonates for clinical evidence of postasphyxial encephalopathy. Computed tomographic studies were done during the first two weeks of life and repeated at six months of age. All children were followed a minimum of 18 months, at which time they underwent a psychometric and a neurologic evaluation. Major neurodevelopmental sequelae consisted of: hydrocephalus; spastic quadriplegia, hemiplegia, or diplegia; or a mean Bayley score less than 70. Major sequelae were present in 29 (47%) of the children: all were severely handicapped. Five other children scored between 70 and 85 on the Bayley test. Computed tomographic scans were highly predictive of status at 18 months. Eleven of the 15 with intraventricular or parenchymal hemorrhage were severely handicapped. Eighteen of 20 with extensive areas of hypodensity of the white and gray matter (neonatal CT) were abnormal at 18 months. All but two were severely handicapped. The results suggest that CT studies are very useful in the care of the asphyxiated term infant who has clinical signs of encephalopathy.

Hospital office leasing is on the rise.

Eighty percent of medical office buildings currently under construction are being built by hospitals.

The status at two years of low-birth-weight infants born in 1974 with birth weights of less than 1,001 gm.

A two-year follow-up study of 43 infants of birth weight less than or equal to 1,000 gm born during 1974 revealed the following: average height at two years was between the tenth and twenty-fifth percentiles; average weight between the third and tenth percentiles. Fifteen (35%) developed lower respiratory tract infections during the first two years. Seven (16%) had retrolental fibroplasia. Major neurologic defects occurred in four (9%); severe developmental delay (mean developmental quotient less than 80) was found in nine others (21%). Defects of the central nervous system were closely associated with a neonatal history of intracranial hemorrhage or seizures or both.

Present status of the infant of very low birth weight treated in a referral neonatal intensive care unit in 1974.

In 1974, 250 infants with birth weights of 1500 g or less were referred to the Intensive Care Unit at the Hospital for Sick Children, Toronto. Sixty-six per cent survived. Prospective follow-up studies of the survivors have been completed over a minimum of two years. Infants at highest risk for handicapping defects (about 85%) are those who survived intracranial haemorrhage during the neonatal period. Neurological defects encountered in these children were severe--hydrocephalus, spastic quadriplegia, hemiplegia or microcephalus--and were usually associated with low psychometric scoring. The second highest risk group were small for gestational age infants. Of these, 53% were significantly handicapped at two years of age, and 43% had developmental quotients of less than 80. These defects could not be related to postnatal events. The third category at high risk were infants with birth weights of 1000 g or less. Among these, 30% had a significant handicap by two years of age. The outcome in the remainder of the sample was generally good. These results suggest that the decreased mortality of the very premature infant is associated with an increased number of relatively normal survivors and that the infants at highest risk for subsequent defects can be identified at or shortly after birth.