| 1. |
- Eklind-Cervenka, Maria, et al.
(författare)
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Association of Candesartan vs Losartan With All-Cause Mortality in Patients With Heart Failure
- 2011
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Ingår i: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. - : Ama American Medical Association. - 0098-7484 .- 1538-3598. ; 305:2, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Context Angiotensin II receptor blockers (ARBs) reduce combined mortality and hospitalization in patients with heart failure (HF) with reduced left ventricular ejection fraction. Different agents have different affinity for the AT(1) receptor and may have different clinical effects, but have not been tested against each other in HF. Objective To assess the association of candesartan vs losartan with all-cause mortality in patients with HF. Design, Setting, and Patients An HF registry (the Swedish Heart Failure Registry) of 30 254 unique patients registered from 62 hospitals and 60 outpatient clinics between 2000 and 2009. A total of 5139 patients (mean [SD] age, 74 [11] years; 39% women) were treated with candesartan (n=2639) or losartan (n=2500). Survival as of December 14, 2009, by ARB agent was analyzed by Kaplan-Meier method and predictors of survival determined by univariate and multivariate proportional hazard regression models, with and without adjustment for propensity scores and interactions. Stratified analyses and quantification of residual confounding were also performed. Main Outcome Measures All-cause mortality at 1 and 5 years. Results One-year survival was 90% (95% confidence interval [CI], 89%-91%) for patients receiving candesartan and 83% (95% CI, 81%-84%) for patients receiving losartan, and 5-year survival was 61% (95% CI, 54%-68%) and 44% (95% CI, 41%-48%), respectively (log-rank Pandlt;.001). In multivariate analysis with adjustment for propensity scores, the hazard ratio for mortality for losartan compared with candesartan was 1.43 (95% CI, 1.23-1.65; Pandlt;.001). The results persisted in stratified analyses. Conclusion In this registry of patients with HF, the use of candesartan compared with losartan was associated with a lower mortality risk.
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| 2. |
- Fellman, Vineta, et al.
(författare)
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One-year survival of extremely preterm infants after active perinatal care in Sweden.
- 2009
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Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
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Tidskriftsartikel (refereegranskat)abstract
- Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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| 3. |
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| 4. |
- Gheorghiade, Mihai, et al.
(författare)
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Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction : The SOCRATES-REDUCED Randomized Trial.
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:21, s. 2251-2262
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem.OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF).DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic.INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks.MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point.RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively.CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01951625.
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| 5. |
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| 6. |
- Knip, Mikael, et al.
(författare)
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Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
- 2018
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:1, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
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| 7. |
- Knip, Mikael, et al.
(författare)
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Hydrolyzed infant formula and early β-cell autoimmunity : a randomized clinical trial.
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:22, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.
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| 8. |
- Lund, Lars H., et al.
(författare)
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Association Between Use of beta-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA): JAMA. - 0098-7484 .- 1538-3598. ; 312:19, s. 2008-2018
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). beta-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF. OBJECTIVE To test the hypothesis that beta-blockers are associated with reduced all-cause mortality in HFPEF. DESIGN Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for beta-blacker use were derived from 52 baseline clinical and socioeconomic variables. SETTING Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012. PARTICIPANTS From a consecutive sample of 41 976 patients, 19 083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for beta-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22 893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients. EXPOSURES beta-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization. RESULTS Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279(41%) vs 1244(45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% Cl, 0.86-0.996; P =.04). beta-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368(61%) vs 1753(64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% Cl, 0.92-1.04; P = .46). In the matched HFREF cohort, beta-blockers were associated with reduced mortality (HR, 0.89; 95% Cl, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% Cl, 0.84-0.95; P =.001). CONCLUSIONS AND RELEVANCE In patients with HFPEF, use of beta-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. beta-Blockers in HFPEF should be examined in a large randomized clinical trial.
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| 9. |
- Lund, Lars H, et al.
(författare)
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Association Between Use of Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure and Preserved Ejection Fraction
- 2012
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA): JAMA. - 0098-7484 .- 1538-3598. ; 308:20, s. 2108-2117
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT:Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered.OBJECTIVE:To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF.DESIGN, SETTING, AND PATIENTS:Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction ≥40%; mean [SD] age, 75 [11] years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction <40%) in the same registry.MAIN OUTCOME MEASURE:All-cause mortality.RESULTS:In the matched HFPEF cohort, 1-year survival was 77% (95% CI, 75%-78%) for treated patients vs 72% (95% CI, 70%-73%) for untreated patients, with a hazard ratio (HR) of 0.91 (95% CI, 0.85-0.98; P = .008). In the overall HFPEF cohort, crude 1-year survival was 86% (95% CI, 86%-87%) for treated patients vs 69% (95% CI, 68%-71%) for untreated patients, with a propensity score-adjusted HR of 0.90 (95% CI, 0.85-0.96; P = .001). In the HFPEF dose analysis, the HR was 0.85 (95% CI, 0.78-0.83) for 50% or greater of target dose vs no treatment (P < .001) and 0.94 (95% CI, 0.87-1.02) for less than 50% of target dose vs no treatment (P = .14). In the age and propensity score-matched HFREF analysis, the HR was 0.80 (95% CI, 0.74-0.86; P < .001).CONCLUSION:Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.
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| 10. |
- Mattsson, Niklas, 1979, et al.
(författare)
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CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.
- 2009
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Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 385-93
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
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