Advancing Legislation on Drug Pricing — Is There a Path Forward?
28-11-2019 – Stacie B. Dusetzina,Jonathan Oberlander
Which Drug Prices Should Medicare Negotiate? A “Too Little” or “Too Late” Approach
28-11-2019 – Peter B. Bach
28-11-2019 – Heather Kovich
Supplemental MRI Screening for Women with Extremely Dense Breast Tissue
28-11-2019 – Marije F. Bakker,Stéphanie V. de Lange,Ruud M. Pijnappel,Ritse M. Mann,Petra H.M. Peeters,Evelyn M. Monninkhof,Marleen J. Emaus,Claudette E. Loo,Robertus H.C. Bisschops,Marc B.I. Lobbes,Matthijn D.F. de Jong,Katya M. Duvivier,Jeroen Veltman,Nico Karssemeijer,Harry J. de Koning,Paul J. van Diest,Willem P.T.M. Mali,Maurice A.A.J. van den Bosch,Wouter B. Veldhuis,Carla H. van Gils
Journal Article, Research Support, Non-U.S. Gov’t
Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to improve early detection and reduce interval breast cancers in such patients.
In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period.
The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval [CI], 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.
The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE Clinical
Trials.gov number, NCT01315015.).
Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus
28-11-2019 – Jaideep Kapur,Jordan Elm,James M. Chamberlain,William Barsan,James Cloyd,Daniel Lowenstein,Shlomo Shinnar,Robin Conwit,Caitlyn Meinzer,Hannah Cock,Nathan Fountain,Jason T. Connor,Robert Silbergleit
Journal Article, Research Support, N.I.H., Extramural
The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.
In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents – levetiracetam, fosphenytoin, and valproate – in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.
A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.
In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT Clinical
Trials.gov number, NCT01960075.).
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
28-11-2019 – Takashi Yamamura,Ingo Kleiter,Kazuo Fujihara,Jacqueline Palace,Benjamin Greenberg,Beata Zakrzewska-Pniewska,Francesco Patti,Ching-Piao Tsai,Albert Saiz,Hayato Yamazaki,Yuichi Kawata,Padraig Wright,Jerome De Seze
Journal Article, Research Support, Non-U.S. Gov’t
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-Ig
G) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear. In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-Ig
G to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed. A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-Ig
G-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-Ig
G-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups. Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; Clinical
Trials.gov number, NCT02028884.).
Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability
28-11-2019 – Clive Kearon,Kerstin de Wit,Sameer Parpia,Sam Schulman,Marc Afilalo,Andrew Hirsch,Frederick A. Spencer,Sangita Sharma,Frédérick D’Aragon,Jean-François Deshaies,Gregoire Le Gal,Alejandro Lazo-Langner,Cynthia Wu,Lisa Rudd-Scott,Shannon M. Bates,Jim A. Julian
Journal Article, Research Support, Non-U.S. Gov’t
Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP.
We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism.
A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9).
A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGe
Trials.gov number, NCT02483442.).
28-11-2019 – Ayalew Tefferi,Animesh Pardanani
Journal Article, Review
Genome Sequencing during a Patient’s Journey through Cancer
28-11-2019 – Jyoti Nangalia,Peter J. Campbell
Journal Article, Review
28-11-2019 – Antonio C. Arrieta,Jasjit Singh
Case Reports, Journal Article
28-11-2019 – Francesco Guerra,Diego Coletta
Case Reports, Journal Article
28-11-2019 – Cristina Thomas,Anand Vaidya,David J. Kwiatkowski,Deepak A. Rao,Ruth Ann Vleugels
Case Reports, Journal Article
Case 37-2019: A 20-Month-Old Boy with Severe Anemia
28-11-2019 – Brian M. Cummings,Randheer Shailam,Ana M. Rosales,Mary S. Huang,Valentina Nardi
Case Reports, Journal Article
Detecting Breast Cancer in Women with Dense Breasts
28-11-2019 – Dan L. Longo
Management of Established Status Epilepticus
28-11-2019 – Phil E. Smith
Transforming Culture in Health Care
28-11-2019 – Michael Nurok,Thomas H. Lee
Imbalance in T-Helper 17 Cells and Targeted Therapy in an Infant with SAM-like Syndrome
28-11-2019 – Angela Hernández-Martín,Rebeca Kennedy-Batalla,Elvira Cañedo,Esther Bernaldo-de-Quirós,Begoña Carazo-Gallego,Angel Vera,Antonio Torrelo,Lucero Noguera-Morel,Rogelio González-Sarmiento,Marieke Bolling,Marta Martínez-Bonet,Marjorie Pion,Rafael Correa-Rocha
Trial of SAGE-217 in Patients with Major Depressive Disorder
28-11-2019 – H Gunduz-Bruce,SJ Kanes,CF Zorumski
Universal Testing and Treatment for HIV Infection in Botswana
28-11-2019 – S Lockman,J Makhema,M Essex
Macrolide Resistance and Longer-Term Assessment of Azithromycin in MORDOR I
28-11-2019 – TM Lietman,T Doan,JD Keenan
Monoclonal Antibody Therapy for Ebola Virus Disease
28-11-2019 – Myron M. Levine
A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics
28-11-2019 – Sabue Mulangu,Lori E. Dodd,Richard T. Davey,Olivier Tshiani Mbaya,Michael Proschan,Daniel Mukadi,Mariano Lusakibanza Manzo,Didier Nzolo,Antoine Tshomba Oloma,Augustin Ibanda,Rosine Ali,Sinaré Coulibaly,Adam C. Levine,Rebecca Grais,Janet Diaz,H. Clifford Lane,Jean-Jacques Muyembe-Tamfum
Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.
We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days.
A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs.
Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM Clinical
Trials.gov number, NCT03719586.).
PrEParing to End the HIV Epidemic — California’s Route as a Road Map for the United States
28-11-2019 – Dhruv S. Kazi,Ingrid T. Katz,Ashish K. Jha
Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC
22-11-2019 – Suresh S. Ramalingam,Johan Vansteenkiste,David Planchard,Byoung Chul Cho,Jhanelle E. Gray,Yuichiro Ohe,Caicun Zhou,Thanyanan Reungwetwattana,Ying Cheng,Busyamas Chewaskulyong,Riyaz Shah,Manuel Cobo,Ki Hyeong Lee,Parneet Cheema,Marcello Tiseo,Thomas John,Meng-Chih Lin,Fumio Imamura,Takayasu Kurata,Alexander Todd,Rachel Hodge,Matilde Saggese,Yuri Rukazenkov,Jean-Charles Soria
Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. Among patients with previously untreated advanced NSCLC with an
More on the Pathology of Vaping-Associated Lung Injury
21-11-2019 – BT Larsen,YM Butt,ML Smith
Pulmonary Illness Related to E-Cigarette Use
21-11-2019 – JE Layden,BA King,J Meiman
Who Pays in Medicare Part D? Giving Plans More Skin in the Game
21-11-2019 – Erin E. Trish,Paul B. Ginsburg,Geoffrey F. Joyce,Dana P. Goldman
Statins and Stroke — It’s Complicated
19-11-2019 – Lawrence R. Wechsler
A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke
19-11-2019 – Pierre Amarenco,Jong S. Kim,Julien Labreuche,Hugo Charles,Jérémie Abtan,Yannick Béjot,Lucie Cabrejo,Jae-Kwan Cha,Grégory Ducrocq,Maurice Giroud,Celine Guidoux,Cristina Hobeanu,Yong-Jae Kim,Bertrand Lapergue,Philippa C. Lavallée,Byung-Chul Lee,Kyung-Bok Lee,Didier Leys,Marie-Hélène Mahagne,Elena Meseguer,Norbert Nighoghossian,Fernando Pico,Yves Samson,Igor Sibon,P. Gabriel Steg,Sang-Min Sung,Pierre-Jean Touboul,Emmanuel Touzé,Olivier Varenne,Éric Vicaut,Nessima Yelles,Eric Bruckert
The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.
In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.
A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.
After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target Clinical
Trials.gov number, NCT01252875.).
Inflammation as a Treatment Target after Acute Myocardial Infarction
17-11-2019 – L. Kristin Newby
Timing of Intervention in Aortic Stenosis
17-11-2019 – Patrizio Lancellotti,Mani A. Vannan
A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement
17-11-2019 – George D. Dangas,Jan G.P. Tijssen,Jochen Wöhrle,Lars Søndergaard,Martine Gilard,Helge Möllmann,Raj R. Makkar,Howard C. Herrmann,Gennaro Giustino,Stephan Baldus,Ole De Backer,Ana H.C. Guimarães,Lars Gullestad,Annapoorna Kini,Dirk von Lewinski,Michael Mack,Raúl Moreno,Ulrich Schäfer,Julia Seeger,Didier Tchétché,Karen Thomitzek,Marco Valgimigli,Pascal Vranckx,Robert C. Welsh,Peter Wildgoose,Albert A. Volkl,Ana Zazula,Ronald G.M. van Amsterdam,Roxana Mehran,Stephan Windecker
Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear.
We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns.
After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53).
In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO Clinical
Trials.gov number, NCT02556203.).
Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement
17-11-2019 – Ole De Backer,George D. Dangas,Hasan Jilaihawi,Jonathon A. Leipsic,Christian J. Terkelsen,Raj Makkar,Annapoorna S. Kini,Karsten T. Veien,Mohamed Abdel-Wahab,Won-Keun Kim,Prakash Balan,Nicolas Van Mieghem,Ole N. Mathiassen,Raban V. Jeger,Martin Arnold,Roxana Mehran,Ana H.C. Guimarães,Bjarne L. Nørgaard,Klaus F. Kofoed,Philipp Blanke,Stephan Windecker,Lars Søndergaard
Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known.
In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed.
A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively).
In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D Clinical
Trials.gov number, NCT02833948.).
Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction
17-11-2019 – Jean-Claude Tardif,Simon Kouz,David D. Waters,Olivier F. Bertrand,Rafael Diaz,Aldo P. Maggioni,Fausto J. Pinto,Reda Ibrahim,Habib Gamra,Ghassan S. Kiwan,Colin Berry,José López-Sendón,Petr Ostadal,Wolfgang Koenig,Denis Angoulvant,Jean C. Grégoire,Marc-André Lavoie,Marie-Pierre Dubé,David Rhainds,Mylène Provencher,Lucie Blondeau,Andreas Orfanos,Philippe L. L’Allier,Marie-Claude Guertin,François Roubille
Experimental and clinical evidence support the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.
We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.
A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03).
Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT Clinical
Trials.gov number, NCT02551094.).
Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis
17-11-2019 – Duk-Hyun Kang,Sung-Ji Park,Seung-Ah Lee,Sahmin Lee,Dae-Hee Kim,Hyung-Kwan Kim,Sung-Cheol Yun,Geu-Ru Hong,Jong-Min Song,Cheol-Hyun Chung,Jae-Kwan Song,Jae-Won Lee,Seung-Woo Park
Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov’t
The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.
In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm
In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.
Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY Clinical
Trials.gov number, NCT01161732.).
A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus
09-11-2019 – Steven Fishbane,Aamir Jamal,Catherine Munera,Warren Wen,Frédérique Menzaghi
Difelikefalin is a peripherally restricted and selective agonist of kappa opioid receptors that are considered to be important in modulating pruritus in conditions such as chronic kidney disease.
In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients undergoing hemodialysis who had moderate-to-severe pruritus to receive either intravenous difelikefalin (at a dose of 0.5 μg per kilogram of body weight) or placebo three times per week for 12 weeks. The primary outcome was the percentage of patients with an improvement (decrease) of at least 3 points from baseline at week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS; scores range from 0 to 10, with higher scores indicating greater itch intensity). The secondary outcomes included the change from baseline in itch-related quality-of-life measures, the percentage of patients with an improvement of at least 4 points in the WI-NRS score at week 12, and safety.
A total of 378 patients underwent randomization. A total of 82 of 158 patients (51.9%) in the difelikefalin group had a decrease of at least 3 points in the WI-NRS score (primary outcome), as compared with 51 of 165 (30.9%) in the placebo group. The imputed percentage of patients with a decrease of at least 3 points in the WI-NRS score was 49.1% in the difelikefalin group, as compared with 27.9% in the placebo group (P<0.001). Difelikefalin also resulted in a significant improvement from baseline to week 12 in itch-related quality of life as measured by the 5-D itch scale and the Skindex-10 scale. The imputed percentage of patients with a decrease of at least 4 points in the WI-NRS score at week 12 was significantly greater in the difelikefalin group than in the placebo group (37.1% [observed data: 64 of 158 patients] vs. 17.9% [observed data: 35 of 165 patients], P<0.001). Diarrhea, dizziness, and vomiting were more common in the difelikefalin group than in the placebo group.
Patients treated with difelikefalin had a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo. (Funded by Cara Therapeutics; KALM-1 Clinical
Trials.gov number, NCT03422653.).
Where Were the Women? Gender Parity in Clinical Trials
31-10-2019 – Robert H. Goldstein,Rochelle P. Walensky
Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis
30-10-2019 – Dereck R. Tait,Mark Hatherill,Olivier Van Der Meeren,Ann M. Ginsberg,Elana Van Brakel,Bruno Salaun,Thomas J. Scriba,Elaine J. Akite,Helen M. Ayles,Anne Bollaerts,Marie-Ange Demoitié,Andreas Diacon,Thomas G. Evans,Paul Gillard,Elizabeth Hellström,James C. Innes,Maria Lempicki,Mookho Malahleha,Neil Martinson,Doris Mesia Vela,Monde Muyoyeta,Videlis Nduba,Thierry G. Pascal,Michele Tameris,Friedrich Thienemann,Robert J. Wilkinson,François Roman
Results of an earlier analysis of a trial of the M72/AS01 From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01 Among adults infected with
Beta-Blockers in COPD — A Controversy Resolved?
22-10-2019 – William MacNee
Metoprolol for the Prevention of Acute Exacerbations of COPD
22-10-2019 – Mark T. Dransfield,Helen Voelker,Surya P. Bhatt,Keith Brenner,Richard Casaburi,Carolyn E. Come,J. Allen D. Cooper,Gerard J. Criner,Jeffrey L. Curtis,MeiLan K. Han,Umur Hatipoğlu,Erika S. Helgeson,Vipul V. Jain,Ravi Kalhan,David Kaminsky,Robert Kaner,Ken M. Kunisaki,Allison A. Lambert,Matthew R. Lammi,Sarah Lindberg,Barry J. Make,Fernando J. Martinez,Charlene McEvoy,Ralph J. Panos,Robert M. Reed,Paul D. Scanlon,Frank C. Sciurba,Anthony Smith,Peruvemba S. Sriram,William W. Stringer,Jeremy A. Weingarten,J. Michael Wells,Elizabeth Westfall,Stephen C. Lazarus,John E. Connett
Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.
In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.
A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV
Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD Clinical
Trials.gov number, NCT02587351.).
Conservative Oxygen Therapy during Mechanical Ventilation in the ICU
16-10-2019 – Geen auteurs bekend
Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the New Zealand Health Research Council; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.).
Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm
03-10-2019 – Jean-Baptiste Lascarrou,Hamid Merdji,Amélie Le Gouge,Gwenhael Colin,Guillaume Grillet,Patrick Girardie,Elisabeth Coupez,Pierre-François Dequin,Alain Cariou,Thierry Boulain,Noelle Brule,Jean-Pierre Frat,Pierre Asfar,Nicolas Pichon,Mickael Landais,Gaëtan Plantefeve,Jean-Pierre Quenot,Jean-Charles Chakarian,Michel Sirodot,Stéphane Legriel,Julien Letheulle,Didier Thevenin,Arnaud Desachy,Arnaud Delahaye,Vlad Botoc,Sylvie Vimeux,Frederic Martino,Bruno Giraudeau,Jean Reignier
Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated.
We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed.
From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups.
Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION Clinical
Trials.gov number, NCT01994772.).
Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer
01-10-2019 – Ronald de Wit,Johann de Bono,Cora N. Sternberg,Karim Fizazi,Bertrand Tombal,Christian Wülfing,Gero Kramer,Jean-Christophe Eymard,Aristotelis Bamias,Joan Carles,Roberto Iacovelli,Bohuslav Melichar,Ásgerður Sverrisdóttir,Christine Theodore,Susan Feyerabend,Carole Helissey,Ayse Ozatilgan,Christine Geffriaud-Ricouard,Daniel Castellano
The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear.
We randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling-targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed.
A total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling-targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling-targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling-targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P = 0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling-targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P = 0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen-signaling-targeted inhibitor. No new safety signals were observed.
Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide). (Funded by Sanofi; CARD Clinical
Trials.gov number, NCT02485691.).
Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer
29-09-2019 – Robert L. Coleman,Gini F. Fleming,Mark F. Brady,Elizabeth M. Swisher,Karina D. Steffensen,Michael Friedlander,Aikou Okamoto,Kathleen N. Moore,Noa Efrat Ben-Baruch,Theresa L. Werner,Noelle G. Cloven,Ana Oaknin,Paul A. DiSilvestro,Mark A. Morgan,Joo-Hyun Nam,Charles A. Leath,Shibani Nicum,Andrea R. Hagemann,Ramey D. Littell,David Cella,Sally Baron-Hay,Jesus Garcia-Donas,Mika Mizuno,Katherine Bell-McGuinn,Danielle M. Sullivan,Bruce A. Bach,Sudipta Bhattacharya,Christine K. Ratajczak,Peter J. Ansell,Minh H. Dinh,Carol Aghajanian,Michael A. Bookman
Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma.
In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the
A total of 1140 patients underwent randomization. In the
Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by Abb
Vie; VELIA/GOG-3005 Clinical
Trials.gov number, NCT02470585.).
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
29-09-2019 – Antonio González-Martín,Bhavana Pothuri,Ignace Vergote,René DePont Christensen,Whitney Graybill,Mansoor R. Mirza,Colleen McCormick,Domenica Lorusso,Paul Hoskins,Gilles Freyer,Klaus Baumann,Kris Jardon,Andrés Redondo,Richard G. Moore,Christof Vulsteke,Roisin E. O’Cearbhaill,Bente Lund,Floor Backes,Pilar Barretina-Ginesta,Ashley F. Haggerty,Maria J. Rubio-Pérez,Mark S. Shahin,Giorgia Mangili,William H. Bradley,Ilan Bruchim,Kaiming Sun,Izabela A. Malinowska,Yong Li,Divya Gupta,Bradley J. Monk
Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of
In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.
Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.
Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by Glaxo
Kline; PRIMA/ENGOT-OV26/GOG-3012 Clinical
Trials.gov number, NCT02655016.).
Total Hip Arthroplasty or Hemiarthroplasty for Hip Fracture
27-09-2019 – Geen auteurs bekend
Globally, hip fractures are among the top 10 causes of disability in adults. For displaced femoral neck fractures, there remains uncertainty regarding the effect of a total hip arthroplasty as compared with hemiarthroplasty.
We randomly assigned 1495 patients who were 50 years of age or older and had a displaced femoral neck fracture to undergo either total hip arthroplasty or hemiarthroplasty. All enrolled patients had been able to ambulate without the assistance of another person before the fracture occurred. The trial was conducted in 80 centers in 10 countries. The primary end point was a secondary hip procedure within 24 months of follow-up. Secondary end points included death, serious adverse events, hip-related complications, health-related quality of life, function, and overall health end points.
The primary end point occurred in 57 of 718 patients (7.9%) who were randomly assigned to total hip arthroplasty and 60 of 723 patients (8.3%) who were randomly assigned to hemiarthroplasty (hazard ratio, 0.95; 95% confidence interval [CI], 0.64 to 1.40; P = 0.79). Hip instability or dislocation occurred in 34 patients (4.7%) assigned to total hip arthroplasty and 17 patients (2.4%) assigned to hemiarthroplasty (hazard ratio, 2.00; 99% CI, 0.97 to 4.09). Function, as measured with the total Western Ontario and Mc
Master Universities Osteoarthritis Index (WOMAC) total score, pain score, stiffness score, and function score, modestly favored total hip arthroplasty over hemiarthroplasty. Mortality was similar in the two treatment groups (14.3% among the patients assigned to total hip arthroplasty and 13.1% among those assigned to hemiarthroplasty, P = 0.48). Serious adverse events occurred in 300 patients (41.8%) assigned to total hip arthroplasty and in 265 patients (36.7%) assigned to hemiarthroplasty. Among independently ambulating patients with displaced femoral neck fractures, the incidence of secondary procedures did not differ significantly between patients who were randomly assigned to undergo total hip arthroplasty and those who were assigned to undergo hemiarthroplasty, and total hip arthroplasty provided a clinically unimportant improvement over hemiarthroplasty in function and quality of life over 24 months. (Funded by the Canadian Institutes of Health Research and others; Clinical
Trials.gov number, NCT00556842.).
Vaping-Induced Lung Injury
07-09-2019 – David C. Christiani
Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin — Preliminary Report
07-09-2019 – Jennifer E. Layden,Isaac Ghinai,Ian Pray,Anne Kimball,Mark Layer,Mark Tenforde,Livia Navon,Brooke Hoots,Phillip P. Salvatore,Megan Elderbrook,Thomas Haupt,Jeffrey Kanne,Megan T. Patel,Lori Saathoff-Huber,Brian A. King,Josh G. Schier,Christina A. Mikosz,Jonathan Meiman
E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of pulmonary disease associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation. We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools. There were 53 case patients, 83% of whom were male; the median age of the patients was 19 years. The majority of patients presented with respiratory symptoms (98%), gastrointestinal symptoms (81%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging (which was part of the case definition). A total of 94% of the patients were hospitalized, 32% underwent intubation and mechanical ventilation, and one death was reported. A total of 84% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018. Case patients presented with similar clinical characteristics. Although the features of e-cigarette use that were responsible for injury have not been identified, this cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.