A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP

A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection.

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Association of cardiovascular disease and 10 other pre-existing comorbidities with COVID-19 mortality: A systematic review and meta-analysis

BACKGROUND: Estimating the risk of pre-existing comorbidities on coronavirus disease 2019 (COVID-19) mortality may promote the importance of targeting populations at risk to improve survival. This systematic review and meta-analysis aimed to estimate the association of pre-existing comorbidities with COVID-19 mortality. METHODS: We searched MEDLINE, SCOPUS, OVID, and Cochrane Library databases, and medrxiv.org from December 1st, 2019, to July 9th, 2020. The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing comorbidities. We analyzed 11 comorbidities: cardiovascular diseases, hypertension, diabetes, congestive heart failure, cerebrovascular disease, chronic kidney disease, chronic liver disease, cancer, chronic obstructive pulmonary disease, asthma, and HIV/AIDS. Two reviewers independently extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. RESULTS: Eleven pre-existing comorbidities from 25 studies were included in the meta-analysis (n = 65, 484 patients with COVID-19; mean age; 61 years; 57% male). Overall, the between-study heterogeneity was medium, and studies had low publication bias and high quality. Cardiovascular disease (risk ratio (RR) 2.25, 95% CI = 1.60–3.17, number of studies (n) = 14), hypertension (1.82 [1.43 to 2.32], n = 13), diabetes (1.48 [1.02 to 2.15], n = 16), congestive heart failure (2.03 [1.28 to 3.21], n = 3), chronic kidney disease (3.25 [1.13 to 9.28)], n = 9) and cancer (1.47 [1.01 to 2.14), n = 10) were associated with a significantly greater risk of mortality from COVID-19. CONCLUSIONS: Patients with COVID-19 with cardiovascular disease, hypertension, diabetes, congestive heart failure, chronic kidney disease and cancer have a greater risk of mortality compared to patients with COVID-19 without these comorbidities. Tailored infection prevention and treatment strategies targeting this high-risk population might improve survival

Sudden death in individuals with obstructive sleep apnoea: a systematic review and meta-analysis

Objectives Over 1 billion individuals worldwide experience some form of sleep apnoea, and this number is steadily rising. Obstructive sleep apnoea (OSA) can negatively influence one’s quality of life and potentially increase mortality risk. However, the association between OSA and mortality has not been reliably estimated. This meta-analysis estimates the risk of all-cause and cardiovascular mortality in individuals with OSA.Design Systematic review and meta-analysis.Data sources MEDLINE, Cochrane Library, Scopus and Joanna Briggs Institute Evidence-Based Practice databases were searched from inception through 1 January 2020.Eligibility criteria for selecting studies We included observational studies assessing the association of sudden deaths in individuals with and without OSA.Data extraction and synthesis Two independent reviewers (AES and ESH) extracted data and assessed the risk of bias using the Newcastle-Ottawa Scale quality assessment tool. Data were pooled using the random-effects models and reported as risk ratios (RRs) with 95% CIs. Heterogeneity was quantified with I2 statistic.Results We identified 22 observational studies (n=42 099 participants). The mean age was 62 years and 64% were men. OSA was associated with all-cause sudden death (RR=1.74, 95% CI: 1.44 to 2.10, I2=72%) and cardiovascular mortality (RR=1.94, 95% CI: 1.39 to 2.70, I2=32%). A marginally significant dose–response relationship between severity of OSA and the risk of death was observed (p for interaction=0.05): mild OSA (RR=1.16, 95% CI: 0.70 to 1.93), moderate OSA (RR=1.72, 95% CI: 1.11 to 2.67) and severe OSA (RR=2.87, 95% CI: 1.70 to 4.85). Meta-regression analysis showed that older age was a significant contributing factor in the relationship between OSA and mortality. The median study methodological quality was considered high.Conclusions OSA is a significant risk factor for all-cause mortality and cardiac mortality. Prevention and treatment strategies to optimise survival and quality of life in individuals with OSA are urgently needed.PROSPERO registration number CRD42020164941

Risk of suicidal ideation, suicide attempts, and suicide deaths in persons with sleep apnea: Protocol for a systematic review and meta-analysis.

AIM:To estimate the pooled prevalence and incidence of suicidal ideation, attempts, and deaths in people with sleep apnea. METHOD:We will identify epidemiological studies reporting the prevalence or incidence rate of suicide in people with sleep apnea. We will search the following databases: PubMed (MEDLINE), Scopus, Cochrane Library, OVID (HEALTH STAR), OVID (MEDLINE) and Joana Briggs Institute EBF Database. No age, geographical location, study-design or language limits will be applied. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. Two reviewers (YY and YP) will independently screen citations, abstracts and will identify full-text articles for inclusion, extract data, and appraise the quality and bias of included studies. Discrepancies will be resolved by consulting with a third researcher (MC). Study quality will be assessed by the Newcastle-Ottawa Scale. The primary outcomes will be the overall prevalence or incidence of suicidal ideation, attempts and completion and the risk of suicide in people with sleep apnea. For pooling of the studies, we will use a random-effects model with a logit transformation. The DerSimonian and Laird (DL) random-effects method will be used to estimate the pooled inter-study variance. We will assess the between-study heterogeneity using I2 statistics, and Cochrane's Q statistic (significance level 75%), we will perform subgroup meta-analyses and conduct a meta-regression analysis to explore sources of study heterogeneity using study level median age, study-level proportions of race, gender, depression and quality scores. We will report effect estimates as suicide risk per 1000 individuals. Egger's test and funnel plots will be used to assess publication bias, and adjusted estimates using trim and fill methods will be reported if publication bias is suspected. ETHICS AND DISSEMINATION:No ethics clearance is required as no primary data will be collected. The results of this systematic review and meta-analysis will be presented at scientific conferences and published in a peer-review journal. The results may shed more light on the burden of suicide risk among individuals with sleep apnea and may guide future population-specific interventions. TRIAL REGISTRATION:PROSPERO registration number: CRD42020165404

Rates and risk factors for suicidal ideation, suicide attempts and suicide deaths in persons with HIV: a systematic review and meta-analysis

Background People living with HIV/AIDS (PLWHA) must contend with a significant burden of disease. However, current studies of this demographic have yielded wide variations in the incidence of suicidality (defined as suicidal ideation, suicide attempt and suicide deaths).Aims This systematic review and meta-analysis aimed to assess the lifetime incidence and prevalence of suicidality in PLWHA.Methods Publications were identified from PubMed (MEDLINE), SCOPUS, OVID (MEDLINE), Joanna Briggs Institute EBP and Cochrane Library databases (from inception to before 1 February 2020). The search strategy included a combination of Medical Subject Headings associated with suicide and HIV. Researchers independently screened records, extracted outcome measures and assessed study quality. Data were pooled using a random-effects model. Subgroup and meta-regression analyses were conducted to explore the associated risk factors and to identify the sources of heterogeneity. Main outcomes were lifetime incidence of suicide completion and lifetime incidence and prevalence of suicidal ideation and suicide attempt.Results A total of 185 199 PLWHA were identified from 40 studies (12 cohorts, 27 cross-sectional and 1 nested case-control). The overall incidence of suicide completion in PLWHA was 10.2/1000 persons (95%CI: 4.5 to 23.1), translating to 100-fold higher suicide deaths than the global general population rate of 0.11/1000 persons. The lifetime prevalence of suicide attempts was 158.3/1000 persons (95%CI: 106.9 to 228.2) and of suicidal ideation was 228.3/1000 persons (95%CI: 150.8 to 330.1). Meta-regression revealed that for every 10-percentage point increase in the proportion of people living with HIV with advanced disease (AIDS), the risk of suicide completion increased by 34 per 1000 persons. The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations for the suicide deaths was graded as ‘moderate’ quality.Conclusions The risk of suicide death is 100-fold higher in people living with HIV than in the general population. Lifetime incidence of suicidal ideation and attempts are substantially high. Suicide risk assessments should be a priority in PLWHA, especially for those with more advanced disease

Intractable myoclonic seizures in an allogeneic stem cell transplant recipient: A rare case of myoclonic epilepsy

Introduction: Myoclonus may be a rare complication of stem cell transplant but has limited discussion in the scientific literature. Case: We present a case of an acute myeloid leukemia survivor who developed refractory myoclonic epilepsy four years after graft versus host disease (GVHD) developed six days following matched unrelated allogeneic hematopoietic stem cell transplant. Discussion: Graft versus host disease occurs in 30–50% of allogenic hematopoietic stem cell transplant patients and may cause pharmacoresistant myoclonic epilepsy; however, the mechanisms by which GVHD leads to recurrent myoclonic seizures are not well understood (Lee, 2005) [1]. The paucity of clinical reports of such manifestation makes it difficult to diagnose and effectively manage these patients

Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection : A sytematic review

Importance: Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region. Objective: To estimate organ system–specific frequency and evolution of PASC. Evidence Review: PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references. Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility. Findings: From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55.0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders. Conclusions and Relevance: In this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries