Antiseizure medications prescribing for behavioural and psychiatric concerns in adults with an intellectual disability living in England.

Antiseizure medications (ASMs) are the second most widely prescribed psychotropic for people with intellectual disabilities in England. Multiple psychotropic prescribing is prevalent in almost half of people with intellectual disabilities on ASMs. This analysis identifies limited evidence of ASM benefit in challenging behaviour management and suggests improvements needed to inform clinical practice.

Patterns of antiseizure medications prescribing in people with intellectual disability and epilepsy: A narrative review and analysis.

People with intellectual disabilities (PwID) have a bidirectional relationship with epilepsy. Nearly 25% of PwID have seizures and 30% people with epilepsy are thought to have a significant intellectual impairment. Furthermore, 70% of PwID are thought to have treatment-resistant epilepsy. In the United Kingdom, antiseizure medications (ASMs) are the second most widely prescribed psychotropic agent for PwID. However, it is unclear what the current evidence and patterns is on current prescribing of ASMs, including when and how a case is made to withdraw them. A narrative review along with an analysis of large-scale NHS Digital published data (2015-2020) on several aspects of ASM prescribing by general practices for PwID was undertaken. The review results and data analysis are consolidated and presented as 11 themes to provide a comprehensive overview of the study topic. Recent studies estimate that one-third and one-fifth of PwID are prescribed ASMs. A history of epilepsy is seen as the primary prescribing reason; however, often it is a legacy, and the indication is no longer clear. The proportion receiving ASMs continues to rise with age. This pattern of use does not correlate well with seizure onset. There are limited data on de-prescribing ASMs in PwID. The study population heterogenicity, associated polypharmacy, multimorbidity and higher sudden unexpected death in epilepsy risks are outlined. Suggestions are made from available evidence for improving prescribing practices for PwID and seizures, and key areas for further research in this complex clinical area are outlined.

Editor's Choice - Calcification of Thoracic and Abdominal Aneurysms is Associated with Mortality and Morbidity.

INTRODUCTION: Cardiovascular events are common in people with aortic aneurysms. Arterial calcification is a recognised predictor of cardiovascular outcomes in coronary artery disease. Whether calcification within abdominal and thoracic aneurysm walls is correlated with poor cardiovascular outcomes is not known. PATIENTS AND METHODS: Calcium scores were derived from computed tomography (CT) scans of consecutive patients with either infrarenal (AAA) or descending thoracic aneurysms (TAA) using the modified Agatston score. The primary outcome was subsequent all cause mortality during follow-up. Secondary outcomes were cardiovascular mortality and morbidity. RESULTS: A total of 319 patients (123 TAA and 196 AAA; median age 77 [71-84] years, 72% male) were included with a median follow-up of 30 months. The primary outcome occurred in 120 (37.6%) patients. In the abdominal aortic aneurysm group, the calcium score was significantly related to both all cause mortality and cardiac mortality (odds ratios (OR) of 2.246 (95% CI 1.591-9.476; p < 0.001) and 1.321 (1.076-2.762; p = 0.003)) respectively. In the thoracic aneurysm group, calcium score was significantly related to all cause mortality (OR 6.444; 95% CI 2.574-6.137; p < 0.001), cardiac mortality (OR 3.456; 95% CI 1.765-4.654; p = 0.042) and cardiac morbidity (OR 2.128; 95% CI 1.973-4.342; p = 0.002). CONCLUSIONS: Aortic aneurysm calcification, in either the thoracic or the abdominal territory, is significantly associated with both higher overall and cardiovascular mortality. Calcium scoring, rapidly derived from routine CT scans, may help identify high risk patients for treatment to reduce risk.

Mechanochemical Ablation for Treatment of Truncal Venous Insufficiency: A Review of the Current Literature.

Mechanochemical ablation (MOCA) is a nonthermal nontumescent technique used in the treatment of superficial venous disease. This review analyzed the available data on the efficacy and safety of MOCA. A systematic literature search was performed. Of 101 studies identified, 14 were suitable for inclusion. The studies were found to be heterogeneous in design, and the quality of evidence was found to be low or very low. MOCA was demonstrated to be effective in the short-term with minimal complications. Consensus guidelines and definitions of reporting outcome measures must be standardized to allow comparison with other techniques.

Gradient between dorsalis pedis and radial arterial blood pressures during sevoflurane anaesthesia: A self-control study in patients undergoing neurosurgery.

BACKGROUND: The dorsalis pedis artery (DPA) is a good alternative to the radial artery (RA) for invasive blood pressure monitoring when the upper limb is burned or injured, or if the RA is not available. Understanding the pattern of pressure difference between DPA and the commonly used RA during inhalational anaesthesia is helpful for haemodynamic management and therapeutic decisions. OBJECTIVES: The objective of this study was to investigate the time-dependent variation of DPA-to-RA pressure gradient during sevoflurane anaesthesia and the overall difference between the two pressures during neurosurgery, together with the causes of the pressure gradient change. DESIGN: A prospective, self-control, single-centre study. SETTING: The operating room of a teaching hospital from 1 January 2013 to 1 September 2013. PATIENTS: Thirty-seven patients between 18 and 60 years of age, American Society of Anesthesiologists' physical status 1-3, scheduled for neurosurgery in the supine position and requiring invasive arterial pressure monitoring. MAIN OUTCOME MEASURES: The time-dependent change of DPA-to-RA pressure gradient and skin temperature gradient, the difference between absolute values and average values of SBP, DBP and mean blood pressure (MBP) between RA and DPA during surgery, and the internal cross-sections and systolic blood flow velocities of RA and DPA at the baseline and at the end of surgery. RESULTS: Data from 30 patients were analysed. The mean ±â€Šstandard deviation DPA-to-RA pressure gradient gradually decreased with time from 9.7 ±â€Š8.8 to -1.8 ±â€Š7.6 mmHg for systolic pressure, -2.3 ±â€Š2.7 to -3.7 ±â€Š2.8 mmHg for diastolic pressure and -2.1 ±â€Š3.2 to -5.4 ±â€Š3.4 mmHg for MBP. Biases during the entire procedure were 2.2 ±â€Š10.1, -3.1 ±â€Š3.4 and -4.3 ±â€Š4.2 mmHg for SBP, DBP and MBP, respectively. The DPA-to-RA skin temperature gradient gradually reduced from -3.6 ±â€Š2.4 to -1.1 ±â€Š1.3°C. A greater increase in the inner cross-sectional area and blood flow from the baseline was observed at DPA compared with RA. CONCLUSION: The blood pressure, temperature and inner cross-sectional area differences between DPA and RA reduced gradually during sevoflurane anaesthesia in patients undergoing neurosurgery. Therapeutic decisions may rely on DPA pressure as long as the anaesthetists are aware of the pattern of change in DPA pressure during surgery. TRIAL REGISTRATION: www.chictr.org with registry number ChiCTR-RNRC-13003853.

Necroptosis and parthanatos are involved in remote lung injury after receiving ischemic renal allografts in rats.

Early renal graft injury could result in remote pulmonary injury due to kidney-lung cross talk. Here we studied the possible role of regulated necrosis in remote lung injury in a rat allogeneic transplantation model. In vitro, human lung epithelial cell A549 was challenged with TNF-α and conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. In vivo, the Brown-Norway rat renal grafts were extracted and stored in 4 °C Soltran preserving solution for up to 24 h and transplanted into Lewis rat recipients, and the lungs were harvested on day 1 and day 4 after grafting for further analysis. Ischemia-reperfusion injury in the renal allograft caused pulmonary injury following engraftment. PARP-1 (marker for parthanatos) and receptor interacting protein kinase 1 (Rip1) and Rip3 (markers for necroptosis) expression was significantly enhanced in the lung. TUNEL assays showed increased cell death of lung cells. This was significantly reduced after treatment with necrostatin-1 (nec-1) or/and 3-aminobenzamide (3-AB). Acute immune rejection exacerbated the remote lung injury and 3-AB or/and Nec-1 combined with cyclosporine A conferred optimal lung protection. Thus, renal graft injury triggered remote lung injury, likely through regulated necrosis. This study could provide the molecular basis for combination therapy targeting both pathways of regulated necrosis to treat such complications after renal transplantation.

Mortality risk in adults with intellectual disabilities and epilepsy: an England and Wales case-control study.

BACKGROUND: People with epilepsy (PWE) and people with intellectual disabilities (ID) both live shorter lives than the general population and both conditions increase the risk of death further. We aimed to measure associations between certain risk factors for death in PWE and ID. METHODS: A retrospective case-control study was conducted in ten regions in England and Wales. Data were collected on PWE registered with secondary care ID and neurology services between 2017 and 2021. Prevalence rates of neurodevelopmental, psychiatric and medical diagnoses, seizure frequency, psychotropic and antiseizure medications (ASM) prescribed, and health activity (epilepsy reviews/risk assessments/care plans/compliance etc.) recorded were compared between the two groups. RESULTS: 190 PWE and ID who died were compared with 910 living controls. People who died were less likely to have had an epilepsy risk assessment but had a greater prevalence of genetic conditions, older age, poor physical health, generalized tonic-clonic seizures, polypharmacy (not ASMs) and antipsychotic use. The multivariable logistic regression for risk of epilepsy-related death identified that age over 50, medical condition prevalence, antipsychotic medication use and the lack of an epilepsy review in the last 12 months as associated with increased risk of death. Reviews by psychiatrists in ID services was associated with a 72% reduction in the odds of death compared neurology services. CONCLUSIONS: Polypharmacy and use of antipsychotics may be associated with death but not ASMs. Greater and closer monitoring by creating capable health communities may reduce the risk of death. ID services maybe more likely to provide this holistic approach.

Epilepsy related multimorbidity, polypharmacy and risks in adults with intellectual disabilities: a national study.

BACKGROUND: A quarter of people with Intellectual Disability (ID) in the UK have epilepsy compared to 0.6% in the general population and die much younger. Epilepsy is associated with two-fifths of all deaths with related polypharmacy and multi-morbidity. Epilepsy research on this population has been poor. This study describes real-world clinical and risk characteristics of a large cohort across England and Wales. METHODS: A retrospective multi-centre cohort study was conducted. Information on seizure characteristics, ID severity, relevant co-morbidities, psychotropic and antiseizure drugs (ASDs), SUDEP and other risk factors was collected across a year. RESULTS: Of 904 adults across 10 centres (male:female, 1.5:1), 320 (35%) had mild ID and 584 (65%) moderate-profound (M/P) ID. The mean age was 39.9 years (SD 15.0). Seizures were more frequent in M/P ID (p < 0.001). Over 50% had physical health co-morbidities, more in mild ID (p < 0.01). A third had psychiatric co-morbidity and a fifth had an underlying genetic disorder. Autism Spectrum Disorder was seen in over a third (37%). Participants were on median two ASDs and overall, five medications. Over quarter were on anti-psychotics. Over 90% had an epilepsy review in the past year but 25% did not have an epilepsy care plan, particularly those with mild ID (p < 0.001). Only 61% had a documented discussion of SUDEP, again less likely with mild ID or their care stakeholders (p < 0.001). CONCLUSIONS: Significant levels of multi-morbidity, polypharmacy and a lack of systemised approach to treatment and risk exist. Addressing these concerns is essential to reduce premature mortality.

Seizure and Sudden Unexpected Death in Epilepsy (SUDEP) characteristics in an urban UK intellectual disability service.

PURPOSE: This study identifies epilepsy-related characteristics and SUDEP risk factors in people with epilepsy (PWE) attending an urban community ID service in the UK where managing epilepsy is not part of the service remit, to understand the care provided to this vulnerable population. METHODS: An electronic database search in a north London community ID service (catchment population approx. 290,000) identified relevant ID/epilepsy characteristics in PWE to compare those with mild ID to moderate-profound ID. The SUDEP and Seizure Safety Checklist ("Checklist"), was administered to patients and families/carers. Risk management data was compared to similar data from Cornwall UK where PWE are supported within the ID service and the Checklist is used annually. RESULTS: One fifth (137/697) of people attending the service had epilepsy. Over 3/4 had moderate-profound ID. Neurodevelopmental disorders were coexistent in 2/3, psychiatric conditions in 1/3 (1/4 of which was psychosis). The mean number of anti-seizure drugs was 1.45 ± 0.98, and 1/4 were taking psychotropic medications. Over a third did not have an epilepsy care plan. None contacted (n = 103) had SUDEP awareness. The median number of Checklist risk factors was seven (IQR 4.5-9). A third had experienced seizures lasting >5 min or status epilepticus. In comparison to the Cornish ID data significant differences were evident in four of seven modifiable risk factors. CONCLUSIONS: This real world study highlights the complexity and risks among PWE and ID. The lack of a "joined up" approach can undermine the safety of this vulnerable population. Person-centred risk communication and care plans are easily achievable and essential.

Dexmedetomidine attenuates oxidative stress induced lung alveolar epithelial cell apoptosis in vitro.

BACKGROUND: Oxidative stress plays a pivotal role in the lung injuries of critical ill patients. This study investigates the protection conferred by α 2 adrenoceptor agonist dexmedetomidine (Dex) from lung alveolar epithelial cell injury induced by hydrogen peroxide (H2O2) and the underlying mechanisms. METHODS: The lung alveolar epithelial cell line, A549, was cultured and then treated with 500 µM H2O2 with or without Dex (1 nM) or Dex in combination with atipamezole (10 nM), an antagonist of α 2 receptors. Their effect on mitochondrial membrane potential (Δψ m), reactive oxygen species (ROS), and the cell cycle was assessed by flow cytometry. Cleaved-caspases 3 and 9, BAX, Bcl-2, phospho-mTOR (p-mTOR), ERK1/2, and E-cadherin expression were also determined with immunocytochemistry. RESULTS: Upregulation of cleaved-caspases 3 and 9 and BAX and downregulation of Bcl-2, p-mTOR, and E-cadherin were found following H2O2 treatment, and all of these were reversed by Dex. Dex also prevented the ROS generation, cytochrome C release, and cell cycle arrest induced by H2O2. The effects of Dex were partially reversed by atipamezole. CONCLUSION: Our study demonstrated that Dex protected lung alveolar epithelial cells from apoptotic injury, cell cycle arrest, and loss of cell adhesion induced by H2O2 through enhancing the cell survival and proliferation.

Odontoma of the middle ear: case report with 25-year follow-up.

We report the 25-year follow-up on the first reported case of odontoma in the middle ear. Diagnosis of odontoma had been made on the basis of radiography films that showed a middle ear mass with multiple toothlike areas of radiopacity. No clinical intervention was recommended. At 25-year follow-up, audiometry showed progressive mixed hearing loss on the affected side and mild ipsilateral sensorineural hearing loss. Computed tomography better characterized the discrete mass, which was shaped similar to a dental crown. To avoid jeopardizing cochlear and facial nerve function, no surgical intervention was pursued, and we recommended use of a BiCROS (bilateral contralateral routing of signal) hearing aid.

Lipoblastomatosis of the neck causing hemiparesis: a case report and review of the literature.

BACKGROUND: Lipoblastoma and lipoblastomatosis are rare pediatric adipose tumors that sometimes affect the neck or spinal cord. This case is the third report of lipoblastoma extending into the spinal canal, the first report of intradural tumor extension, and the first report of hemiparesis resulting from lipoblastoma compressing the spinal cord. METHODS: A 13-month-old boy was seen by a pediatrician for a firm, supraclavicular neck mass on the left side. After being evaluated by CT and MRI scanning, the tumor was partially resected. RESULTS: Postoperative microscopic examination of the tumor showed adipose cells with mature nuclei and well-formed fat vacuoles interspersed with fibrovascular septa, a finding consistent with maturing lipoblastoma. CONCLUSIONS: Although lipoblastomatous tumors are treated with complete surgical resection when possible, location of these tumors in the neck may dictate partial resection to avoid intraoperative injury to the spinal cord.