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Sepsis-associated encephalopathy (SAE) is a clinical syndrome that is associated with diffuse brain dysfunction and is secondary to infection in the body. Severity of SAE ranges from mild delirium to deep coma, and mortality reaches almost 70% in severe cases. In this Review, Gofton and Young provide an overview of the epidemiology and clinical presentation of SAE. They discuss current evidence relating to the pathophysiology and prognosis of SAE, and present a diagnostic approach and management strategy for patients with the disease. Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed. Key Points Sepsis-associated encephalopathy (SAE) is an early feature of infection in the body and might appear before other systemic features of sepsis are obvious SAE has a spectrum of degrees of severity, ranging from delirium to deep coma Hyperventilation can be an early feature and paratonic rigidity might be the only neurological finding, besides delirium, in early SAE; advanced disease is associated with critical illness polyneuropathy in 70% of cases No specific markers for SAE exist, so diagnosis relies on exclusion of primary CNS infection and other causes of encephalopathy Although early stages of SAE might have a uniform pathogenesis, multiple mechanisms, which can operate alone or in combination, could be involved in advanced disease Morbidity and mortality increase with disease severity; early investigation and prompt treatment of underlying infection when delirium presents are, therefore, important

Reading skills are foundational for daily lives, academic achievement, and careers. In this study, we systematically reviewed literacy interventions in low- and middle-income countries, and estimated their effects on children's reading skills using a meta-analytic approach. A total of 67 studies (N = 213,464) from 32 countries found in various databases (e.g., PsycINFO, ERIC) and sources (e.g., United States Agency for International Development) met our inclusion criteria. The results revealed an overall effect of .30 across various literacy outcomes. Effects varied for different outcomes, such that largest effects were found in emergent literacy skills (e.g., .40) and the smallest effects in reading comprehension (.25) and oral language skills (.20). Effects also varied as a function of other features such as teacher training support.

Silicone oil (SO) is commonly used for tamponade purposes in retinal detachment (RD) surgery, but the long-term visual prognosis after removal of the oil, and in particular, what is known about the recurrence of RD after SO removal, remains unclear. The purpose of this study is to evaluate the long-term vision prognosis after SO removal, and to understand the frequency and characteristics of RD recurrence. We retrospectively reviewed the medical charts of 1017 eyes of patients with a diagnosis of RD who had a pars plana vitrectomy with SO tamponade between January 2009 and December 2018. Best-corrected visual acuity (BCVA) was obatained before and after vitrectomy and also at the last visit. After SO removal, the group who showed improvement in visual acuity and the group who did not were compared. The anatomical results were compared between the group in which the retina was detached again after SO removal and the group in which the retina was not detached. To determine whether the duration of SO tamponade affects RD recurrence, further analysis was performed by dividing subgroups according to SO tamponade duration. RD recurrence, visual acuity, SO tamponade period were investigated. Mean follow-up period was 56.65 ± 72.02 months. An average SO tamponade period was 6.68 ± 11.39 months. The average logMAR BCVA was 1.75 ± 0.91 before SO injection, 1.60 ± 0.75 before SO removal and 1.29 ± 0.96 after the removal. After SO removal, 926 of the 1017 (91.1%) patients had well attached retina without recurrence. There was no significant difference in visual acuity before SO removal in re-detachment group compared to no re-detachment group, but visual acuity of re-detachment group was worse than no re-detachment group after SO removal (p<0.001). The SO tamponade period in the group with improved vision after SO removal was 5.09 ± 9.87 months, and the period was significantly shorter than the 9.09 ± 13.05 months in the group not showing vision recovery (p = 0.005). The occurrence of corneal opacity was significantly higher in the group with SO over 6 months, than those of the two groups with SO tamponade duration of less than 3 months and between 3 and 6 months (p = 0.038). The longest tamponade group showed the worst final vision after SO removal (p<0.001). The prognosis for final vision is generally good when performing surgery using SO in RD, but considering the complications that arise after surgery, long-term retention of SO is not recommended and the timing of SO removal should be considered.

Accurate, comprehensive, and timely detection of drug-resistant tuberculosis (TB) is essential to inform patient treatment and enable public health surveillance. This is crucial for effective control of TB globally. Whole-genome sequencing (WGS) and targeted next-generation sequencing (NGS) approaches have potential as rapid in vitro diagnostics (IVDs), but the complexity of workflows, interpretation of results, high costs, and vulnerability of instrumentation have been barriers to broad uptake outside of reference laboratories, especially in low- and middle-income countries. A new, solid-state, tabletop sequencing instrument, Illumina iSeq100, has the potential to decentralize NGS for individual patient care. In this study, we evaluated WGS and targeted NGS for TB on both the new iSeq100 and the widely used MiSeq (both manufactured by Illumina) and compared sequencing performance, costs, and usability. We utilized DNA libraries produced from Mycobacterium tuberculosis clinical isolates for the evaluation. We conducted WGS on three strains and observed equivalent uniform genome coverage with both platforms and found the depth of coverage obtained was consistent with the expected data output. Utilizing the standardized, cloud-based ReSeqTB bioinformatics pipeline for variant analysis, we found the two platforms to have 94.0% (CI 93.1%-94.8%) agreement, in comparison to 97.6% (CI 97%-98.1%) agreement for the same libraries on two MiSeq instruments. For the targeted NGS approach, 46 M. tuberculosis-specific amplicon libraries had 99.6% (CI 98.0%-99.9%) agreement between the iSeq100 and MiSeq data sets in drug resistance-associated SNPs. The upfront capital costs are almost 5-fold lower for the iSeq100 ($19,900 USD) platform in comparison to the MiSeq ($99,000 USD); however, because of difference in the batching capabilities, the price per sample for WGS was higher on the iSeq100. For WGS of M. tuberculosis at the minimum depth of coverage of 30x, the cost per sample on the iSeq100 was $69.44 USD versus $28.21 USD on the MiSeq, assuming a 2 × 150 bp run on a v3 kit. In terms of ease of use, the sequencing workflow of iSeq100 has been optimized to only require 27 minutes total of hands-on time pre- and post-run, and the maintenance is simplified by a single-use cartridge-based fluidic system. As these are the first sequencing attempts on the iSeq100 for M. tuberculosis, the sequencing pool loading concentration still needs optimization, which will affect sequencing error and depth of coverage. Additionally, the costs are based on current equipment and reagent costs, which are subject to change. The iSeq100 instrument is capable of running existing TB WGS and targeted NGS library preparations with comparable accuracy to the MiSeq. The iSeq100 has reduced sequencing workflow hands-on time and is able to deliver sequencing results in <24 hours. Reduced capital and maintenance costs and lower-throughput capabilities also give the iSeq100 an advantage over MiSeq in settings of individualized care but not in high-throughput settings such as reference laboratories, where sample batching can be optimized to minimize cost at the expense of workflow complexity and time.

A 55-year-old man collapses while jogging through the park. A bystander finds him unconscious and without a pulse and initiates cardiopulmonary resuscitation while an ambulance is summoned. On arrival in the emergency room, the patient is in ventricular fibrillation. Spontaneous circulation is reestablished, but he remains comatose with absent pupillary reflexes. He remains unconscious after treatment with hypothermia for 24 hours. What would you advise regarding his neurologic prognosis? A 55-year-old man collapses while jogging through the park. Spontaneous circulation is reestablished, but he remains comatose with absent pupillary reflexes. What would you advise regarding his neurologic prognosis? Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. Stage A 55-year-old man collapses while jogging through the park. A bystander finds him unconscious and without a pulse and initiates cardiopulmonary resuscitation (CPR) while an ambulance is summoned. On arrival in the emergency room, the patient is in ventricular fibrillation; the partial pressure of oxygen in arterial blood is 200 mm Hg, the pH is 7.25, and the bicarbonate level is 18 mmol per liter. Spontaneous circulation is reestablished, but he remains comatose with absent pupillary reflexes. He is then treated with hypothermia, achieving a core temperature of 34°C in 4 hours, which is maintained for 24 hours, after . . .