183 results on '"Malaga, German"'
Search Results
152. Additional file 3: of Glucagon-like peptide-1 receptor agonists and heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies
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Li, Ling, Sheyu Li, Jiali Liu, Deng, Ke, Busse, Jason, Vandvik, Per, Wong, Evelyn, Sohani, Zahra, Malgorzata Bala, Rios, Lorena, Malaga, German, Shanil Ebrahim, Jiantong Shen, Longhao Zhang, Pujing Zhao, Qunfei Chen, Yingqiang Wang, Guyatt, Gordon, and Sun, Xin
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3. Good health - Abstract
Subgroup analysis of heart failure risk by type of control based on raw data of randomized controlled trials. (DOC 47 kb)
153. COMMENTARY.
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Montori, Victor M. and Malaga, German
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BLOOD sugar , *TYPE 2 diabetes , *DIABETES , *BLOOD sugar monitoring , *VASCULAR diseases , *PEOPLE with diabetes - Abstract
The article presents a commentary on a study on the intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. The author provides his views on the study's design called ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation. He also comments on the study's results which show that intensive glucose control did not stop relevant complications in type 2 diabetes.
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- 2008
154. 2008 - Intensive glucose control did not prevent important complications in type 2 diabetes.
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Montori, Victor M. and Malaga, German
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TYPE 2 diabetes , *GLUCOSE - Abstract
The article provides an answer to the question if intensive glucose control prevents adverse outcomes more than standard glucose control in type 2 diabetes.
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- 2008
155. 2008 - Intensive glucose control increased mortality and did not prevent cardiovascular events in type 2 diabetes.
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Montori, Victor M. and Malaga, German
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TYPE 2 diabetes , *CARDIOVASCULAR diseases - Abstract
The article provides an answer to the question whether intensive glucose control prevents cardiovascular events more than standard glucose control in patients suffering from type 2 diabetes and cardiovascular disease or risk factors.
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- 2008
156. Credibility of claims of subgroup effects in randomised controlled trials: systematic review
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Sun, Xin, Briel, Matthias, Busse, Jason W, You, John J, Akl, Elie A, Mejza, Filip, Bala, Malgorzata M, Bassler, Dirk, Mertz, Dominik, Diaz-Granados, Natalia, Vandvik, Per Olav, Malaga, German, Srinathan, Sadeesh K, Dahm, Philipp, Johnston, Bradley C, Alonso-Coello, Pablo, Hassouneh, Basil, Walter, Stephen D, Heels-Ansdell, Diane, Bhatnagar, Neera, Altman, Douglas G, and Guyatt, Gordon H
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OBJECTIVE: To investigate the credibility of authors’ claims of subgroup effects using a representative sample of recently published randomised controlled trials. Design Systematic review. DATA SOURCE: Core clinical journals, as defined by the National Library of Medicine, in Medline. STUDY SELECTION: Randomised controlled trials published in 2007. Using prespecified criteria, teams of trained reviewers independently judged whether authors claimed subgroup effects and the strength of their claims. Reviewers assessed each of these claims against 10 predefined criteria, developed through a search of existing criteria and a consensus process. RESULTS: Of 207 randomised controlled trials reporting subgroup analyses, 64 (31%) made claims for the primary outcome. Of those, 20 were strong claims and 28 claims of a likely effect. Authors included subgroup variables measured at baseline in 60 (94%) trials, used subgroup variable as a stratification factor at randomisation in 13 (20%), clearly prespecified their hypotheses in 26 (41%), correctly prespecified direction in 4 (6%), tested a small number of hypotheses in 28 (44%), carried out a test of interaction that proved statistically significant in 6 (9%), documented replication of a subgroup effect with previous related studies in 21 (33%), identified consistency of a subgroup effect across related outcomes in 19 (30%), and provided a compelling indirect evidence for the effect in 14 (22%). In the 19 trials making more than one claim, only one (5%) checked the independence of the interaction. Of the 64 claims, 54 (84%) met four or fewer of the 10 criteria. For strong claims, more than 50% failed each of the individual criteria, and only three (15%) met more than five criteria. CONCLUSION: Authors often claim subgroup effects in their trial report. However, the credibility of subgroup effects, even when claims are strong, is usually low. Users of the information should treat claims that fail to meet most criteria with scepticism. Trial researchers should report the conduct of subgroup analyses and provide sufficient evidence when claiming a subgroup effect or suggesting a possible effect.
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- 2012
157. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes : systematic review and meta-analysis of randomised and observational studies
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Li, Ling, Li, Sheyu, Deng, Ke, Liu, Jiali, Vandvik, Per Olav, Zhao, Pujing, Zhang, Longhao, Shen, Jiantong, Bala, Malgorzata M, Sohani, Zahra N, Wong, Evelyn, Busse, Jason W, Ebrahim, Shanil, Malaga, German, Rios, Lorena P, Wang, Yingqiang, Chen, Qunfei, Guyatt, Gordon H, and Sun, Xin
158. One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery
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Patrice Forget, Joel L. Parlow, Christian S. Meyhoff, Yannick Le Manach, Alben Sigamani, Matthew T. V. Chan, Mohammed Amir, Giovanni Landoni, Bruce M Biccard, Alparslan Turan, Andrea Kurz, Denis Xavier, Richard P. Whitlock, Gordon H. Guyatt, Germán Málaga, Ekaterina Popova, Juan Carlos Villar, Andre Lamy, David Torres, Kate Leslie, Daniel I. Sessler, Priya A. Kumar, Kumar Balasubramanian, Ian Gilron, Sadeesh Srinathan, Marko Mrkobrada, Michelle M. Graham, Pilar Paniagua, Chew Yin Wang, Shirley Pettit, Edith Fleischmann, Salim Yusuf, Otavio Berwanger, Philip J. Devereaux, David Conen, Sessler, Daniel I, Conen, David, Leslie, Kate, Yusuf, Salim, Popova, Ekaterina, Graham, Michelle, Kurz, Andrea, Villar, Juan Carlo, Mrkobrada, Marko, Sigamani, Alben, Biccard, Bruce M, Meyhoff, Christian S, Parlow, Joel L, Guyatt, Gordon, Xavier, Deni, Chan, Matthew T V, Kumar, Priya A, Forget, Patrice, Malaga, German, Fleischmann, Edith, Amir, Mohammed, Torres, David, Wang, C Y, Paniagua, Pilar, Berwanger, Otavio, Srinathan, Sadeesh, Landoni, Giovanni, Manach, Yannick Le, Whitlock, Richard, Lamy, André, Balasubramanian, Kumar, Gilron, Ian, Turan, Alparslan, Pettit, Shirley, and Devereaux, P J
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Male ,Internationality ,Time Factors ,medicine.medical_treatment ,Myocardial Infarction ,Infarction ,030204 cardiovascular system & hematology ,Placebo ,Clonidine ,Perioperative Care ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,medicine ,Humans ,030212 general & internal medicine ,Myocardial infarction ,Aged ,Aspirin ,Analgesics ,business.industry ,Hazard ratio ,Anti-Inflammatory Agents, Non-Steroidal ,Percutaneous coronary intervention ,Perioperative ,Middle Aged ,medicine.disease ,Anesthesiology and Pain Medicine ,Anesthesia ,Female ,business ,medicine.drug ,Follow-Up Studies - Abstract
Background The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. Methods The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. Results Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). Conclusions Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
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- 2020
159. Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE).
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O'Donnell MJ, McQueen M, Sniderman A, Pare G, Wang X, Hankey GJ, Rangarajan S, Chin SL, Rao-Melacini P, Ferguson J, Xavier D, Lisheng L, Zhang H, Pais P, Lopez-Jaramillo P, Damasceno A, Langhorne P, Rosengren A, Dans AL, Elsayed A, Avezum A, Mondo C, Judge C, Diener HC, Ryglewicz D, Czlonkowska A, Pogosova N, Weimar C, Iqbal R, Diaz R, Yusoff K, Yusufali A, Oguz A, Penaherrera E, Lanas F, Ogah OS, Ogunniyi A, Iversen HK, Malaga G, Rumboldt Z, Oveisgharan S, Al Hussain F, Nilanont Y, and Yusuf S
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Background and Purpose: The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes., Methods: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH)., Results: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001)., Conclusions: The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.
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- 2022
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160. Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case-Control Study.
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Judge C, O'Donnell MJ, Hankey GJ, Rangarajan S, Chin SL, Rao-Melacini P, Ferguson J, Smyth A, Xavier D, Lisheng L, Zhang H, Lopez-Jaramillo P, Damasceno A, Langhorne P, Rosengren A, Dans AL, Elsayed A, Avezum A, Mondo C, Ryglewicz D, Czlonkowska A, Pogosova N, Weimar C, Diaz R, Yusoff K, Yusufali A, Oguz A, Wang X, Lanas F, Ogah OS, Ogunniyi A, Iversen HK, Malaga G, Rumboldt Z, Oveisgharan S, Al Hussain F, and Yusuf S
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- Case-Control Studies, Humans, Potassium, Dietary administration & dosage, Risk Assessment, Sodium, Dietary administration & dosage, Sodium, Dietary adverse effects, Hemorrhagic Stroke epidemiology, Ischemic Stroke epidemiology, Potassium urine, Sodium urine
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Background: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke., Methods: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes., Results: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke., Conclusions: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)
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- 2021
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161. Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study.
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Smyth A, Judge C, Wang X, Pare G, Rangarajan S, Canavan M, Chin SL, Al-Hussain F, Yusufali AM, Elsayed A, Damasceno A, Avezum A, Czlonkowska A, Rosengren A, Dans AL, Oguz A, Mondo C, Weimar C, Ryglewicz D, Xavier D, Lanas F, Malaga G, Hankey GJ, Iversen HK, Zhang H, Yusoff K, Pogosova N, Lopez-Jamarillo P, Langhorne P, Diaz R, Oveisgharan S, Yusuf S, and O'Donnell M
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- Aged, Case-Control Studies, Cerebral Hemorrhage, Female, Glomerular Filtration Rate, Humans, Middle Aged, Risk Factors, Stroke epidemiology
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Background: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association., Aims: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations., Methods: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke., Results: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month)., Conclusion: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes., (© 2021 S. Karger AG, Basel.)
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- 2021
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162. Prevalence, awareness, treatment and control of hypertension in rural and urban communities in Latin American countries.
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Lamelas P, Diaz R, Orlandini A, Avezum A, Oliveira G, Mattos A, Lanas F, Seron P, Oliveros MJ, Lopez-Jaramillo P, Otero J, Camacho P, Miranda J, Bernabe-Ortiz A, Malaga G, Irazola V, Gutierrez L, Rubinstein A, Castellana N, Rangarajan S, and Yusuf S
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- Adult, Blood Pressure, Brazil, Colombia, Cross-Sectional Studies, Female, Humans, Hypertension drug therapy, Latin America epidemiology, Male, Middle Aged, Prevalence, Risk Factors, Self Report, South America epidemiology, Antihypertensive Agents therapeutic use, Health Knowledge, Attitudes, Practice ethnology, Hypertension epidemiology, Rural Population statistics & numerical data, Urban Population statistics & numerical data
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Objectives: The objective is to describe hypertension (HTN) prevalence, awareness, treatment and control in urban and rural communities in Latin America to inform public and policy-makers., Methods: Cross-sectional analysis from urban (n = 111) and rural (n = 93) communities including 33 276 participants from six Latin American countries (Argentina, Brazil, Chile, Colombia, Peru and Uruguay) were included. HTN was defined as self-reported HTN on blood pressure (BP) medication or average BP over 140/90 mmHg, awareness as self-reported HTN, and controlled as those with BP under 140/90 mmHg., Results: Mean age was 52 years, 60% were Female and 32% belonged to rural communities. HTN prevalence was 44.0%, with the lowest rates in Peru (17.7%) and the highest rates in Brazil (52.5%). 58.9% were aware of HTN diagnosis and 53.3% were receiving treatment. Prevalence of HTN were higher in urban (44.8%) than rural (42.1%) communities in all countries. Most participants who were aware of HTN were receiving medical treatment (90.5%), but only 37.6% of patients receiving medical treatment had their BP controlled (<140/<90 mmHg), with the rates being higher in urban (39.6%) than in rural (32.4%) communities. The rate of use of two or more drugs was low [36.4%, lowest in Argentina (29.6%) and highest in Brazil (44.6%)]. Statin use was low (12.3%), especially in rural areas (7.0%). Most modifiable risk factors were higher in people with HTN than people without HTN., Conclusion: HTN prevalence is high but BP control is low in Latin America, with marked differences between countries and between urban and rural settings. There is an urgent need for systematic approaches for better detection, treatment optimization and risk factor modification among those with HTN in Latin America.
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- 2019
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163. Association between complications and death within 30 days after noncardiac surgery.
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Spence J, LeManach Y, Chan MTV, Wang CY, Sigamani A, Xavier D, Pearse R, Alonso-Coello P, Garutti I, Srinathan SK, Duceppe E, Walsh M, Borges FK, Malaga G, Abraham V, Faruqui A, Berwanger O, Biccard BM, Villar JC, Sessler DI, Kurz A, Chow CK, Polanczyk CA, Szczeklik W, Ackland G, X GA, Jacka M, Guyatt GH, Sapsford RJ, Williams C, Cortes OL, Coriat P, Patel A, Tiboni M, Belley-Côté EP, Yang S, Heels-Ansdell D, McGillion M, Parlow S, Patel M, Pettit S, Yusuf S, and Devereaux PJ
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- Aged, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Postoperative Hemorrhage mortality, Prospective Studies, Sepsis mortality, Postoperative Complications mortality, Surgical Procedures, Operative mortality
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Background: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications., Methods: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model., Results: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%)., Interpretation: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109., Competing Interests: Competing interests: Clara Chow received support from the National Health and Medical Research Council of Australia and The Heart Foundation (Australia) for a career development fellowship. Robert Sapsford received nonfinancial support in the form of a research nurse funded by the National Institutes of Health Research, and lecture fees from Eli Lilly, MSD and Novo Nordisk. Denis Xavier received grants from Cadila Pharmaceuticals, Boehringer Ingelheim, Astra Zeneca India, Sanofi Aventis, Pfizer, Bristol–Myers Squibb, Medical Research Council (United Kingdom) and Wellcome Trust outside the submitted work. Emmanuelle Duceppe received a grant as a coapplicant on an investigator-initiated study and lecture fees from Roche Diagnostics. Philip J. Devereaux is a member of a research group with a policy of not accepting honorariums or other payments from industry for their own personal financial gain. They do accept honorariums or payments from industry to support research endeavours and costs to participate in meetings. Based on study questions Dr. Devereaux has originated and grants he has written, he has received grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens and Stryker. Dr Devereaux has participated in advisory board meetings for GlaxoSmithKline and Boehringer Ingelheim. He also attended an expert panel meeting with AstraZeneca and Boehringer Ingelheim. Roche Diagnostics provided Troponin T assays and financial support for the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study. No other competing interests were declared., (© 2019 Joule Inc. or its licensors.)
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- 2019
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164. Myocardial Injury After Noncardiac Surgery (MINS) in Vascular Surgical Patients: A Prospective Observational Cohort Study.
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Biccard BM, Scott DJA, Chan MTV, Archbold A, Wang CY, Sigamani A, Urrútia G, Cruz P, Srinathan SK, Szalay D, Harlock J, Tittley JG, Rapanos T, Elias F, Jacka MJ, Malaga G, Abraham V, Berwanger O, Montes FR, Heels-Ansdell DM, Hutcherson MT, Chow CK, Polanczyk CA, Szczeklik W, Ackland GL, Dubois L, Sapsford RJ, Williams C, Cortés OL, Le Mananch Y, and Devereaux PJ
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- Aged, Aged, 80 and over, Biomarkers blood, Female, Humans, Incidence, Male, Middle Aged, Myocardial Ischemia blood, Myocardial Ischemia epidemiology, Myocardial Ischemia etiology, Odds Ratio, Postoperative Complications blood, Postoperative Complications epidemiology, Prognosis, Proportional Hazards Models, Prospective Studies, Myocardial Ischemia diagnosis, Postoperative Complications diagnosis, Troponin T blood, Vascular Surgical Procedures
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Objective: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients., Background: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described., Methods: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring., Results: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4)., Conclusions: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.
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- 2018
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165. Troponin T monitoring to detect myocardial injury after noncardiac surgery: a cost-consequence analysis.
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Buse GL, Manns B, Lamy A, Guyatt G, Polanczyk CA, Chan MTV, Wang CY, Villar JC, Sigamani A, Sessler DI, Berwanger O, Biccard BM, Pearse R, Urrútia G, Szczeklik W, Garutti I, Srinathan S, Malaga G, Abraham V, Chow CK, Jacka MJ, Tiboni M, Ackland G, Macneil D, Sapsford R, Leuwer M, Le Manach Y, and Devereaux PJ
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Risk, Cost-Benefit Analysis, Myocardial Ischemia blood, Myocardial Ischemia diagnosis, Myocardial Ischemia economics, Myocardial Ischemia mortality, Outcome Assessment, Health Care economics, Postoperative Care economics, Postoperative Care methods, Postoperative Care standards, Postoperative Complications blood, Postoperative Complications diagnosis, Postoperative Complications economics, Postoperative Complications mortality, Surgical Procedures, Operative adverse effects, Troponin T blood
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Background: Myocardial injury after noncardiac surgery (MINS) is a mostly asymptomatic condition that is strongly associated with 30-day mortality; however, it remains mostly undetected without systematic troponin T monitoring. We evaluated the cost and consequences of postoperative troponin T monitoring to detect MINS., Methods: We conducted a model-based cost-consequence analysis to compare the impact of routine troponin T monitoring versus standard care (troponin T measurement triggered by ischemic symptoms) on the incidence of MINS detection. Model inputs were based on Canadian patients enrolled in the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study, which enrolled patients aged 45 years or older undergoing inpatient noncardiac surgery. We conducted probability analyses with 10 000 iterations and extensive sensitivity analyses., Results: The data were based on 6021 patients (48% men, mean age 65 [standard deviation 12] yr). The 30-day mortality rate for MINS was 9.6%. We determined the incremental cost to avoid missing a MINS event as $1632 (2015 Canadian dollars). The cost-effectiveness of troponin monitoring was higher in patient subgroups at higher risk for MINS, e.g., those aged 65 years or more, or with a history of atherosclerosis or diabetes ($1309)., Conclusion: The costs associated with a troponin T monitoring program to detect MINS were moderate. Based on the estimated incremental cost per health gain, implementation of postoperative troponin T monitoring seems appealing, particularly in patients at high risk for MINS.
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- 2018
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166. Geographic differences in overweight and obesity prevalence in Peruvian children, 2010-2015.
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Torres-Roman JS, Urrunaga-Pastor D, Avilez JL, Helguero-Santin LM, and Malaga G
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- Child, Preschool, Geography, Humans, Infant, Peru epidemiology, Prevalence, Spatial Analysis, Health Status Disparities, Pediatric Obesity epidemiology
- Abstract
Background: Childhood obesity is emerging as a major public health problem worldwide. To date, most studies of obesity and overweight in Peru are focused on adults, with few of them involving children, a population at a critical stage of development. The trend in overweight and obesity prevalence in Peruvian children under the age of five has not yet been determined. Thus, the objective of the present study is to evaluate the prevalence rates of overweight and obesity between 2010 and 2015 in children under the age of five, stratified by geographical areas in Peru., Methods: Data were obtained from the Nutritional Status Information System of Peru. The total number of children evaluated was 14,155,914. For the Geographic Information Systems (GIS), the program Geo Da 1.8® was used to ascertain the spatial distribution of prevalence rates and was mapped for children under five. To assess the degree of spatial dependence, exploratory spatial data analysis was performed using the Moran's I statistic and was assessed with the Local Indicators of Spatial Association (LISA) analysis to identify geographic concentrations of high and low of obesity and overweight levels., Results: Between 2010 and 2015, the national prevalence of childhood overweight and obesity ranged from 6.2%- 6.8% and 1.5%-2.7%, respectively. The highest prevalence of childhood overweight and obesity was found in 2014 and 2013, respectively. During these years, we observed that obesity decreased, but overweight remained stable. The highest prevalence of overweight and obesity was found in the departments located on the coast. Significant positive spatial autocorrelation was found for both overweight and obesity. The departments with the highest prevalence of overweight and obesity were concentrated in Lima, Callao, Ica, Moquegua and Tacna. The lowest were found in Loreto, Cusco and San Martin., Conclusion: The decrease in obesity and the stabilisation of overweight are positive results for the Peruvian childhood. However, in comparison with other Latin American countries, Peru still lags in obesity prevention.
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- 2018
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167. Subcutaneous mycoses in Peru: a systematic review and meta-analysis for the burden of disease.
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Ramírez Soto MC and Malaga G
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- Chromoblastomycosis epidemiology, Humans, Lobomycosis epidemiology, Peru epidemiology, Phaeohyphomycosis epidemiology, Endemic Diseases, Sporotrichosis epidemiology, Subcutaneous Tissue
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Background: There is a worrying lack of epidemiological data on the geographical distribution and burden of subcutaneous mycoses in Peru, hindering the implementation of surveillance and control programs., Objectives: This study aimed to estimate the disease burden of subcutaneous mycoses in Peru and identify which fungal species were commonly associated with these mycoses., Methods: We performed a meta-analysis after a systematic review of the published literature in PubMed, LILACS, and SciELO to estimate the burden of subcutaneous mycoses in 25 regions in Peru. The disease burden was determined in terms of prevalence (number of cases per 100,000 inhabitants) and the number of reported cases per year per region., Results: A total of 26 studies were eligible for inclusion. Results showed that sporotrichosis was the most common subcutaneous mycosis (99.7%), whereas lobomycosis, chromoblastomycosis, and subcutaneous phaeohyphomycosis were rare. Cases of eumycetoma and subcutaneous zygomycosis were not found. Of the 25 regions, the burden of sporotrichosis was estimated for four regions classified as endemic; in nine regions, only isolated cases were reported. The highest burden of sporotrichosis was in Apurimac (15 cases/100,000 inhabitants; 57 cases/year), followed by Cajamarca (3/100,000 inhabitants; 30/year), Cusco (0.5/100,000 inhabitants; 4/year), and La Libertad (0.2/100,000 inhabitants; 2/year). In two regions, the mycoses predominantly affected children., Conclusions: Sporotrichosis is the most common subcutaneous mycosis in Peru, with a high disease burden in Apurimac. Chromoblastomycosis, lobomycosis, and subcutaneous phaeohyphomycosis are rare mycoses in Peru., (© 2017 The International Society of Dermatology.)
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- 2017
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168. Peruvian "Economic Success" in the Emergency Department: Close to Hell, No Place for Heaven.
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Castaneda-Guarderas A, Malaga AS, and Malaga G
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- 2017
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169. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.
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O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, Rao-Melacini P, Zhang X, Pais P, Agapay S, Lopez-Jaramillo P, Damasceno A, Langhorne P, McQueen MJ, Rosengren A, Dehghan M, Hankey GJ, Dans AL, Elsayed A, Avezum A, Mondo C, Diener HC, Ryglewicz D, Czlonkowska A, Pogosova N, Weimar C, Iqbal R, Diaz R, Yusoff K, Yusufali A, Oguz A, Wang X, Penaherrera E, Lanas F, Ogah OS, Ogunniyi A, Iversen HK, Malaga G, Rumboldt Z, Oveisgharan S, Al Hussain F, Magazi D, Nilanont Y, Ferguson J, Pare G, and Yusuf S
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- Adult, Africa epidemiology, Aged, Alcohol Drinking adverse effects, Alcohol Drinking epidemiology, Apolipoprotein A-I blood, Apolipoproteins B blood, Asia epidemiology, Atrial Fibrillation complications, Atrial Fibrillation epidemiology, Australia epidemiology, Biomarkers blood, Brain Ischemia blood, Brain Ischemia complications, Case-Control Studies, Cerebral Hemorrhage blood, Cerebral Hemorrhage complications, China epidemiology, Diabetes Complications epidemiology, Diabetes Complications prevention & control, Europe epidemiology, Evidence-Based Medicine, Feeding Behavior, Female, Health Behavior, Humans, Hypertension blood, International Cooperation, Male, Middle Aged, Middle East epidemiology, Motor Activity, Obesity, Abdominal complications, Obesity, Abdominal epidemiology, Odds Ratio, Risk Factors, Self Report, Smoking adverse effects, Smoking epidemiology, Stroke blood, Stroke etiology, Stroke pathology, Waist-Hip Ratio, Brain Ischemia epidemiology, Cerebral Hemorrhage epidemiology, Hypertension complications, Hypertension epidemiology, Risk Reduction Behavior, Stroke epidemiology, Stroke prevention & control
- Abstract
Background: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke., Methods: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals., Findings: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001)., Interpretation: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke., Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
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- 2016
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170. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.
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Li L, Li S, Deng K, Liu J, Vandvik PO, Zhao P, Zhang L, Shen J, Bala MM, Sohani ZN, Wong E, Busse JW, Ebrahim S, Malaga G, Rios LP, Wang Y, Chen Q, Guyatt GH, and Sun X
- Subjects
- Cardiovascular Diseases complications, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Hospitalization statistics & numerical data, Humans, Hypoglycemic Agents therapeutic use, Observational Studies as Topic, Odds Ratio, Randomized Controlled Trials as Topic, Risk Factors, Diabetes Mellitus, Type 2 drug therapy, Dipeptidyl-Peptidase IV Inhibitors adverse effects, Heart Failure chemically induced, Hypoglycemic Agents adverse effects
- Abstract
Objectives: To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes., Design: Systematic review and meta-analysis of randomised and observational studies., Data Sources: Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts., Eligibility Criteria: Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure., Data Collection and Analysis: Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach., Results: Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use., Conclusions: The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
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- 2016
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171. Weaknesses in the reporting of cross-sectional studies according to the STROBE statement: the case of metabolic syndrome in adults from Peru.
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Tapia JC, Ruiz EF, Ponce OJ, Malaga G, and Miranda J
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- Adult, Guidelines as Topic, Humans, Observational Studies as Topic standards, Peru epidemiology, Prevalence, Sensitivity and Specificity, Cross-Sectional Studies standards, Metabolic Syndrome epidemiology
- Abstract
Introduction: The inadequate reporting of cross-sectional studies, as in the case of the prevalence of metabolic syndrome, could cause problems in the synthesis of new evidence and lead to errors in the formulation of public policies., Objective: To evaluate the reporting quality of the articles regarding metabolic syndrome prevalence in Peruvian adults using the STROBE recommendations., Methods: We conducted a thorough literature search with the terms "Metabolic Syndrome", "Sindrome Metabolico" and "Peru" in MEDLINE/PubMed, LILACS, SciELO, LIPECS and BVS-Peru until December 2014. We selected those who were population-based observational studies with randomized sampling that reported prevalence of metabolic syndrome in adults aged 18 or more of both sexes. Information was analysed through the STROBE score per item and recommendation., Results: Seventeen articles were included in this study. All articles met the recommendations related to the report of the study's rationale, design, and provision of summary measures. The recommendations with the lowest scores were those related to the sensitivity analysis (8%, n= 1/17), participant flowchart (18%, n= 3/17), missing data analysis (24%, n= 4/17), and number of participants in each study phase (24%, n= 4/17)., Conclusion: Cross-sectional studies regarding the prevalence of metabolic syndrome in peruvian adults have an inadequate reporting on the methods and results sections. We identified a clear need to improve the quality of such studies.
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- 2015
172. Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.
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Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh CR, Mizera R, Jones PM, Tiboni M, Font A, Cegarra V, Gomez MF, Meyhoff CS, VanHelder T, Chan MT, Torres D, Parlow J, Clanchet Mde N, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov PS, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Wijeysundera DN, Leslie K, Forget P, Whitlock R, Yusuf S, and Devereaux PJ
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- Administration, Cutaneous, Administration, Oral, Adrenergic alpha-2 Receptor Agonists adverse effects, Aged, Clonidine adverse effects, Creatinine blood, Drug Administration Schedule, Female, Hemorrhage chemically induced, Humans, Hypotension chemically induced, Male, Middle Aged, Perioperative Care, Platelet Aggregation Inhibitors adverse effects, Postoperative Complications, Risk, Acute Kidney Injury prevention & control, Adrenergic alpha-2 Receptor Agonists administration & dosage, Aspirin administration & dosage, Aspirin adverse effects, Clonidine administration & dosage, Platelet Aggregation Inhibitors administration & dosage
- Abstract
Importance: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm., Objective: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury., Design, Setting, and Participants: A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013., Interventions: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery., Main Outcomes and Measures: Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery., Results: Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58)., Conclusions and Relevance: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury., Trial Registration: clinicaltrials.gov Identifier: NCT01082874.
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- 2014
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173. Aspirin in patients undergoing noncardiac surgery.
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Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S, and Yusuf S
- Subjects
- Aged, Aspirin adverse effects, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction epidemiology, Perioperative Care, Platelet Aggregation Inhibitors adverse effects, Treatment Failure, Aspirin therapeutic use, Myocardial Infarction prevention & control, Platelet Aggregation Inhibitors therapeutic use, Postoperative Complications prevention & control, Postoperative Hemorrhage chemically induced, Surgical Procedures, Operative mortality
- Abstract
Background: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not., Methods: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days., Results: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata., Conclusions: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
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- 2014
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174. Clonidine in patients undergoing noncardiac surgery.
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Devereaux PJ, Sessler DI, Leslie K, Kurz A, Mrkobrada M, Alonso-Coello P, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, Vanhelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Chow C, Pettit S, Chrolavicius S, and Yusuf S
- Subjects
- Adrenergic alpha-2 Receptor Agonists adverse effects, Aged, Clonidine adverse effects, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Perioperative Care, Postoperative Complications chemically induced, Treatment Failure, Adrenergic alpha-2 Receptor Agonists therapeutic use, Clonidine therapeutic use, Hypotension chemically induced, Myocardial Infarction prevention & control, Postoperative Complications prevention & control, Surgical Procedures, Operative mortality
- Abstract
Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability., Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days., Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02)., Conclusions: Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
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- 2014
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175. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies.
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Li L, Shen J, Bala MM, Busse JW, Ebrahim S, Vandvik PO, Rios LP, Malaga G, Wong E, Sohani Z, Guyatt GH, and Sun X
- Subjects
- Clinical Trials as Topic, Dipeptidyl-Peptidase IV Inhibitors adverse effects, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Glucagon-Like Peptide-1 Receptor, Humans, Hypoglycemic Agents adverse effects, Hypoglycemic Agents therapeutic use, Incretins adverse effects, Randomized Controlled Trials as Topic, Receptors, Glucagon agonists, Diabetes Mellitus, Type 2 drug therapy, Incretins therapeutic use, Pancreatitis chemically induced
- Abstract
Objective: To investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus., Design: Systematic review and meta-analysis., Data Sources: Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov., Eligibility Criteria: Randomised and non-randomised controlled clinical trials, prospective or retrospective cohort studies, and case-control studies of treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared with placebo, lifestyle modification, or active anti-diabetic drugs., Data Collection and Analysis: Pairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. A modified Cochrane tool for randomised controlled trials and a modified version of the Newcastle-Ottawa scale for observational studies were used to assess bias. We pooled data from randomised controlled trials using Peto odds ratios, and conducted four prespecified subgroup analyses and a post hoc subgroup analysis. Because of variation in outcome measures and forms of data, we describe the results of observational studies without a pooled analysis., Results: 60 studies (n=353,639), consisting of 55 randomised controlled trials (n=33,350) and five observational studies (three retrospective cohort studies, and two case-control studies; n=320,289) were included. Pooled estimates of 55 randomised controlled trials (at low or moderate risk of bias involving 37 pancreatitis events, raw event rate 0.11%) did not suggest an increased risk of pancreatitis with incretins versus control (odds ratio 1.11, 95% confidence interval 0.57 to 2.17). Estimates by type of incretin suggested similar results (1.05 (0.37 to 2.94) for GLP-1 agonists v control; 1.06 (0.46 to 2.45) for DPP-4 inhibitors v control). Analyses according to the type of control, mode, duration of treatment, and individual incretin agents suggested no differential effect by subgroups, and sensitivity analyses by alternative statistical modelling and effect measures did not show important differences in effect estimates. Three retrospective cohort studies (moderate to high risk of bias, involving 1466 pancreatitis events, raw event rate 0.47%) also did not suggest an increased risk of pancreatitis associated with either exenatide (adjusted odds ratios 0.93 (0.63 to 1.36) in one study and 0.9 (0.6 to 1.5) in another) or sitagliptin (adjusted hazard ratio 1.0, 0.7 to 1.3); a case-control study at moderate risk of bias (1003 cases, 4012 controls) also suggested no significant association (adjusted odds ratio 0.98, 0.69 to 1.38). Another case-control study (1269 cases, 1269 controls) at moderate risk of bias, however, suggested that the use of either exenatide or sitagliptin was associated with significantly increased odds of acute pancreatitis (use within two years v no use, adjusted odds ratio 2.07, 1.36 to 3.13)., Conclusions: The available evidence suggests that the incidence of pancreatitis among patients using incretins is low and that the drugs do not increase the risk of pancreatitis. Current evidence, however, is not definitive, and more carefully designed and conducted observational studies are warranted to definitively establish the extent, if any, of increased risk.
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- 2014
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176. Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial.
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Garg AX, Kurz A, Sessler DI, Cuerden M, Robinson A, Mrkobrada M, Parikh C, Mizera R, Jones PM, Tiboni M, Rodriguez RG, Popova E, Rojas Gomez MF, Meyhoff CS, Vanhelder T, Chan MT, Torres D, Parlow J, de Nadal Clanchet M, Amir M, Bidgoli SJ, Pasin L, Martinsen K, Malaga G, Myles P, Acedillo R, Roshanov P, Walsh M, Dresser G, Kumar P, Fleischmann E, Villar JC, Painter T, Biccard B, Bergese S, Srinathan S, Cata JP, Chan V, Mehra B, Leslie K, Whitlock R, and Devereaux PJ
- Subjects
- Acute Kidney Injury blood, Creatinine blood, Glomerular Filtration Rate, Humans, Intraoperative Care, Postoperative Complications blood, Preoperative Care, Renal Insufficiency, Chronic complications, Research Design, Acute Kidney Injury prevention & control, Adrenergic alpha-2 Receptor Agonists administration & dosage, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Aspirin administration & dosage, Clonidine administration & dosage, Postoperative Complications prevention & control
- Abstract
Introduction: Perioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce the risk of postoperative acute kidney injury (AKI)., Methods and Analysis: After receipt of grant funding, serial postoperative serum creatinine measurements began to be recorded in consecutive patients enrolled at substudy participating centres. With respect to the study schedule, the last of over 6500 substudy patients from 82 centres in 21 countries were randomised in December 2013. The authors will use logistic regression to estimate the adjusted OR of AKI following surgery (compared with the preoperative serum creatinine value, a postoperative increase ≥26.5 μmol/L in the 2 days following surgery or an increase of ≥50% in the 7 days following surgery) comparing each intervention to placebo, and will report the adjusted relative risk reduction. Alternate definitions of AKI will also be considered, as will the outcome of AKI in subgroups defined by the presence of preoperative chronic kidney disease and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome., Ethics and Dissemination: The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this POISE-2 AKI substudy. Ethics approval was obtained for additional kidney data collection in consecutive patients enrolled at participating centres, which first began for patients enrolled after January 2011. In patients who provided consent, the remaining longer term serum creatinine data will be collected throughout 2014. The results of this study will be reported no later than 2015., Clinical Trial Registration Number: NCT01082874.
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- 2014
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177. Treatment outcomes of human bartonellosis: a systematic review and meta-analysis.
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Prutsky G, Domecq JP, Mori L, Bebko S, Matzumura M, Sabouni A, Shahrour A, Erwin PJ, Boyce TG, Montori VM, Malaga G, and Murad MH
- Subjects
- Anti-Bacterial Agents pharmacology, Doxycycline pharmacology, Doxycycline therapeutic use, Gentamicins pharmacology, Gentamicins therapeutic use, Humans, Observational Studies as Topic, Randomized Controlled Trials as Topic, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Bartonella drug effects, Bartonella Infections drug therapy
- Abstract
Background: Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis are responsible for the majority of cases of bartonellosis in humans. These species have various unique epidemiologic characteristics, clinical manifestations, and treatment approaches. The objective of this study was to summarize the evidence on the treatment for the three most common species of Bartonella in humans., Methods: We searched electronic databases through August 2011 for randomized controlled trials and observational studies designed to evaluate the efficacy and safety of the regimens used to treat diseases produced by B. henselae, B. quintana, and B. bacilliformis. Study selection and appraisal were done in duplicate., Results: We found two randomized and seven non-randomized studies at high risk of bias. For cat scratch disease, antibiotics did not significantly affect the cure rate or time to achieve cure. In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate. The recommended treatment was not better than other regimens for infectious endocarditis and bacillary angiomatosis., Conclusions: Current clinical practice for the treatment of bartonellosis relies mostly on expert opinion and antimicrobial susceptibility data. Randomized controlled trials are needed in the field to compare different treatment options., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2013
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178. Randomized trials published in higher vs. lower impact journals differ in design, conduct, and analysis.
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Bala MM, Akl EA, Sun X, Bassler D, Mertz D, Mejza F, Vandvik PO, Malaga G, Johnston BC, Dahm P, Alonso-Coello P, Diaz-Granados N, Srinathan SK, Hassouneh B, Briel M, Busse JW, You JJ, Walter SD, Altman DG, and Guyatt GH
- Subjects
- Bias, Data Interpretation, Statistical, Humans, Periodicals as Topic statistics & numerical data, Randomized Controlled Trials as Topic methods, Research Design standards, Sample Size, Journal Impact Factor, Periodicals as Topic standards, Randomized Controlled Trials as Topic standards
- Abstract
Objective: To compare methodological characteristics of randomized controlled trials (RCTs) published in higher vs. lower impact Core Clinical Journals., Study Design and Setting: We searched MEDLINE for RCTs published in 2007 in Core Clinical Journals. We randomly sampled 1,140 study reports in a 1:1 ratio in higher (five general medicine journals with the highest total citations in 2007) and lower impact journals., Results: Four hundred sixty-nine RCTs proved eligible: 219 in higher and 250 in lower impact journals. RCTs in higher vs. lower impact journals had larger sample sizes (median, 285 vs. 39), were more likely to receive industry funding (53% vs. 28%), declare concealment of allocation (66% vs. 36%), declare blinding of health care providers (53% vs. 41%) and outcome adjudicators (72% vs. 54%), report a patient-important primary outcome (69% vs. 50%), report subgroup analyses (64% vs. 26%), prespecify subgroup hypotheses (42% vs. 20%), and report a test for interaction (54% vs. 27%); P < 0.05 for all differences., Conclusion: RCTs published in higher impact journals were more likely to report methodological safeguards against bias and patient-important outcomes than those published in lower impact journals. However, sufficient limitations remain such that publication in a higher impact journal does not ensure low risk of bias., (Copyright © 2013 Elsevier Inc. All rights reserved.)
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- 2013
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179. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.
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Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, and Yusuf S
- Subjects
- Aged, Female, Humans, Inpatients statistics & numerical data, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Postoperative Period, Predictive Value of Tests, Prognosis, Prospective Studies, Risk Assessment, Biomarkers blood, Surgical Procedures, Operative mortality, Troponin T blood
- Abstract
Context: Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days., Objective: To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality., Design, Setting, and Participants: A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery., Main Outcome Measures: Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death., Results: A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001)., Conclusion: Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.
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- 2012
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180. Credibility of claims of subgroup effects in randomised controlled trials: systematic review.
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Sun X, Briel M, Busse JW, You JJ, Akl EA, Mejza F, Bala MM, Bassler D, Mertz D, Diaz-Granados N, Vandvik PO, Malaga G, Srinathan SK, Dahm P, Johnston BC, Alonso-Coello P, Hassouneh B, Walter SD, Heels-Ansdell D, Bhatnagar N, Altman DG, and Guyatt GH
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- Humans, MEDLINE, Observer Variation, Periodicals as Topic, Randomized Controlled Trials as Topic methods, Randomized Controlled Trials as Topic standards, Research Design statistics & numerical data, Treatment Outcome, Data Interpretation, Statistical, Randomized Controlled Trials as Topic statistics & numerical data, Research Design standards
- Abstract
Objective: To investigate the credibility of authors' claims of subgroup effects using a representative sample of recently published randomised controlled trials., Design: Systematic review., Data Source: Core clinical journals, as defined by the National Library of Medicine, in Medline., Study Selection: Randomised controlled trials published in 2007. Using prespecified criteria, teams of trained reviewers independently judged whether authors claimed subgroup effects and the strength of their claims. Reviewers assessed each of these claims against 10 predefined criteria, developed through a search of existing criteria and a consensus process., Results: Of 207 randomised controlled trials reporting subgroup analyses, 64 (31%) made claims for the primary outcome. Of those, 20 were strong claims and 28 claims of a likely effect. Authors included subgroup variables measured at baseline in 60 (94%) trials, used subgroup variable as a stratification factor at randomisation in 13 (20%), clearly prespecified their hypotheses in 26 (41%), correctly prespecified direction in 4 (6%), tested a small number of hypotheses in 28 (44%), carried out a test of interaction that proved statistically significant in 6 (9%), documented replication of a subgroup effect with previous related studies in 21 (33%), identified consistency of a subgroup effect across related outcomes in 19 (30%), and provided a compelling indirect evidence for the effect in 14 (22%). In the 19 trials making more than one claim, only one (5%) checked the independence of the interaction. Of the 64 claims, 54 (84%) met four or fewer of the 10 criteria. For strong claims, more than 50% failed each of the individual criteria, and only three (15%) met more than five criteria., Conclusion: Authors often claim subgroup effects in their trial report. However, the credibility of subgroup effects, even when claims are strong, is usually low. Users of the information should treat claims that fail to meet most criteria with scepticism. Trial researchers should report the conduct of subgroup analyses and provide sufficient evidence when claiming a subgroup effect or suggesting a possible effect.
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- 2012
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181. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.
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Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q, Heels-Ansdell D, Walter SD, Guyatt GH, Flynn DN, Elamin MB, Murad MH, Abu Elnour NO, Lampropulos JF, Sood A, Mullan RJ, Erwin PJ, Bankhead CR, Perera R, Ruiz Culebro C, You JJ, Mulla SM, Kaur J, Nerenberg KA, Schünemann H, Cook DJ, Lutz K, Ribic CM, Vale N, Malaga G, Akl EA, Ferreira-Gonzalez I, Alonso-Coello P, Urrutia G, Kunz R, Bucher HC, Nordmann AJ, Raatz H, da Silva SA, Tuche F, Strahm B, Djulbegovic B, Adhikari NK, Mills EJ, Gwadry-Sridhar F, Kirpalani H, Soares HP, Karanicolas PJ, Burns KE, Vandvik PO, Coto-Yglesias F, Chrispim PP, and Ramsay T
- Subjects
- Bias, Clinical Trials Data Monitoring Committees, Data Collection, Randomized Controlled Trials as Topic methods, Randomized Controlled Trials as Topic statistics & numerical data, Treatment Outcome
- Abstract
Context: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping., Objective: To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect., Data Sources: Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008., Study Selection: Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs., Data Extraction: Reviewers with methodological expertise conducted data extraction independently., Results: The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit., Conclusions: Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.
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- 2010
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182. Choice of data extraction tools for systematic reviews depends on resources and review complexity.
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Elamin MB, Flynn DN, Bassler D, Briel M, Alonso-Coello P, Karanicolas PJ, Guyatt GH, Malaga G, Furukawa TA, Kunz R, Schünemann H, Murad MH, Barbui C, Cipriani A, and Montori VM
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- Data Collection economics, Humans, Meta-Analysis as Topic, Software, Data Collection methods, Systematic Reviews as Topic
- Abstract
Objective: To assist investigators planning, coordinating, and conducting systematic reviews in the selection of data-extraction tools for conducting systematic reviews., Study Design and Setting: We constructed an initial table listing available data-collection tools and reflecting our experience with these tools and their performance. An international group of experts iteratively reviewed the table and reflected on the performance of the tools until no new insights and consensus resulted., Results: Several tools are available to manage data in systematic reviews, including paper and pencil, spreadsheets, web-based surveys, electronic databases, and web-based specialized software. Each tool offers benefits and drawbacks: specialized web-based software is well suited in most ways, but is associated with higher setup costs. Other approaches vary in their setup costs and difficulty, training requirements, portability and accessibility, versatility, progress tracking, and the ability to manage, present, store, and retrieve data., Conclusion: Available funding, number and location of reviewers, data needs, and the complexity of the project should govern the selection of a data-extraction tool when conducting systematic reviews.
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- 2009
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183. Intensive glucose control increased mortality and did not prevent cardiovascular events in type 2 diabetes.
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Montori VM and Malaga G
- Published
- 2008
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