The Impact of Ambulatory Dementia Care Models on Hospitalization of Persons Living With Dementia: A Systematic Review

This systematic review presents an overview of the existing dementia care models in various ambulatory care settings under three categories (i.e., home- and community-based care models, partnership between health systems and community-based resources, and consultation models) and their impact on hospitalization among Persons Living with Dementia (PLWD). PRISMA guidelines were applied, and our search resulted in a total of 13 studies focusing on 11 care models. Seven studies reported that utilization of dementia care models was associated with a modest reduction in hospitalization among community-residing PLWD. Only two studies reported statistically significant results. Dementia care models that were utilized in specialty ambulatory care settings such as memory care showed more promising results than traditional primary care. To develop a better understanding of how dementia care models can be improved, future studies should explore how confounders (e.g., stage of dementia) influence hospitalization.

Rewarming With Closed Thoracic Lavage Following 3-h CPR at 27°C Failed to Reestablish a Perfusing Rhythm

Introduction: Previously, we showed that the cardiopulmonary resuscitation (CPR) for hypothermic cardiac arrest (HCA) maintained cardiac output (CO) and mean arterial pressure (MAP) to the same reduced level during normothermia (38°C) vs. hypothermia (27°C). In addition, at 27°C, the CPR for 3-h provided global O2 delivery (DO2) to support aerobic metabolism. The present study investigated if rewarming with closed thoracic lavage induces a perfusing rhythm after 3-h continuous CPR at 27°C.Materials and Methods: Eight male pigs were anesthetized, and immersion-cooled. At 27°C, HCA was electrically induced, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed by combining closed thoracic lavage and continued CPR. Organ blood flow was measured using microspheres.Results: After cooling with spontaneous circulation to 27°C, MAP and CO were initially reduced by 37 and 58% from baseline, respectively. By 15 min after the onset of CPR, MAP, and CO were further reduced by 58 and 77% from baseline, respectively, which remained unchanged throughout the rest of the 3-h period of CPR. During CPR at 27°C, DO2 and O2 extraction rate (VO2) fell to critically low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. During rewarming with closed thoracic lavage, all animals displayed ventricular fibrillation, but only one animal could be electro-converted to restore a short-lived perfusing rhythm. Rewarming ended in circulatory collapse in all the animals at 38°C.Conclusion: The CPR for 3-h at 27°C managed to sustain lower levels of CO and MAP sufficient to support global DO2. Rewarming accidental hypothermia patients following prolonged CPR for HCA with closed thoracic lavage is not an alternative to rewarming by extra-corporeal life support as these patients are often in need of massive cardio-pulmonary support during as well as after rewarming.

Progress of the Delta variant and erosion of vaccine effectiveness, a warning from Utah

Since the emergence of SARS-CoV-2, vaccines have been heralded as the best way to curtail the pandemic. Clinical trials have shown SARS-CoV-2 vaccines to be highly efficacious against both disease and infection. However, those currently in use were primarily tested against early lineages. Data on vaccine effectiveness (VE) against variants of concern (VOC), including the Delta variant (B.1.617.2), remain limited. To examine the effectiveness of vaccination in Utah we compared the proportion of cases reporting vaccination to that expected at different VEs, then estimated the combined daily vaccine effectiveness using a field evaluation approach. Delta has rapidly outcompeted all other variants and, as of June 20th, represents 70% of all SARS-CoV-2 viruses sequenced in Utah. If we attribute the entire change in VE to the Delta variant, the estimated vaccine effectiveness against Delta would be 82% (95% CI: 78%, 85%). We show a modest reduction in vaccine effectiveness against COVID-19 in Utah corresponding to the expansion of the Delta lineage in the state. This reduction in the effectiveness of available vaccines correlated with the arrival of novel VOCs, rather than waning immunity, is highly concerning.

A physicochemical model of odor sampling

We present a general physicochemical sampling model for olfaction, based on established pharmacological laws, in which arbitrary combinations of odorant ligands and receptors can be generated and their individual and collective effects on odor representations and olfactory performance measured. Individual odor ligands exhibit receptor-specific affinities and efficacies; that is, they may bind strongly or weakly to a given receptor, and can act as strong agonists, weak agonists, partial agonists, or antagonists. Ligands interacting with common receptors compete with one another for dwell time; these competitive interactions appropriately simulate the degeneracy that fundamentally defines the capacities and limitations of odorant sampling. The outcome of these competing ligand-receptor interactions yields a pattern of receptor activation levels, thereafter mapped to glomerular presynaptic activation levels based on the convergence of sensory neuron axons. The metric of greatest interest is the mean discrimination sensitivity, a measure of how effectively the olfactory system at this level is able to recognize a small change in the physicochemical quality of a stimulus. This model presents several significant outcomes, both expected and surprising. First, adding additional receptors reliably improves the system’s discrimination sensitivity. Second, in contrast, adding additional ligands to an odor scene initially can improve discrimination sensitivity, but eventually will reduce it as the number of ligands increases. Third, the presence of antagonistic ligand-receptor interactions produced clear benefits for sensory system performance, generating higher absolute discrimination sensitivities and increasing the numbers of competing ligands that could be present before discrimination sensitivity began to be impaired. Finally, the model correctly reflects and explains the modest reduction in odor discrimination sensitivity exhibited by transgenic mice in which the specificity of glomerular targeting by primary olfactory neurons is partially disrupted.

Two distinct mechanisms underlie dosage sensitivity in Pumilio1-associated diseases

SUMMARYThe RNA-binding protein (RBP) Pumilio1 (PUM1) is associated with two distinct diseases: a late-onset ataxia and a neurodevelopmental syndrome. The ataxia patients retain 75% of normal PUM1 levels, the syndromic patients ∼50%, but this seems inadequate to explain the difference in phenotypes. We hypothesized that mild disease results from dysregulation of PUM1 targets, whereas severe disease involves disruption of PUM1 complexes and deregulation of shared targets. We therefore developed a PUM1 interactome for the murine brain and found that PUM1 shares targets with several RBP interactors (PUM2, FMRP, AGO2, and RBFOX3). PUM1 haploinsufficiency destabilizes these RBPs to varying degrees by brain region and sex, and alters expression of their shared targets, but the milder disease-causing mutation affects only PUM1-specific targets. These data indicate that dosage-sensitive proteins can produce different phenotypes by different mechanisms, and that there may be more intimate cooperation among RBPs than expected.HIGHLIGHTS•RNA-binding proteins can cause disease via their targets or interactors•Interactions among RNA-binding proteins can differ by brain region and sex•A modest reduction in PUM1 levels affects PUM1-specific targets•Greater reductions in PUM1 levels disrupt interactors and shared targets

The effect of sertraline on depression and associations with persistent depression in survivors of HIV-related cryptococcal meningitis

Background: Depression is a risk factor for worse outcomes in persons living with HIV/AIDS and has a prevalence more than three times as high as in the general population. Despite this, there are few randomized studies of antidepressants in HIV-infected Africans. Methods: We enrolled 460 HIV-infected Africans with cryptococcal meningitis into a randomized clinical trial of adjunctive sertraline vs placebo (2015-2017). We defined depression using depression using a Center for Epidemiologic Studies Depression Scale (CES-D) score of >15, and severe depression as >26 at one and three months after meningitis diagnosis and initiation of treatment.We evaluated the relationship between sertraline and depression, as well as associations with persistent depression, at three months. Results: At one- and three-months post meningitis diagnosis, 62% (108/174) and 44% (74/169) of all subjects had depression (CES>15), respectively. At three months, sertraline-treated subjects had consistent risk for depression as placebo-treated subjects but were significantly less likely to have severe depression (CES>26) (OR 0.335; 95%CI, 0.130-0.865). Of those with depression at one month, sertraline-treated subjects were less likely than placebo-treated subjects to be depressed at three months (p=0.05). Sertraline was the only factor we found significant in predicting persistent depression at three months among those who had depression at one month. Conclusions: Depression is highly prevalent in HIV-infected persons who have survived cryptococcal meningitis. We found that sertraline is associated with a modest reduction in depression in those with depression at baseline and a significant decrease in severe depression.

Applications of intraoperative Duplex ultrasound in vascular surgery: a systematic review

Objective This review aims to summarise the contemporary uses of intraoperative completion Duplex ultrasound (IODUS) for the assessment of lower extremity bypass surgery (LEB) and carotid artery endarterectomy (CEA). Methods We performed a systematic literature search using the databases of MEDLINE. Eligible studies evaluated the use of IODUS during LEB or CEA. Results We found 22 eligible studies; 16 considered the use of IODUS in CEA and 6 in LEB. There was considerable heterogeneity between studies in terms of intervention, outcome measures and follow-up. In the assessment of CEA, there is conflicting evidence regarding the benefits of completion imaging. However, analysis from the largest study suggests a modest reduction in adjusted risk of stroke/mortality when using IODUS selectively (RR 0.74, CI 0.63–0.88, p = 0.001). Evidence also suggests that uncorrected residual flow abnormalities detected on IODUS are associated with higher rates of restenosis (range 2.1% to 20%). In the assessment of LEB, we found a paucity of evidence when considering the benefit of IODUS on patency rates or when considering its utility as compared to other imaging modalities. However, the available evidence suggests higher rates of thrombosis or secondary intervention in grafts with uncorrected residual flow abnormalities (up to 36% at 3 months). Conclusions IODUS can be used to detect defects in both CEA and LEB procedures. However, there is a need for more robust prospective studies to determine the best scanning strategy, criteria for intervention and the impact on clinical outcomes.

Caffeine may disrupt the impact of real-time drowsiness on cognitive performance: a double-blind, placebo-controlled small-sample study

Caffeine is widely used to promote alertness and cognitive performance under challenging conditions, such as sleep loss. Non-digestive modes of delivery typically reduce variability of its effect. In a placebo-controlled, 50-h total sleep deprivation (TSD) protocol we administered four 200 mg doses of caffeine-infused chewing-gum during night-time circadian trough and monitored participants' drowsiness during task performance with infra-red oculography. In addition to the expected reduction of sleepiness, caffeine was found to disrupt its degrading impact on performance errors in tasks ranging from standard cognitive tests to simulated driving. Real-time drowsiness data showed that caffeine produced only a modest reduction in sleepiness (compared to our placebo group) but substantial performance gains in vigilance and procedural decisions, that were largely independent of the actual alertness dynamics achieved. The magnitude of this disrupting effect was greater for more complex cognitive tasks.

Impacts of Timber Harvest on Communities of Small Mammals, Ticks, and Tick-Borne Pathogens in a High-Risk Landscape in Northern California

Timber harvest may impact tick-borne disease by affecting small mammal and tick community structures. We assessed tick and small mammal populations in older second-growth redwood (Sequoia sempervirens (D. Don) Endl) habitat at two harvested sites in Santa Cruz County, California, where local risk of tick-borne disease is high and determined the prevalence of tick-borne pathogens in ticks. After single-tree removal harvest in 2014, there was a modest reduction in canopy, primarily toward the end of the study. Harvested sites showed strong reductions in California mouse (Peromyscus californicus, (Gambel)) captures 2-yr after harvest, resolving such that treatments and controls were comparable by the end of the study. Following harvest, treated sites experienced a transient decreased tick infestation while control plots experienced an increase. Ixodes angustus (Neumann) infestation probability on harvested plots decreased immediately after harvest, increasing with time but remaining lower than control plots, whereas I. pacificus (Cooley and Kohls) prevalence was higher shortly after the harvest on harvested plots, and continued to increase. Mean abundance of ticks on vegetation increased on control plots. We detected Borrelia burgdorferi ((Johnson et al.) Baranton) and Anaplasma phagocytophilum ((Foggie 1949) Dumler) in 3.8 and 3.1% of ticks on rodents, but no differences were associated with harvest. Impacts of forest harvest on tick-borne disease depend on removal practice and intensity, whether or not hosts are habitat specialists, and whether or not ticks are host specialists.