The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

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Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association

Atomic layer deposition(ALD), a chemical vapor deposition technique based on sequential self-terminating gas–solid reactions, has for about four decades been applied for manufacturing conformal inorganic material layers with thickness down to the nanometer range. Despite the numerous successful applications of material growth by ALD, many physicochemical processes that control ALD growth are not yet sufficiently understood. To increase understanding of ALD processes, overviews are needed not only of the existing ALD processes and their applications, but also of the knowledge of the surface chemistry of specific ALD processes. This work aims to start the overviews on specific ALD processes by reviewing the experimental information available on the surface chemistry of the trimethylaluminum/water process. This process is generally known as a rather ideal ALD process, and plenty of information is available on its surface chemistry. This in-depth summary of the surface chemistry of one representative ALD process aims also to provide a view on the current status of understanding the surface chemistry of ALD, in general. The review starts by describing the basic characteristics of ALD, discussing the history of ALD—including the question who made the first ALD experiments—and giving an overview of the two-reactant ALD processes investigated to date. Second, the basic concepts related to the surface chemistry of ALD are described from a generic viewpoint applicable to all ALD processes based on compound reactants. This description includes physicochemical requirements for self-terminating reactions,reaction kinetics, typical chemisorption mechanisms, factors causing saturation, reasons for growth of less than a monolayer per cycle, effect of the temperature and number of cycles on the growth per cycle (GPC), and the growth mode. A comparison is made of three models available for estimating the sterically allowed value of GPC in ALD. Third, the experimental information on the surface chemistry in the trimethylaluminum/water ALD process are reviewed using the concepts developed in the second part of this review. The results are reviewed critically, with an aim to combine the information obtained in different types of investigations, such as growth experiments on flat substrates and reaction chemistry investigation on high-surface-area materials. Although the surface chemistry of the trimethylaluminum/water ALD process is rather well understood, systematic investigations of the reaction kinetics and the growth mode on different substrates are still missing. The last part of the review is devoted to discussing issues which may hamper surface chemistry investigations of ALD, such as problematic historical assumptions, nonstandard terminology, and the effect of experimental conditions on the surface chemistry of ALD. I hope that this review can help the newcomer get acquainted with the exciting and challenging field of surface chemistry of ALD and can serve as a useful guide for the specialist towards the fifth decade of ALD research.

Surface chemistry of atomic layer deposition: A case study for the trimethylaluminum/water process

Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression. Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database. Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of 42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients. Conclusion. APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10187

Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the clinical association of antiphospholipid autoantibodies (aPL) with a syndrome of hypercoagulability that can affect any blood vessel, irrespective of type or size. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or embolism, whereas involvement of smaller vessels, including capillaries, arterioles, and venules, manifests as thrombotic microangiopathy. Virtually any organ in the body, including the kidney, can be affected. Here, we review the basic principles and recent advances in our understanding of APS, and discuss the broad spectrum of renal diseases that have been observed in association with this syndrome. We also discuss the impact that APS may have on pre-existing renal disease as well as current recommendations for treatment of APS.

The antiphospholipid syndrome.

OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.

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Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

The future pregnancy outcome of 201 consecutive women, median age 34 years (range 22-43), with a history of unexplained recurrent first trimester miscarriage (median 3; range 3-13), was studied. All women and their partners had normal peripheral blood karyotypes; none had antiphospholipid antibodies and none hypersecreted luteinizing hormone (LH). No pharmacological treatment was prescribed and early pregnancy supportive care was encouraged. Women aged or = 40 years (P = 0.02). After three consecutive miscarriages, the risk of miscarriage of the next pregnancy was 29% (34/119) but increased to 53% (9/17) after six or more previous losses (P = 0.04). A past history of a livebirth did not influence the outcome of the next pregnancy. Supportive care in early pregnancy conferred a significant beneficial effect on pregnancy outcome. Of 160 women who attended the early pregnancy clinic, 42 (26%) miscarried in the next pregnancy compared with 21 out of 41 (51%) who did not attend the clinic (P = 0.002). After thorough investigation, women with unexplained recurrent first trimester miscarriage have an excellent pregnancy outcome without pharmacological intervention if offered supportive care alone in the setting of a dedicated miscarriage clinic.

Future pregnancy outcome in unexplained recurrent first trimester miscarriage.

Antiphospholipid antibodies (APA), lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA), are associated with thrombosis and recurrent miscarriage. We studied the outcome of 20 pregnancies in women (median age 32 years; range 23-41) with APA (14 LA positive; three immunoglobulin (Ig) G ACA positive; two IgM ACA positive and one LA and IgG ACA positive) and history of recurrent miscarriage (median 4; range 3-11) who declined pharmacological treatment in their next pregnancy. Comparison was made with a cohort of 100 consecutive women (median age 33 years; range 23-44) with recurrent miscarriage (median 4; range 3-10), in whom no underlying cause to account for their pregnancy losses was found. Of the 20 women with APA, 18 (90%) miscarried compared to 34 of the 100 women (34%) with normal investigations (P < 0.001). The majority (94%) of miscarriages in women with APA occurred in the first trimester. Fetal heart activity was seen prior to fetal death in 86% of women with APA compared to 43% of women with normal investigations (P < 0.01). The first trimester loss of embryonic pregnancies is the most common type of miscarriage in women with APA. This may be a result of defective implantation and subsequent placentation.

High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies

Five hundred consecutive women (median age 33 years; range 19-45) with a history of recurrent miscarriage (median 4; range 3-16) were screened for the presence of antiphospholipid antibodies (APA)-lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA). The prevalence of persistently positive tests for LA was 9.6% and for immunoglobulin G (IgG) and immunoglobulin M (IgM) ACA was 3.3 and 2.2% respectively. Only seven women (1.4%) were LA and ACA positive. Repeat testing, after an interval of at least 8 weeks, demonstrated that only 65.7% of LA positive, 36.6% IgG ACA positive and 36.0% IgM ACA positive women on initial testing had a second positive test result. The dilute Russell's viper venom time detected the LA significantly more often than either the activated partial thromboplastin time or the kaolin clotting time (P < 0.001). There was no difference in the gestation of previous miscarriages between APA positive and APA negative women. There was no difference in the plasma beta 2-glycoprotein-I concentrations between APA positive and APA negative women with miscarriages and normal women. All women with a history of recurrent miscarriage should be tested for the presence of both LA and ACA. A second confirmatory test should be performed in those with an initial positive test result.

Raj Rai

Papers

Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

Future pregnancy outcome in unexplained recurrent first trimester miscarriage.

High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies

Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach.

Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin