16 results on '"Kiran Javaid"'
Search Results
2. Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials
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Ian Roberts, Raoul Mansukhani, Danielle Prowse, Kiran Javaid, Haleema Shakur-Still, Bellington Vwalika, Eni Balogun, Amy Brenner, Charlotte Fleming, Folasade A. Bello, Aasia Kayani, Mwansa Ketty Lubeya, Oladapo Olayemi, and Rizwana Chaudhri
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medicine.medical_specialty ,business.industry ,Obstetrics ,Postpartum Hemorrhage ,Outcome measures ,Medicine (miscellaneous) ,Anemia ,Delivery, Obstetric ,Postpartum haemorrhage ,Clinical trial ,Tranexamic Acid ,Pregnancy ,Outcome Assessment, Health Care ,Medicine ,Humans ,Pharmacology (medical) ,Female ,business - Abstract
Background Postpartum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH, and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures. Main body The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a ‘clinical diagnosis of PPH’, is defined as estimated blood loss > 500 ml or any blood loss within 24 h sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4521 participants. For each outcome, we assessed its: (1) frequency, (2) specificity for significant bleeding defined as shock index ≥1.0 and (3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth. Conclusion Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial. Trial registration ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.
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- 2022
3. A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT
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Jack Williams, Haleema Shakur-Still, Andrew Veitch, Richard Pollok, Muhammad Nadeem, Timothy J Coats, Monica Arribas, Raoul Mansukhani, Ian Roberts, Alec Miners, Muttiullah Mutti, Kiran Bal, Aasia Kayani, AO Afolabi, Kiran Javaid, Simon J. Stanworth, Emma Austin, Adegboyega Akere, Kenneth Halligan, Vipul Jairath, Jonathan Simmons, Nuha Bazeer, Rizwana Chaudhri, Irshad Hussain, Amy Brenner, Ton Lisman, Ian Gilmore, Laura Carrington, Danielle Prowse, Danielle Beaumont, and Groningen Institute for Organ Transplantation (GIOT)
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Adult ,medicine.medical_specialty ,Gastrointestinal bleeding ,Lower gastrointestinal bleeding ,pulmonary embolism ,gastrointestinal haemorrhage ,blood transfusion ,Placebo ,tranexamic acid ,Internal medicine ,Intensive care ,medicine ,Medical technology ,Humans ,blood loss ,R855-855.5 ,Stroke ,Intention-to-treat analysis ,business.industry ,Health Policy ,cost-benefit analysis ,medicine.disease ,stroke ,Antifibrinolytic Agents ,Relative risk ,venous thrombosis ,business ,Gastrointestinal Hemorrhage ,Tranexamic acid ,medicine.drug - Abstract
Background Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. Objective The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. Design A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. Setting The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. Participants Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. Intervention Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. Main outcome measures The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. Results A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. Conclusions Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. Future work These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. Limitations Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. Trial registration Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.
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- 2021
4. WOMAN-PharmacoTXA trial: Study protocol for a randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of tranexamic acid in women giving birth by caesarean section [version 1; peer review: 2 approved]
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Mwansa Ketty Lubeya, Danielle Prowse, Haleema Shakur-Still, Aasia Kayani, Rizwana Chaudhri, Ian Roberts, Amber Geer, Monica Arribas, Stanislas Grassin-Delyle, and Kiran Javaid
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Tranexamic acid ,Antifibrinolytic ,medicine.drug_class ,viruses ,medicine.medical_treatment ,Science ,Medicine (miscellaneous) ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Study Protocol ,oral ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Randomized controlled trial ,law ,Medicine ,Caesarean section ,030212 general & internal medicine ,Adverse effect ,intramuscular ,business.industry ,virus diseases ,clinical trial ,Articles ,biochemical phenomena, metabolism, and nutrition ,digestive system diseases ,Pharmacodynamics ,caesarean section ,030220 oncology & carcinogenesis ,Anesthesia ,PPH ,business ,Intramuscular injection ,medicine.drug - Abstract
Background: Intravenous tranexamic acid (TXA) within 3 hours of birth significantly reduces death due to bleeding in women with postpartum haemorrhage (PPH). Most PPH deaths occur in the first hours after giving birth and treatment delay decreases survival. One barrier to rapid TXA treatment is the need for intravenous injection. Intramuscular injection and oral solution of TXA would be easier and faster to administer and would require less training. However, the pharmacokinetics (PK), pharmacodynamics and safety of TXA administered by different routes in pregnant women have not been established. The main aim of this study is to ascertain whether IM and oral solution of TXA will be absorbed at levels sufficient to inhibit fibrinolysis in pregnant women. Methods: WOMAN-PharmacoTXA is a prospective, randomised, open label trial to be conducted in Zambia and Pakistan. Adult women undergoing caesarean section with at least one risk factor for PPH will be included. Women will be randomised to receive one of the following about 1 hour prior to caesarean section: 1-gram TXA IV, 1-gram TXA IM, 4-grams TXA oral solution or no TXA. Randomisation will continue until 120 participants with at least six post randomisation PK samples are included. TXA concentration in maternal blood samples will be measured at baseline and at different time points during 24 hours after receipt of intervention. Blood TXA concentration will be measured from the umbilical cord and neonate. The primary endpoint is maternal blood TXA concentrations over time. Secondary outcomes include umbilical cord and neonate TXA concentration D-dimer concentration, blood loss and clinical diagnosis of PPH, injection site reactions and maternal and neonate adverse events. Discussion: The WOMAN-PharmacoTXA trial will provide important data on pharmacokinetics, pharmacodynamics and safety of TXA after IV, intramuscular and oral administration in women giving birth by caesarean section. Trial registration: ClincalTrials.gov, NCT04274335 (18/02/2020).
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- 2021
5. Acceptability and feasibility of screening pregnant women for sexually transmitted infections in Rawalpindi, Pakistan
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Nimra Khan, Lamar W Hayes, Ameen E Chaudry, Rizwana Chaudhri, Aasia Kayani, Kiran Javaid, Jeffrey D. Klausner, Claire C. Bristow, Bushra Yasmeen, and Sana Akhlaque
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medicine.medical_specialty ,030231 tropical medicine ,Sexually Transmitted Diseases ,Chlamydia trachomatis ,HIV Infections ,Dermatology ,urologic and male genital diseases ,medicine.disease_cause ,03 medical and health sciences ,Gonorrhea ,0302 clinical medicine ,Pregnancy ,medicine ,Prevalence ,Trichomonas vaginalis ,Humans ,Pharmacology (medical) ,Pakistan ,Pregnancy Complications, Infectious ,030304 developmental biology ,0303 health sciences ,business.industry ,Obstetrics ,Public Health, Environmental and Occupational Health ,virus diseases ,Chlamydia Infections ,female genital diseases and pregnancy complications ,Neisseria gonorrhoeae ,Infectious Diseases ,Feasibility Studies ,Female ,Pregnant Women ,business - Abstract
Objectives: To understand the acceptability and feasibility of sexually transmitted infection (STI) testing during antenatal care, along with the prevalence of STIs, in Rawalpindi, Pakistan. Methods: We enrolled pregnant women seeking antenatal care and performed STI testing using Cepheid GeneXpert® CT/NG and TV kits and Alere Determine™ HIV and syphilis tests. We used interviewer-administered surveys to collect medical, social, and sexual histories. Participants testing positive for STIs and their partners were treated. Results: We enrolled 1001 women from September to December 2019. Nearly all women offered to participate in this study enrolled. Most women understood the effects an STI can have on their pregnancy (99.6%) and valued STI screening during pregnancy (98.1%). 11 women tested positive for any STI: ( Chlamydia trachomatis = 4, Neisseria gonorrhoeae = 1, and Trichomonas vaginalis = 6). Of those, six presented for a test-of-cure, and two were positive for Trichomonas vaginalis. None tested positive for HIV infection or syphilis ( n = 503). Conclusions: STI testing during antenatal care in Rawalpindi was acceptable, valued, understood, and feasible. The prevalence of STIs in pregnant women was low. Continued prevalence monitoring is warranted.
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- 2021
6. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial
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Ian Roberts, Haleema Shakur-Still, Adefemi Afolabi, Adegboyega Akere, Monica Arribas, Amy Brenner, Rizwana Chaudhri, Ian Gilmore, Kenneth Halligan, Irshad Hussain, Vipul Jairath, Kiran Javaid, Aasia Kayani, Ton Lisman, Raoul Mansukhani, Muttiullah Mutti, Muhammad Arif Nadeem, Richard Pollok, Jonathan Simmons, Majid Soomro, Simon Stanworth, Andrew Veitch, Christopher Hawkey, Jack Cuzick, David Henry, Chris Metcalfe, Richard Gray, Alan Barkun, Suresh David, Philip Devereaux, Tony Brady, Timothy Coats, Phil Edwards, Katharine Ker, Daniela Manno, Emma Austin, Kiran Bal, Eni Balogun, Collette Barrow, Danielle Beaumont, Myriam Benyahia, Imogen Brooks, Madeleine Cargill, Laura Carrington, Lauren Frimley, Amber Geer, Daniel Gilbert, Catherine Gilliam, Julio Gil Onandia, Nayia Golfi, Daniel Hetherington, Courtenay Howe, Carolyn Hughes, David I'anson, Rob Jackson, Miland Joshi, Sneha Kansagra, Taemi Kawahara, Sergey Kostrov, Hakim Miah, Bernard Ndungu, Kelly Needham, Aroudra Outtandy, Daniel Pearson, Tracey Pepple, Danielle Prowse, Nigel Quashi, Anna Quinn, Maria Ramos, Laura Ranopa, Mia Reid, Chris Roukas, Chelci Squires, Jemma Tanner, Andrew Thayne, Ruhama Uddin, Bukola Fawole, Folasade Adenike Bello, Oladapo Olayemi, Olujide Okunade, Olusade Adetayo, Hussein Khamis, Mohammad Shukri Bin Jahit, Tamar Gogichaishvili, Radu Bogdan Mateescu, Ajay Adhikaree, Abdelmounem Eltayeib Abdo, Mohammad Zaher, Conor Deasy, Joaquin Alvarez Gregori, Bobby Wellsh, Luke Lawton, Raghavendra Kamath, Adrian Barry, Racquel Carpio, Kay Finney, Holly Maguire, Martin James, Frank Coffey, Chris Gough, Lisa Sawers, Aye-Aye Thi, Claire Burnett, Nicola Jacques, Victoria Murray, Heather Jarman, Christine Lambe, Sarah Rounding, Simon Tucker, Romaih Al-Idari, Samuel Guest, Emma Stoddard, David Yeo, Colin Bergin, Elaine Hardy, Joanne Thunder, Paul Jhalli, Edward Hartley, Catherine Jarvis, Carly Swann, Matthew Reed, Bernadette Gallagher, Julia Grahamslaw, Rachel O'Brien, Timothy Harris, Geoffrey Bellhouse, Olivia Boulton, Imogen Skene, Adrian Stanley, Janet Johnstone, Donogh Maguire, Susan Thornton, Matthew Banks, Georgia Bercades, Daniel Marks, Jung Ryu, Claire Dowty, Jason Pott, James East, Adam Bailey, Sally Beer, Sian Davies, Andrew Appelboam, Daisy Mackle, Jennifer Small, Christiane Vorwerk, Rachel Atkins, Isobel Bradbury, Catriona Bryceland, Lisa McClelland, Martin Thomas, Kate Clayton, Angiy Michael, Stephen Haig, Saif Al-Nahhas, Tim Godfrey, Philip Boger, Rachel Comer, Barbara Watkins, Ola Afolabi, Shazad Afzal, Amanda Cowton, Simon Everett, Ruth Fazakerley, Felicia Onoviran, Jonathon Snook, Jackie Berry, Diane Simpson, Jeff Keep, Hannah Cotton, Sinead Helyar, Matthew Rutter, Tracey Johnston, Laura O'Rourke, Louisa Chan, Joanna Tambellini, Dawn Trodd, James Shutt, Sarah Moreton, Abby Oglesby, Adrian Boyle, Nicola Haeger, Susie Hardwick, Jason Kendall, Beverley Faulkner, Ruth Worner, Sarah Hearnshaw, Mary Doona, Maria Price, Laura Hunter, Maggie Bell, Vania Loureiro, Anthony Kehoe, Alison Jefferey, Rosalyn Squire, David Hartin, Stephanie Bell, Alexandra Newman, James Gagg, Jayne Foot, Sue Wakeford, Gabrielle May, Thomas Bartram, Paul Cumpstay, Lucy Parker, Rita Das, Sheik Pahary, Gavin Wright, Georgina Butt, Natasha Christmas, Sarah Wilson, Mohammed Ashfaq, Louise Chandler, Carrie Demetriou, Philip Kaye, Simon Carley, Andrew Brown, Lucy Jones, Amanda Whileman, John Greenaway, Julie Tregonning, Avril Kuhrt, Steve Goodacre, John Jones, Charlotte Owen, Anu Mitra, Abby Harper-Payne, Nigel Trudgill, Anne Hayes, Faheem Butt, Gayle Clifford, Andrew Kinnon, Susan Fowler, Kris Pillay, Shweta Gidwani, Alistair McNair, Omer Omer, Tanya de Weymarn, Adnan Amin, Jane Martin, Nick Mathieu, Simon Barnes, James Turvill, Helen Sweeting, Morten Draegebo, Marion McNaught, Mandy Grocutt, Jordi Margalef, Julian Humphrey, Richard Jackson, Fionn Bellis, Jane Hunt, Alastair Stevenson, Nicholas Watson, Steven Barden, Stuart Paterson, Chris Macdonald, David Hobday, Olu Orugun, Andrew Allison, Tristan Dyer, Samuel McBride, Wojciech Sawicki, Ben Rayner, Lynsey Flowerdew, Jamie Barbour, Jason Klein, Stephen Hood, Nicola Palmer, Jacob de Wolff, Achuth Shenoy, Peter Swallow, Rajaventhan Srirajaskanthan, Hamza Arshad, Naeem Aslam, Anam Bangash, Muhammad Qamar, Haroon Zahoor, Saba Arshad, Quratul ain Ghalib, Tehseen Hameed, Tayyaba Saif, Wajahat Shafi, Abid Ali, Shehroze Khan, Muhammad Muaaz, Ahmad Taj, Aamir Ghafoor, Aamir Afridi, Mansoor Ahmad, Mujahid Aslam, Sandeep Kumar, Mohsin Ali, Ubedullah Bughio, Adil Chang, Sana Shaikh, Syed Ahmad, Zeeshan Ali, Marium Waqar, Aiman Mushir, Sadaf Sattar, Saifullah Goraya, Sharmeen Aslam, Nighat Fatima, Saadia Noreen, Sheraz Saleem, Fazal Rahman, Nadeem Iqbal, Mohammad Khalid, Umar Riaz, Muhammad Umar, Tayyab Akhter, Javaria Khan, Noureen Misbah, Muhammad Afzal, Mobeen Kayani, Syed Shah, Shahida Tarar, Sherbat Khan, Yasir Iqbal, Essa Khan, Maqbool Reki, Tanveer Hussain, Shafqat Iqbal, Muhammad Khurram, Muhammad Shafi, Abrar Shaikh, Aijaz Ahmed, Ameet Kumar, Pinkey Sachdev, Khalid Mahmood Nasir, Zafar Iqbal Chaudhry, Muhammad Zubair, Ghias Tayyab, Junaid Mushtaq, Muhammad Nasir, Amir Khan, Amjad Ali, Sajjad Ali, Wasim Uddin, Sohaib Ahmed, Tazaeen Kazmi, Saleh Channa, Adeeqa Aman, Mouzam Shaikh, Tahir Rizvi, Amjad Hussain, Haider Zaigham Baqai, Zakawat Rasheed, Abdus Khan, Adeela Irfan, Aamir Husain, Asifa Aslam, Khalid Yahya, Salman Azhar, Mansoor Ul Haq, Adeel Afzal, Muhammad Imran, Iram Saeed, Aasim Yusuf, Mariam Hassan, Mumtaz Marwat, Muhammad Ishfaq, Tahir Bashir, Santosh Kumar, Sajjad Yaqoob, Abdul Wahid, Tinuola Fakoya, Temitope Oke, Edries Tejan, Oluwole Olaomi, Olawale Badejo, Okafor Nnaemaka, Nancy Ukwu, Olukayode Arowolo, Adewale Aderounmu, Funmilola Wuraola, Rose Ugiagbe, Alexander Atiri, Enadeghe Eghaghe, Adeleke Adekoya, Adedayo Oluyomi Tade, Olatunji Shonoiki, Samuel Olatoke, Toafiq Raji, Christopher Ekwunife, Chigozirim Onyekpere, Adamu Ahmed, Daniyan Muhammad, Emuobor Odeghe, Olufunmilayo Lesi, Azeberoje Osueni, Adamu Samaila, Aminu Nahuche, Akande Ajayi, Andrew Dongo, Uchenna Ijoma, Ademola Tolulope Adebanjo, Rufina Igetei, Monday Yilkudi, Kehinde Osisanya, Edith Nonyelum Okeke, Oguamanam Okezie Enwere, Serag Esmat, Omar Ashoush, Mazen Naga, Fady Nagy, Mostafa Saiid, Ahmed Shaker, Ashraf Helmy, Saafan Saafan, Mohammed Abdel Monem, Jiffre Din, Khairul Azis, Muhyuddin Brukan, Sanjay Singh, Andee Zakaria, Shaik Farid, Nizam Hashim, Masykurin Mafauzy, Wan Najmi, Nil Amri, Xin Yi, Mohammad Hisyam, Elaine Ng, Zuhrirahimi Ramli, Shyang Yee Lim, Kelvin Voon, Sir Young Yam, Mohammad Jahit, Lee Joon, Besik Melikidze, Davit Kazaishvili, Nino Grubelashvili, Baadur Mosidze, Gia Tomadze, Avto Megreladze, Ruxandra Oprita, Dorina Pestroiu Calescu, Camelia Chioncel, Andrei Ragea, Bogdan Mateescu, Bogdan Busuioc, Andrei Voiosu, Adrian Cotirlet, Iulia Pintilie, Mariana Jinga, Daniel Balaban, Marcel Tanău, Lucian Negreanu, Simona Bataga, Khushboo Priya, Shankar Baral, Anuj K.C., Vijay Sah, Vijay Yadav, Abdelmounem Abdo, Dalia Ahmed, Marzouqah Al Anazi, Areej Al Balkhi, Joaquín Álvarez Gregori, Helio Fornieles Pérez, and Arben Beqiri
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Gastrointestinal bleeding ,Lower gastrointestinal bleeding ,business.industry ,Maintenance dose ,Placebo-controlled study ,General Medicine ,030204 cardiovascular system & hematology ,A300 ,medicine.disease ,Placebo ,Loading dose ,03 medical and health sciences ,0302 clinical medicine ,Anesthesia ,Medicine ,030212 general & internal medicine ,business ,Stroke ,Tranexamic acid ,medicine.drug - Abstract
Summary Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding UK National Institute for Health Research Health Technology Assessment Programme.
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- 2020
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7. Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients
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Francois-Xavier Ageron, Angele Gayet-Ageron, Katharine Ker, Timothy J. Coats, Haleema Shakur-Still, Ian Roberts, Aasia Kayani, Amber Geer, Bernard Ndungu, Bukola Fawole, Catherine Gilliam, Cecelia Adetayo, Collette Barrow, Danielle Beaumont, Danielle Prowse, David I'Anson, Eni Balogun, Hakim Miah, Imogen Brooks, Julio Onandia, Kiran Javaid, Laura Suncuan, Lauren Frimley, Mia Reid, Monica Arribas, Myriam Benyahia, Olujide Okunade, Phil Edwards, Rizwana Chaudhri, Sergey Kostrov, Sneha Kansagra, Tracey Pepple, Antifibrinolytics Trials Collaboration, Kayani, A., Geer, A., Ndungu, B., Fawole, B., Gilliam, C., Adetayo, C., Barrow, C., Beaumont, D., Prowse, D., I'Anson, D., Balogun, E., Miah, H., Shakur-Still, H., Roberts, I., Brooks, I., Onandia, J., Ker, K., Javaid, K., Suncuan, L., Frimley, L., Reid, M., Arribas, M., Benyahia, M., Okunade, O., Edwards, P., Chaudhri, R., Kostrov, S., Kansagra, S., and Pepple, T.
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Adult ,Male ,Risk ,medicine.medical_specialty ,Antifibrinolytic ,medicine.drug_class ,Baseline risk ,Hemorrhage ,Antifibrinolytic Agents/therapeutic use ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,030202 anesthesiology ,Internal medicine ,medicine ,Coagulopathy ,Humans ,ddc:613 ,Randomized Controlled Trials as Topic ,ddc:618 ,business.industry ,Acute bleeding ,medicine.disease ,Postpartum haemorrhage ,Antifibrinolytic Agents ,3. Good health ,Anesthesiology and Pain Medicine ,Tranexamic Acid ,Patient level data ,Acute Disease ,Female ,Hemorrhage/drug therapy ,Tranexamic Acid/therapeutic use ,antifibrinolytics ,bleeding ,coagulopathy ,mortality ,postpartum haemorrhage ,trauma ,Meta-analysis ,business ,Tranexamic acid ,medicine.drug - Abstract
Background Early administration of the antifibrinolytic drug tranexamic acid reduces death from bleeding in trauma and postpartum haemorrhage. We examined how the effectiveness and safety of antifibrinolytic drugs varies by the baseline risk of death as a result of bleeding. Methods We performed an individual patient-level data meta-analysis of randomised trials including more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials performed between January 1, 1946 and July 5, 2018 (PROSPERO, number 42016052155). Results Two randomised trials were selected where 28 333 patients received tranexamic acid treatment within 3 h after the onset of acute bleeding. Baseline characteristics to estimate the risk of death as a result of bleeding were divided into four categories: Low (0–5%), intermediate (6–10%), high (11–20%), and very high (>20%). Most patients had a low baseline risk of death as a result of bleeding (23 008 [81%]). Deaths as a result of bleeding occurred in all baseline risk categories with 240 (1%), 202 (8%), 232 (14%), and 357 (30%) deaths in the low-, intermediate-, high-, and very high-risk categories, respectively. The effectiveness of tranexamic acid did not vary by baseline risk when given within 3 h after bleeding onset (P=0.51 for interaction term). There was no increased risk of vascular occlusive events with tranexamic acid and it did not vary by baseline risk categories (P=0.25). Conclusions Tranexamic acid appears to be safe and effective regardless of baseline risk of death. Because many deaths are in patients at low and intermediate risk, tranexamic acid use should not be restricted to the most severely injured or bleeding patients.
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- 2020
8. 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
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Haleema Shakur, Ian Roberts, Bukola Fawole, Rizwana Chaudhri, Mohamed El-Sheikh, Adesina Akintan, Zahida Qureshi, Hussein Kidanto, Bellington Vwalika, Abdulfetah Abdulkadir, Saturday Etuk, Shehla Noor, Etienne Asonganyi, Zarko Alfirevic, Danielle Beaumont, Carine Ronsmans, Sabaratnam Arulkumaran, Adrian Grant, Kaosar Afsana, Metin Gülmezoglu, Beverley Hunt, Oladapo Olayemi, Iain Chalmers, Pisake Lumbiganon, Gilda Piaggio, Tony Brady, Diana Elbourne, Eni Balogun, Tracey Pepple, Danielle Prowse, Nigel Quashi, Lin Barneston, Collette Barrow, Lisa Cook, Lauren Frimley, Daniel Gilbert, Catherine Gilliam, Rob Jackson, Taemi Kawahara, Hakim Miah, Sergey Kostrov, Maria Ramos, Phil Edwards, Tom Godec, Sumaya Huque, Olujide Okunade, Olusade Adetayo, Aasia Kayani, Kiran Javaid, Chrstine Biryabarema, Robert Tchounzou, Mohan Regmi, Kastriot Dallaku, Mateus Sahani, Sayeba Akhter, Nicolas Meda, Anthony Kwame Dah, Olufemi Odekunle, Oluwabusola Monehin, Austin Ojo, Grace Akinbinu, Ifeoma Offiah, Ubong Akpan, Uduak Udofia, Useneno Okon, Ezukwa Omoronyia, Okpe James, Nike Bello, Blessed Adeyemi, Chris Aimakhu, Olufemi Akinsanya, Bamidele Adeleye, Oluwaseun Adeyemi, Kayode Oluwatosin, Abiodun Aboyeji, Abiodun Adeniran, Adebayo Adewale, Noah Olaomo, Lawrence Omo-Aghoja, Emmanuel Okpako, Lucky Oyeye, Francis Alu, John Ogudu, Ezekiel Ladan, Ibrahim Habib, Babasola Okusanya, Olatunde Onafowokan, David Isah, Abalaka Aye, Felix Okogbo, Egbaname Aigere, Mark Ogbiti, Temitope Onile, Olaide Salau, Yinka Amode, Kamil Shoretire, Adebola Owodunni, Kehinde Ologunde, Akintunde Ayinde, Moses Alao, Olalekan Awonuga, Babatunde Awolaja, Omololu Adegbola, Fatimah Habeebu-Adeyemi, Adeyemi Okunowo, Hadiza Idris, Ola Okike, Nneka Madueke, Josiah Mutihir, Nankat Joseph, Babatunde Adebudo, Adeniyi Fasanu, Olugbenga Akintunde, Olufemi Abidoye, Owigho Opreh, Sophia Udonwa, Gladys Dibia, Simeon Bazuaye, Arafat Ifemeje, Aniefiok Umoiyoho, Emmanuel Inyang-Etoh, Sununu Yusuf, Kayode Olayinka, Babalola Adeyemi, Olusegun Ajenifuja, Umar Ibrahim, Yusuf Baffah Adamu, Oluwarotimi Akinola, Grace Adekola-Oni, Paul Kua, Roseline Iheagwam, Audu Idrisa, Ado Geidam, Andrea Jogo, Joseph Agulebe, Joseph Ikechebelu, Onyebuchi Udegbunam, Jacob Awoleke, Oluseyi Adelekan, Hajaratu Sulayman, Nkeiruka Ameh, Nurudeen Onaolapo, Affiss Adelodun, William Golit, Dachollom Audu, Adetunji Adeniji, Folasade Oyelade, Lamaran Dattijo, Palmer Henry, Olabisi Loto, Odidika Umeora, Abraham Onwe, Emily Nzeribe, Bartthy Okorochukwu, Augustine Adeniyi, Emmanuel Gbejegbe, Akpojaro Ikpen, Ikemefuna Nwosu, Abdulrasaq Sambo, Olubunmi Ladipo, Sola Abubakar, Ola Nene Okike, Enyinnaya Chikwendu Nduka, Eziamaka Pauline Ezenkwele, Daniel Onwusulu, Theresa Azonima Irinyenikan, Swati Singh, Amaitari Bariweni, Hadiza Galadanci, Peter Achara, Osagie Osayande, Mohammed Gana, Kiran Jabeen, Ayesha Mobeen, Sadaf Mufti, Maliha Zafar, Basharat Ahmad, Maimoona Munawar, Jeharat Gul, Naseema Usman, Fehmida Shaheen, Mariam Tariq, Nadia Sadiq, Rabia Batool, Habiba Sharaf Ali, Manahil Jaffer, Asma Baloch, Noonari Mukhtiar, Tasneem Ashraf, Raheela Asmat, Salma Khudaidad, Ghazala Taj, Roshan Qazi, Saira Dars, Faryal Sardar, Sanobar Ashfaq, Saeeda Majeed, Sadaqat Jabeen, Rukhsana Karim, Farzana Burki, Syeda Rabia Bukhari, Fouzia Gul, Musarrat Jabeen, Akhtar Sherin, Qurratul Ain, Shahid Rao, Uzma Shaheen, Samina Manzoor, Shabween Masood, Shabana Rizvi, Anita Ali, Abida Sajid, Aisha Iftikhar, Shazia Batool, Lubna Dar, Shahenzad Sohail, Shazia Rasul, Shamsa Humayun, Rashida Sultana, Sofia Manzoor, Syeda Mazhar, Afshan Batool, Asia Nazir, Nasira Tasnim, Hajira Masood, Razia Khero, Neelam Surhio, Samana Aleem, Naila Israr, Saba Javed, Lubna Bashir, Samina Iqbal, Faiza Aleem, Rubina Sohail, Saima Iqbal, Samina Dojki, Alia Bano, Naseem Saba, Maimoona Hafeez, Nishat Akram, Riffat Shaheen, Haleema Hashmi, Sharmeen Arshad, Rubina Hussain, Sadia Khan, Nighat Shaheen, Safia Khalil, Pushpa Sachdev, Gulfareen Arain, Amtullah Zarreen, Sara Saeed, Shamayela Hanif, Nabia Tariq, Mahwish Jamil, Shama Chaudhry, Hina Rajani, Tayyiba Wasim, Summera Aslam, Nilofar Mustafa, Huma Quddusi, Sajila Karim, Shazia Sultana, Misbah Harim, Mohd Chohan, Nabila Salman, Fareesa Waqar, Shamsunnisa Sadia, Lubna Kahloon, Shehla Manzoor, Samar Amin, Umbreen Akram, Ambreen Ikram, Samina Kausar, Tahira Batool, Brigadier Naila, Tahir Kyani, Christine Biryabarema, Ruth Bulime, Regina Akello, Bernadette Nakawooya Lwasa, Joselyn Ayikoru, Christine Namulwasira, Patrick Komagum, Isabirye Rebecca, Nayiga Annet, Nakirigya Nuulu, Elizabeth Nionzima, Rose Bwotya, Margret Nankya, Sarah Babirye, Joseph Ngonzi, Cesar Sanchez, Nkonwa Innocent, Kusasira Anitah, Ayiko Jackson, Elizabeth Ndagire, Christine Nanyongo, Dominic Drametu, Grace Meregurwa, Francis Banya, Rita Atim, Emmanuel Byaruhanga, Lema Felix, Hussein Iman, Vincent Oyiengo, Peninah Waigi, Rose Wangui, Faiza Nassir, Musimbi Soita, Rophina Msengeti, Zeinab Zubier, Hillary Mabeya, Antony Wanjala, Henry Mwangi, Brian Liyayi, Evelyn Muthoka, Alfred Osoti, Amos Otara, Veronicah Ongwae, Victor Wanjohi, Bonface Musila, Kubasu Wekesa, Alex Nyakundi Bosire, Alice Ntem, Angeline Njoache, Alice Ashu, André Simo, Dorothy Keka, Kenfack Bruno, Amadou Ndouoya, Martin Saadio, Mesack Tchana, Odel Gwan, Pauline Assomo, Venantius Mutsu, Nji Eric, Pascal Foumane, Philemon Nsem, Jeanne Fouedjio, Ymele Fouelifack, Pierre Marie Tebeu, Georges Nko'ayissi, Eta Ngole Mbong, Wisal Nabag, Riham Desougi, Hadia Mustafa, Huida Eltaib, Taha Umbeli, Khalid Elfadl, Murwan Ibrahim, Abdalla Mohammed, Awadia Ali, Somia Abdelrahiem, Mohammed Musa, Khidir Awadalla, Samirra Ahmed, Mahdi Bushra, Omer Babiker, Hala Abdullahi, Mohamed Ahmed, Elhassan Safa, Huida Almardi, Duria Rayis, Saeed Abdelrahman Abdelgabar, Gillian Houghton, Andrew Sharpe, Jim Thornton, Nick Grace, Carys Smith, Kim Hinshaw, Dawn Edmundson, Paul Ayuk, Alison Bates, George Bugg, Joanne Wilkins, Clare Tower, Alysha Allibone, Eugene Oteng-Ntim, Ahmad Kazumari, Anna Danford, Matilda Ngarina, Muzdalifat Abeid, Khadija Mayumba, Magreth Zacharia, George Mtove, Leonard Madame, Anthony Massinde, Berno Mwambe, Rwakyendela Onesmo, Sebastian Kitengile Ganyaka, Shyam Gupta, Rabindra Bhatt, Ajay Agrawal, Pramila Pradhan, Nikita Dhakal, Punita Yadav, Gyanendra Karki, Bhola Ram Shrestha, Mwansa Lubeya, Jane Mumba, Willies Silwimba, Isaiah Hansingo, Noojiri Bopili, Ziche Makukula, Alexander Kawimbe, Mwansa Ketty Lubeya, Willard Mtambo, Mathew Ng'ambi, Saimir Cenameri, Ilir Tasha, Aferdita Kruja, Besnik Brahimaj, Armida Tola, Leon Kaza, Desire Tshombe, Elizabeth Buligho, Roger Paluku-Hamuli, Charles Kacha, Kato Faida, Badibanga Musau, Herman Kalyana, Phanny Simisi, Serge Mulyumba, Nzanzu Kikuhe Jason, Jean Robert Lubamba, Willis Missumba, Ferdousi Islam, Nazneen Begum, Ferdousi Chowdhury, Rokeya Begum, Farjana Basher, Nazlima Nargis, Abu Kholdun, Shahela Jesmin, Shrodha Paul, Hailemariam Segni, Getachew Ayana, William Haleke, Hassen Hussien, Fikre Geremew, Moussa Bambara, Adolphe Somé, Amadou Ly, Roamba Pabakba, Horace Fletcher, Leslie Samuels, Henry Opare-Addo, Roderick Larsen-Reindorf, Kwadwo Nyarko-Jectey, Glen Mola, Malts Wai, Magdy El Rahman, Wafaa Basta, Hussein Khamis, Maria Fernanda Escobar, Liliana Vallecilla, and Gabriel Essetchi Faye
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medicine.medical_specialty ,Hysterectomy ,business.industry ,medicine.medical_treatment ,Placebo-controlled study ,General Medicine ,030204 cardiovascular system & hematology ,Placebo ,medicine.disease ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Relative risk ,Anesthesia ,Clinical endpoint ,medicine ,Caesarean section ,Maternal death ,030212 general & internal medicine ,business ,Tranexamic acid ,medicine.drug - Abstract
Background\ud 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.\ud \ud Methods\ud 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.\ud \ud Findings\ud 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.\ud \ud Interpretation\ud 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.\ud \ud Funding\ud London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.
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- 2017
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9. Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial
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Christopher J. Hawkey, Muhammad Nadeem, Simon J. Stanworth, Andrew Veitch, Kiran Javaid, Rizwana Chaudhri, Timothy J Coats, Muttiullah Mutti, Amy Brenner, Monica Arribas, Ian Gilmore, Ian Roberts, Jack Cuzick, Syed Masroor Ahmad, Haleema Shakur-Still, Vipul Jairath, AO Afolabi, and Aasia Kayani
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medicine.medical_specialty ,Tranexamic acid ,Placebo-controlled study ,Medicine (miscellaneous) ,Gastrointestinal haemorrhage ,Placebo ,Loading dose ,Update ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Antifibrinolytic agent ,Intensive care ,medicine ,Humans ,Multicenter Studies as Topic ,Pharmacology (medical) ,030212 general & internal medicine ,Randomized Controlled Trials as Topic ,lcsh:R5-920 ,business.industry ,Antifibrinolytic Agents ,Clinical trial ,Treatment Outcome ,Statistical analysis ,Data Interpretation, Statistical ,Gastrointestinal Hemorrhage ,business ,Rockall score ,lcsh:Medicine (General) ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer/erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5–40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The Haemorrhage ALleviation with Tranexamic acid – Intestinal system (HALT-IT) trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods The HALT-IT trial is an international, randomised, double-blind, placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive TXA (1-g loading dose followed by 3-g maintenance dose over 24 h) or matching placebo. The main analysis will compare those randomised to TXA with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are: rebleeding; all-cause and cause-specific mortality; thromboembolic events; complications; endoscopic, radiological and surgical interventions; blood transfusion requirements; disability (defined by a measure of patient’s self-care capacity); and number of days spent in intensive care or high-dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was unblinded. Trial registration Current Controlled Trials, ID: ISRCTN11225767. Registered on 3 July 2012; Clinicaltrials.gov, ID: NCT01658124. Registered on 26 July 2012. Electronic supplementary material The online version of this article (10.1186/s13063-019-3561-7) contains supplementary material, which is available to authorized users.
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- 2019
10. Tranexamic acid for acute gastrointestinal bleeding (The HALT-IT trial): Statistical analysis plan for an international, randomised, double blind, placebo-controlled trial
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Amy Charlotte Brenner, Adefemi Afolabi, Syed Masroor Ahmad, Monica Arribas, Rizwana Chaudhri, Timothy Coats, Jack Cuzick, Ian Gilmore, Christopher Hawkey, Vipul Jairath, Kiran Javaid, Aasia Kayani, Muttiullah Mutti, Muhammad Arif Nadeem, Haleema Shakur-Still, Simon Stanworth, Andrew Veitch, and Ian Roberts
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Background: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer / erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The HALT-IT trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. Methods: The HALT-IT trial is an international, randomised, double blind, placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8,000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive tranexamic acid (1g loading dose followed by 3g maintenance dose over 24 hours) or matching placebo. The main analysis will compare those randomised to tranexamic acid with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative and absolute risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are rebleeding, all-cause and cause-specific mortality, thromboembolic events, complications, endoscopic, radiological and surgical interventions, blood transfusion requirements, disability (defined by a measure of patient’s self-care capacity) and number of days spent in intensive care or high dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. Discussion: We present the statistical analysis of the HALT-IT trial. This plan was prepared and submitted for publication before the treatment allocation was un-blinded. Trial Registration: Current Controlled Trials ISRCTN11225767 (3/07/2012); Clinicaltrials.gov NCT01658124 (26/07/2012). Keywords: Gastrointestinal haemorrhage, tranexamic acid, clinical trial, statistical analysis.
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- 2019
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11. Abstract 104: The Use of Nitrated apolipoprotein A1 (NT-ApoA1) to Predict Mortality in Patients with Known or Suspected Coronary Artery Disease
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Abid Ullah, Jonathan D. Marmur, Kiran Javaid, Mohammed Al-Sadawi, Haroon Kamran, Alexander Parpas, Erdal Cavusoglu, Sriya Avadhani, Lena Woo, and Samantha Cavusoglu
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medicine.medical_specialty ,biology ,business.industry ,medicine.disease ,Coronary artery disease ,Internal medicine ,medicine ,biology.protein ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Apolipoprotein A1 ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Cardiovascular mortality - Abstract
Background: Studies have suggested that nitrated apolipoprotein A1 (NT-apoA1) levels may be associated with coronary artery disease (CAD). We therefore hypothesized that NT-apoA1 might be associated with the prediction of all-cause mortality in CAD patients. Methods: Using an ELISA, we measured plasma NT-apoA1 levels in 236 patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography. The patients were then followed prospectively for the development of all-cause mortality for up to 7 years. Results: Lower NT-apoA1 levels were associated with worse renal function, lower HDL levels, higher triglyceride levels and lower ejection fraction. There was positive correlation between NT-apoA1 and HDL cholesterol levels (correlation coefficient 0.366; p Conclusions: Higher NT-apoA1 levels are significantly associated with lower all-cause mortality in CAD patients, which may relate to HDL cholesterol function. Further studies are warranted to investigate this paradoxical finding.
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- 2019
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12. Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: study protocol for an international, randomised, double-blind, placebo-controlled trial
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Katharine Ker, Ian Roberts, Rizwana Chaudhri, Bukola Fawole, Danielle Beaumont, Eni Balogun, Danielle Prowse, Tracey Pepple, Kiran Javaid, Aasia Kayani, Sabaratnam Arulkumaran, Imelda Bates, Haleema Shakur-Still, and on behalf of the WOMAN-2 trial collaborators
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Clinical trial ,Tranexamic acid ,lcsh:R5-920 ,Maternal anaemia ,Antifibrinolytic ,lcsh:Medicine (General) ,Postpartum haemorrhage - Abstract
Background Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, most of which occur in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases blood loss in surgery and reduces death due to bleeding after trauma. When given within 3 h of birth, TXA reduces deaths due to bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. Over one third of pregnant women in the world are anaemic and many are severely anaemic. These women have an increased risk of PPH and suffer more severe outcomes if PPH occurs. There is an urgent need to identify a safe and effective way to reduce postpartum bleeding in anaemic women. Methods/design The WOMAN-2 trial is an international, multicentre, randomised, double-blind, placebo-controlled trial to quantify the effects of TXA on postpartum bleeding in women with moderate or severe anaemia. Ten thousand women with moderate or severe anaemia who have given birth vaginally will be randomised to receive 1 g of TXA or matching placebo by intravenous injection immediately (within 15 min) after the umbilical cord is cut or clamped. The primary outcome is the proportion of women with a clinical diagnosis of primary PPH. The cause of PPH will be described. Data on maternal health and wellbeing, maternal blood loss and its consequences, and other health outcomes will be collected as secondary outcomes. The main analyses will be on an ‘intention-to-treat’ basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses will be based on the severity of anaemia (moderate versus severe) and type of labour (induced or augmented versus spontaneous). A study with 10,000 patients will have over 90% power to detect a 25% relative reduction from 10 to 7.5% in PPH. The trial will be conducted in hospitals in Africa and Asia. Discussion The WOMAN-2 trial should provide reliable evidence for the effects of TXA for preventing postpartum bleeding in women with anaemia. Trial registration ISRCTN, ISRCTN62396133. Registered on 7 December 2017; ClincalTrials.gov, ID: NCT03475342. Registered on 23 March 2018.
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- 2018
13. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients
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Angèle Gayet-Ageron, David Prieto-Merino, Katharine Ker, Haleema Shakur, François-Xavier Ageron, Ian Roberts, Aasia Kayani, Amber Geer, Bernard Ndungu, Bukola Fawole, Catherine Gilliam, Cecelia Adetayo, Collette Barrow, Danielle Beaumont, Danielle Prowse, David I'Anson, Eni Balogun, Hakim Miah, Imogen Brooks, Julio Onandia, Kiran Javaid, Laura Suncuan, Lauren Frimley, Mia Reid, Monica Arribas, Myriam Benyahia, Olujide Okunade, Phil Edwards, Rizwana Chaudhri, Sergey Kostrov, Sneha Kansagra, and Tracey Pepple
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Adult ,Male ,medicine.medical_specialty ,MEDLINE ,Hemorrhage ,030204 cardiovascular system & hematology ,Time-to-Treatment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pregnancy ,Internal medicine ,Childbirth ,Medicine ,Humans ,030212 general & internal medicine ,Young adult ,Aged ,ddc:618 ,business.industry ,Postpartum Hemorrhage ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Antifibrinolytic Agents ,3. Good health ,Surgery ,Clinical trial ,Logistic Models ,Meta-analysis ,Acute Disease ,Wounds and Injuries ,Female ,business ,Tranexamic acid ,medicine.drug - Abstract
BACKGROUND: Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics. METHODS: We did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155. FINDINGS: We obtained data for 40 138 patients from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage). Overall, there were 3558 deaths, of which 1408 (40%) were from bleeding. Most (884 [63%] of 1408) bleeding deaths occurred within 12 h of onset. Deaths from post-partum haemorrhage peaked 2-3 h after childbirth. Tranexamic acid significantly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08-1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243). Treatment delay reduced the treatment benefit (p
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- 2017
14. GNK-PIMS Score: A Predictive Model for Success of External Cephalic Version
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Kiran Javaid, Ghazala Mahmud, Narendra Malhotra, Nasira Tasnim, and Randhir Puri
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business.industry ,External cephalic version ,medicine.medical_treatment ,Statistics ,Econometrics ,Obstetrics and Gynecology ,Medicine ,Stepwise regression ,business ,Test (assessment) - Abstract
Objective To determine association of GNK-PIMS score vs Newmann Peacock score with success of external cephalic version (ECV). Materials and methods This comparative cross-sectional analysis was carried out at MCH center Unit I, PIMS, Islamabad, from 1st January 2006 to 31st December 2009. Characteristics of 166 breech versions performed during study period were integrated into both Newmann Peacock score and GNK-PIMS score. Association of the two scoring systems with success of ECV was determined using Student t-test, correlation coefficient, Chi-square test and Cox and Snell test. The individual characteristics of two scores were also evaluated by stepwise linear regression model. Results The success rate of ECV was 49.9%. Newman Peacock score had weaker correlation with success of ECV (r = 0.234, p = 0.001) than GNK-PIMS score (r = 0.716, p = 0.000). The success rate was 6.3% at a score of 8 with Newmann Peacock score while that with GNKPIMS score was nil at a score of 8. All individual parameters of the GNK-PIMS score had significant association with success of ECV compared to only three variables of Newman Peacock score. Conclusion GNK-PIMS score is stronger predictor of ECV success than Newman Peacock score. Larger randomized controlled trials should be conducted based on this scoring system. How to cite this article Tasnim N, Mahmud G, Javaid K. GNKPIMS Score: A Predictive Model for Success of External Cephalic Version. J South Asian Feder Obst Gynae 2012;4(2): 99-102.
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- 2012
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15. Where does ergometrine stand in prevention of postpartum haemorrhage in caesarean section?
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Ghazala, Mahmud, Kiran, Javaid, Nasira, Tasnim, Arfa, Tabassum, and Kausar Tasneem, Bangash
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Adult ,Maternal Mortality ,Treatment Outcome ,Cesarean Section ,Pregnancy ,Oxytocics ,Postpartum Hemorrhage ,Humans ,Female ,Pakistan ,Ergonovine ,Oxytocin - Abstract
To compare the safety and efficacy of 10 units of intravenous syntocinon alone with 10 units intravenous syntocinon and 0.25 mg intramuscular ergometrine in the prevention of atonic uterine haemorrhage during caesarean section.The quasi-experimental study was conducted at the Maternal and Child Health Centre, Unit I, Pakistan Institute of Medical Sciences, Islamabad, from November 1, 2010 to February 28, 2011. All women undergoing caesarean section were included in the study. Patients were given intravenous 10 units syntocinon alone intraoperatively from November 1 to December 31,2010, while 0.25 mg ergometrine intramuscular was added to 10 units intravenous syntocinon from January 1 to February 28, 2011. Frequency of postpartum haemorrhage, adverse effects of drugs and maternal morbidity and mortality were assessed by using chi square test. P0.05 was taken as statistically significant.Of the total number of 701 subjects, 378 (54%) women were given 10 units syntocinon and 323 (46%) were given 0.25 mg ergometrine in addition to 10 units syntocinon. The mean age in the syntocinon group was 28 +/- 3.5 yrs with gestational age of 37.5 +/- 2 wks, while that in syntocinon-ergometrine group was 29 +/- 3.4 years and 38 +/- 2 weeks respectively. Postpartum haemorrhage in the syntocinon group was found in 38 (10%) women versus 05 (1.5%) women) in the other group (p0.001). Adverse effects like nausea, vomiting and raised blood pressure were slightly more with syntocinon-ergometrine than syntocinon alone (n = 56; 15.3% vs n = 35; 9.2%), but it was not statistically significant. Post partum haemorrhage was responsible for 40% of maternal mortality during the study period and that was in the syntocinon group.Prophylactic ergometrine in addition to syntocinon is superior to syntocinon alone in decreasing frequency of postpartum haemorrhage in caesarean section and associated maternal morbidity and mortality. Regarding safety profile, the two groups showed no statistically significant change.
- Published
- 2014
16. Pakistan-India Bilateral Trade in Sports Goods Sector
- Author
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Kiran Javaid, Hadia Majid, and Farah Shahid Hassan
- Subjects
Product (business) ,Bilateral trade ,Index (economics) ,Gravity model of trade ,Economics ,Monetary economics ,Revealed comparative advantage ,Random effects model ,Comparative advantage - Abstract
Using the gravity model to estimate the trade flows for the major trading partners of Pakistan and India in the sports goods sector, we find, as expected, that the distance between the two countries has a negative impact on exports, while the exporter and importer GDPs affect exports positively. For Pakistan and India, specifically, we find that trade between Pakistan and India is 288 % lower (according to the pooled OLS) and 249 % lower (according to random effects model) than trade between any two similar countries. The trade that is already taking place between the sports goods sectors of the two countries is in accordance with their revealed comparative advantage. However, there is a need for the two countries to export sports goods in which they have higher RCAs. We also found that both countries export the same product lines, so there is a need for further disaggregated analysis within product lines. When we calculated the trade concentration index, we found that Pakistan’s exports to India have become more diversified, but Indian exports to Pakistan are more concentrated in terms of product lines. We also found evidence for the presence of both inter- and intra-industry trade in the sports goods sector of Pakistan.
- Published
- 2014
- Full Text
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