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| 33. |
- Cnattingius, Sven, et al.
(författare)
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Maternal Obesity and Risk of Preterm Delivery
- 2013
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:22, s. 2362-2370
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Tidskriftsartikel (refereegranskat)abstract
- Importance Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. Objective To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. Design, Setting, and Participants Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. Main Outcomes and Measures Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. Results Among 1 599 551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67 059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI >= 30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. Conclusions and Relevance In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.
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| 35. |
- Coelho, Teresa, et al.
(författare)
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Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy
- 2023
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 330:15, s. 1448-1458
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis.Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy.Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group.Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60).Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights.Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P <.001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group.Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo.Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.
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| 36. |
- Coresh, Josef, et al.
(författare)
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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:24, s. 2518-2531
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
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| 37. |
- Crump, Casey, et al.
(författare)
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Gestational Age at Birth and Mortality in Young Adulthood
- 2011
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 306:11, s. 1233-1240
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Tidskriftsartikel (refereegranskat)abstract
- Context Preterm birth is the leading cause of infant mortality in developed countries, but the association between gestational age at birth and mortality in adulthood remains unknown. Objective To examine the association between gestational age at birth and mortality in young adulthood. Design, Setting, and Participants National cohort study of 674 820 individuals born as singletons in Sweden in 1973 through 1979 who survived to age 1 year, including 27 979 born preterm (gestational age <37 weeks), followed up to 2008 (ages 29-36 years). Main Outcome Measures All-cause and cause-specific mortality. Results A total of 7095 deaths occurred in 20.8 million person-years of follow-up. Among individuals still alive at the beginning of each age range, a strong inverse association was found between gestational age at birth and mortality in early childhood (ages 1-5 years: adjusted hazard ratio [aHR] for each additional week of gestation, 0.92; 95% CI, 0.89-0.94; P<.001), which disappeared in late childhood (ages 6-12 years: aHR, 0.99; 95% CI, 0.95-1.03; P=.61) and adolescence (ages 13-17 years: aHR, 0.99; 95% CI, 0.95-1.03; P=.64) and then reappeared in young adulthood (ages 18-36 years: aHR, 0.96; 95% CI, 0.94-0.97; P<.001). In young adulthood, mortality rates (per 1000 person-years) by gestational age at birth were 0.94 for 22 to 27 weeks, 0.86 for 28 to 33 weeks, 0.65 for 34 to 36 weeks, 0.46 for 37 to 42 weeks (full-term), and 0.54 for 43 or more weeks. Preterm birth was associated with increased mortality in young adulthood even among individuals born late preterm (34-36 weeks, aHR, 1.31; 95% CI, 1.13-1.50; P<.001), relative to those born full-term. In young adulthood, gestational age at birth had the strongest inverse association with mortality from congenital anomalies and respiratory, endocrine, and cardiovascular disorders and was not associated with mortality from neurological disorders, cancer, or injury. Conclusion After excluding earlier deaths, low gestational age at birth was independently associated with increased mortality in early childhood and young adulthood. JAMA. 2011;306(11):1233-1240 www.jama.com
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| 38. |
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| 39. |
- Danesh, John, et al.
(författare)
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Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
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