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1.
  • Maret-Ouda, John, et al. (författare)
  • Association between laparoscopic antireflux surgery and recurrence of gastroesophageal reflux
  • 2017
  • Ingår i: Journal of the American Medical Association. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0098-7484 .- 1538-3598.
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: Cohort studies, mainly based on questionnaires and interviews, have reported high rates of reflux recurrence after antireflux surgery, which may have contributed to a decline in its use. Reflux recurrence after laparoscopic antireflux surgery has not been assessed in a long-term population-based study of unselected patients. OBJECTIVES: To determine the risk of reflux recurrence after laparoscopic antireflux surgery and to identify risk factors for recurrence. DESIGN AND SETTING: Nationwide population-based retrospective cohort study in Sweden between January 1, 2005, and December 31, 2014, based on all Swedish health care and including 2655 patients who underwent laparoscopic antireflux surgery according to the Swedish Patient Registry. Their records were linked to the Swedish Causes of Death Registry and Prescribed Drug Registry. EXPOSURES: Primary laparoscopic antireflux surgery due to gastroesophageal reflux disease in adults (>18 years). MAIN OUTCOMES AND MEASURES: The outcomewas recurrence of reflux, defined as use of antireflux medication (proton pump inhibitors or histamine2 receptor antagonists for >6 months) or secondary antireflux surgery. Multivariable Cox regression was used to assess risk factors for reflux recurrence. RESULTS: Among all 2655 patients who underwent antireflux surgery (median age, 51.0 years; interquartile range, 40.0-61.0 years; 1354 men [51.0%]) and were followed up for a median of 5.6 years, 470 patients (17.7%) had reflux recurrence; 393 (83.6%) received long-term antireflux medication and 77 (16.4%) underwent secondary antireflux surgery. Risk factors for reflux recurrence included female sex (hazard ratio [HR], 1.57 [95%CI, 1.29-1.90]; 286 of 1301 women [22.0%] and 184 of 1354 men [13.6%] had recurrence of reflux), older age (HR, 1.41 [95%CI, 1.10-1.81] for age 61 years compared with 45 years; recurrence among 156 of 715 patients and 133 of 989 patients, respectively), and comorbidity (HR, 1.36 [95%CI, 1.13-1.65] for Charlson comorbidity index score 1 compared with 0; recurrence among 180 of 804 patients and 290 of 1851 patients, respectively). Hospital volume of antireflux surgery was not associated with risk of reflux recurrence (HR, 1.09 [95%CI, 0.77-1.53] for hospital volume 24 surgeries compared with 76 surgeries; recurrence among 38 of 266 patients [14.3%] and 271 of 1526 patients [17.8%], respectively). CONCLUSIONS AND RELEVANCE: Among patients who underwent primary laparoscopic antireflux surgery, 17.7%experienced recurrent gastroesophageal reflux requiring long-term medication use or secondary antireflux surgery. Risk factors for recurrence were older age, female sex, and comorbidity. Laparoscopic antireflux surgery was associated with a relatively high rate of recurrent gastroesophageal reflux disease requiring treatment, diminishing some of the benefits of the operation.
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  • Sujan, Ayesha C, et al. (författare)
  • Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring
  • 2017
  • Ingår i: JAMA. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0098-7484 .- 1538-3598.
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding. Objective: To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Design, Setting, and Participants: This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations. Exposures: Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations. Main Outcomes and Measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring. Results: Among 1580629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n = 22544] with maternal first-trimester self-reported antidepressant use) born to 943776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons. Conclusions and Relevance: Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.
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  • Abdul-Aziz, Mohd H., et al. (författare)
  • Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults with Sepsis or Septic Shock : A Systematic Review and Meta-Analysis
  • 2024
  • Ingår i: JAMA. - 0098-7484.
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2= 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.
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  • Alehagen, Urban, et al. (författare)
  • Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure
  • 2011
  • Ingår i: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. - : Ama American Medical Association. - 0098-7484. ; 305:20, s. 2088-2095
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. Objective To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Design, Setting, and Participants Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. Main Outcome Measures All-cause mortality and cardiovascular mortality. Results After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P=.01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; Pandlt;.001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P=.048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; Pandlt;.001). Conclusion Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.
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  • Andrén Aronsson, Carin, et al. (författare)
  • Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk
  • 2019
  • Ingår i: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 322:6, s. 514-523
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: High gluten intake during childhood may confer risk of celiac disease. Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.
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  • Aspvall, K., et al. (författare)
  • Effect of an Internet-Delivered Stepped-Care Program vs In-Person Cognitive Behavioral Therapy on Obsessive-Compulsive Disorder Symptoms in Children and Adolescents: A Randomized Clinical Trial
  • 2021
  • Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 325:18, s. 1863-1873
  • Tidskriftsartikel (refereegranskat)abstract
    • Key PointsQuestionIs internet-delivered cognitive behavioral therapy (CBT) implemented in a stepped-care model noninferior to in-person CBT for children and adolescents with obsessive-compulsive disorder? FindingsIn this randomized, noninferiority clinical trial, 152 children and adolescents with obsessive-compulsive disorder were treated with an internet-delivered CBT program followed by traditional in-person CBT if necessary vs in-person CBT alone. After 6 months, the mean Children's Yale-Brown Obsessive-Compulsive Scale score was 11.57 in those treated with internet-delivered CBT vs 10.57 in those treated with in-person CBT, a difference that met the noninferiority criterion of 4 points. MeaningTreating children and adolescents with obsessive-compulsive disorder with an internet intervention followed by traditional face-to-face therapy if necessary was noninferior to in-person therapy alone. ImportanceIn most countries, young people with obsessive-compulsive disorder have limited access to specialist cognitive behavioral therapy (CBT), a first-line treatment. ObjectiveTo investigate whether internet-delivered CBT implemented in a stepped-care model is noninferior to in-person CBT for pediatric obsessive-compulsive disorder. Design, Setting and ParticipantsA randomized clinical noninferiority trial conducted at 2 specialist child and adolescent mental health clinics in Sweden. Participants included 152 individuals aged 8 to 17 years with obsessive-compulsive disorder. Enrollment began in October 2017 and ended in May 2019. Follow-up ended in April 2020. InterventionsParticipants randomized to the stepped-care group (n=74) received internet-delivered CBT for 16 weeks. Nonresponders at the 3-month follow-up were then offered a course of traditional face-to-face treatment. Participants randomized to the control group (n=78) immediately received in-person CBT for 16 weeks. Nonresponders at the 3-month follow-up received additional face-to-face treatment. Main Outcomes and MeasuresThe primary outcome was the masked assessor-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score at the 6-month follow-up. The scale includes 10 items rated from 0(no symptoms) to 4(extreme symptoms), yielding a total score range of 0 to 40, with higher scores indicating greater severity. Assessors were masked to treatment allocation at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up assessments. The predefined noninferiority margin was 4 points on the CY-BOCS. ResultsAmong the 152 randomized participants (mean age, 13.4 years; 94 [62%] females), 151 (99%) completed the trial. At the 3-month follow-up, 34 participants (46%) in the stepped-care group and 23 (30%) in the in-person CBT group were nonresponders. At the 6-month follow-up, the CY-BOCS score was 11.57 points in the stepped-care group vs 10.57 points in the face-to-face treatment group, corresponding to an estimated mean difference of 0.91 points ([1-sided 97.5% CI, -infinity to 3.28]; P for noninferiority=.02). Increased anxiety (30%-36%) and depressive symptoms (20%-28%) were the most frequently reported adverse events in both groups. There were 2 unrelated serious adverse events (1 in each group). Conclusions and RelevanceAmong children and adolescents with obsessive-compulsive disorder, treatment with an internet-delivered CBT program followed by in-person CBT if necessary compared with in-person CBT alone resulted in a noninferior difference in symptoms at the 6-month follow-up. Further research is needed to understand the durability and generalizability of these findings. Trial RegistrationClinicalTrials.gov Identifier: NCT03263546 This noninferiority trial compares the effects of an internet-delivered cognitive behavioral therapy (CBT) program followed by traditional in-person CBT if necessary vs in-person CBT alone on symptoms of obsessive compulsive disorder (OCD) in children and adolescents.
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