| 1. |
- Ahmad, Shafqat, et al.
(författare)
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Association of the Mediterranean Diet With Onset of Diabetes in the Women’s Health Study
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear.Objective To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population.Design, Setting, and Participants This cohort study was conducted among 25 317 apparently healthy women. The participants with missing information regarding all traditional and novel metabolic biomarkers or those with baseline diabetes were excluded. Participants were invited for baseline assessment between September 1992 and May 1995. Data were collected from November 1992 to December 2017 and analyzed from December 2018 to December 2019.Exposures MED intake score (range, 0 to 9) was computed from self-reported dietary intake, representing adherence to Mediterranean diet intake.Main Outcomes and Measures Incident cases of type 2 diabetes, identified through annual questionnaires; reported cases were confirmed by either telephone interview or supplemental questionnaire. Proportion of reduced risk of type 2 diabetes explained by clinical risk factors and a panel of 40 biomarkers that represent different physiological pathways was estimated.Results The mean (SD) age of the 25 317 female participants was 52.9 (9.9) years, and they were followed up for a mean (SD) of 19.8 (5.8) years. Higher baseline MED intake (score ≥6 vs ≤3) was associated with as much as a 30% lower type 2 diabetes risk (age-adjusted and energy-adjusted hazard ratio, 0.70; 95% CI, 0.62-0.79; when regression models were additionally adjusted with body mass index [BMI]: hazard ratio, 0.85; 95% CI, 0.76-0.96). Biomarkers of insulin resistance made the largest contribution to lower risk (accounting for 65.5% of the MED–type 2 diabetes association), followed by BMI (55.5%), high-density lipoprotein measures (53.0%), and inflammation (52.5%), with lesser contributions from branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%), and minimal contribution (≤2%) from hemoglobin A1c. In post hoc subgroup analyses, the inverse association of MED diet with type 2 diabetes was seen only among women who had BMI of at least 25 at baseline but not those who had BMI of less than 25 (eg, women with BMI <25, age- and energy-adjusted HR for MED score ≥6 vs ≤3, 1.01; 95% CI, 0.77-1.33; P for trend = .92; women with BMI ≥25: HR, 0.76; 95% CI, 0.67-0.87; P for trend < .001).Conclusions and Relevance In this cohort study, higher MED intake scores were associated with a 30% relative risk reduction in type 2 diabetes during a 20-year period, which could be explained in large part by biomarkers of insulin resistance, BMI, lipoprotein metabolism, and inflammation.
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| 2. |
- Almquist, Ylva B., et al.
(författare)
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Association of Child Placement in Out-of-Home Care With Trajectories of Hospitalization Because of Suicide Attempts From Early to Late Adulthood
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Importance Children placed in out-of-home care (OHC) have higher rates of suicidal behaviors, including suicide attempts, compared with those who grow up in their family of origin. Several studies have shown that this elevated risk persists into young adulthood. Yet, our knowledge about any longer-term associations of OHC with suicide attempts is limited. Objective To examine how childhood experiences of placement in OHC are associated with trajectories of hospitalization because of suicide attempts (HSA) from early into late adulthood. Design, Setting, and Participants This prospective birth cohort study that was conducted in Stockholm, Sweden, and analyzed in March 2020 included 14559 individuals born in 1953 who were living in the greater metropolitan of Stockholm in November 1963 and followed through registers up until December 2016. Exposures Childhood experiences of OHC based on information from the Social Register (age 0-19 years). Main Outcomes and Measures Hospitalization because of suicide attempts based on in-patient care data from the National Patient Register. Group-based trajectory modeling was used to cluster individuals according to their probabilities of HSA across adulthood (age 20-63 years). Results In this cohort of 14559 individuals (7146 women [49.1%]), 1320 individuals (9.1%) had childhood experiences of OHC, whereas 525 individuals ( 3.6%) had HSA. A Cox regression analysis showed a substantially higher risk of HSA among those with childhood experiences of OHC (hazard ratio, 3.58; 95% CI, 2.93-4.36) and after adjusting for a range of adverse childhood living conditions (hazard ratio, 2.51; 95% CI, 2.00-3.15). Those with at least 1 HSA were grouped into 4 trajectories: (1) peak in middle adulthood (66 [12.6%]), (2) stable low across adulthood (167 [31.8%]), (3) peak in early adulthood (210 [40.0%]), and (4) peak in emerging adulthood (82 [15.6%]). A multinomial regression analysis suggested that those with experiences of OHC had higher risks of following any of these trajectories (trajectory 1: relative risk ratio [RRR], 2.91; 95% CI, 1.61-5.26; trajectory 2: RRR, 3.18; 95% CI, 2.21-4.59; trajectory 3: RRR, 4.32; 95% CI, 3.18-5.86; trajectory 4: RRR, 3.26; 95% CI, 1.94-5.46). The estimates were reduced after adjusting for adverse childhood living conditions. Conclusions and Relevance The findings suggest that the elevated risk of suicide attempts among former child welfare clients does not cease after young adulthood, indicating the necessity for clinical attention to childhood experiences of OHC as a risk marker for suicidal behavior across the life span. Question How are childhood experiences of placement in out-of-home care associated with trajectories of hospitalization because of suicide attempts from early into late adulthood? Findings In this cohort study of 14559 individuals, individuals were grouped into 4 trajectories with differential onset of suicide attempts across adulthood. Childhood experiences of placement in out-of-home care were associated with increased risks of following each of these trajectories. Meaning The elevated risk of suicide attempts among former child welfare clients persists into young adulthood, indicating the necessity for clinical attention to childhood experiences of out-of-home care as a risk marker for suicidal behavior across the life span. This cohort study examines the association between childhood experiences of placement in out-of-home care and trajectories of hospitalization because of suicide attempts from early into late adulthood in Sweden.
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| 3. |
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| 4. |
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| 5. |
- Brunström, Mattias, et al.
(författare)
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Association of physician education and feedback on hypertension management with patient blood pressure and hypertension control
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Elevated systolic blood pressure (SBP) is the most important risk factor for premature death worldwide. However, hypertension detection and control rates continue to be suboptimal.To assess the association of education and feedback to primary care physicians with population-level SBP and hypertension control rates.This pooled series of 108 population-based cohort studies involving 283 079 patients used data from primary care centers in 2 counties (Västerbotten and Södermanland) in Sweden from 2001 to 2009. Participants were individuals aged 18 years or older who had their blood pressure (BP) measured and recorded in either county during the intervention period. All analyses were performed in February 2019.An intervention comprising education and feedback for primary care physicians in Västerbotten County (intervention group) compared with usual care in Södermanland County (control group).Difference in mean SBP levels between counties and likelihood of hypertension control in the intervention county compared with the control county during 24 months of follow-up.A total of 136 541 unique individuals (mean [SD] age at inclusion, 64.6 [16.1] years; 57.0% female; mean inclusion BP, 142/82 mm Hg) in the intervention county were compared with 146 538 individuals (mean [SD] age at inclusion, 65.7 [15.9] years; 58.3% female; mean inclusion BP, 144/80 mm Hg) in the control county. Mean SBP difference between counties during follow-up, adjusted for inclusion BP and other covariates, was 1.1 mm Hg (95% CI, 1.0-1.1 mm Hg). Hypertension control improved by 8.4 percentage points, and control was achieved in 37.8% of participants in the intervention county compared with 29.4% in the control county (adjusted odds ratio, 1.30; 95% CI, 1.29-1.31). Differences between counties increased during the intervention period and were more pronounced in participants with higher SBP at inclusion. Results were consistent across all subgroups.This study suggests that SBP levels and hypertension control rates in a county population may be improved by educational approaches directed at physicians and other health care workers. Similar strategies may be adopted to reinforce the implementation of clinical practice guidelines for hypertension management.
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| 6. |
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| 7. |
- Clausen, Henning, et al.
(författare)
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Evaluation of Circulating Cardiovascular Biomarker Levels for Early Detection of Congenital Heart Disease in Newborns in Sweden
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Congenital heart disease (CHD) is the most common congenital malformation in humans worldwide. Circulating cardiovascular biomarkers could potentially improve the early detection of CHD, even in asymptomatic newborns. Objectives: To assess the performance of a dried blood spot (DBS) test to measure the cardiovascular biomarker amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) levels in newborns and to compare DBS with standard EDTA analysis in control newborns during the first week of life. Design, Setting, and Participants: This diagnostic study was conducted in a single regional pediatric service in southern Sweden. Healthy, term neonates born between July 1, 2018, and May 31, 2019, were prospectively enrolled and compared against retrospectively identified newborns with CHD born between September 1, 2003, and September 30, 2019. Neonates who required inpatient treatment beyond the standard postnatal care were excluded. Exposure: New DBS test for NT-proBNP quantification in newborns that used 3 μL of blood vs the current screening standard. Main Outcomes and Measures: Performance of the new test and when combined with pulse oximetry screening was measured by receiver operating characteristic curve analysis. Performance of the new test and EDTA screening was compared using Pearson linear correlation analysis. Results: The DBS samples of 115 neonates (81 control newborns and 34 newborns with CHD, of whom 63 were boys [55%] and the mean [SD] gestational age was 39.6 [1.4] weeks) were analyzed. The new NT-proBNP test alone identified 71% (n = 24 of 34) of all CHD cases and 68% (n = 13 of 19) of critical CHD cases as soon as 2 days after birth. Detection of any CHD type improved to 82% (n = 28 of 34 newborns) and detection of critical CHD improved to 89% (n = 17 of 19 newborns) when combined pulse oximetry screening and NT-proBNP test results were used. Performance of the NT-proBNP test was excellent when control newborns were matched to newborns with CHD born between July 1, 2018, and May 31, 2019 (area under the curve, 0.96; SE, 0.027; 95% CI, 0.908-1.0; asymptotic P < .05). Conclusions and Relevance: This study found that NT-proBNP assay using minimal DBS samples appears to be timely and accurate in detecting CHD in newborns and to discriminate well between healthy newborns and newborns with various types of CHD. This finding warrants further studies in larger cohorts and highlights the potential of NT-proBNP to improve neonatal CHD screening.
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| 8. |
- Dandoy, Christopher E., et al.
(författare)
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Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant
- 2020
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other).Objective: To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.Design, Setting, and Participants: A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018.Main Outcomes and Measures: Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups.Results: Of the 16875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]).Conclusions and Relevance: In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population. This cohort study examines the incidence, timing, risk factors, and outcomes of patients who develop mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI) in the first 100 days after hematopoietic stem cell transplant (HSCT).
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| 11. |
- Goralnick, Eric, et al.
(författare)
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Defining a Research Agenda for Layperson Prehospital Hemorrhage Control A Consensus Statement
- 2020
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- Importance Trauma is the leading cause of death for US individuals younger than 45 years, and uncontrolled hemorrhage is a major cause of trauma mortality. The US military’s medical advancements in the field of prehospital hemorrhage control have reduced battlefield mortality by 44%. However, despite support from many national health care organizations, no integrated approach to research has been made regarding implementation, epidemiology, education, and logistics of prehospital hemorrhage control by layperson immediate responders in the civilian sector.Objective To create a national research agenda to help guide future work for prehospital hemorrhage control by laypersons.Evidence Review The 2-day, in-person, National Stop the Bleed (STB) Research Consensus Conference was conducted on February 27 to 28, 2019, to identify and achieve consensus on research gaps. Participants included (1) subject matter experts, (2) professional society–designated leaders, (3) representatives from the federal government, and (4) representatives from private foundations. Before the conference, participants were provided a scoping review on layperson prehospital hemorrhage control. A 3-round modified Delphi consensus process was conducted to determine high-priority research questions. The top items, with median rating of 8 or more on a Likert scale of 1 to 9 points, were identified and became part of the national STB research agenda.Findings Forty-five participants attended the conference. In round 1, participants submitted 487 research questions. After deduplication and sorting, 162 questions remained across 5 a priori–defined themes. Two subsequent rounds of rating generated consensus on 113 high-priority, 27 uncertain-priority, and 22 low-priority questions. The final prioritized research agenda included the top 24 questions, including 8 for epidemiology and effectiveness, 4 for materials, 9 for education, 2 for global health, and 1 for health policy.Conclusions and Relevance The National STB Research Consensus Conference identified and prioritized a national research agenda to support laypersons in reducing preventable deaths due to life-threatening hemorrhage. Investigators and funding agencies can use this agenda to guide their future work and funding priorities.
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| 12. |
- Hijazi, Ziad, et al.
(författare)
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Evaluation of the Age, Biomarkers, and Clinical History-Bleeding Risk Score in Patients With Atrial Fibrillation With Combined Aspirin and Anticoagulation Therapy Enrolled in the ARISTOTLE and RE-LY Trials
- 2020
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:9
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Most patients with atrial fibrillation (AF) and coronary artery disease have indications for preventing stroke with oral anticoagulation therapy and preventingmyocardial infarction and stent thrombosis with platelet inhibition. OBJECTIVE To evaluate whether the recently developed ABC (age, biomarkers, and clinical history)bleeding risk score might be useful to identify patients with AF with different risks of bleeding during concomitant aspirin and anticoagulation therapy. DESIGN, SETTING, AND PARTICIPANTS The biomarkers in the ABC-bleeding risk score (growth differentiation factor 15, hemoglobin, and troponin) were measured in blood samples collected at randomization between 2006 and 2010 in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial and between 2005 and 2009 in the RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial, both of which were multinational randomized clinical trials. The trials were reported 2011 and 2009, respectively. A total of 24 349 patients with AF (14 980 patients from the ARISTOTLE trial and 9369 patients from the RE-LY trial) were analyzed in the present cohort study. The median (interquartile range) length of follow-up was 1.8 (1.3-2.3) years in the ARISTOTLE cohort and 2.0 (1.6-2.3) years in the RE-LY cohort. Data analysis was performed from February 2018 to June 2019. EXPOSURES Concomitant aspirin treatment during study follow-up. MAIN OUTCOMES AND MEASURES Time to first occurrence of a major bleeding was determined according to International Society on Thrombosis and Hemostasis definition. Hazard ratios were estimated with Cox models adjusted for ABC-bleeding risk score and randomized treatment. RESULTS The median (interquartile range) age was 70 (63-76) years in the ARISTOTLE cohort and 72 (67-77) years in the RE-LY cohort (5238 patients [35.6%] in the ARISTOTLE cohort and 3086 patients [36.4%] in the RE-LY cohort were women). The total number of patients with a first major bleeding event was 651 (207 with aspirin and 444 without) in ARISTOTLE and 463 (238 with aspirin and 225 without) in RE-LY. For both cohorts, in those with a lowABC-bleeding risk score, the absolute bleeding rate was low even with concomitant aspirin treatment, whereas in those with a higher ABC-bleeding risk score, the rate of bleedingwas higher with concomitant aspirin compared with oral anticoagulation alone (ARISTOTLE, hazard ratio, 1.65; 95% CI, 1.40-1.95; P <.001; RE-LY, hazard ratio, 1.70; 95% CI, 1.42-2.04; P <.001). Thus, a low annual ABC-bleeding risk (eg, 0.5% without aspirin use) would with concomitant aspirin result in an annual rate of 0.8%, and a high estimated ABC-bleeding risk (eg, 3.0%) would result in a substantially higher rate of 5.0%. CONCLUSIONS AND RELEVANCE These findings suggest that the ABC-bleeding risk score identifies patients with different risks of bleeding when combining aspirin and oral anticoagulation. The ABC-bleeding risk score may, therefore, be a useful tool for decision support concerning intensity and duration of combination antithrombotic treatment in patients with AF and coronary artery disease.
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| 14. |
- Kivimäki, Mika, et al.
(författare)
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Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 3:9
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective: To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants: Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131 415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures: Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures: Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results: Of the 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96 591 participants with data on loss of consciousness, 10 004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (<65 y: HR, 2.21; 95% CI, 1.46-3.34) and late-onset (≥65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54). Conclusions and Relevance: The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia.
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| 16. |
- Kovac, E., et al.
(författare)
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Association of Baseline Prostate-Specific Antigen Level With Long-term Diagnosis of Clinically Significant Prostate Cancer Among Patients Aged 55 to 60 Years: A Secondary Analysis of a Cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
- 2020
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The use of prostate-specific antigen (PSA) screening for prostate cancer is controversial because of the risk of overdiagnosis and overtreatment of indolent cancers. Optimal screening strategies are highly sought. Objective: To estimate the long-term risk of any prostate cancer and clinically significant prostate cancer based on baseline PSA levels among men aged 55 to 60 years. Design, Setting, and Participants: This secondary analysis of a cohort in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial uses actuarial analysis to analyze the association of baseline PSA levels with long-term risk of any prostate cancer and of clinically significant prostate cancer among men aged 55 to 60 years enrolled in the screening group of the trial between 1993 and 2001. Exposure: Single PSA measurement at study entry. Main Outcomes and Measures: Long-term risk of any prostate cancer and clinically significant prostate cancer diagnoses. Results: There were 10968 men aged 55 to 60 years (median [interquartile range] age, 57 [55-58] years) at study enrollment in the screening group of the PLCO Cancer Screening Trial who had long-term follow-up. Actuarial 13-year incidences of clinically significant prostate cancer diagnosis among participants with a baseline PSA of 0.49 ng/mL or less was 0.4% (95% CI, 0%-0.8%); 0.50-0.99 ng/mL, 1.5% (95% CI, 1.1%-1.9%); 1.00-1.99 ng/mL, 5.4% (95% CI, 4.4%-6.4%); 2.00-2.99 ng/mL, 10.6% (95% CI, 8.3%-12.9%); 3.00-3.99 ng/mL, 15.3% (95% CI, 11.4%-19.2%); and 4.00 ng/mL and greater, 29.5% (95% CI, 24.2%-34.8%) (all pairwise log-rank P≤.004). Only 15 prostate cancer-specific deaths occurred during 13 years of follow-up, and 9 (60.0%) were among men with a baseline PSA level of 2.00 ng/mL or higher. Conclusions and Relevance: In this secondary analysis of a cohort from the PLCO Cancer Screening Trial, baseline PSA levels among men aged 55 to 60 years were associated with long-term risk of clinically significant prostate cancer. These findings suggest that repeated screening can be less frequent among men aged 55 to 60 years with a low baseline PSA level (ie, <2.00 ng/mL) and possibly discontinued among those with baseline PSA levels of less than 1.00 ng/mL.
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| 17. |
- Kvale, Gerd, et al.
(författare)
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Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder : A Randomized Clinical Trial
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD.OBJECTIVE: To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD.DESIGN, SETTING, AND PARTICIPANTS: The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019.INTERVENTIONS: All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo.MAIN OUTCOMES AND MEASURES: Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life.RESULTS: The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, -0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, -0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire-9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, -0.17 to 0.76; Generalized Anxiety Disorder-7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, -0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, -0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, -0.19 to 0.86). No serious adverse effects were reported.CONCLUSIONS AND RELEVANCE: In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. This randomized clinical trial evaluates whether D-cycloserine potentiates the effect of concentrated exposure and response prevention among patients with difficult-to-treat obsessive-compulsive disorder.
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| 18. |
- Leong, Karen S. W., et al.
(författare)
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Associations of Prenatal and Childhood Antibiotic Exposure With Obesity at Age 4 Years
- 2020
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Importance Although antibiotics are associated with obesity in animal models, the evidence in humans is conflicting. Objective To assess whether antibiotic exposure during pregnancy and/or early childhood is associated with the development of childhood obesity, focusing particularly on siblings and twins. Design, Setting, and Participants This cross-sectional national study included 284 & x202f;211 participants (132 & x202f;852 mothers and 151 & x202f;359 children) in New Zealand. Data analyses were performed for 150 & x202f;699 children for whom data were available, 30 & x202f;696 siblings, and 4188 twins using covariate-adjusted analyses, and for 6249 siblings and 522 twins with discordant outcomes using fixed-effects analyses. Data analysis was performed November 2017 to March 2019. Exposure Exposure to antibiotics during pregnancy and/or early childhood. Main Outcomes and Measures The main outcome is odds of obesity at age 4 years. Anthropometric data from children born between July 2008 and June 2011 were obtained from the B4 School Check, a national health screening program that records the height and weight of 4-year-old children in New Zealand. These data were linked to antibiotics (pharmaceutical records) dispensed to women before conception and during all 3 trimesters of pregnancy and to their children from birth until age 2 years. Results The overall study population consisted of 132 & x202f;852 mothers and 151 & x202f;359 children (77 & x202f;610 [51.3%] boys) who were aged 4 to 5 years when their anthropometrical measurements were assessed. Antibiotic exposure was common, with at least 1 course dispensed to 35.7% of mothers during pregnancy and 82.3% of children during the first 2 years of life. Results from covariate-adjusted analyses showed that both prenatal and early childhood exposures to antibiotics were independently associated with obesity at age 4 years, in a dose-dependent manner. Every additional course of antibiotics dispensed to the mothers yielded an adjusted odds ratio (aOR) of obesity in their children (siblings) of 1.02 (95% CI, 0.99-1.06), which was similar to the odds across pregnancy for the whole population (aOR, 1.06; 95% CI, 1.04-1.07). For the child's exposure, the aOR for the association between antibiotic exposure and obesity was 1.04 (95% CI, 1.03-1.05) among siblings and 1.05 (95% CI, 1.02-1.09) among twins. However, fixed-effects analyses of siblings and twins showed no associations between antibiotic exposure and obesity, with aORs of 0.95 (95% CI, 0.90-1.00) for maternal exposure, 1.02 (95% CI, 0.99-1.04) for child's exposure, and 0.91 (95% CI, 0.81-1.02) for twins' exposure. Conclusions and Relevance Although covariate-adjusted analyses demonstrated an association between antibiotic exposure and odds of obesity, further analyses of siblings and twins with discordant outcomes showed no associations. Thus, these discordant results likely reflect unmeasured confounding factors. Question Is antibiotic exposure during pregnancy and/or during early childhood associated with the development of childhood obesity? Findings This cross-sectional national study of 284 & x202f;211 participants (132 & x202f;852 mothers and 151 & x202f;359 children) in New Zealand found that both prenatal and early childhood exposures to antibiotics were independently associated with obesity at age 4 years in a dose-dependent manner. However, fixed-effects analyses of siblings and twins with discordant outcomes showed no associations between antibiotic exposure and obesity. Meaning Although judicious use of antibiotics is necessary, antibiotics are unlikely to be a major contributor to childhood obesity. This cross-sectional study of mothers and their children in New Zealand assesses whether exposure to antibiotics during pregnancy and/or early childhood is associated with the development of childhood obesity.
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- Leong, Karen S. W., et al.
(författare)
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Effects of Fecal Microbiome Transfer in Adolescents With Obesity The Gut Bugs Randomized Controlled Trial
- 2020
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- Importance Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.
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- Peultier, Anne-Claire, et al.
(författare)
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Cost-effectiveness of Mechanical Thrombectomy More Than 6 Hours After Symptom Onset Among Patients With Acute Ischemic Stroke
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- Importance Two 2018 randomized controlled trials (DAWN and DEFUSE 3) demonstrated the clinical benefit of mechanical thrombectomy (MT) more than 6 hours after onset in acute ischemic stroke (AIS). Health-economic evidence is needed to determine whether the short-term health benefits of late MT translate to a cost-effective option during a lifetime in the United States. Objective To compare the cost-effectiveness of 2 strategies (MT added to standard medical care [SMC] vs SMC alone) for various subgroups of patients with AIS receiving care more than 6 hours after symptom onset. Design, Setting, and Participants This economic evaluation study used the results of the DAWN and DEFUSE 3 trials to populate a cost-effectiveness model from a US health care perspective combining a decision tree and Markov trace. The DAWN and DEFUSE 3 trials enrolled 206 international patients from 2014 to 2017 and 182 US patients from 2016 to 2017, respectively. Patients were followed until 3 months after stroke. The clinical outcome at 3 months was available for 29 subgroups of patients with AIS and anterior circulation large vessel occlusions. Data analysis was conducted from July 2018 to October 2019. Exposures MT with SMC in the extended treatment window vs SMC alone. Main Outcomes and Measures Expected costs and quality-adjusted life-years (QALYs) during lifetime were estimated. Deterministic results (incremental costs and effectiveness, incremental cost-effectiveness ratios, and net monetary benefit) were presented, and probabilistic analyses were performed for the total populations and 27 patient subgroups. Results In the DAWN study, the MT group had a mean (SD) age of 69.4 (14.1) years and 42 of 107 (39.3%) were men, and the control group had a mean (SD) age of 70.7 (13.2) years and 51 of 99 (51.5%) were men. In the DEFUSE 3 study, the MT group had a median (interquartile range) age of 70 (59-79) years, and 46 of 92 (50.0%) were men, and the control group had a median (interquartile range) age of 71 (59-80) years, and 44 of 90 (48.9%) were men. For the total trial population, incremental cost-effectiveness ratios were $662/QALY and $13877/QALY based on the DAWN and DEFUSE 3 trials, respectively. MT with SMC beyond 6 hours had a probability greater than 99.9% of being cost-effective vs SMC alone at a willingness-to-pay threshold of $100 000/QALY. Subgroup analyses showed a wide range of probabilities for MT with SMC to be cost-effective at a willingness-to-pay threshold of $50000/QALY, with the greatest uncertainty observed for patients with a National Institute of Health Stroke Scale score of at least 16 and for those aged 80 years or older. Conclusions and Relevance The results of this study suggest that late MT added to SMC is cost-effective in all subgroups evaluated in the DAWN and DEFUSE 3 trials, with most results being robust in probabilistic sensitivity analyses. Future MT evidence-gathering could focus on older patients and those with National Institute of Health Stroke Scale scores of 16 and greater.Question Is mechanical thrombectomy in the extended treatment window cost-effective across patient subgroups in the United States? Findings This economic evaluation study found that mechanical thrombectomy provides good value for money in all the defined subgroups the 2 randomized clinical trials evaluated. Sensitivity analyses revealed a wide range of probabilities for late mechanical thrombectomy to be cost-effective at the willingness-to-pay threshold of $50 000 per quality-adjusted life-year. Meaning The results of this study suggest that attention should be placed on increasing access to mechanical thrombectomy rather than on developing subgroup-specific guidelines unless workforce and budget constraints require prioritization.This economic evaluation study compares the cost-effectiveness of 2 strategies (mechanical thrombectomy with standard medical care vs standard medical care alone) for various subgroups of patients with acute ischemic stroke who were receiving care more than 6 hours after symptom onset.
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