Sudden unexpected death in epilepsy: mechanisms, risk factors and the role of the nurse

Epilepsy is a disease which can have significant effects upon a person’s life. A subject discussed less frequently is sudden unexpected death in epilepsy (SUDEP). This article summarises the main risk factors for its occurrence; notably, seizure types, medications management and sleeping position. It discusses potential pathophysiological mechanisms, including the emerging research on laryngospasm and the role that genetics may play in increasing risk. Finally, it identifies several nursing responsibilities within the structure of a SUDEP checklist that has been shown to improve patient outcomes. It discusses how these responsibilities are underpinned by patient education and the need for all nurses to develop their own knowledge of epilepsy and SUDEP to facilitate this

Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis

AbstractBackgroundPulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)≥8 mmol L−1 (airway threshold), and are associated with acquisition of respiratory infection.MethodsTo determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry.ResultsAG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5–3 mmol L−1-vs.-0.5–1 mmol L−1, p<0.0001) when BG was ≥8 mmol L−1-vs.-<8 mmol L−1. Daily time with BG≥8 mmol L−1 was CFRD (49±25%), CF-NGT (6±5%), healthy volunteers (1±3%), p<0.0001. Staphylococcus aureus growth increased at ≥0.5 mmol L−1 (p=0.006) and Pseudomonas aeruginosa growth above 1–4 mmol L−1 glucose (p=0.039).ConclusionsBG≥8 mmol L−1 predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent ∼ 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD

Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose

Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection. Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected. Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas. Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Assessing dysphagia via telerehabilitation: patient perceptions and satisfaction

To gain insight into factors which may infl uence future acceptance of dysphagia management via telerehabilitation, patients’ perceptions were examined before and after a telerehabilitation assessment session. Forty adult patients with dysphagia(M = 66 years, SD = 16.25) completed pre- and post-session questionnaires which consisted of 14 matched questions worded to suit pre- and post-conditions. Questions explored comfort with the use of telerehabilitation, satisfaction with audio and video quality, benefi ts of telerehabilitation assessments and patients’ preferred assessment modality. Questions were rated on a 5-point scale (1 = strongly disagree, 3 = unsure, 5 = strongly agree). Patients’ comfort with assessment via telerehabilitation was high in over 80% of the group both pre- and post-assessment. Pre-assessment, patients were unsure what to expect with the auditory and visual aspects of the videoconference, however there were signifi cant positive changes reported post-experience. In relation to perceived benefits of telerehabilitation services in general, most patients believed in the value of telerehabilitation and post-assessment this increased to 90 – 100% agreement. Although 92% felt they would be comfortable receiving services via telerehabilitation, 45% of patients indicated ultimate preference for a traditional faceto-face assessment. The data highlight that patients are interested in and willing to receive services via telerehabilitation; however, any concerns should be addressed pre-assessment

HIV-1 recombinants with multiple parental strains in low-prevalence, remote regions of Cameroon: Evolutionary relics?

<p>Abstract</p> <p>Background</p> <p>The HIV pandemic disseminated globally from Central West Africa, beginning in the second half of the twentieth century. To elucidate the virologic origins of the pandemic, a cross-sectional study was conducted of the genetic diversity of HIV-1 strains in villagers in 14 remote locations in Cameroon and in hospitalized and STI patients. DNA extracted from PBMC was PCR amplified from HIV(+) subjects. Partial <it>pol </it>amplicons (N = 164) and nearly full virus genomes (N = 78) were sequenced. Among the 3956 rural villagers studied, the prevalence of HIV infection was 4.9%; among the hospitalized and clinic patients, it was 8.6%.</p> <p>Results</p> <p>Virus genotypes fell into two distinctive groups. A majority of the genotyped strains (109/164) were the circulating recombinant form (CRF) known to be endemic in West Africa and Central West Africa, CRF02_AG. The second most common genetic form (9/164) was the recently described CRF22_01A1, and the rest were a collection of 4 different subtypes (A2, D, F2, G) and 6 different CRFs (-01, -11, -13, -18, -25, -37). Remarkably, 10.4% of HIV-1 genomes detected (17/164) were heretofore undescribed unique recombinant forms (URF) present in only a single person. Nearly full genome sequencing was completed for 78 of the viruses of interest. HIV genetic diversity was commonplace in rural villages: 12 villages each had at least one newly detected URF, and 9 villages had two or more.</p> <p>Conclusions</p> <p>These results show that while CRF02_AG dominated the HIV strains in the rural villages, the remainder of the viruses had tremendous genetic diversity. Between the trans-species transmission of SIV_cpzand the dispersal of pandemic HIV-1, there was a time when we hypothesize that nascent HIV-1 was spreading, but only to a limited extent, recombining with other local HIV-1, creating a large variety of recombinants. When one of those recombinants began to spread widely (i.e. became epidemic), it was recognized as a subtype. We hypothesize that the viruses in these remote Cameroon villages may represent that pre-epidemic stage of viral evolution.</p

The side effects of service changes: exploring the longitudinal impact of participation in a randomised controlled trial (DOORWAYS) on staff perceptions of barriers to change

Background: Staff and service users have expressed concerns that service improvements in British mental health wards have been slow or transient. It is possible that certain changes are positive for some (e.g. service users), but negative for others (e.g. staff), which may affect implementation success. In this study, we explore whether a programme of change to improve the therapeutic milieu on mental health wards influenced staff perceptions of barriers to change, 12 months after implementation. Method: A cluster randomised controlled trial called DOORWAYS was conducted on eight British, inner-city acute mental health wards. Randomisation was achieved using a list randomly generated by a computer. A psychologist trained ward staff (mainly nurses) to deliver evidence-based groups and supported their initial implementation. The impact of these changes was measured over 12 months (when 4 wards were randomised), according to nurses’ perceptions of barriers to change (VOCALISE), using unstructured multivariate linear regression models. This innovative analysis method allows maximum use of data in randomised controlled trials with reduced sample sizes due to substantial drop out rates. The contextual influences of occupational status (staff) and of workplace setting (ward) were also considered. Results: Staff who participated in the intervention had significantly worse perceptions of barriers to change at follow up. The perceptions of staff in the control group did not change over time. In both groups (N = 120), direct care staff had more negative perceptions of barriers to change, and perceptions varied according to ward. Across time, direct care staff in the intervention group became more negative than those in the control group. Conclusion: Participation in this program of change, worsened staff perceptions of barriers to change. In addition, occupational status (being from the direct care group) had a negative effect on perceptions of barriers to change, an effect that continued across time and was worse in the intervention group. Those providing direct care should be offered extra support when changes are introduced and through the implementation process. More effort should be placed around reducing the perceived burden of innovation for staff in mental health wards

The Intracellular DNA Sensor IFI16 Gene Acts as Restriction Factor for Human Cytomegalovirus Replication

Human interferon (IFN)-inducible IFI16 protein, an innate immune sensor of intracellular DNA, modulates various cell functions, however, its role in regulating virus growth remains unresolved. Here, we adopt two approaches to investigate whether IFI16 exerts pro- and/or anti-viral actions. First, the IFI16 gene was silenced using specific small interfering RNAs (siRNA) in human embryo lung fibroblasts (HELF) and replication of DNA and RNA viruses evaluated. IFI16-knockdown resulted in enhanced replication of Herpesviruses, in particular, Human Cytomegalovirus (HCMV). Consistent with this, HELF transduction with a dominant negative form of IFI16 lacking the PYRIN domain (PYD) enhanced the replication of HCMV. Second, HCMV replication was compared between HELFs overexpressing either the IFI16 gene or the LacZ gene. IFI16 overexpression decreased both virus yield and viral DNA copy number. Early and late, but not immediate-early, mRNAs and proteins were strongly down-regulated, thus IFI16 may exert its antiviral effect by impairing viral DNA synthesis. Constructs with the luciferase reporter gene driven by deleted or site-specific mutated forms of the HCMV DNA polymerase (UL54) promoter demonstrated that the inverted repeat element 1 (IR-1), located between −54 and −43 relative to the transcription start site, is the target of IFI16 suppression. Indeed, electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated that suppression of the UL54 promoter is mediated by IFI16-induced blocking of Sp1-like factors. Consistent with these results, deletion of the putative Sp1 responsive element from the HCMV UL44 promoter also relieved IFI16 suppression. Together, these data implicate IFI16 as a novel restriction factor against HCMV replication and provide new insight into the physiological functions of the IFN-inducible gene IFI16 as a viral restriction factor