Outweigh Risks Research Articles

Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This chapter about antithrombotic therapy in neonates and children is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs, and Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see Guyatt et al in this supplement, pages 123S-131S). In this chapter, many recommendations are based on extrapolation of adult data, and the reader is referred to the appropriate chapters relating to guidelines for adult populations. Within this chapter, the majority of recommendations are separate for neonates and children, reflecting the significant differences in epidemiology of thrombosis and safety and efficacy of therapy in these two populations. Among the key recommendations in this chapter are the following: In children with first episode of venous thromboembolism (VTE), we recommend anticoagulant therapy with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) [Grade 1B]. Dosing of IV UFH should prolong the activated partial thromboplastin time (aPTT) to a range that corresponds to an anti-factor Xa assay (anti-FXa) level of 0.35 to 0.7 U/mL, whereas LMWH should achieve an anti-FXa level of 0.5 to 1.0 U/mL 4 h after an injection for twice-daily dosing. In neonates with first VTE, we suggest either anticoagulation or supportive care with radiologic monitoring and subsequent anticoagulation if extension of the thrombosis occurs during supportive care (Grade 2C). We recommend against the use of routine systemic thromboprophylaxis for children with central venous lines (Grade 1B). For children with cerebral sinovenous thrombosis (CSVT) without significant intracranial hemorrhage (ICH), we recommend anticoagulation initially with UFH, or LMWH and subsequently with LMWH or vitamin K antagonists (VKAs) for a minimum of 3 months (Grade 1B). For children with non-sickle-cell disease-related acute arterial ischemic stroke (AIS), we recommend UFH or LMWH or aspirin (1 to 5 mg/kg/d) as initial therapy until dissection and embolic causes have been excluded (Grade 1B). For neonates with a first AIS, in the absence of a documented ongoing cardioembolic source, we recommend against anticoagulation or aspirin therapy (Grade 1B).

The Primary and Secondary Prevention of Coronary Artery Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the “Grades of Recommendation” chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S–131S). Among the key recommendations in this chapter are the following: for patients with non–ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75–100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75–100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75–100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75–100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A).

Valvular and Structural Heart Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This chapter about antithrombotic therapy for valvular heart disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values might lead to different choices (for a full understanding of the grading see Guyatt et al, <i>CHEST</i> 2008; 133[suppl]:123S–131S). Among the key recommendations in this chapter are the following: for patients with rheumatic mitral valve disease complicated singly or in combination by the presence of atrial fibrillation (AF), previous systemic embolism, or left atrial thrombus, we recommend vitamin K antagonist (VKA) therapy (Grade 1A). For patients with rheumatic mitral valve disease and normal sinus rhythm, without left atrial enlargement, we do not suggest antithrombotic therapy unless a separate indication exists (Grade 2C). For patients with mitral valve prolapse (MVP), not complicated by AF, who have not had systemic embolism, unexplained transient ischemic attacks, or ischemic stroke, we recommend against antithrombotic therapy (Grade 1C). In patients with mitral annular calcification complicated by systemic embolism or ischemic stroke, we recommend antiplatelet agent (APA) therapy (Grade 1B). For patients with isolated calcific aortic valve disease, we suggest against antithrombotic therapy (Grade 2C). But, for those with aortic valve disease who have experienced ischemic stroke, we suggest APA therapy (Grade 2C). For patients with stroke associated with aortic atherosclerotic lesions, we recommend low-dose aspirin (ASA) therapy (Grade 1C). For patients with cryptogenic ischemic stroke and a patent foramen ovale (PFO), we recommend APA therapy (Grade 1A). For patients with mechanical heart valves, we recommend VKA therapy (Grade 1A). For patients with mechanical heart valves and history of vascular disease or who have additional risk factors for thromboembolism, we recommend the addition of low-dose aspirin ASA to VKA therapy (Grade 1B). We suggest ASA not be added to long-term VKA therapy in patients with mechanical heart valves who are at particularly high risk of bleeding (Grade 2C). For patients with bioprosthetic heart valves, we recommend ASA (Grade 1B). For patients with bioprosthetic heart valves and additional risk factors for thromboembolism, we recommend VKA therapy (Grade 1C). For patients with infective endocarditis, we recommend against antithrombotic therapy, unless a separate indication exists (Grade 1B).

Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the "Grades of Recommendation" chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).

Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see "Grades of Recommendation" chapter). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE), we recommend anticoagulant therapy with subcutaneous (SC) low-molecular-weight heparin (LMWH), monitored IV, or SC unfractionated heparin (UFH), unmonitored weight-based SC UFH, or SC fondaparinux (all Grade 1A). For patients with a high clinical suspicion of DVT or PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C). For patients with confirmed PE, we recommend early evaluation of the risks to benefits of thrombolytic therapy (Grade 1C); for those with hemodynamic compromise, we recommend short-course thrombolytic therapy (Grade 1B); and for those with nonmassive PE, we recommend against the use of thrombolytic therapy (Grade 1B). In acute DVT or PE, we recommend initial treatment with LMWH, UFH or fondaparinux for at least 5 days rather than a shorter period (Grade 1C); and initiation of vitamin K antagonists (VKAs) together with LMWH, UFH, or fondaparinux on the first treatment day, and discontinuation of these heparin preparations when the international normalized ratio (INR) is > or = 2.0 for at least 24 h (Grade 1A). For patients with DVT or PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with unprovoked DVT or PE, we recommend treatment with a VKA for at least 3 months (Grade 1A), and that all patients are then evaluated for the risks to benefits of indefinite therapy (Grade 1C). We recommend indefinite anticoagulant therapy for patients with a first unprovoked proximal DVT or PE and a low risk of bleeding when this is consistent with the patient's preference (Grade 1A), and for most patients with a second unprovoked DVT (Grade 1A). We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). We recommend at least 3 months of treatment with LMWH for patients with VTE and cancer (Grade 1A), followed by treatment with LMWH or VKA as long as the cancer is active (Grade 1C). For prevention of postthrombotic syndrome (PTS) after proximal DVT, we recommend use of an elastic compression stocking (Grade 1A). For DVT of the upper extremity, we recommend similar treatment as for DVT of the leg (Grade 1C). Selected patients with lower-extremity (Grade 2B) and upper-extremity (Grade 2C). DVT may be considered for thrombus removal, generally using catheter-based thrombolytic techniques. For extensive superficial vein thrombosis, we recommend treatment with prophylactic or intermediate doses of LMWH or intermediate doses of UFH for 4 weeks (Grade 1B).

Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy, and Pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This article discusses the management of venous thromboembolism (VTE) and thrombophilia, as well as the use of antithrombotic agents, during pregnancy and is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that benefits do, or do not, outweigh risks, burden, and costs. Grade 2 recommendations are weaker and imply that the magnitude of the benefits and risks, burden, and costs are less certain. Support for recommendations may come from high-quality, moderate-quality or low-quality studies; labeled, respectively, A, B, and C.Among the key recommendations in this chapter are the following: for pregnant women, in general, we recommend that vitamin K antagonists should be substituted with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) [Grade 1A], except perhaps in women with mechanical heart valves. For pregnant patients, we suggest LMWH over UFH for the prevention and treatment of VTE (Grade 2C). For pregnant women with acute VTE, we recommend that subcutaneous LMWH or UFH should be continued throughout pregnancy (Grade 1B) and suggest that anticoagulants should be continued for at least 6 weeks postpartum (for a total minimum duration of therapy of 6 months) [Grade 2C].For pregnant patients with a single prior episode of VTE associated with a transient risk factor that is no longer present and no thrombophilia, we recommend clinical surveillance antepartum and anticoagulant prophylaxis postpartum (Grade 1C). For other pregnant women with a history of a single prior episode of VTE who are not receiving long-term anticoagulant therapy, we recommend one of the following, rather than routine care or full-dose anticoagulation: antepartum prophylactic LMWH/UFH or intermediate-dose LMWH/UFH or clinical surveillance throughout pregnancy plus postpartum anticoagulants (Grade 1C). For such patients with a higher risk thrombophilia, in addition to postpartum prophylaxis, we suggest antepartum prophylactic or intermediate-dose LMWH or prophylactic or intermediate-dose UFH, rather than clinical surveillance (Grade 2C). We suggest that pregnant women with multiple episodes of VTE who are not receiving long-term anticoagulants receive antepartum prophylactic, intermediate-dose, or adjusted-dose LMWH or intermediate or adjusted-dose UFH, followed by postpartum anticoagulants (Grade 2C). For those pregnant women with prior VTE who are receiving long-term anticoagulants, we recommend LMWH or UFH throughout pregnancy (either adjusted-dose LMWH or UFH, 75% of adjusted-dose LMWH, or intermediate-dose LMWH) followed by resumption of long-term anticoagulants postpartum (Grade 1C).We suggest both antepartum and postpartum prophylaxis for pregnant women with no prior history of VTE but antithrombin deficiency (Grade 2C). For all other pregnant women with thrombophilia but no prior VTE, we suggest antepartum clinical surveillance or prophylactic LMWH or UFH, plus postpartum anticoagulants, rather than routine care (Grade 2C). For women with recurrent early pregnancy loss or unexplained late pregnancy loss, we recommend screening for antiphospholipid antibodies (APLAs) [Grade 1A].For women with these pregnancy complications who test positive for APLAs and have no history of venous or arterial thrombosis, we recommend antepartum administration of prophylactic or intermediate-dose UFH or prophylactic LMWH combined with aspirin (Grade 1B). We recommend that the decision about anticoagulant management during pregnancy for pregnant women with mechanical heart valves include an assessment of additional risk factors for thromboembolism including valve type, position, and history of thromboembolism (Grade 1C). While patient values and preferences are important for all decisions regarding antithrombotic therapy in pregnancy, this is particularly so for women with mechanical heart valves. For these women, we recommend either adjusted-dose bid LMWH throughout pregnancy (Grade 1C), adjusted-dose UFH throughout pregnancy (Grade 1C), or one of these two regimens until the thirteenth week with warfarin substitution until close to delivery before restarting LMWH or UFH) [Grade 1C]. However, if a pregnant woman with a mechanical heart valve is judged to be at very high risk of thromboembolism and there are concerns about the efficacy and safety of LMWH or UFH as dosed above, we suggest vitamin K antagonists throughout pregnancy with replacement by UFH or LMWH close to delivery, after a thorough discussion of the potential risks and benefits of this approach (Grade 2C).

The Dangers of Advocacy in Science

In matters of policy, many scientists view “advocacy” as a dangerous word. In peer-reviewed literature, many scientists practice a subtler form of advocacy in pushing their methods, results, and conclusions. Call this IMRAD (Introduction, Methods, Results, and Discussion) advocacy: Once bold claims about a poorly tested method or weak result are published, their sins are forgiven and they can be worked into future introductions and discussions at will. IMRAD advocates often stretch available data, gloss over uncertainties in their evidence, and ignore contrary results. This occurs throughout the hierarchy of journals. One would hope that it would be least common in prestigious journals. On the other hand, top journals have limited space; they emphasize papers with broad, seemingly decisive conclusions but passively encourage readers not to worry about methods (or rebuttals). Often, this form of advocacy is obvious only to the small percentage of any journal's readers that have scientific expertise in a specialized area—a small pool of appropriate reviewers ([1][1]). As with policy advocacy, there is a gray area between objective justification and flagrant, half-supported promotion. Somewhere in the middle sits the honest, often acrimonious debate necessary for scientific progress. Would anyone disagree that publishing overly liberal conclusions is poor science, that the personal rewards of doing so far outweigh risks, or that the peer-review process should strip papers of this garbage? Humiliation could assist rebuttals and time in the self-correcting process of science. For example, each professional society should survey members at year's end to decide on the five papers in their field with the most overly inflated claims. The authors, approving reviewers, and subject editors could receive suitable prizes. 1. 1.[↵][2]1. R. Hilborn , Fisheries 31, 554 (2006). [OpenUrl][3] [1]: #ref-1 [2]: #xref-ref-1-1 View reference 1. in text [3]: {openurl}?query=rft.jtitle%253DFisheries%26rft.volume%253D31%26rft.spage%253D554%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx

Benefits Said to Outweigh Risks of Antidepressants

Benefits Said to Outweigh Risks of Antidepressants

Antidepressants in paediatric patients: likelihood of benefit outweighs risk of harm

Antidepressants in paediatric patients: likelihood of benefit outweighs risk of harm

Cognitive Benefits of Seafood During Pregnancy Outweigh Risks, New Study Finds

Cognitive Benefits of Seafood During Pregnancy Outweigh Risks, New Study Finds

Hormone therapy after the Women's Health Initiative: a qualitative study

BackgroundPublication of results from the Women's Health Initiative study in July 2002 was a landmark event in biomedical science related to postmenopausal women. The purpose of this study was to describe the impact of new hormone therapy recommendations on patients' attitudes and decision-making in a primary care practice.MethodsA questionnaire including structured and open-ended questions was administered in a family practice office waiting room from August through October 2003. Rationale for taking or not taking hormone therapy was specifically sought. Women 50–70 years old attending for office visits were invited to participate. Data were analyzed qualitatively and with descriptive statistics. Chart review provided medication use rates for the entire practice cohort of which the sample was a subset.ResultsRespondents (n = 127) were predominantly white and well educated, and were taking hormone therapy at a higher rate (38%) than the overall rate (26%) for women of the same age range in this practice. Belief patterns about hormone therapy were, in order of frequency, 'use is risky', 'vindication or prior beliefs', 'benefit to me outweighs risk', and 'unaware of new recommendations'. Twenty-eight out of 78 women continued hormones use after July 2002. Of 50 women who initially stopped hormone therapy after July 2002, 12 resumed use. Women who had stopped hormone therapy were a highly symptomatic group. Responses with emotional overtones such as worry, confusion, anger, and grief were common.ConclusionStrategies for decision support about hormone therapy should explicitly take into account women's preferences about symptom relief and the trade-offs among relevant risks. Some women may need emotional support during transitions in hormone therapy use.

High-resolution computed tomography (HRCT) should not be considered as a routine assessment method in cystic fibrosis lung disease

High-resolution computed tomography (HRCT) scanning of the chest should not be considered a routine clinical investigation in the management of CF. Although it demonstrates the detection of early lung damage in children with cystic fibrosis (CF), before HRCT can be considered for routine clinical use in CF it needs to be shown that the benefit from the information obtained will out-weigh potential risks. There is insufficient evidence for the benefit of HRCT for its inclusion into routine care. Moreover, in the absence of information resulting in change in management, HRCT has the potential to increase anxiety for both clinicians and families. In order to advocate for incorporating this technology into routine CF care, further support for its role in management decisions is needed.

Influenza vaccination status and influenza-related perspectives and practices among US physicians

The influenza vaccination rate among US healthcare workers (HCWs) remains low. This survey was designed to assess influenza vaccination status and related knowledge, attitudes, and beliefs among a national sample of primary care physicians and subspecialists likely to see patients at high risk for complications from influenza. We used a mail survey of a national random sample of 495 family physicians (FPs), 491 internists (IMs), 498 geriatricians (GERs), and 497 pulmonologists (PUDs). The overall response rate was 38%. Almost all respondents (87%) reported receiving an influenza vaccine during the 2003-2004 influenza season, with no significant difference across specialty groups (84% FPs, 87% IMs, 87% GERs, 91% PUDs). In a multivariate model, adjusted for physician specialty and age group, significant predictors of vaccination were: strong agreement that HCWs have professional responsibility to be vaccinated, access to vaccination on site and free of charge, strong worksite recommendation for HCWs to be vaccinated, and strong agreement that benefits of vaccination outweigh risk of side effects. Physicians reported a high influenza vaccination rate. To improve these rates further, with likely benefits for other HCWs, worksite policies that facilitate access to vaccination and documentation of reductions in nosocomial influenza associated with HCW vaccination should continue to be pursued.

An overview of preharvest factors influencing postharvest quality of horticultural products

Postharvest product quality develops during growing of the product and is maintained, not improved by postharvest technologies. Available genetic material allows discrimination of external and internal quality attributes that must satisfy consumer requirements and indulgences. Farmers face challenges in utilising technologies for producing high quality crops; meaningful manipulation of light, nutrients, water and plants is possible only when plant responses to environmental conditions are understood. Genetic engineering can produce plants with desirable characteristics, but society is not yet convinced that benefits gained outweigh risks. Protected cropping enables growers to produce consistent crops in environments where production is often variable, and production of high value crops 'out of season'. Farmers, scientists, extension specialists and market personnel must work together to provide knowledge, best practices and enabling tools for growers to ensure preharvest conditions are optimised for production of high quality horticultural crops that titillate, satisfy and reward discerning consumers.

Prognosis in transplant‐eligible patients with agnogenic myeloid metaplasia

Allogeneic hematopoietic stem cell transplantation is potentially curative in agnogenic myeloid metaplasia (AMM) but is associated with substantial mortality and morbidity that necessitates accurate identification of patients in whom benefit outweighs risk. The current study describes the natural history of AMM in transplant-eligible patients and proposes a new prognostic scoring system that favorably compares with other established models. Patients diagnosed with AMM before the age of 60 years and seen at Mayo Clinic were identified and the diagnosis confirmed. Relevant demographic, clinical, and laboratory characteristics were abstracted, and the impact of various parameters on overall survival (OS) was evaluated with univariate and multivariate analyses. A cohort of 160 patients with AMM is described. OS was 78 months. Multivariate analysis identified a hemoglobin level of <10 g/dL, white blood cell count of either <4 or >30x10(9)/L, platelet count of <100x10(9)/L, presence of constitutional symptoms, and hepatomegaly as independent predictors of inferior survival. The first 3 complete blood count-based parameters were combined into a new scoring system that resulted in median survivals of 155, 69, and 24 months in the presence of 0, 1, or >or=2 adverse features. The chi-square value for the new model was 80.6 compared with 51.4, 48.4, and 43.7 for the models by Dupriez, Cervantes, and Visani, respectively. A new scoring system based on blood count at the time of diagnosis can adequately stratify by risk transplant-eligible patients with AMM and can accurately identify high-risk as well as intermediate-risk disease. The new system displayed a stronger discriminative value, between risk categories, compared with currently existing prognostic models.

Thrombocytopenia Is a Strong Adverse Feature in Transplant-Eligible Patients with Myelofibrosis: Utility for an Improved CBC-Based Scoring System.

Background: Allogeneic hematopoietic stem cell transplantation is potentially curative in agnogenic myeloid metaplasia (AMM) but is associated with substantial mortality and morbidity that necessitates accurate identification of patients in whom benefit outweighs risk. The current single institutional study investigates prognostic variables in transplant-eligible patients with AMM with the main objective of improved discrimination between intermediate- and high-risk patient categories.Methods: Patients diagnosed with AMM before the age of 60 years and seen at Mayo Clinic were identified and the diagnosis confirmed. Relevant demographic, clinical and laboratory characteristics were abstracted and the impact of various parameters on overall survival was evaluated with univariate and multivariate analysis.Results: A cohort of 159 patients (median age 52 years, range 18–60; 89 males) with AMM is described. Median follow-up from initial diagnosis was 63 months (range 0–300). During this period, 102 patients have died; overall median survival 79 months. Multivariate analysis of parameters measured in all study patients at diagnosis identified thrombocytopenia (platelet count < 100 x 109/L) as the strongest predictor of inferior survival (p=0.002). In addition, a hemoglobin level of <10 g/dL (p=0.003), white blood cell count of either <4 or >30 x 109/L (p=0.03), and older age (p=0.02) were also found to be independent indicators of poor prognosis. However, when the analysis included parameters that were measured in variable proportion of the study population, the independent prognostic factors for poor survival were thrombocytopenia (p=0.0001), anemia (p=0.01), and the presence of unfavorable cytogenetic abnormalities (0.001).Based on the above findings, we constructed a new complete blood count (CBC)-based prognostic scoring system (Figure 1) that performed better than the Dupriez scoring system in discriminating intermediate- from high-risk patient categories(Figure 2). [Display omitted] Conclusions: Thrombocytopenia is a strong predictor of poor survival in transplant-eligible patients with AMM. The incorporation of platelet count into the Dupriez prognostic scoring system might allow the construction of an improved, CBC-based scoring system that can accurately identify high-risk as well as intermediate-risk patients with AMM.

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

This chapter about treatment and prevention of stroke is part of the 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke (AIS), we recommend administration of i.v. tissue plasminogen activator (tPA), if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with extensive and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B). For unselected patients with AIS of > 3 h but < 6 h, we suggest clinicians not use i.v. tPA (Grade 2A). For patients with AIS, we recommend against streptokinase (Grade 1A) and suggest clinicians not use full-dose anticoagulation with i.v. or subcutaneous heparins or heparinoids (Grade 2B). For patients with AIS who are not receiving thrombolysis, we recommend early aspirin therapy, 160 to 325 mg qd (Grade 1A). For AIS patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low molecular weight heparins or heparinoids (Grade 1A); and for patients who have contraindications to anticoagulants, we recommend use of intermittent pneumatic compression devices or elastic stockings (Grade 1C). In patients with acute intracerebral hematoma, we recommend the initial use of intermittent pneumatic compression (Grade 1C+). In patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A) including aspirin, 50 to 325 mg qd; the combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid; or clopidogrel, 75 mg qd. In these patients, we suggest use of the combination of aspirin and extended-release dipyridamole, 25/200 mg bid, over aspirin (Grade 2A) and clopidogrel over aspirin (Grade 2B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1C+). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low molecular weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.

Heparin-Induced Thrombocytopenia: Recognition, Treatment, and Prevention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

This chapter about the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients in whom the risk of HIT is considered to be > 0.1%, we recommend platelet count monitoring (Grade 1C). For patients who are receiving therapeutic-dose unfractionated heparin (UFH), we suggest at least every-other-day platelet count monitoring until day 14, or until UFH is stopped, whichever occurs first (Grade 2C). For patients who are receiving postoperative antithrombotic prophylaxis with UFH (HIT risk > 1%), we suggest at least every-other-day platelet count monitoring between postoperative days 4 to 14 (or until UFH is stopped, whichever occurs first) [Grade 2C]. For medical/obstetric patients who are receiving prophylactic-dose UFH, postoperative patients receiving prophylactic-dose low molecular weight heparin (LMWH), postoperative patients receiving intravascular catheter UFH "flushes," or medical/obstetrical patients receiving LMWH after first receiving UFH (risk, 0.1 to 1%), we suggest platelet count monitoring every 2 days or 3 days from day 4 to day 14, or until heparin is stopped, whichever occurs first (Grade 2C). For medical/obstetrical patients who are only receiving LMWH, or medical patients who are receiving only intravascular catheter UFH flushes (risk < 0.1%), we suggest clinicians do not use routine platelet count monitoring (Grade 2C). For patients with strongly suspected (or confirmed) HIT, whether or not complicated by thrombosis, we recommend use of an alternative anticoagulant, such as lepirudin (Grade 1C+), argatroban (Grade 1C), bivalirudin (Grade 2C), or danaparoid (Grade 1B). For patients with strongly suspected (or confirmed) HIT, we recommend routine ultrasonography of the lower-limb veins for investigation of deep venous thrombosis (Grade 1C); against the use of vitamin K antagonist (VKA) [coumarin] therapy until after the platelet count has substantially recovered; that the VKA antagonist be administered only during overlapping alternative anticoagulation (minimum 5-day overlap); and begun with low, maintenance doses (all Grade 2C). For patients receiving VKAs at the time of diagnosis of HIT, we recommend use of vitamin K (Grade 2C) [corrected] For patients with a history of HIT who are HIT antibody negative and require cardiac surgery, we recommend use of UFH (Grade 1C).

Antithrombotic Therapy for Coronary Artery Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

This chapter about antithrombotic therapy for coronary artery disease (CAD) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients presenting with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS), we recommend immediate and then daily oral aspirin (Grade 1A). For patients with an aspirin allergy, we recommend immediate treatment with clopidogrel, 300-mg bolus po, followed by 75 mg/d indefinitely (Grade 1A). In all NSTE ACS patients in whom diagnostic catheterization will be delayed or when coronary bypass surgery will not occur until > 5 days, we recommend clopidogrel as bolus therapy (300 mg), followed by 75 mg/d for 9 to 12 months in addition to aspirin (Grade 1A). In NSTE ACS patients in whom angiography will take place within 24 h, we suggest beginning clopidogrel after the coronary anatomy has been determined (Grade 2A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we recommend discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). In moderate- to high-risk patients presenting with NSTE ACS, we recommend either eptifibatide or tirofiban for initial (early) treatment in addition to treatment with aspirin and heparin (Grade 1A). For the acute treatment of NSTE ACS, we recommend low molecular weight heparins over unfractionated heparin (UFH) [Grade 1B] and UFH over no heparin therapy use with antiplatelet therapies (Grade 1A). We recommend against the direct thrombin inhibitors as routine initial antithrombin therapy (Grade 1B). For patients after myocardial infarction, after ACS, and with stable CAD, we recommend aspirin in doses from 75 to 325 mg as initial therapy and in doses of 75 to 162 mg as indefinite therapy (Grade 1A). For patients with contraindications to aspirin, we recommend long-term clopidogrel (Grade 1A). For primary prevention in patients with at least moderate risk for a coronary event, we recommend aspirin, 75 to 162 mg/d, over either no antithrombotic therapy or vitamin K antagonist (VKA) [Grade 2A]; for patients at particularly high risk of events in whom the international normalized ratio (INR) can be monitored without difficulty, we suggest low-dose VKA (target INR, 1.5) [Grade 2A].

Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

This chapter about antithrombotic therapy during percutaneous coronary intervention (PCI) is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see Guyatt et al, CHEST 2004;126:179S-187S). Among the key recommendations in this chapter are the following: For patients undergoing PCI, we recommend pretreatment with aspirin, 75 to 325 mg (Grade 1A). For long-term treatment after PCI, we recommend aspirin, 75 to 162 mg/d (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend lower-dose aspirin, 75 to 100 mg/d (Grade 1C+). For patients who undergo stent placement, we recommend the combination of aspirin and a thienopyridine derivative (ticlopidine or clopidogrel) over systemic anticoagulation therapy (Grade 1A). We recommend clopidogrel over ticlopidine (Grade 1A). For all patients undergoing PCI, particularly those undergoing primary PCI, or those with refractory unstable angina or other high-risk features, we recommend use of a glycoprotein (GP) IIb-IIIa antagonist (abciximab or eptifibatide) [Grade 1A]. In patients undergoing PCI for ST-segment elevation MI, we recommend abciximab over eptifibatide (Grade 1B). In patients undergoing PCI, we recommend against the use of tirofiban as an alternative to abciximab (Grade 1A). In patients after uncomplicated PCI, we recommend against routine postprocedural infusion of heparin (Grade 1A). For patients undergoing PCI who are not treated with a GP IIb-IIIa antagonist, we recommend bivalirudin over heparin during PCI (Grade 1A). In PCI patients who are at low risk for complications, we recommend bivalirudin as an alternative to heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In PCI patients who are at high risk for bleeding, we recommend that bivalirudin over heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In patients who undergo PCI with no other indication for systemic anticoagulation therapy, we recommend against routine use of vitamin K antagonists after PCI (Grade 1A).