Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Urdu Short Story and Psychological Problems

It is a complicated process to understand human psychology. Man has both good and evil, is striving with the crown of being the supreme creature. However, it has been evidently seen that in the absence of supremacy of law, this bearer of humanity descends to the level of damnation and commits in human acts. This kind of characters have been presented with remarkable skill in short stories written in the context of advent of Pakistan and Fall of Dhaka. The short story writers are seen there, arguing strange and ambiguous psychy of such characters. We are bound to conclude after analysing these characters that man infact persues the sanctity of social norms and values, however when there is disintegration in societal laws, the attitudes deteriorate accordingly and such acts are committeed that are beyond national comprehension

منٹو بحیثیت افسانوی کردار

Saadat Hasan Manto is a great literary figure of Urdu language and literature. He is a versatile writer who has penned in many genres but chiefly he is admired for subtlety in weaving of short stories. He enjoys unmatched popularity in story writing that his name and Urdu short story has become synonymous. Manto has time and again drags his personal traits in his stories. This article is a study of Manto's person as a character of his short stories. </p

Urdu Short Story and Psychological Problems

It is a complicated process to understand human psychology. Man has both good and evil, is striving with the crown of being the supreme creature. However, it has been evidently seen that in the absence of supremacy of law, this bearer of humanity descends to the level of damnation and commits in human acts. This kind of characters have been presented with remarkable skill in short stories written in the context of advent of Pakistan and Fall of Dhaka. The short story writers are seen there, arguing strange and ambiguous psychy of such characters. We are bound to conclude after analysing these characters that man infact persues the sanctity of social norms and values, however when there is disintegration in societal laws, the attitudes deteriorate accordingly and such acts are committeed that are beyond national comprehension

Urdu Short Story and Psychological Problems

It is a complicated process to understand human psychology. Man has both good and evil, is striving with the crown of being the supreme creature. However, it has been evidently seen that in the absence of supremacy of law, this bearer of humanity descends to the level of damnation and commits in human acts. This kind of characters have been presented with remarkable skill in short stories written in the context of advent of Pakistan and Fall of Dhaka. The short story writers are seen there, arguing strange and ambiguous psychy of such characters. We are bound to conclude after analysing these characters that man infact persues the sanctity of social norms and values, however when there is disintegration in societal laws, the attitudes deteriorate accordingly and such acts are committeed that are beyond national comprehension

Urdu Short Story and Psychological Problems

It is a complicated process to understand human psychology. Man has both good and evil, is striving with the crown of being the supreme creature. However, it has been evidently seen that in the absence of supremacy of law, this bearer of humanity descends to the level of damnation and commits in human acts. This kind of characters have been presented with remarkable skill in short stories written in the context of advent of Pakistan and Fall of Dhaka. The short story writers are seen there, arguing strange and ambiguous psychy of such characters. We are bound to conclude after analysing these characters that man infact persues the sanctity of social norms and values, however when there is disintegration in societal laws, the attitudes deteriorate accordingly and such acts are committeed that are beyond national comprehension

PEACE EDUCATION IN PAKISTAN; ANALYSIS OF EDUCATIONAL POLICIES TO EXAMINE THE REALITY

During the past decade in Pakistan societal apprehension has been increased about terrible forms of terrorism. This corresponds to the evolution of peace education in academia. Considering the importance of this societal need this paper seeks to provide a comprehensive chronological analysis of the state educational policies from 1947 to 2009 and the place of peace education within these policies. By adopting the framework for analysis, guided by Levander &amp; Mikkola, in 2009, the analysis of policies was carried out in two phases. At first phase policies were reviewed to find out the aspects of peace education. At the second phase of analysis founded aspects of peace education were further explored to establish the quality of descriptionFindings, shows that the different educational policies focused on few aspects of peace education i.e.tolerance, justice, cultural diversity, environmental education, and human values. The findings build on analysis suggests that the new policy of education should focus on peace education extensively so that the issues of violence and terrorism could be minimized from the society

Associations between BCL11A and HBS1L-MYB polymorphisms and thalassemia risk

الملخص: أهداف البحث: تناولت هذه الدراسة التحقيق في العلاقة بين ثلاثة متغيرات جينية: آر اس 4671393 و آر اس 1427407 و آر اس 11886868 تقع داخل جين ''بي سي ال 11 أ'' ومتغير واحد آر اس 9399137 في جين ''اتش بي اس 1 ال-ام واي بي''، وارتباطهم المحتمل بمرض الثلاسيميا لدى المرضى من سكان البنجاب، باكستان. طريقة البحث: تم استقطاب مجموعة مكونة من 600 مشارك من مستشفيات مختلفة في البنجاب، باكستان. وقد ضمت المجموعة 300 مريض بالثلاسيميا و300 من الضوابط الأصحاء المطابقين في العمر والجنس. وتم استخراج الحمض النووي من عينات الدم الكاملة لجميع المشاركين. وتم تضخيم مناطق الحمض النووي المحددة التي تحتوي على أربعة متغيرات وراثية ذات أهمية باستخدام تفاعل البوليميراز المتسلسل. النتائج: تشير الترددات الجينية تعدد أشكال النوكليوتيد المفردة لـ آر اس 4671393 من جين ''بي سي ال 11 أ'' إلى أن النمط الجيني المتغاير (أ ج) لـ تعدد أشكال النوكليوتيد المفردة كان مرتبطا بشكل كبير بزيادة خطر الإصابة بالثلاسيميا بمقدار الضعف تقريبا مقارنة بالمجموعة المرجعية. كما أكد الجمع بين جميع الأنماط الجينية في نموذج مشترك وجود ارتباط كبير بزيادة خطر الإصابة بالثلاسيميا. وعلى غرار آر اس 4671393، أظهر النمط الجيني المتغاير(س ت) لـ آر اس 11886868 أيضا ارتباطا كبيرا بزيادة خطر الإصابة بالثلاسيميا بمقدار الضعف تقريبا. كشف تحليل كلا النمطين الجينيين معا عن ارتباط طفيف مع زيادة بمقدار ضعف واحد في خطر الإصابة بالثلاسيميا للأفراد الذين يحملون أي أليل متغير من آر اس 11886868. أظهرت حالات التوزيع الأليلي لـ آر اس 1427407 للجين ''بي سي ال 11 أ'' أن النمط الجيني المتغاير (ت ج) لـ آر اس 1427407 أظهر ارتباطا مهما بزيادة في خطر الإصابة بالثلاسيميا بمقدار الضعف تقريبا مقارنة بالمجموعة المرجعية. أكد الجمع بين جميع الأنماط الجينية في نموذج مشترك وجود ارتباط مهم بين وجود أي أليل متغير لـ آر اس 1427407 وزيادة في خطر الإصابة بالثلاسيميا بمقدار الضعف. أظهرت ترددات التوزيع الجيني المتغاير (ت س) لـ آر اس 9399137 لجين ''اتش بي اس 1 ال-ام واي بي'' مشابهة لـ آر اس 1427407، أظهر النمط الجيني المتغاير (س ت) لـ آر اس 9399137 ارتباطا مهما للغاية بزيادة في خطر الإصابة بالثلاسيميا بمقدار الضعف تقريبا. أظهر تحليل كلا النمطين الجينيين معا وجود ارتباط كبير مع زيادة خطر الإصابة بالثلاسيميا بمقدار ضعف واحد للأفراد الذين يحملون أي متغير من أليل آر اس 9399137. Abstract: Objectives: This study investigated the associations of the rs4671393, rs1427407, and rs11886868 genetic variants of the BCL11A gene and the rs9399137 variant of the HBS1L-MYB gene with thalassemia in patients from the population of Punjab, Pakistan. Methods: A cohort of 600 participants, comprising 300 patients with thalassemia and 300 age- and sex-matched healthy controls, was recruited from various hospitals in Punjab, Pakistan. DNA was extracted from whole blood samples from all participants. Specific DNA regions containing four genetic variants of interest were amplified with polymerase chain reaction. Results: The genotypic frequencies of the rs4671393 SNP of BCL11A indicated that the heterozygous (AG) genotype of this SNP was significantly associated with a nearly two-fold increased thalassemia risk, with respect to the control group (OR = 1.77; 95% CI = 1.77–2.80; p = 0.01). Combining all genotypes into a joint model further confirmed their significant association with thalassemia risk. Similarly to the findings for rs4671393, the heterozygous (CT) genotype of rs11886868 exhibited a significant association with thalassemia risk (approximately two-fold increased risk. Analysis of both genotypes together revealed a marginally significant association (one-fold increased risk) with thalassemia in individuals carrying any variant allele of rs11886868. The allelic distribution of the rs1427407 SNP of BCL11A indicated that the heterozygous (GT) genotype of this SNP was significantly associated with thalassemia (approximately two-fold increased risk, with respect to the control group). Combining all genotypes into a joint model confirmed a significant association between the presence of any variant allele of rs1427407 and thalassemia (two-fold increased risk). The genotypic distribution frequencies of the heterozygous (CT) genotype for the rs9399137 SNP of HBS1L-MYB was similar to that of rs1427407, and exhibited a highly significant association with thalassemia risk (nearly two-fold increased risk). Analysis of both genotypes together revealed a significant association with thalassemia risk (one-fold increase) for individuals carrying any variant allele of rs9399137. Conclusion: BCL11A and HBS1L-MYB polymorphisms were significantly associated with increased thalassemia risk