Population Screening and Prevention Strategies for Thalassemias and other Hemoglobinopathies of Eastern India: Experience of 18,166 cases

Abstract

We evaluated population screening programs (1999–2011), conducted by the Thalassaemia Foundation, Kolkata, India, for the first time in Eastern India in different districts of West Bengal, for prevention of thalassemia comprising screening of heterozygotes and β-thalassemia intermedia (β-TI) cases [β⁺, β⁺⁺, β⁰/β⁺, β^E/β^E (codon 26 or HBB: c.79G?>?A), Hb-E-β-thalassemia (Hb E-β-thal)]. Among 18,166 cases, we found 2092 heterozygotes and 2245 β-TI individuals (who had no information about their disorders). Results were evaluated with standard hematological analyses including erythrocyte indices, hemoglobin (Hb) typing and quantification. Participants were divided into five groups (children, pre-marriage cases, pre-pregnancy cases, affected family members, pregnant women). The objectives of this evaluation were to fix cut-off values of red blood cells (RBCs), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), red blood cell distribution width (RDW) and Hb A₂, as the standard World Health Organization (WHO) guidelines were not strictly followed in mass-scale screening programs. We have observed many dilemmas in considering the status of the thalassemia subject, due to presence of some other clinical conditions such as iron deficiency anemia, α-thalassemia (α-thal), δ-thalassemia (δ-thal), clinically silent Hb variants, and some cases of non hemoglobinopathies (such as pregnancy) along with thalassemia. The MCV values varied greatly in different conditions of hemoglobinopathies, whereas MCH provided a more stable measurement. We found an MCH value of <27.0?pg is a suitable cut-off point for screening in this population. Participants with an MCH of <27.0?pg should be investigated further to confirm or exclude a diagnosis of β-thal trait.     

Stroke Prevention and Statin Treatment

Randomized trials with statins have shown a modest but significant absolute reduction in the incidence of stroke in patients with a previous myocardial infarction. The reasons for the positive statin effect on stroke endpoint are unclear, because a link between serum cholesterol level and stroke never has been established. However, positive results of statin trials were mainly obtained in patients with an average or a low serum cholesterol level. Statins have a good overall safety profile. Statins reduced stroke incidence in high-risk (mainly coronary heart disease, diabetics, and hypertensives) population even with a normal baseline blood cholesterol level.

In patients with prior strokes, statins reduce the incidence of coronary events, but it is not yet proven if drugs of this class actually reduce the incidence of recurrent strokes in terms of secondary prevention.     

Antithrombotic Therapy for Prevention and Treatment of Ischemic Stroke

Atherosclerosis involving the cervical vessels, intracranial vessels, or the aorta is the most common cause of ischemic stroke. Occlusive lesions of small penetrating brain arteries cause small lacunar strokes, which account for about 20% of ischemic strokes. Emboli from a variety of cardiac sources, particularly atrial fibrillation, account for about 25%. Efforts to prevent and treat ischemic stroke are complicated by the variety of etiologies underlying it and the selection of antithrombotic or thrombolytic therapy appropriate to the particular etiology.     

缺血性卒中治疗和预防的现有证据

随着医学的发展,人们对缺血性卒中的防治观念不断更新,但其防治措施的现有证据与临床实践之间仍然存在一定差距。参照科学的证据分级标准,文章对缺血性卒中治疗和预防的现有证据进行循证分析,以便缩小这一领域证据与临床实践之间的差距。     

Antithrombotic Therapy in Stroke Prevention and Treatment: A Review

Current knowledge of antithrombotic therapy based on controlled clinical trials has revolutionized the way clinicians approach stroke prevention and treatment. This review article addresses the pathogenesis of stroke and summarizes information from clinical trials regarding the use of antiplatelet agents, heparin, warfarin (particularly in nonvalvular atrial fibrillation), and thrombolytics in stroke prevention and treatment.     

Antithrombotic Therapy in Stroke Prevention and Treatment: A Review

Current knowledge of antithrombotic therapy based on controlled clinical trials has revolutionized the way clinicians approach stroke prevention and treatment. This review article addresses the pathogenesis of stroke and summarizes information from clinical trials regarding the use of antiplatelet agents, heparin, warfarin (particularly in nonvalvular atrial fibrillation), and thrombolytics in stroke prevention and treatment.     

Treatment Strategies for the Prevention of Heart Failure

With the astounding morbidity and mortality associated with heart failure (HF), preventive approaches have been explored. Controlling hypertension to prevent HF is well-established, especially with sodium restriction and thiazide-based antihypertensive therapies showing potential advantages. Control of dyslipidemia with aggressive statin therapy is particularly beneficial in preventing HF in the setting of acute coronary syndrome. The HOPE study also established the benefit of ACE inhibitors in the prevention of HF in high-risk subjects. Meanwhile old data supporting tight glycemic control in preventing HF have not been confirmed, suggesting the complexity of diabetic cardiomyopathy. Avoiding tobacco use and other known cardiotoxins are likely helpful. While there has been substantial development in identifying biomarkers predicting future development of HF, therapeutic interdiction guided by biomarker levels have yet to be established, even though it offers hope in modulating the natural history of the development of HF in at-risk individuals.     

Pharmacologic Strategies for the Prevention of Stroke in Patients With Atrial Fibrillation

Stroke is a dreaded complication of atrial fibrillation. In the past, preventive therapy included aspirin and oral anticoagulation. Selected patients who are not suitable for oral anticoagulation may benefit from the addition of clopidogrel with aspirin. This combination, when compared with aspirin, offers a reduced risk of stroke at a cost of more major bleeding. We use this therapy in patients with atrial fibrillation who have unstable coronary syndromes or in patients who receive coronary artery stents who are not good candidates for “triple therapy” with aspirin, clopidogrel, and warfarin. The duration of therapy is tempered by many variables. In the case of coronary stents, we ask the interventionalist to consider a bare metal stent to shorten the duration of need for clopidogrel plus aspirin. After several months of combination therapy, we stop this therapy and begin warfarin therapy. Dabigatran is commercially available in the United States. In patients who have difficult to control International Normalized Ratio (INR) values or who do not wish to have regular coagulation monitoring, dabigatran offers a huge advantage. The benefit seems less if the INR is consistently within range. We are impressed with the superior reduction in stroke and systemic embolism with 150 mg of dabigatran twice daily compared to warfarin and also its low risk of intracranial hemorrhage. The results of clinical trials involving factor Xa agents are now being presented. How these agents fit into the marketplace remains to be seen but they will offer clinicians additional therapy for stroke prevention in atrial fibrillation.     

缺血性卒中的药物预防治疗研究进展

目前脑血管疾病占我国死因的第一位,卒中是大多数发达国家的第三位死因,也是最常见的致死、长期致残和住院的原因之一。卒中有诸多的危险因素,但高血压、高胆固醇血症、心房颤动是导致卒中的独立危险因素,因而重视并对其进行积极的干预治疗对卒中的原发和继发性预防至关重要。大量的循证医学研究结果证实对具有诸多危险因素的高危病人,予以降压、降脂和抗血小板治疗以及对行为危险因素进行干预可明显降低卒中的发生率和死亡率。     

Relapse Prevention Strategies for the Treatment of Cocaine Abuse

ABSTRACT

A variety of promising pharmcotherapies, psychotherapies, and other treatments for cocaine abuse have recently been developed, many of which may facilitate the initiation of abstinence in cocaine abusers. This paper describes specific interventions and therapeutic strategies used in the treatment of cocaine abuse, adapted from Marlatt's theory of relapse prevention. These strategies extend Marlatt's primarily psychoeducational approach to address the unique difficulties presented in the treatment of cocaine abuse, which may include wide variations in patients' severity of abuse, available psychosocial resources, and coexistent psychopathology. This approach attempts to integrate relapse prevention techniques into a psychotherapeutic, rather than a purely psychoeducational approach, in order to enhance its effectiveness with cocaine abusers.     

卒中治疗的抗氧化策略

众所周知,自由基生成过多会在许多种疾病如脑缺血中导致细胞损伤。大量研究对局灶性脑缺血中这种氧化应激和抗氧化策略的有效性进行了探讨,本文对其中的一部分进行阐述。除应用转基因小鼠外,这些抗氧化策略可分为3类:(1)抑制自由基产生;(2)清除自由基;(3)应用模拟内源性抗氧化物酶活性的药物增加自由基降解。最后,对已经结束或正在进行的评价卒中患者抗氧化剂疗效的临床试验进行回顾。结果显示抗氧化剂是非常有前景的治疗缺血性卒中的药物。     

卒中防治中的血压调控

文章探讨了卒中防治中的血压调控问题,包括卒中一级、二级预防以及卒中急性期血压的调控,升压治疗与缺血性脑血管病,颅内外血管狭窄的血压调控,抗凝治疗与血压调控,血压节律、变异性与卒中等。     

颈动脉内膜切除术预防和治疗缺血性卒中的疗效分析

目的:评估颅外段颈内动脉重度狭窄患者颈动脉内膜切除术预防和治疗缺血性卒中的临床价值。方法:22例患者均由经颅多普勒(TCD)筛选、数字减影血管造影(DSA)或CT血管造影(CTA)检查证实为颈内动脉重度狭窄,其中21例为有症状颈动脉狭窄。22例患者住院期间接受24侧次颈动脉内膜切除术,术后随访并行TCD检查。结果:21例(23侧次)手术过程顺利,随访2~30个月,未再发TIA或脑梗死,19例症状减轻或缓解。1例术后死于脑栓塞和肺部感染。随访期复查TCD 1～2次,20例未发现明显再狭窄。结论:颈动脉内膜切除术对治疗重度颈内动脉狭窄,预防TIA和缺血性卒中有效。TCD可作为对重度颈内动脉狭窄的筛选、术中监测和术后随访的重要手段。     

氯吡格雷在缺血性脑血管病二级预防中的应用

卒中是世界范围内人口死亡的第三位病因和成人残疾的首要原因,同时,也是老年人认知功能障碍和情感障碍的重要原因之一。我国为卒中高发国家,卒中年发病率为(185~219)/10万,估计每年有200万新发卒中病例,每年有150万人死于脑血管病,有卒中存活者700万人。脑血管病是我国人口死亡     

Stroke Prevention: Let's Prepare for Generation X TAVR

• Stroke leads to significant morbidity, disability, and mortality after TAVR. CKD and prior stroke are risk factors for stroke.
• Stratification of stroke risk would improve outcomes associated with TAVR.
• Ongoing prospective randomized trials on embolic protection and post implant anticoagulation are promising strategies to reduce stroke risk and new brain MRI lesions.

     

New Strategies for Prevention and Treatment of Graft-versus-Host Disease and for Induction of Graft-versus-Leukemia Effects

Graft-versus-host disease (GVHD) continues to be a problem in allogeneic hemopoietic stem cell transplantation; however, our understanding of the basic pathophysiology of GVHD has improved. Although not all data obtained from murine or other animal models can be extrapolated to the clinic, there are leads that deserve to be pursued. The skin, intestinal tract, and liver are the 3 major target organs of GVHD and share the feature of presenting a barrier to the "environment" of the host. There is evidence that the damage inflicted to these organs, the epithelial and endothelial cells in particular, by the conditioning regimen causes a release of various cytokines and a penetration of endotoxin into the systemic circulation. According to these observations, the nonimmunologic aspects of GVHD have been likened to an inflammatory process. If this characterization is valid, blocking these nonspecific inflammatory changes would ameliorate GVHD without interfering with the graft-versus-leukemia (GVL) reaction. In fact, one study has shown a substantial amelioration of GVHD with a molecule that directly blocks endotoxin. Clinical data also suggest that patients with organ dysfunction early after transplantation that is presumed to be treatment related may benefit from preemptive interventions aimed at controlling GVHD. Furthermore, there is growing evidence that the mechanisms involved in GVHD may differ from organ to organ (for example, Fas/Fas-ligand interactions in the liver versus tumor necrosis factor alpha/receptor interactions in the intestinal tract), and from a therapeutic point of view, the time of onset of clinical GVHD may be important in choosing the appropriate therapy. Thus, combinations of interventions chosen and timed appropriately may be more effective in preventing and managing GVHD than are the standard across-the-board approaches that have been used so far. Such a strategy may also be successful in maintaining a GVL effect and possibly in incorporating direct antileukemic therapy, such as the use of cytotoxic T-cells directed at minor histocompatibility antigens, without increasing the risk of GVHD. The development of nonmyeloablative conditioning regimens and the observations on GVHD kinetics and the progression or eradication of leukemia with that strategy are likely to add new insights into how one can optimally combine various modalities to achieve engraftment, prevent GVHD, and at the same time maintain a GVL effect.