Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid antibodies (aPL). The diagnosis ...and management of thrombotic APS continues to prove challenging for clinicians. We provide a practical guide to the diagnosis of APS including who to test for aPL and which tests to do. We also consider clinical practice points on the management of venous, arterial and small vessel thrombosis, in the context of first and recurrent thrombotic events. Non-criteria manifestations of APS are reviewed. An approach to recurrent thrombosis and anticoagulant-refractory APS is discussed, with options including increasing the anticoagulation intensity of vitamin K antagonists, switching to low-molecular-weight-heparin, the use of fondaparinux and/or the addition of antiplatelet treatment. Adjunctive options such as vitamin D, hydroxychloroquine and statins are also addressed.
•Approaches to diagnosis and management of thrombotic APS considered in recent guidelines are summarised.•Clinical practice points are suggested.•Recurrent thrombotic events while on anticoagulation are reviewed.
Abstract
Objective
To examine the association between perceived social support, cognition, and physical functioning in older adults with and without Multiple Sclerosis (MS).
Method
Participants were ...dementia-free older adults with MS (N = 89; M age = 64.75, SD + 4.25 years; 66.3% female) and community-residing older adults (N = 102; M age = 68.74, SD + 7.12 years; 62.7% female). The medical outcomes study modified social support survey (MSSS), oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures. Linear regressions stratified by group status assessed the associations between PSS, cognition, and physical functioning.
Results
Higher total MSSS scores were associated with higher SDMT scores in the MS group (β = 0.24, p = 0.02) and in the control group (β = 0.26, p = 0.005). Positive social interaction (β = 0.27, p = 0.011) was associated with SDMT performance in the MS group. Emotional/informational support (β = 0.27, p = 0.003) and positive social interaction (β = 0.25, p = 0.007) were associated with SDMT performance in the control group. Depression scores attenuated associations between perceived social support and SDMT performance in the MS group (p > 0.05) but not the control group. In contrast, higher MSSS scores were not associated with higher T25FW scores in either group.
Conclusions
Among older adults with and without MS, perceived social support was associated with cognition but not physical functioning. Depressive symptoms attenuated associations between perceived social support and cognition in the MS group only.
Endoplasmic reticulum (ER) stress activates a set of signaling pathways, collectively termed the unfolded protein response (UPR). The three UPR branches (IRE1, PERK, and ATF6) promote cell survival ...by reducing misfolded protein levels. UPR signaling also promotes apoptotic cell death if ER stress is not alleviated. How the UPR integrates its cytoprotective and proapoptotic outputs to select between life or death cell fates is unknown. We found that IRE1 and ATF6 activities were attenuated by persistent ER stress in human cells. By contrast, PERK signaling, including translational inhibition and proapoptotic transcription regulator Chop induction, was maintained. When IRE1 activity was sustained artificially, cell survival was enhanced, suggesting a causal link between the duration of UPR branch signaling and life or death cell fate after ER stress. Key findings from our studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa.
Abstract
Objectives
To evaluate the impact of an oral health integration training program on children's receipt of oral health and dental services in Southern Oregon.
Methods
Children under 19 years ...with at least 6 months of Medicaid enrolment and at least one healthcare visit from 2014 to 2018 were included. The treatment group included children with at least one visit with a trained provider (
n
= 5541); children with no visits with trained providers (
n
= 8273) were the control group. The percentage of the treatment group who received oral health assessments was calculated, and regression models were developed to estimate the difference in likelihood of receiving fluoride varnish and dental services between treatment and control groups.
Results
The percentage of children receiving oral health assessments increased over time. Visiting a trained provider was consistently associated, each year, with a greater likelihood of receipt of fluoride varnish and preventive and diagnostic dental services but was not associated with treatment dental services or dental sealants.
Conclusions
This study reports evidence for the overall impact of an oral health integration training on children's receipt of oral and dental services. Health systems implementing these types of training strategies should consider how to reach specific underserved subgroups, increase paediatric dentists, and expand efforts to include older children.
INTRODUCTION
The effects of sleep–wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR).
...METHODS
CR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis.
RESULTS
In amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep‐related impairments (SRIs), and fatigability at low CR (CRIq < 105.8, p = 0.004) and mean CR (CRIq = 126.9, p = 0.03) but not high CR (CRIq > 145.9, p = 0.65) levels. SRI affected cognitive abilities mediated by fatigability at low CR (p < 0.001) and mean CR (p = 0.003) levels. In healthy controls (n = 13), SRI in fatigability did not alter cognitive abilities across CR levels; controls had higher leisure scores than patients with aMCI (p = 0.003, effect size = 0.93).
DISCUSSION
SRI can amplify impaired cognitive abilities through exacerbation of fatigability in patients with aMCI with below‐mean CR. Therefore, improving sleep–wake regulation and leisure activities may protect against fatigability and cognitive decline.
Highlights
Clinical fatigue and fatigability cannot be alleviated by rest.
Clinical fatigability disrupts daily activities during preclinical Alzheimer's.
High cognitive reserve mitigates sleep–wake disturbance effects.
High cognitive reserve attenuates clinical fatigability effects on daily functioning.
Untreated obstructive sleep apnea potentiates Alzheimer's pathology in the brain.
Summary
The Serious Hazards of Transfusion (SHOT) UK confidential haemovigilance reporting scheme began in 1996. Over the 16 years of reporting, the evidence gathered has prompted changes in ...transfusion practice from the selection and management of donors to changes in hospital practice, particularly better education and training. However, half or more reports relate to errors in the transfusion process despite the introduction of several measures to improve practice. Transfusion in the UK is very safe: 2·9 million components were issued in 2012, and very few deaths are related to transfusion. The risk of death from transfusion as estimated from SHOT data in 2012 is 1 in 322 580 components issued and for major morbidity, 1 in 21 413 components issued; the risk of transfusion‐transmitted infection is much lower. Acute transfusion reactions and transfusion‐associated circulatory overload carry the highest risk for morbidity and death. The high rate of participation in SHOT by National Health Service organizations, 99·5%, is encouraging. Despite the very useful information gained about transfusion reactions, the main risks remain human factors. The recommendations on reduction of errors through a ‘back to basics’ approach from the first annual SHOT report remain absolutely relevant today.
•Emotional support is associated with cognition in older adults with MS.•Depression attenuates associations between social support and cognition in MS.•Positive social interaction is associated with ...cognition in healthy controls.
Advances in treatments for Multiple Sclerosis (MS) have resulted in a growing number of aging individuals with MS. Research has shown that perceived social support has protective effects against age-related cognitive decline but no study to date has examined the relationship between perceived social support and cognition in older adults with MS. The current study addressed this gap in knowledge examining the association between perceived social support and cognition in older adults with and without MS.
Participants were older adults with MS (n = 67, mean age = 64.75 years;%female = 64.2) and controls (n = 71, mean age = 68.25 years;%female = 57.7) Linear regression models examined the associations of total and domain scores of perceived social support with cognition in the entire sample, and then stratified by group status.
Analyses revealed that total perceived social support, emotional/informational support, and positive social interaction were associated with cognition in the total sample. In stratified analyses, emotional/informational support was significantly associated with cognition in the MS group; however, this association became insignificant when analyses adjusted for depressive symptoms. Positive social interaction was significantly associated with cognition in the control group. Notably, this association remained significant even after adjusting for depressive symptoms.
These findings suggest that distinct dimensions of perceived social support may have differential relationships with cognitive function in older adults with MS and healthy controls.
Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life‐long warfarin or an alternative vitamin K ...antagonist. The role of direct oral anticoagulants for thrombotic APS is not established due to the lack of definitive evidence and has recently been addressed in international guidance. Other anticoagulant options include low molecular weight heparin, unfractionated heparin, and fondaparinux. In APS patients, lupus anticoagulant can affect phospholipid‐dependent coagulation monitoring tests, so that they may not reflect true anticoagulation intensity. Accurate assessment of anticoagulation intensity is essential, to optimize anticoagulant dosing and facilitate thrombus resolution; minimize the risk of recurrent thrombosis or bleeding; inform assessment of whether recurrent thrombosis is related to breakthrough thrombosis while on therapeutic anticoagulation, subtherapeutic anticoagulation, non‐adherence, or spurious results; and guide the management of bleeding. Knowledge of anticoagulant intensity also informs assessment and comparison of anticoagulation regimens in clinical studies. Considerations regarding anticoagulation dosing and/or monitoring of thrombotic APS patients underpin appropriate management in special situations, notably APS‐related severe renal impairment, which can occur in APS or APS/systemic lupus erythematosus‐related nephropathy or catastrophic APS; and APS‐related thrombocytopenia. Anticoagulant dosing and monitoring in thrombotic APS patients also require consideration in anticoagulant‐refractory APS and during pregnancy. In this review, we summarize the tests generally used in monitoring anticoagulant therapy, use of the main anticoagulants considered for thrombotic APS, lupus anticoagulant effects on anticoagulation monitoring tests, and strategies for appropriate anticoagulant monitoring in thrombotic APS.
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