Browsing by Author "School of Medicine"
Now showing 1 - 14 of 14
- Results Per Page
- Sort Options
Publication Metadata only American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19(2021-02-09) Adam Cuker; Eric K. Tseng; Robby Nieuwlaat; Pantep Angchaisuksiri; Clifton Blair; Kathryn Dane; Jennifer Davila; Maria T. DeSancho; David Diuguid; Daniel O. Griffin; Susan R. Kahn; Frederikus A. Klok; Alfred Ian Lee; Ignacio Neumann; Ashok Pai; Menaka Pai; Marc Righini; Kristen M. Sanfilippo; Deborah Siegal; Mike Skara; Kamshad Touri; Elie A. Akl; Imad Bou Akl; Mary Boulos; Romina Brignardello-Petersen; Rana Charide; Matthew Chan; Karin Dearness; Andrea J. Darzi; Philipp Kolb; Luis E. Colunga-Lozano; Razan Mansour; Gian Paolo Morgano; Rami Z. Morsi; Atefeh Noori; Thomas Piggott; Yuan Qiu; Yetiani Roldan; Finn Schünemann; Adrienne Stevens; Karla Solo; Matthew Ventresca; Wojtek Wiercioch; Reem A. Mustafa; Holger J. Schünemann; Ramathibodi Hospital; Michael G. DeGroote School of Medicine; School of Medicine; Albert Ludwigs Universität Freiburg, Medizinische Fakultät; L'Hôpital d'Ottawa; American University of Beirut; King Hussein Cancer Center; McMaster University; Pontificia Universidad Católica de Chile; The University of Chicago; McMaster University, Faculty of Health Sciences; Universitätsklinikum Freiburg; Penn Medicine; Washington University School of Medicine in St. Louis; New York Presbyterian Hospital; Yale School of Medicine; Kaiser Permanente; Saint Michael's Hospital University of Toronto; Leids Universitair Medisch Centrum; Vagelos College of Physicians and Surgeons; St. Joseph's Healthcare Hamilton; Hôpitaux Universitaires de Genève; Universidad de Guadalajara; University of Kansas Medical Center; Albert Einstein College of Medicine of Yeshiva University; Ottawa Hospital Research Institute; The Johns Hopkins Hospital; Research and Development; Prohealth NYBackground: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE. Conclusions: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.Publication Metadata only American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients(2021-10-26) Adam Cuker; Eric K. Tseng; Robby Nieuwlaat; Pantep Angchaisuksiri; Clifton Blair; Kathryn Dane; Jennifer Davila; Maria T. DeSancho; David Diuguid; Daniel O. Griffin; Susan R. Kahn; Frederikus A. Klok; Alfred Ian Lee; Ignacio Neumann; Ashok Pai; Marc Righini; Kristen M. Sanfilippo; Deborah Siegal; Mike Skara; Deirdra R. Terrell; Kamshad Touri; Elie A. Akl; Imad Bou Akl; Antonio Bognanni; Mary Boulos; Romina Brignardello-Petersen; Rana Charide; Matthew Chan; Karin Dearness; Andrea J. Darzi; Philipp Kolb; Luis E. Colunga-Lozano; Razan Mansour; Gian Paolo Morgano; Rami Z. Morsi; Giovanna Muti-Schunemann; Atefeh Noori; Binu A. Philip; Thomas Piggott; Yuan Qiu; Yetiani Roldan; Finn Schunemann; Adrienne Stevens; Karla Solo; Wojtek Wiercioch; Reem A. Mustafa; Holger J. Schunemann; Ramathibodi Hospital; Michael G. DeGroote School of Medicine; School of Medicine; Albert Ludwigs Universität Freiburg, Medizinische Fakultät; American University of Beirut; King Hussein Cancer Center; McMaster University; University of Oklahoma Health Sciences Center; Pontificia Universidad Católica de Chile; The University of Chicago; Universitätsklinikum Freiburg; Penn Medicine; Washington University School of Medicine in St. Louis; New York Presbyterian Hospital; Yale School of Medicine; Kaiser Permanente; Saint Michael's Hospital University of Toronto; Leids Universitair Medisch Centrum; Vagelos College of Physicians and Surgeons; St. Joseph's Healthcare Hamilton; Hôpitaux Universitaires de Genève; Universidad de Guadalajara; University of Kansas Medical Center; Albert Einstein College of Medicine of Yeshiva University; Ottawa Hospital Research Institute; The Johns Hopkins Hospital; Research and Development at United Health Group Minnetonka; NJ; Prohealth NYBackground: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.Publication Metadata only APQS consensus regarding patient shielding during routine radiographic imaging(2021-07-01) Russell Oliver Kosik; Swee Tian Quek; Elaine Kan; Shigeki Aoki; Chin Hua Yang; Napapong Pongnapang; Maryastuti Setioko; Wing P. Chan; School of Medicine; RSUP Persahabatan; National University Health System; National Taiwan University Hospital; Taipei Municipal Wan-Fang Hospital; Juntendo University; Mahidol University; Hong Kong Children's Hospital; Taoyuan General HospitalShielding, particularly of the gonads, has been a routine part of diagnostic radiographic imaging for many years. However, recent thinking suggests that such shielding may offer little benefit, and in some cases may actually cause harm, e.g. by obscuring anatomy or paradoxically increasing patient radiation dose secondary to the need for repeat imaging. This thinking has led many institutions in the West to abandon routine shielding. However, in Asia, shielding is still commonplace. It was felt that the Asia-Pacific Forum on Quality and Safety in Medical Imaging (APQS) was an ideal place to discuss the merits of shielding and deliver a pan-Asian consensus. The APQS is an annual meeting that convenes radiation safety and imaging quality experts from all of the major Asian regions. During the 2020 APQS meeting, radiation safety experts from each region discussed their opinions of shielding during a dedicated session. These experts’ views were mostly in line with the views of Western radiologists. However, important country specific and cultural factors were noted by each of the experts. A pan-Asian consensus was issued by the forum. It is hoped that this consensus will guide the development of future shielding policies throughout Asia.Publication Metadata only Association of left ventricular ejection fraction with worsening renal function in patients with acute heart failure: insights from the RELAX-AHF-2 study(2021-01-01) Siting Feng; Satit Janwanishstaporn; John R. Teerlink; Marco Metra; Gad Cotter; Beth Davison; G. Michael Felker; Gerasimos Filippatos; Peter Pang; Piotr Ponikowski; Iziah E. Sama; Adriaan A. Voors; Barry Greenberg; San Francisco VA Health Care System; Momentum Research, Inc; Beijing Anzhen Hospital, Capital Medical University; University of Cyprus; School of Medicine; Indiana University School of Medicine; Università degli Studi di Brescia; Faculty of Medicine Siriraj Hospital, Mahidol University; Rijksuniversiteit Groningen; Wroclaw Medical University; David Geffen School of Medicine at UCLA; Duke University School of MedicineAims: Whether risk of worsening renal function (WRF) during acute heart failure (AHF) hospitalization or the association between in-hospital WRF and post-discharge outcomes vary according to left ventricular ejection fraction (LVEF) is uncertain. We assessed incidence of WRF, factors related to its development and impact of WRF on post-discharge outcomes across the spectrum of LVEF in patients enrolled in RELAX-AHF-2. Methods and results: A total of 6112 patients who had LVEF measured on admission and renal function determined prospectively during hospitalization were included. WRF, defined as a rise in serum creatinine ≥0.3 mg/dL from baseline through day 5, occurred in 1722 patients (28.2%). Incidence increased progressively from lowest to highest LVEF quartile (P < 0.001). After baseline adjustment, WRF risk in Q4 (LVEF >50%) remained significantly greater than in Q1 (LVEF ≤29%; hazard ratio 1.2, 95% confidence interval 1–1.43; P = 0.050). Age and comorbidity burden including chronic kidney disease increased as LVEF increased. Neither admission haemodynamic abnormalities, extent of diuresis during hospitalization nor residual congestion explained the increased incidence of WRF in patients with higher LVEF. Serelaxin treatment and diuretic responsiveness were associated with reduced risk of WRF in all LVEF quartiles. WRF in patients in the upper three LVEF quartiles increased risk of post-discharge events. Conclusions: Worsening renal function incidence during AHF hospitalization increases progressively with LVEF. Greater susceptibility of patients with higher LVEF to WRF appears more related to their advanced age and worse underlying kidney function rather than haemodynamic or treatment effects. WRF is associated with increased risk of post-discharge events except in patients in the lowest LVEF quartile.Publication Metadata only Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial(2021-07-01) Arya Aminorroaya; Hamed Tavolinejad; Saeed Sadeghian; Arash Jalali; Farshid Alaeddini; Zahra Emkanjoo; Reza Mollazadeh; Ali Bozorgi; Saeed Oraii; Mohamadreza Kiarsi; Javad Shahabi; Mohammad Ali Akbarzadeh; Behzad Rahimi; Adel Joharimoghadam; Abolfazl Mohsenizade; Roghayeh Mohammadi; Alireza Oraii; Hamid Ariannejad; Sanatcha Apakuppakul; Tachapong Ngarmukos; Masih Tajdini; Rajaie Cardiac Electrophysiology Research Center; Ramathibodi Hospital; Cardiac Rehabilitation Research Center, Isfahan UMS; Tehran Heart Center; Non-Communicable Diseases Research Center; Aja University of Medical Sciences; Ahvaz Jundishapur University of Medical Sciences; Shahid Beheshti University of Medical Sciences; School of Medicine; Imam Khomeini Hospital; Tehran Arrhythmia CenterBackground: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. Methods: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. Conclusion: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.Publication Metadata only Generating and characterizing monoclonal and polyclonal antibodies against avian H5N1 hemagglutinin protein(2009-05-15) Sheng Fan Wang; Kuan Hsuan Chen; Arunee Thitithanyanont; Ling Yao; Yuan Ming Lee; Yu Jiun Chan; Shih Jen Liu; Pele Chong; Wu Tse Liu; Jason C. Huang; Yi Ming Arthur Chen; National Yang-Ming University Taiwan; School of Medicine; Mahidol University; Laboratory Medicine; Veterans General Hospital-Taipei; Taipei City Hospital Taiwan; National Health Research Institutes TaiwanAccurate and timely diagnoses are central to H5N1 infection control. Here we describe the cloning and expression of the HA1 protein of the A/Vietnam/1203/04 strain in a bacterial system to generate mono-/polyclonal antibodies. All of the eight generated monoclonal antibodies recognized the same linear epitope on the top globular region of the HA structure-a highly conserved epitope among all circulating H5N1 clades identified by amino acid alignment. Results from immunofluorescence staining and Western blotting indicate that all monoclonal antibodies interacted with a denatured form of HA proteins, while the resultant polyclonal antibodies recognized both denatured and native HA proteins on H5N1 reverse-genetics (RG) viruses. Results from flow cytometry and microneutralization assays indicate that the polyclonal antibodies blocked viral binding and neutralized H5N1-RG viruses. Our results may prove useful to establishing future H5N1 mono-and polyclonal antibodies, and perhaps contribute to the development of an alternative H5N1 vaccine. © 2009 Elsevier Inc. All rights reserved.Publication Metadata only Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study(2021-12-01) Tomoko Fujii; Andrew A. Udy; Alistair Nichol; Rinaldo Bellomo; Adam M. Deane; Khaled El-Khawas; Naorungroj Thummaporn; Ary Serpa Neto; Hannah Bergin; Robert Short-Burchell; Chin Ming Chen; Kuang Hua Cheng; Kuo Chen Cheng; Clemente Chia; Feng Fan Chiang; Nai Kuan Chou; Timothy Fazio; Pin Kuei Fu; Victor Ge; Yoshiro Hayashi; Jennifer Holmes; Ting Yu Hu; Shih Feng Huang; Naoya Iguchi; Sarah L. Jones; Toshiyuki Karumai; Shinshu Katayama; Shih Chi Ku; Chao Lun Lai; Bor Jen Lee; Wen Jinn Liaw; Chelsea T.W. Ong; Lisa Paxton; Chloe Peppin; Owen Roodenburg; Shinjiro Saito; John D. Santamaria; Yahya Shehabi; Aiko Tanaka; Ravindranath Tiruvoipati; Hsiao En Tsai; An Yi Wang; Chen Yu Wang; Yu Chang Yeh; Chong Jen Yu; Kuo Ching Yuan; Ary Serpa Neto; Allison Bone; Sarah Jones; Lee Anne Clavarino; Steven Hirth; Jun Shima; Fumie Takatsudo; Kumie Suzuki; School of Medicine; Siriraj Hospital; Graduate School of Medicine; Melbourne Medical School; Jichi Medical University; Chi Mei Medical Center; Chung Shan Medical University Hospital; National Taiwan University Hospital; Kameda Medical Center; Mackay Memorial Hospital Taiwan; Barwon Health; Monash University; Hospital Israelita Albert Einstein; Faculty of Medicine, Nursing and Health Sciences; Eastern Health; Peninsula Health; Royal Darwin Hospital; Veterans General Hospital-Taichung Taiwan; Royal Melbourne Hospital; University College Dublin; Austin Hospital; Taipei Medical University Hospital; St. Vincent's Hospital Melbourne; Jikei University Hospital; Monash HealthBackground: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. Method: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < –4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. Results: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. Conclusions: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation. [Figure not available: see fulltext.]Publication Metadata only Misclassification of drug failure in plasmodium falciparum clinical trials in southeast asia(2009-08-15) Jonathan J. Juliano; Frederic Ariey; Rithy Sem; Noppadon Tangpukdee; Srivicha Krudsood; Carol Olson; Sornchai Looareesuwan; William O. Rogers; Chansuda Wongsrichanalai; Steven R. Meshnick; School of Medicine; The University of North Carolina at Chapel Hill; Lmmtech Pharmaceuticals; Institut Pasteur du Cambodge; Mahidol University; Naval Medical Research Unit NoMost trials of antimalarials occur in areas in which reinfections are possible. For Plasmodium falciparum, reinfections are distinguished from recrudescences by polymerase chain reaction analysis of 3 polymorphic genes. However, the validity of this approach has never been rigorously tested. We tested for misclassification in 6 patients from clinical trials in Thailand and Cambodia who were classified as being reinfected by the standard polymerase chain reaction protocol. Using heteroduplex tracking assays and direct DNA sequencing, we found that 5 (83%) of 6 patients were misclassified. Misclassification in this manner overestimates the efficacy of antimalarials and delays the recognition of decreasing therapeutic efficacy, thus delaying potential changes in policy. © 2009 by the Infectious Diseases Society of America. All rights reserved.Publication Metadata only The modulatory effect of substance P on rat pineal norepinephrine release and melatonin secretion(2009-09-15) Sujira Mukda; Morten Møller; Manuchair Ebadi; Piyarat Govitrapong; The Institute of Science and Technology for Research and Development, Mahidol University; Panum Institute; School of Medicine; Mahidol UniversitySecretion of melatonin by the mammalian pineal gland is primarily regulated by the release of norepinephrine (NE) from sympathetic nerve terminals that originate from the superior cervical ganglia. Peptidergic nerves that originate in the perikarya located in the sensory trigeminal ganglia also innervate the pineal gland. Some of these peptidergic nerve fibers contain substance P. Previously, we have characterized neurokinin 1 type substance P receptors in the pineal gland. However, the function of this receptor in the pineal gland remains unclear. Here, we examined the modulatory effect of substance P on rat pineal NE transmission. We show that at the presynaptic level, substance P stimulates the KCl-induced [3H]NE release from the pineal nerve ending. However, we found that substance P did not affect the basal levels of either arylalkylamine-N-acetyltransferase (AANAT) activity or melatonin secretion in rat pineal organ cultures. However, in the presence of NE, substance P inhibited the NE-induced increase in AANAT activity and melatonin secretion. This is the first time that a function for substance P in the mammalian pineal gland has been demonstrated. © 2009 Elsevier Ireland Ltd. All rights reserved.Publication Metadata only Pembrolizumab plus Ipilimumab or Placebo for Metastatic Non–Small-Cell Lung Cancer with PDL1 Tumor Proportion Score ‡ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study(2021-07-20) Michael Boyer; Mehmet A.N. Şendur; Delvys Rodríguez-Abreu; Keunchil Park; Dae Ho Lee; Irfan Çiçin; Perran Fulden Yumuk; Francisco J. Orlandi; Ticiana A. Leal; Olivier Molinier; Nopadol Soparattanapaisarn; Adrian Langleben; Raffaele Califano; Balazs Medgyasszay; Te Chun Hsia; Gregory A. Otterson; Lu Xu; Bilal Piperdi; Ayman Samkari; Martin Reck; Siriraj Hospital; School of Medicine; Ankara Yildirim Beyazit University; Centre Hospitalier Le Mans; Asan Medical Center; China Medical University Hospital; Complejo Hospitalario Universitario Insular Materno-Infantil; SKKU School of Medicine; University of Wisconsin Carbone Cancer Center; Merck & Co., Inc.; Marmara Üniversitesi Tip Fakültesi; Trakya Üniversitesi; The University of Manchester; The Ohio State University Comprehensive Cancer Center; Orlandi-Oncología; Veszprém Megyei Tüdőgyógyintézet Farkasgyepű; Chris O'Brien Lifehouse; German Center for Lung ResearchPURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) $ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS $ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P 5 .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P 5 .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. CONCLUSION Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS $ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.Publication Metadata only Reorganization of Substance Use Treatment and Harm Reduction Services During the COVID-19 Pandemic: A Global Survey(2021-04-29) Seyed Ramin Radfar; Cornelis A.J. De Jong; Ali Farhoudian; Mohsen Ebrahimi; Parnian Rafei; Mehrnoosh Vahidi; Masud Yunesian; Christos Kouimtsidis; Shalini Arunogiri; Omid Massah; Abbas Deylamizadeh; Kathleen T. Brady; Anja Busse; Marc N. Potenza; Hamed Ekhtiari; Alexander Mario Baldacchino; Adrian Octavian Abagiu; Franck David Noel Abouna; Mohamed Hassan Ahmed; Basma Al-ansari; Feda Mahmmoud Abu Al-khair; Mandhar Humaid Almaqbali; Atul Ambekar; Hossein Mohaddes Ardabili; Sidharth Arya; Victor Olufolahan Lasebikan; Murad Ali Ayasreh; Debasish Basu; Zoubir Benmebarek; Roshan Bhad; Mario Blaise; Nicolas Bonnet; Jennifer Brasch; Barbara Broers; Jenna L. Butner; Moses Camilleri; Giovanna Campello; Giuseppe Carra; Ivan Celic; Fatemeh Chalabianloo; Abhishek Chaturvedi; José de Jesús Eduardo Noyola Cherpitel; Kelly J. Clark; Melissa Anne Cyders; Ernesto de Bernardis; John Edward Derry; Naveen Kumar Dhagudu; Pavla Dolezalova; Geert Dom; Adrian John Dunlop; Mahmoud Mamdouh Elhabiby; Hussien Elkholy; Nsidibe Francis Essien; Ghandi Ilias Farah; Marica Ferri; Georgios D. Floros; Catherine Friedman; Clara Hidalgo Fuderanan; Gilberto Gerra; Abhishek Ghosh; Maka Gogia; Ilias A. Grammatikopoulos; Paolo Grandinetti; Amira Guirguis; David Gutnisky; Paul Steven Haber; Peyman Hassani-Abharian; Zahra Hooshyari; Islam Ibrahim Mokhtar Ibrahim; Hada Fong ha Ieong; Regina Nova Indradewi; Shelly Iskandar; Shobhit Jain; Sandi James; Seyyed Mohammad hossein Javadi; Keun Ho Joe; Darius Jokubonis; Acka Tushevska Jovanova; Rama Mohamed Kamal; Alexander Ivanov Kantchelov; Preethy Kathiresan; Gary Katzman; Paul Kawale; Audrey Margaret Kern; Felix Henrique Paim Kessler; Sung Gon Sue Kim; Ann Marie Kimball; Zeljko Kljucevic; Kristiana Siste; Roneet Lev; Hae Kook Lee; Aiste Lengvenyte; Shaul Lev-ran; Geni Seseja Mabelya; Mohamed Ali El Mahi; J. Maphisa Maphisa; Icro Maremmani; Laura Masferrer; Orlagh McCambridge; Garrett Gregory McGovern; Pusan National University Yangsan Hospital; Iranian National Center for Addiction Studies; College of Medicine, University of Ibadan; Michael G. DeGroote School of Medicine; School of Public Health; School of Advanced Technologies in Medicine; Swansea University Medical School; Surrey and Borders Partnership NHS Foundation Trust; Laureate Institute for Brain Research; The University of Sydney School of Medicine; Pandit Bhagwat Dayal Sharma University of Health Sciences; Melaka-Manipal Medical College, Manipal University; Národní Ústav Duševního Zdraví, Klecany; Psychiatric Hospital Vrap?e; United Nations Office on Drugs and Crime, Austria; University of Social Welfare and Rehabilitation Sciences; Ministry of Health Oman; Université de Yaoundé I; Universitas Padjadjaran; Universitas Indonesia, RSUPN Dr. Cipto Mangunkusumo; Vilniaus Universitetas; Al-Ahliyya Amman University; European Monitoring Centre for Drugs and Drug Addiction; Ospedale Santa Chiara Pisa; Haukeland Universitetssjukehus; CUNY School of Medicine; Southern Health and Social Care Trust; Tehran University of Medical Sciences; The University of Sydney; Materials and Energy Research Centre Iran; Indiana University-Purdue University Indianapolis; Medical University of South Carolina; University of Tehran; University of Botswana; Yale School of Medicine; Universiti Malaysia Sabah; Ain Shams University; Radboud Universiteit; Aristotle University of Thessaloniki; Ain Shams University, Faculty of Medicine; Scripps Mercy Hospital; Universiteit Antwerpen; Università degli Studi di Milano-Bicocca; Brown University; Eastern Health; School of Medicine; Hôpitaux Universitaires de Genève; Universitat de Girona; All India Institute of Medical Sciences, New Delhi; Universidade Federal do Rio Grande do Sul; Jane & Terry Semel Institute for Neuroscience & Human Behavior; Tel Aviv University; The Catholic University of Korea; Universidad de Buenos Aires; Mashhad University of Medical Sciences, School of Medicine; The Mount Sinai Medical Center; Postgraduate Institute of Medical Education & Research, Chandigarh; Chatham House; Aġenzija Sedqa; Organization Against Drugs; Addiction medicine clinic; Division for Operations; Addiction Medicine Clinic; Addiction medicine clinic; Addiction medicine clinic; Hayat Center for Treatment and Psycho-social Rehabilitation; National Narcotics Board of Indonesia; SerT Lentini; Serenity Vista Addiction Treatment Center; Addiction Crisis Solutions; Community Health Work; Addiction medicine clinic; Priority Medical Clinic; Israel Center on Addiction; Fuderanan Mental Health Clinic; Sobriety Centers of New Hampshire; Naufar Institute; Al-Amal Psychiatric Hospital; National Center for Mental Health; Georgian Harm Reduction Network; African Institute for Development Policy; ESIC Medical College; Drug and Alcohol Clinical Services; Rebirth Charity Society NGO; Réseau de prévention des addictions (RESPADD); Marmottan Medical Center; Institute for Cognitive Science Studies; Public Health Institute of Split-Dalmatia County; Republican Centre for Addictive Disorders; Heritage Institute of Medical Sciences; Kantchelov Clinic; Center for Research and Information on Substance Abuse; ASL Teramo; National Institute for Infectious DiseasesBackground: The coronavirus disease 2019 (COVID-19) pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic. Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health responses were categorized around (1) managerial measures and systems, (2) logistics, (3) service providers, and (4) vulnerable groups. Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. Fifty-seven percent of overdose prevention interventions and 81% of outreach services were also negatively impacted. Conclusions: Participants reported that SUD treatment and harm-reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we highlight several issues and complications resulting from the pandemic concerning people with SUDs that should be tackled more efficiently during the future waves or similar pandemics. The issues and potential strategies comprise the following: (1) helping policymakers to generate business continuity plans, (2) maintaining the use of evidence-based interventions for people with SUDs, (3) being prepared for adequate medication supplies, (4) integrating harm reduction programs with other treatment modalities, and (5) having specific considerations for vulnerable groups such as immigrants and refugees.Publication Metadata only Selective cutoff reporting in studies of the accuracy of the Patient Health Questionnaire-9 and Edinburgh Postnatal Depression Scale: Comparison of results based on published cutoffs versus all cutoffs using individual participant data meta-analysis(2021-09-01) Dipika Neupane; Brooke Levis; Parash M. Bhandari; Brett D. Thombs; Andrea Benedetti; Ying Sun; Chen He; Yin Wu; Ankur Krishnan; Zelalem Negeri; Mahrukh Imran; Danielle B. Rice; Kira E. Riehm; Nazanin Saadat; Marleine Azar; Tatiana A. Sanchez; Matthew J. Chiovitti; Alexander W. Levis; Jill T. Boruff; Pim Cuijpers; Simon Gilbody; John P.A. Ioannidis; Lorie A. Kloda; Scott B. Patten; Ian Shrier; Roy C. Ziegelstein; Liane Comeau; Nicholas D. Mitchell; Marcello Tonelli; Simone N. Vigod; Dickens H. Akena; Rubén Alvarado; Bruce Arroll; Muideen O. Bakare; Hamid R. Baradaran; Cheryl Tatano Beck; Charles H. Bombardier; Adomas Bunevicius; Gregory Carter; Marcos H. Chagas; Linda H. Chaudron; Rushina Cholera; Kerrie Clover; Yeates Conwell; Tiago Castro e Couto; Janneke M. de Man-van Ginkel; Jaime Delgadillo; Jesse R. Fann; Nicolas Favez; Daniel Fung; Lluïsa Garcia-Esteve; Bizu Gelaye; Felicity Goodyear-Smith; Thomas Hyphantis; Masatoshi Inagaki; Khalida Ismail; Nathalie Jetté; Dina Sami Khalifa; Mohammad E. Khamseh; Jane Kohlhoff; Zoltán Kozinszky; Laima Kusminskas; Shen Ing Liu; Manote Lotrakul; Sonia R. Loureiro; Bernd Löwe; Sherina Mohd Sidik; Sandra Nakić Radoš; Flávia L. Osório; Susan J. Pawlby; Brian W. Pence; Tamsen J. Rochat; Alasdair G. Rooney; Deborah J. Sharp; Lesley Stafford; Kuan Pin Su; Sharon C. Sung; Meri Tadinac; S. Darius Tandon; Pavaani Thiagayson; Annamária Töreki; Anna Torres-Giménez; Alyna Turner; Christina M. van der Feltz-Cornelis; Johann M. Vega-Dienstmaier; Paul A. Vöhringer; Jennifer White; Mary A. Whooley; Kirsty Winkley; Mitsuhiko Yamada; Ramathibodi Hospital; Makerere University College of Health Sciences; School of Medicine; School of Medicine and Public Health; Bristol Medical School; Lietuvos sveikatos mokslų universitetas; Duke-NUS Medical School; Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado; University of New South Wales Faculty of Medicine, School of Psychiatry; University of the Witwatersrand Faculty of Health Sciences; Concordia University; Stanford University School of Medicine; University Medical Center Utrecht; Royal Women's Hospital, Carlton; Harvard T.H. Chan School of Public Health; China Medical University Hospital; University of Alberta; Hospital Clinic Barcelona; McGill Faculty of Medicine and Health Sciences; Faculty of Medicine; Szegedi Tudományegyetem (SZTE); The University of Edinburgh; Danderyds Sjukhus; Universiti Putra Malaysia; The University of North Carolina at Chapel Hill; Iran University of Medical Sciences; University of Rochester Medical Center; University of California, San Francisco; Lady Davis Institute for Medical Research; Monash University; Keele University, School of Medicine; National Center of Neurology and Psychiatry Kodaira; University of Newcastle, Faculty of Health and Medicine; University of Toronto; University of York; University of Washington; Universidade Federal de Uberlândia; Northwestern University Feinberg School of Medicine; University of Rochester School of Medicine and Dentistry; Hospital Clínico Universidad De Chile; King's College London; University of Montreal; Singapore Institute of Mental Health; Shimane University Faculty of Medicine; University of Zagreb; School of Nursing; Universidade de São Paulo; Centre Universitaire de Santé McGill; The University of Auckland; Duke University School of Medicine; Universitätsklinikum Hamburg-Eppendorf; Université de Genève; Medisinske Fakultet; Facultad de Medicina de la Universidad de Chile; Université McGill; Universiteit van Amsterdam; University of Calgary; The University of Sheffield; Johns Hopkins School of Medicine; Cumming School of Medicine; Private Practice; Federal Neuropsychiatric Hospital; Catholic University of CroatiaObjectives: Selectively reported results from only well-performing cutoffs in diagnostic accuracy studies may bias estimates in meta-analyses. We investigated cutoff reporting patterns for the Patient Health Questionnaire-9 (PHQ-9; standard cutoff 10) and Edinburgh Postnatal Depression Scale (EPDS; no standard cutoff, commonly used 10–13) and compared accuracy estimates based on published cutoffs versus all cutoffs. Methods: We conducted bivariate random effects meta-analyses using individual participant data to compare accuracy from published versus all cutoffs. Results: For the PHQ-9 (30 studies, N = 11,773), published results underestimated sensitivity for cutoffs below 10 (median difference: −0.06) and overestimated for cutoffs above 10 (median difference: 0.07). EPDS (19 studies, N = 3637) sensitivity estimates from published results were similar for cutoffs below 10 (median difference: 0.00) but higher for cutoffs above 13 (median difference: 0.14). Specificity estimates from published and all cutoffs were similar for both tools. The mean cutoff of all reported cutoffs in PHQ-9 studies with optimal cutoff below 10 was 8.8 compared to 11.8 for those with optimal cutoffs above 10. Mean for EPDS studies with optimal cutoffs below 10 was 9.9 compared to 11.8 for those with optimal cutoffs greater than 10. Conclusion: Selective cutoff reporting was more pronounced for the PHQ-9 than EPDS.Publication Metadata only Towards harmonization of microscopy methods for malaria clinical research studies(2020-09-04) Mehul Dhorda; El Hadji Ba; J. Kevin Baird; John Barnwell; David Bell; Jane Y. Carter; Arjen Dondorp; Lenny Ekawati; Michelle Gatton; Iveth González; Philippe J. Guérin; Sandra Incardona; Ken Lilley; Didier Menard; François Nosten; Peter Obare; Bernhards Ogutu; Piero L. Olliaro; Ric N. Price; Stéphane Proux; Andrew R. Ramsay; John C. Reeder; Kamolrat Silamut; Cheikh Sokhna; Oxford University Clinical Research Unit; Institut Pasteur du Cambodge; Institut de Recherche pour le Développement Dakar; Kenya Medical Research Institute; Amref Health Africa; Shoklo Malaria Research Unit; Menzies School of Health Research; Centers for Disease Control and Prevention; Mahidol University; Queensland University of Technology QUT; School of Medicine; Nuffield Department of Medicine; UNICEF; Terre des Hommes Foundation; Independent Consultant; FIND; Australian Defence Force Malaria and Infectious Disease Institute; WorldWide Antimalarial Resistance Network; Worldwide Antimalarial Resistance Network© 2020 The Author(s). Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.Publication Metadata only Tracheostomy During the COVID-19 Pandemic: Comparison of International Perioperative Care Protocols and Practices in 26 Countries(2021-06-01) Carol Bier-Laning; John D. Cramer; Soham Roy; Patrick A. Palmieri; Ayman Amin; José Manuel Añon; Cesar A. Bonilla-Asalde; Patrick J. Bradley; Pankaj Chaturvedi; David M. Cognetti; Fernando Dias; Arianna Di Stadio; Johannes J. Fagan; David J. Feller-Kopman; Sheng Po Hao; Kwang Hyun Kim; Petri Koivunen; Woei Shyang Loh; Jobran Mansour; Matthew R. Naunheim; Marcus J. Schultz; You Shang; Davud B. Sirjani; Maie A. St. John; Joshua K. Tay; Sébastien Vergez; Heather M. Weinreich; Eddy W.Y. Wong; Johannes Zenk; Christopher H. Rassekh; Michael J. Brenner; School of Medicine; Hospital Nacional Daniel Alcides Carrión; Universidad Privada San Juan Bautista; Universidad Norbert Wiener; University of Michigan Medical School; Stanford University School of Medicine; Pontifícia Universidade Católica do Rio de Janeiro; NUS Yong Loo Lin School of Medicine; University of Illinois College of Medicine; University of Texas Medical School at Houston; Shin-Kong Wu Ho-Su Memorial Hospital Taiwan; Wayne State University School of Medicine; Tata Memorial Hospital; Loyola University Medical Center; National University of Singapore; Oulu University Hospital; Thomas Jefferson University; University of Nottingham; Mahidol University; Chaim Sheba Medical Center Israel; Cairo University; Nuffield Department of Medicine; Hôpital Rangueil; University of Pennsylvania; David Geffen School of Medicine at UCLA; Massachusetts Eye and Ear Infirmary; Università degli Studi di Perugia; Chinese University of Hong Kong; Universidad Carlos III de Madrid; Tongji Medical College; Amsterdam UMC - University of Amsterdam; Johns Hopkins School of Medicine; Seoul National University College of Medicine; University of Cape Town; Evidence-Based Health Care South America: A Joanna Briggs Institute Affiliated Group; Global Tracheostomy Collaborative; Universitätsklinikum Augsburg Klinik für HNO-HeilkundeObjective: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic. Data Sources: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols. Review Methods: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management. Conclusions: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results. Implications for Practice: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.
