Abstract:
Background:FLU-v is a broad-spectrum influenza vaccine that induces antibodies and cell-mediated immunity. Objective:To compare the safety, immunogenicity, and exploratory efficacy of different formulations and dosing regimens of FLU-v versus placebo. Design:Randomized, double-blind, placebo-controlled, single-center phase 2b clinical trial. (ClinicalTrials.gov: NCT02962908; EudraCT: 2015-001932-38). Setting:The Netherlands. Participants:175 healthy adults aged 18 to 60 years. Intervention:0.5-mL subcutaneous injection of 500 µg of adjuvanted (1 dose) or nonadjuvanted (2 doses) FLU-v (A-FLU-v or NA-FLU-v) or adjuvanted or nonadjuvanted placebo (A-placebo or NA-placebo) (2:2:1:1 ratio). Measurements:Vaccine-specific cellular responses at days 0, 42, and 180 were assessed via flow cytometry and enzyme-linked immunosorbent assay. Solicited information on adverse events (AEs) was collected for 21 days after vaccination. Unsolicited information on AEs was collected throughout the study. Results:The AEs with the highest incidence were mild to moderate injection site reactions. The difference between A-FLU-v and A-placebo in the median fold increase in secreted interferon-γ (IFN-γ) was 38.2-fold (95% CI, 4.7- to 69.7-fold; P = 0.001) at day 42 and 25.0-fold (CI, 5.7- to 50.9-fold; P < 0.001) at day 180. The differences between A-FLU-v and A-placebo in median fold increase at day 42 were 4.5-fold (CI, 2.3- to 9.8-fold; P < 0.001) for IFN-γ-producing CD4+ T cells, 4.9-fold (CI, 1.3- to 40.0-fold; P < 0.001) for tumor necrosis factor-α (TNF-α), 7.0-fold (CI, 3.5- to 18.0-fold; P < 0.001) for interleukin-2 (IL-2), and 1.7-fold (CI, 0.1- to 4.0-fold; P = 0.004) for CD107a. At day 180, differences were 2.1-fold (CI, 0.0- to 6.0-fold; P = 0.030) for IFN-γ and 5.7-fold (CI, 2.0- to 15.0-fold; P < 0.001) for IL-2, with no difference for TNF-α or CD107a. No differences were seen between NA-FLU-v and NA-placebo. Limitation:The study was not powered to evaluate vaccine efficacy against influenza infection. Conclusion:Adjuvanted FLU-v is immunogenic and merits phase 3 development to explore efficacy. Primary Funding Source:SEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project.
journal_name
Ann Intern Medjournal_title
Annals of internal medicineauthors
Pleguezuelos O,Dille J,de Groen S,Oftung F,Niesters HGM,Islam MA,Næss LM,Hungnes O,Aldarij N,Idema DL,Perez AF,James E,Frijlink HW,Stoloff G,Groeneveld P,Hak Edoi
10.7326/M19-0735subject
Has Abstractpub_date
2020-04-07 00:00:00pages
453-462issue
7eissn
0003-4819issn
1539-3704pii
2762723journal_volume
172pub_type
杂志文章,随机对照试验abstract:OBJECTIVE:To determine the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combined with moderate alcohol consumption on lipid profiles and hepatic function in patients with primary hypercholesterolemia. DESIGN:Randomized, placebo-controlled, crossover study. S...
journal_title:Annals of internal medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.7326/0003-4819-122-9-199505010-00006
更新日期:1995-05-01 00:00:00
abstract:BACKGROUND:Exercise rehabilitation programs increase treadmill walking performance in patients with peripheral arterial disease (PAD) and intermittent claudication. However, it is unknown whether patients with PAD who walk for exercise regularly have less functional decline than those with less walking activity. OBJEC...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-144-1-200601030-00005
更新日期:2006-01-03 00:00:00
abstract::The 1950s witnessed prodigious growth in our knowledge of the chemical nature of the gene, the mechanisms by which the information inherent in its sequence of nucleotide units was conveyed to the cell's machinery for synthesizing proteins, and the mode of operation of that machinery. Watson and Crick raised the curtai...
journal_title:Annals of internal medicine
pub_type: 评论,历史文章,杂志文章
doi:10.7326/0003-4819-138-7-200304010-00016
更新日期:2003-04-01 00:00:00
abstract:OBJECTIVE:To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN:Randomized, double-blind comparative trial. SETTING:A tertiary-care hospital. PATIENTS:One hundred and one intravenous drug users hospitalized w...
journal_title:Annals of internal medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.7326/0003-4819-117-5-390
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND:The risk for hypertension after kidney donation remains uncertain. PURPOSE:To see whether normotensive adults who donate a kidney develop higher blood pressure and risk for hypertension compared with nondonor adults acting as control participants. DATA SOURCES:MEDLINE, EMBASE, and Science Citation Index we...
journal_title:Annals of internal medicine
pub_type: 杂志文章,meta分析,评审
doi:10.7326/0003-4819-145-3-200608010-00006
更新日期:2006-08-01 00:00:00
abstract:PURPOSE:To review methods of preventing or minimizing the adverse effects associated with the transfusion of passenger leukocytes present in cellular blood components and to define groups of patients who are at risk for adverse effects. DATA SOURCES:English-language articles on transfusion medicine. STUDY SELECTION:O...
journal_title:Annals of internal medicine
pub_type: 杂志文章,评审
doi:10.7326/0003-4819-117-2-151
更新日期:1992-07-15 00:00:00
abstract::Hepatitis is a significant complication of the treatment of hemophilia A with factor VIII concentrates. Chronic liver disease in these patients is infrequently documented in the literature. The results of percutaneous liver biopsy, under the coverage of glycine-precipitated factor VIII, in six patients with hemophilia...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-86-6-703
更新日期:1977-06-01 00:00:00
abstract::To reduce health care costs, some third-party payers have enlisted primary care physicians as gatekeepers to medical care. In gatekeeper systems, primary care physicians must approve all care provided to their patients. This approval is a condition of payment for the service, with the usual exception of true emergenci...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-102-4-537
更新日期:1985-04-01 00:00:00
abstract::The Biblical Book of Job is a wisdom book. Wisdom, in this context, refers to the intellectual discipline taught by the sages of ancient Isreael to provide professionals with a realistic approach to the problems of life. Chapter 30 of the Book of Job is a key-index of ideas that, if followed through the book, disclose...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-86-5-667
更新日期:1977-05-01 00:00:00
abstract:BACKGROUND:The optimum duration of anticoagulant therapy after an episode of deep venous thrombosis (DVT) is controversial. Contributing to the controversy is uncertainty about whether residual venous thrombosis, as assessed by repeated ultrasonography over time, increases the risk for recurrent thromboembolism. OBJEC...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-137-12-200212170-00008
更新日期:2002-12-17 00:00:00
abstract::Considerable evidence links elevated blood cholesterol levels to the development of atherosclerosis. The National Cholesterol Education Program (NCEP) has recently published revised guidelines for detecting and treating hypercholesterolemia in adults. Included in these guidelines is the recommendation that all adults ...
journal_title:Annals of internal medicine
pub_type: 评论,杂志文章,评审
doi:10.7326/0003-4819-124-5-199603010-00008
更新日期:1996-03-01 00:00:00
abstract:OBJECTIVES:To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of va...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-123-4-199508150-00002
更新日期:1995-08-15 00:00:00
abstract:BACKGROUND:Memphis and Shelby County, Tennessee, experienced an epidemic of hepatitis A in 1994 and 1995. More than 1700 cases were reported. OBJECTIVE:To characterize the clinical features of patients hospitalized during a large urban epidemic of hepatitis A. DESIGN:Retrospective chart review. SETTING:15 acute care...
journal_title:Annals of internal medicine
pub_type: 杂志文章,多中心研究
doi:10.7326/0003-4819-128-2-199801150-00006
更新日期:1998-01-15 00:00:00
abstract::Abdominal aortic aneurysms (AAAs) occur in 1 of 20 older men, remain asymptomatic for many years, and, if left untreated, cause death from rupture in about one third of patients. Ultrasonography is a suitable screening test for AAA, and elective repair can prevent rupture. Although these features suggest a promising t...
journal_title:Annals of internal medicine
pub_type: 杂志文章,评审
doi:10.7326/0003-4819-139-6-200309160-00016
更新日期:2003-09-16 00:00:00
abstract::Four hundred sixty patients and staff from 15 U.S. dialysis centers were surveyed by the immune adherence hemagglutination technique for antibody to hepatitis A antigen (anti-HA). The age-standardized anti-HA prevalence was 42.9% in patients and 42.1% in staff. These rates are almost identical to those of socioeconomi...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-87-1-8
更新日期:1977-07-01 00:00:00
abstract::In patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may have symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disord...
journal_title:Annals of internal medicine
pub_type: 杂志文章,评审
doi:10.7326/0003-4819-109-2-143
更新日期:1988-07-15 00:00:00
abstract:BACKGROUND:Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. OBJECTIVE:To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography scre...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/M15-1241
更新日期:2016-02-16 00:00:00
abstract::Forceful new demands for accountability in medicine are arising from many interested parties. To maintain professional standards, physicians need to establish which demands are desirable and which are not. We adopt a model of stratified accountability that includes three major components: the accountable parties, the ...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-124-2-199601150-00008
更新日期:1996-01-15 00:00:00
abstract::Systematic reviewers increasingly must decide whether and how to incorporate existing systematic reviews into complex systematic reviews that are commissioned to support clinical guideline development or for other health policy uses. To date, however, this issue has been largely unexamined. Reviewers seeking to incorp...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-148-10-200805200-00010
更新日期:2008-05-20 00:00:00
abstract::We prospectively studied the evaluation of dementia in 107 unselected outpatients; 83 had so-called "irreversible" dementias, including 74 who had an Alzheimer-type dementia. Fifteen patients had potentially reversible dementias, of which hypothyroidism and drug toxicity were the commonest causes. Distinguishing featu...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-100-3-417
更新日期:1984-03-01 00:00:00
abstract:OBJECTIVE:To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. DESIGN:A retrospective medical record review. SETTING:A community-wide study in 16 short-stay hospitals in central Massachusetts. PATIENTS:A total of 2017 patients with multiple risk factors for venous th...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-591
更新日期:1991-10-15 00:00:00
abstract:Background:The benefits of pay-for-performance (P4P) programs are uncertain. Purpose:To update and expand a prior review examining the effects of P4P programs targeted at the physician, group, managerial, or institutional level on process-of-care and patient outcomes in ambulatory and inpatient settings. Data Sources...
journal_title:Annals of internal medicine
pub_type: 杂志文章,评审
doi:10.7326/M16-1881
更新日期:2017-03-07 00:00:00
abstract:BACKGROUND:Nearly 25% of patients hospitalized with heart failure (HF) are readmitted within 30 days. PURPOSE:To assess the efficacy, comparative effectiveness, and harms of transitional care interventions to reduce readmission and mortality rates for adults hospitalized with HF. DATA SOURCES:MEDLINE, Cochrane Librar...
journal_title:Annals of internal medicine
pub_type: 杂志文章,meta分析,评审
doi:10.7326/M14-0083
更新日期:2014-06-03 00:00:00
abstract:SOURCE CITATION:Liu J, Li L, Li S, et al. Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020;22:1619-27. 32364674. ...
journal_title:Annals of internal medicine
pub_type: 评论,杂志文章
doi:10.7326/ACPJ202010200-040
更新日期:2020-10-20 00:00:00
abstract:BACKGROUND:Sleep-related accidents often involve healthy young persons who are driving at night. Coffee and napping restore alertness, but no study has compared their effects on real nighttime driving performances. OBJECTIVE:To test the effects of 125 mL of coffee (half a cup) containing 200 mg of caffeine, placebo (d...
journal_title:Annals of internal medicine
pub_type: 杂志文章,随机对照试验
doi:10.7326/0003-4819-144-11-200606060-00004
更新日期:2006-06-06 00:00:00
abstract::Endocarditis is a relatively frequent infection in intravenous drug users. We compared features in the cases of 102 patients with those in intravenous drug users with other causes of fever to identify risk factors predictive of endocarditis. Logistic regression analysis showed cocaine use to be strongly associated wit...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-106-6-833
更新日期:1987-06-01 00:00:00
abstract::A 17-year-old girl with a clinical diagnosis of adult-type juvenile rheumatoid arthritis developed a severe hepatotoxic reaction to 3.6 g of aspirin per day. This was associated with a microangiopathic anemia and transient congestive cardiac failure. She responded well to steroids, and when all laboratory test finding...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-86-2-183
更新日期:1977-02-01 00:00:00
abstract:BACKGROUND:Injection insulin therapy is not readily accepted by patients and many health care providers; therefore, less invasive options for insulin therapy are desirable. PURPOSE:To examine the efficacy, safety, and patient acceptability of inhaled insulin therapy in nonpregnant adults with diabetes mellitus. DATA ...
journal_title:Annals of internal medicine
pub_type: 杂志文章,meta分析
doi:10.7326/0003-4819-145-9-200611070-00009
更新日期:2006-11-07 00:00:00
abstract::A patient with a retained bullet developed lead poisoning in association with thyrotoxicosis. The clinical and laboratory data suggest that lead was mobilized from an increased mobile bone pool during the hypermetabolic period with resultant poisoning. The findings give factual support to earlier concepts that lead po...
journal_title:Annals of internal medicine
pub_type: 杂志文章
doi:10.7326/0003-4819-89-4-509
更新日期:1978-10-01 00:00:00
abstract:PURPOSE:To review the status of emergency, urgent, routine, and selective angiography after intravenous thrombolytic therapy. DATA SOURCES:Relevant English-language articles published from January 1985 to July 1990 were identified through MEDLINE. STUDY SELECTION:For emergency angiography, four major randomized studi...
journal_title:Annals of internal medicine
pub_type: 杂志文章,评审
doi:10.7326/0003-4819-114-10-877
更新日期:1991-05-15 00:00:00