New England Journal of Medicine

Dialogic Praxis — A 16-Year-Old Boy with Anxiety in Southern Brazil

16-01-2020 – Dominique P. Béhague,Raphael G. Frankfurter,Helena Hansen,Cesar G. Victora

Journal Article

Sounding the Alarm on Climate Change, 1989 and 2019

16-01-2020 – James H. Dunk,David S. Jones

Journal Article

Treating Addiction as a Terminal Disease

16-01-2020 – Amy E. Caruso Brown

Journal Article

Trial of Anifrolumab in Active Systemic Lupus Erythematosus

16-01-2020 – Eric F. Morand,Richard Furie,Yoshiya Tanaka,Ian N. Bruce,Anca D. Askanase,Christophe Richez,Sang-Cheol Bae,Philip Z. Brohawn,Lilia Pineda,Anna Berglind,Raj Tummala

Journal Article

Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. We randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate. A total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group. Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by Astra
Zeneca; Clinical
Trials.gov number, NCT02446899.).

A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus

16-01-2020 – Steven Fishbane,Aamir Jamal,Catherine Munera,Warren Wen,Frédérique Menzaghi

Journal Article

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.).

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants

16-01-2020 – Sandra E. Juul,Bryan A. Comstock,Rajan Wadhawan,Dennis E. Mayock,Sherry E. Courtney,Tonya Robinson,Kaashif A. Ahmad,Ellen Bendel-Stenzel,Mariana Baserga,Edmund F. LaGamma,L. Corbin Downey,Raghavendra Rao,Nancy Fahim,Andrea Lampland,Ivan D. Frantz III,Janine Y. Khan,Michael Weiss,Maureen M. Gilmore,Robin K. Ohls,Nishant Srinivasan,Jorge E. Perez,Victor McKay,Phuong T. Vu,Jean Lowe,Karl Kuban,T. Michael O’Shea,Adam L. Hartman,Patrick J. Heagerty

Journal Article

High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT Clinical
Trials.gov number, NCT01378273.).

Lipoprotein(a) Reduction in Persons with Cardiovascular Disease

16-01-2020 – Sotirios Tsimikas,Ewa Karwatowska-Prokopczuk,Ioanna Gouni-Berthold,Jean-Claude Tardif,Seth J. Baum,Elizabeth Steinhagen-Thiessen,Michael D. Shapiro,Erik S. Stroes,Patrick M. Moriarty,Børge G. Nordestgaard,Shuting Xia,Jonathan Guerriero,Nicholas J. Viney,Louis O’Dea,Joseph L. Witztum

Journal Article

Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-L The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-L APO(a)-L

JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency

16-01-2020 – Fahad Alsohime,Marta Martin-Fernandez,Mohamad-Hani Temsah,Majed Alabdulhafid,Tom Le Voyer,Malak Alghamdi,Xueer Qiu,Najla Alotaibi,Areej Alkahtani,Sofija Buta,Emmanuelle Jouanguy,Ayman Al-Eyadhy,Conor Gruber,Gamal M. Hasan,Fahad A. Bashiri,Rabih Halwani,Hamdy H. Hassan,Saleh Al-Muhsen,Nouf Alkhamis,Zobaida Alsum,Jean-Laurent Casanova,Jacinta Bustamante,Dusan Bogunovic,Abdullah A. Alangari

Journal Article

Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on

Suicide

16-01-2020 – Seena Fazel,Bo Runeson

Journal Article, Review

Crazy Paving in Pulmonary Alveolar Proteinosis

16-01-2020 – Brian W. Allwood,Sami Bennji

Case Reports, Journal Article

Skin Discoloration from Amiodarone

16-01-2020 – Robert P. Murphy,Michelle Canavan

Case Reports, Journal Article

Case 2-2020: A 64-Year-Old Man with Fever and Respiratory Failure

16-01-2020 – Marwan M. Azar,Victorine V. Muse,Julian A. Villalba,Sarah E. Turbett

Case Reports, Journal Article

A Successful Trial for Lupus — How Good Is Good Enough?

16-01-2020 – Jane E. Salmon,Timothy B. Niewold

Editorial

Difelikefalin for the Treatment of Uremic Pruritus

16-01-2020 – David J.R. Steele

Editorial

Cytokinesis, Beta-Blockers, and Congenital Heart Disease

16-01-2020 – Katherine E. Yutzey

Journal Article

Extracorporeal Photopheresis for Colitis Induced by Checkpoint-Inhibitor Therapy

16-01-2020 – Petya Apostolova,Susanne Unger,Dagmar von Bubnoff,Frank Meiss,Burkhard Becher,Robert Zeiser

Letter

Medical versus Surgical Treatment for Refractory Heartburn

16-01-2020 – SJ Spechler

Letter, Comment

Effects of Intermittent Fasting on Health, Aging, and Disease

16-01-2020 –

Published Erratum

Abuses of FDA Regulatory Procedures — The Case of Suboxone

09-01-2020 – Rebecca L. Haffajee,Richard G. Frank

Journal Article

Is Obamacare Really Unconstitutional?

02-01-2020 – Nicholas Bagley

Journal Article

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

28-12-2019 –

Published Erratum

Retraction: Retinal Hemorrhage from Blunt Ocular Trauma. N Engl J Med 2019;381:2252.

24-12-2019 – Jitender Jinagal,Poonam Dhiman

Letter, Retraction of Publication

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

21-12-2019 – Benjamin C. Blount,Mateusz P. Karwowski,Peter G. Shields,Maria Morel-Espinosa,Liza Valentin-Blasini,Michael Gardner,Martha Braselton,Christina R. Brosius,Kevin T. Caron,David Chambers,Joseph Corstvet,Elizabeth Cowan,Víctor R. De Jesús,Paul Espinosa,Carolina Fernandez,Cory Holder,Zsuzsanna Kuklenyik,Jennifer D. Kusovschi,Cody Newman,Gregory B. Reis,Jon Rees,Chris Reese,Lalith Silva,Tiffany Seyler,Min-Ae Song,Connie Sosnoff,C.R. Spitzer,Denise Tevis,Lanqing Wang,Cliff Watson,Mark D. Wewers,Baoyun Xia,Douglas T. Heitkemper,Isaac Ghinai,Jennifer Layden,Peter Briss,Brian A. King,Lisa J. Delaney,Christopher M. Jones,Grant T. Baldwin,Anita Patel,Dana Meaney-Delman,Dale Rose,Vikram Krishnasamy,John R. Barr,Jerry Thomas,James L. Pirkle

Journal Article

The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Syndromic Surveillance for E-Cigarette, or Vaping, Product Use–Associated Lung Injury

21-12-2019 – Kathleen P. Hartnett,Aaron Kite-Powell,Megan T. Patel,Brittani L. Haag,Michael J. Sheppard,Taylor P. Dias,Brian A. King,Paul C. Melstrom,Matthew D. Ritchey,Zachary Stein,Nimi Idaikkadar,Alana M. Vivolo-Kantor,Dale A. Rose,Peter A. Briss,Jennifer E. Layden,Loren Rodgers,Jennifer Adjemian

Journal Article

Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer

12-12-2019 – Dennis J. Slamon,Patrick Neven,Stephen Chia,Peter A. Fasching,Michelino De Laurentiis,Seock-Ah Im,Katarina Petrakova,Giulia V. Bianchi,Francisco J. Esteva,Miguel Martín,Arnd Nusch,Gabe S. Sonke,Luis De la Cruz-Merino,J. Thaddeus Beck,Xavier Pivot,Manu Sondhi,Yingbo Wang,Arunava Chakravartty,Karen Rodriguez-Lorenc,Tetiana Taran,Guy Jerusalem

Journal Article

In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival. Patients were randomly assigned in a 2:1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment. Survival was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan-Meier methods. This analysis was based on 275 deaths: 167 among 484 patients (34.5%) receiving ribociclib and 108 among 242 (44.6%) receiving placebo. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant. The estimated overall survival at 42 months was 57.8% (95% confidence interval [CI], 52.0 to 63.2) in the ribociclib group and 45.9% (95% CI, 36.9 to 54.5) in the placebo group, for a 28% difference in the relative risk of death (hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.00455). The benefit was consistent across most subgroups. In a descriptive update, median progression-free survival among patients receiving first-line treatment was 33.6 months (95% CI, 27.1 to 41.3) in the ribociclib group and 19.2 months (95% CI, 14.9 to 23.6) in the placebo group. No new safety signals were observed. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone-receptor-positive, HER2-negative advanced breast cancer. (Funded by Novartis; MONALEESA-3 Clinical
Trials.gov number, NCT02422615.).

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer

12-12-2019 – Shanu Modi,Cristina Saura,Toshinari Yamashita,Yeon Hee Park,Sung-Bae Kim,Kenji Tamura,Fabrice Andre,Hiroji Iwata,Yoshinori Ito,Junji Tsurutani,Joohyuk Sohn,Neelima Denduluri,Christophe Perrin,Kenjiro Aogi,Eriko Tokunaga,Seock-Ah Im,Keun Seok Lee,Sara A. Hurvitz,Javier Cortes,Caleb Lee,Shuquan Chen,Lin Zhang,Javad Shahidi,Antoine Yver,Ian Krop

Journal Article

Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation. In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer who had received previous treatment with trastuzumab emtansine. In the first part of the study, we evaluated three different doses of trastuzumab deruxtecan to establish a recommended dose; in the second part, we evaluated the efficacy and safety of the recommended dose. The primary end point was the objective response, according to independent central review. Key secondary end points were the disease-control rate, clinical-benefit rate, duration of response and progression-free survival, and safety. Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis, a response to therapy was reported in 112 patients (60.9%; 95% confidence interval [CI], 53.4 to 68.0). The median duration of follow-up was 11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached). During the study, the most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). On independent adjudication, the trial drug was associated with interstitial lung disease in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%). Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer. In addition to nausea and myelosuppression, interstitial lung disease was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring. (Funded by Daiichi Sankyo and Astra
Zeneca; DESTINY-Breast01 Clinical
Trials.gov number, NCT03248492.).

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

12-12-2019 – Rashmi K. Murthy,Sherene Loi,Alicia Okines,Elisavet Paplomata,Erika Hamilton,Sara A. Hurvitz,Nancy U. Lin,Virginia Borges,Vandana Abramson,Carey Anders,Philippe L. Bedard,Mafalda Oliveira,Erik Jakobsen,Thomas Bachelot,Shlomit S. Shachar,Volkmar Müller,Sofia Braga,Francois P. Duhoux,Richard Greil,David Cameron,Lisa A. Carey,Giuseppe Curigliano,Karen Gelmon,Gabriel Hortobagyi,Ian Krop,Sibylle Loibl,Mark Pegram,Dennis Slamon,M. Corinna Palanca-Wessels,Luke Walker,Wentao Feng,Eric P. Winer

Journal Article

Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB Clinical
Trials.gov number, NCT02614794.).

More on the Pathology of Vaping-Associated Lung Injury

21-11-2019 – BT Larsen,YM Butt,ML Smith

Letter

Pulmonary Illness Related to E-Cigarette Use

21-11-2019 – JE Layden,BA King,J Meiman

Letter

Conservative Oxygen Therapy during Mechanical Ventilation in the ICU

16-10-2019 – Geen auteurs bekend

Journal Article

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.).

Vaping-Induced Lung Injury

07-09-2019 – David C. Christiani

Editorial

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

Journal Article

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.