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1.
  • Andrén, Per, et al. (författare)
  • Therapist-Supported Internet-Delivered Exposure and Response Prevention for Children and Adolescents with Tourette Syndrome : A Randomized Clinical Trial
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:8
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited.OBJECTIVE: To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD.DESIGN, SETTING, AND PARTICIPANTS: This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022.INTERVENTIONS: Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants).MAIN OUTCOMES AND MEASURES: The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 ("Very much improved") or 2 ("Much improved") on the Clinical Global Impression-Improvement scale.RESULTS: Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, -0.53; 95% CI, -1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective.CONCLUSIONS AND RELEVANCE: Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03916055.
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  • Axelsson, Kristian F, 1973, et al. (författare)
  • Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism
  • 2022
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. OBJECTIVE To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. MAIN OUTCOMES AND MEASURES The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). RESULTS A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pH PT group and 803 522 person-years for the control group. Compared with the control group, the pH PT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). CONCLUSIONS AND RELEVANCE Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
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  • Björk-Eriksson, Thomas, 1960, et al. (författare)
  • Mortality Among Pediatric Patients With Acute Lymphoblastic Leukemia in Sweden From 1988 to 2017
  • 2022
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Acute lymphoblastic leukemia (ALL) constitutes 20% to 30% of all pediatric cancers. The 5-year overall survival among pediatric patients with ALL in high-income countries such as Sweden is currently more than 90%, but long-term unselected nationwide mortality data and mortality data in relation to the general population are lacking. Objective: To compare mortality between pediatric patients with ALL and the general population during a 30-year period in Sweden and to assess the incidence of ALL in Sweden. Design, Setting, and Participants: This cohort study included pediatric patients (aged <18 years) with a morphologically verified ALL diagnosis in the Swedish Cancer Register and/or at least 2 ALL diagnoses in the Swedish National Patient Register between January 1, 1988, and December 31, 2017. Data were cross-linked to the Swedish Cause of Death Register. Data were analyzed from May 2019 to January 2022. Main Outcomes and Measures: The main outcomes were mortality among patients with ALL compared with that in the general population and mortality in different subgroups within the cohort. Standardized mortality ratios (SMRs) were calculated using the general Swedish population as a reference. Within-cohort survival analyses were performed. Results: A total of 2397 patients (1354 [56%] male; mean [SD] age at diagnosis, 6.1 [4.7] years) were included in the study. The mean (SD) incidence of pediatric ALL during the study period was 4.11 (0.60) cases per 100 000 persons per year (females, 3.68 [0.65] cases per 100 000 persons per year; males, 4.52 [0.81] cases per 100 000 persons per year; P<.001). The observed number of deaths among pediatric patients with ALL was 409 vs the 9.5 deaths expected in the general population, resulting in an overall SMR of 43.1 (95% CI, 39.0-47.5); females had a higher SMR than males (57.8 [95% CI, 49.5-67.2] vs 34.5 [95% CI, 32.0-41.4]; P<.001). Analysis within the cohort showed a continued decrease in survival throughout the 30-year follow-up. The association between calendar year of ALL diagnosis, corresponding with different ALL treatment protocols, and mortality showed the lowest survival for the 1988-1991 group and the highest for the 2008-2017 group (χ2=20.3; P<.001). Conclusions and Relevance: In this cohort study, a consistently high SMR was seen among pediatric patients with ALL. Within the ALL cohort, survival evolved to a similar extent as in the young general population of Sweden. Furthermore, survival among patients with ALL decreased throughout the whole follow-up period without any trend difference after the 5-year follow-up time point. The changes in ALL treatment protocols were associated with overall improved absolute survival over time.
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4.
  • Bolk, Jenny, et al. (författare)
  • Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. OBJECTIVE To assess the risk of ADHD in children after pediatric ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. EXPOSURES Pediatric ischemic stroke. MAIN OUTCOMES AND MEASURES Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and international Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. RESULTS Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI, 1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). CONCLUSIONS AND RELEVANCE This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD. particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.
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  • Chen, Hua, et al. (författare)
  • Death of a Parent and the Risk of Ischemic Heart Disease and Stroke in Denmark and Sweden
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Increasing evidence suggests that parental death is associated with unhealthy behaviors and mental ill-health. Knowledge regarding the link between parental death and the risk of ischemic heart disease (IHD) and stroke remains limited.OBJECTIVES To investigate whether parental death is associated with an increased risk of IHD and stroke and whether these associations differ by the characteristics of the loss.DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study, involving linkages between several nationwide registers, included 3 766 918 individuals born between 1973 and 1998 in Denmark and between 1973 and 1996 in Sweden. Participants were followed up until 2016 in Denmark and 2014 in Sweden. Data were analyzed from December 2019 to May 2021.EXPOSURES Death of a parent.MAIN OUTCOMES AND MEASURES Diagnosis with or death due to IHD or stroke. Poisson regression was used to analyze the associations between parental death and IHD and stroke risk.RESULTS Altogether, 48.8% of the participants were women, and 42.7% were from Denmark. A total of 523 496 individuals lost a parent during the study period (median age at loss, 25 years; IQR, 17-32 years). Parental death was associated with a 41% increased risk of IHD (incidence rate ratio [IRR], 1.41; 95% CI, 1.33-1.51) and a 30% increased risk of stroke [IRR, 1.30; 95% CI, 1.21-1.38). The associations were observed not only if the parent died because of cardiovascular or other natural causes but also in cases of unnatural deaths. The associations were stronger when both parents had died (IHD: IRR, 1.87; 95% CI, 1.59-2.21; stroke: IRR, 1.64; 95% CI, 1.35-1.98) than when 1 parent had died (IHD: IRR, 1.37; 95% CI, 1.28-1.47; stroke: IRR, 1.27; 95% CI, 1.19-1.36) but did not differ substantially by the offspring's age at loss or the deceased parents' sex. The risk of acute myocardial infarction was highest in the first 3 months after loss.CONCLUSIONS AND RELEVANCE In this cohort study, parental death in the first decades of life was associated with an increased risk of IHD and stroke. The associations were observed not only in cases of parental cardiovascular and other natural deaths but also in cases of unnatural deaths. Family members and health professionals may need to pay attention to the cardiovascular disease risk among parentally bereaved individuals.
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6.
  • Edén, Arvid, 1975, et al. (författare)
  • Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms.
  • 2022
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF).To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity.This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included.SARS-CoV-2 infection.Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, β2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]).Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r=0.38; P=.03) and interferon γ (r=0.42; P=.01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P=.03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P=.04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P=.002). No differences were seen in any CSF biomarkers in moderate compared with severe disease.In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
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9.
  • Gahm, Jessica, et al. (författare)
  • Effectiveness of single vs multiple doses of prophylactic intravenous antibiotics in implant-based breast reconstruction : A randomized clinical trial
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Multiple-dose antibiotic prophylaxis is widely used to prevent infection after implant-based breast reconstruction despite the lack of high-level evidence regarding its clinical benefit.Objective: To determine whether multiple-dose antibiotic prophylaxis is superior to single-dose antibiotic prophylaxis in preventing surgical site infection (SSI) after implant-based breast reconstruction.Design, Setting, and Participants: This prospective, multicenter, randomized clinical superiority trial was conducted at 7 hospitals (8 departments) in Sweden from April 25, 2013, to October 31, 2018. Eligible participants were women aged 18 years or older who were planned to undergo immediate or delayed implant-based breast reconstruction. Follow-up time was 12 months. Data analysis was performed from May to October 2021.Interventions: Multiple-dose intravenous antibiotic prophylaxis extending over 24 hours following surgery, compared with single-dose intravenous antibiotic. The first-choice drug was cloxacillin (2 g per dose). Clindamycin was used (600 mg per dose) for patients with penicillin allergy.Main Outcomes and Measures: The primary outcome was SSI leading to surgical removal of the implant within 6 months after surgery. Secondary outcomes were the rate of SSIs necessitating readmission and administration of intravenous antibiotics, and clinically suspected SSIs not necessitating readmission but oral antibiotics.Results: A total of 711 women were assessed for eligibility, and 698 were randomized (345 to single-dose and 353 to multiple-dose antibiotics). The median (range) age was 47 (19-78) years for those in the multiple-dose group and 46 (25-76) years for those in the single-dose group. The median (range) body mass index was 23 (18-38) for the single-dose group and 23 (17-37) for the multiple-dose group. Within 6 months of follow-up, 30 patients (4.3%) had their implant removed because of SSI. Readmission for intravenous antibiotics because of SSI occurred in 47 patients (7.0%), and 190 women (27.7%) received oral antibiotics because of clinically suspected SSI. There was no significant difference between the randomization groups for the primary outcome implant removal (odds ratio [OR], 1.26; 95% CI, 0.69-2.65; P = .53), or for the secondary outcomes readmission for intravenous antibiotics (OR, 1.18; 95% CI, 0.65-2.15; P = .58) and prescription of oral antibiotics (OR, 0.72; 95% CI, 0.51-1.02; P = .07). Adverse events associated with antibiotic treatment were more common in the multiple-dose group than in the single-dose group (16.4% [58 patients] vs 10.7% [37 patients]; OR, 1.64; 95% CI, 1.05-2.55; P = .03).Conclusions and Relevance: The findings of this randomized clinical trial suggest that multiple-dose antibiotic prophylaxis is not superior to a single-dose regimen in preventing SSI and implant removal after implant-based breast reconstruction but comes with a higher risk of adverse events associated with antibiotic treatment.Trial Registration: EudraCT 2012-004878-26.
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10.
  • Garcia-Argibay, Miguel, 1988-, et al. (författare)
  • Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:12
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia.OBJECTIVE: To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide.DESIGN, SETTING, AND PARTICIPANTS: This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022.MAIN OUTCOMES AND MEASURES: A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide.EXPOSURES: A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use.RESULTS: Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54]).CONCLUSIONS AND RELEVANCE: This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.
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  • Gedin, Filip, et al. (författare)
  • Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis.
  • 2022
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements.To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention.A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered.Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders.The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model.Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g).Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P<.001). Trials with low risk of bias had greater placebo responses (q1=5.47; I2=87.08; P=.02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes.Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.
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  • Giannoni, E, et al. (författare)
  • Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia
  • 2022
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11, s. e2243691-
  • Tidskriftsartikel (refereegranskat)abstract
    • Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure.ObjectiveTo compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries.Design, Setting, and ParticipantsThis is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022.ExposuresExposure to antibiotics started in the first postnatal week.Main Outcomes and MeasuresThe main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality.ResultsA total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered.Conclusions and RelevanceThe findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.
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  • Grontvedt, GR, et al. (författare)
  • Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden
  • 2022
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11, s. e2243232-
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of proteins and genetic factors that reduce Alzheimer disease (AD) pathology is of importance when searching for novel AD treatments. Heterozygosity of the KL-VS haplotype has been associated with reduced amyloid and tau burden. Whether this association is mediated by the Klotho protein remains unclear.ObjectivesTo assess concentrations of Klotho in cerebrospinal fluid (CSF) and plasma among cognitively healthy controls and patients with AD and to correlate these findings with KL-VS heterozygosity status and amyloid and tau burden.Design, Setting, and ParticipantsThis case-control study combined 2 independent case-control AD cohorts consisting of 243 referred patients with AD and volunteer controls recruited from January 1, 2009, to December 31, 2018. Klotho levels were measured in CSF and plasma and correlated with KL-VS heterozygosity status and levels of CSF amyloid-β 42 (Aβ42), total tau, and phosphorylated tau. Statistical analysis was performed from January 1, 2021, to March 1, 2022.Main Outcomes and MeasuresAssociations of Klotho levels in CSF and plasma with levels of CSF biomarkers were analyzed using linear regression. Association analyses were stratified separately by clinical groups, APOE4 status, and KL-VS heterozygosity. Pearson correlation was used to assess the correlation between CSF and plasma Klotho levels.ResultsA total of 243 participants were included: 117 controls (45 men [38.5%]; median age, 65 years [range, 41-84 years]), 102 patients with mild cognitive impairment due to AD (AD-MCI; 59 men [57.8%]; median age, 66 years [range, 46-80 years]), and 24 patients with dementia due to AD (AD-dementia; 12 men [50.0%]; median age, 64.5 years [range, 54-75 years]). Median CSF Klotho levels were higher in controls (1236.4 pg/mL [range, 20.4-1726.3 pg/mL]; β = 0.103; 95% CI, 0.023-0.183; P = .01) and patients with AD-MCI (1188.1 pg/mL [range, 756.3-1810.3 pg/mL]; β = 0.095; 95% CI, 0.018-0.172; P = .02) compared with patients with AD-dementia (1073.3 pg/mL [range, 698.2-1661.4 pg/mL]). Higher levels of CSF Klotho were associated with lower CSF Aβ42 burden (β = 0.519; 95% CI, 0.201-0.836; P &amp;lt; .001) and tau burden (CSF total tau levels: β = −0.884; 95% CI, 0.223 to −0.395; P &amp;lt; .001; CSF phosphorylated tau levels: β = −0.672; 95% CI, −1.022 to −0.321; P &amp;lt; .001) independent of clinical, KL-VS heterozygosity, or APOE4 status. There was a weak correlation between Klotho CSF and plasma levels among the entire cohort (Pearson correlation r = 0.377; P &amp;lt; .001).Conclusions and RelevanceThe findings of this case-control study suggest that Klotho protein levels were associated with clinical stages of AD, cognitive decline, and amyloid and tau burden and that these outcomes were more clearly mediated by the protein directly rather than the KL-VS heterozygosity variant. When selecting individuals at risk for clinical trials, the Klotho protein level and not only the genetic profile should be considered.
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16.
  • Hermansen, E., et al. (författare)
  • Comparison of 3 Different Minimally Invasive Surgical Techniques for Lumbar Spinal Stenosis A Randomized Clinical Trial
  • 2022
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Operations for lumbar spinal stenosis is the most often performed surgical procedure in the adult lumbar spine. This study reports the clinical outcome of the 3 most commonly used minimally invasive posterior decompression techniques. OBJECTIVE To compare the effectiveness of 3 minimally invasive posterior decompression techniques for lumbar spinal stenosis. DESIGN, SETTING. AND PARTICIPANTS This randomized clinical trial used a parallel group design and included patients with symptomatic and radiologically verified lumbar spinal stenosis without degenerative spondylolisthesis. Patients were enrolled between February 2014 and October 2018 at the orthopedic and neurosurgical departments of 16 Norwegian public hospitals. Statistical analysis was performed in the period from May to June 2021. INTERVENTIONS Patients were randomized to undergo 1 of the 3 minimally invasive posterior decompression techniques: unilateral laminotomy with crossover, bilateral laminotomy, and spinous process osteotomy. MAIN OUTCOMES AND MEASURES Primary outcome was change in disability measured with Oswestry Disability Index (ODI; range 0-100), presented as mean change from baseline to 2-year follow-up and proportions of patients classified as success (>30% reduction in ODI). Secondary outcomes were mean change in quality of life, disease-specific symptom severity measured with Zurich Claudication Questionnaire (ZCQ), back pain and leg pain on a 10-point numeric rating score (NRS), patient perceived benefit of the surgical procedure, duration of the surgical procedure, blood loss, perioperative complications, number of reoperations, and length of hospital stay. RESULTS In total, 437 patients were included with a median (IQR) age of 68 (62-73) years and 230 men (53%). Of the included patients, 146 were randomized to unilateral laminotomy with crossover, 142 to bilateral laminotomy, and 149 to spinous process osteotomy. The unilateral laminotomy with crossover group had a mean change of -17.9 ODI points (95% CI, -20.8 to -14.9), the bilateral laminotomy group had a mean change of -19.7 ODI points (95% CI, -22.7 to -16.8), and the spinous process osteotomy group had a mean change of -19.9 ODI points (95% CI, -22.8 to-17.0). There were no significant differences in primary or secondary outcomes amongthe 3 surgical procedures, except a longer duration of the surgical procedure in the bilateral laminotomy group. CONCLUSIONS AND RELEVANCE No differences in clinical outcomes or complication rates were found among the 3 minimally invasive posterior decompression techniques used to treat patients with lumbar spinal stenosis.
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  • Indremo, Malin, et al. (författare)
  • Association of Media Coverage on Transgender Health With Referrals to Child and Adolescent Gender Identity Clinics in Sweden
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Increasing numbers of transgender and gender diverse children and adolescents have been referred to gender identity clinics in Sweden in the past decade, and previous studies have found an association between media attention and referral counts. Whether the tone of media stories is associated with referrals is not yet known.OBJECTIVE To investigate whether positive or negative media coverage on transgender and gender diverse issues is associated with referral counts to child and adolescent gender identity clinics.DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, referrals counts were collected from all 6 specialized gender identity clinics in Sweden, along with information on referral date, sex assigned at birth, and birth year. Participants were all individuals younger than 19 years, referred to a gender identity clinic between January 1, 2017, and December 31, 2019. Data were analyzed from May 2020 to September 2021.EXPOSURES Exposures included 3 major media events related to transgender health care in 2019; 1 event was categorized as positive and 2 events were categorized as negative press coverage.MAIN OUTCOMES AND MEASURES Referral counts before and after each of the 3 major media events were assessed, and the moderating association of sex assigned at birth and age was examined with stratified analyses. Weekly referral counts and trends were assessed with interrupted time series analysis.RESULTS Among 1784 referrals (359 referrals [21.4%] among individuals aged <13 years; 1034 referrals [72.1%] among individuals assigned female at birth and 401 referrals [27.9%] among individuals assigned male at birth), a negative association between media coverage and referral counts was found for the first of the negative media events. In the 3 months following the event, referrals decreased by 25.4% (95% CI, -31.9% to -18.9%) overall, by 32.2% (95 CI, -41.8% to -22.8%) for individuals assigned female at birth, and by 25.3% (95 CI, -32.4% to -18.3%) for individuals aged 13 to 18 years. In the interrupted time series analysis, a mean weekly decrease of 3% in the referrals was observed in the extended time interval of 39 weeks (incidence rate ratio, 0.97; 95 CI, 0.95 to 0.99). For the other 2 media events, no changes in referral counts or time trends were observed.CONCLUSIONS AND RELEVANCE These findings suggest that an event of negative media coverage on transgender-specific health care was negatively associated with access to health care for transgender children and adolescents; therefore, nuanced and accurate media coverage, as well as increased awareness of these mechanisms among key stakeholders, is essential.
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18.
  • Jönsson, Therese, et al. (författare)
  • Comparison of Face-to-Face vs Digital Delivery of an Osteoarthritis Treatment Program for Hip or Knee Osteoarthritis
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Digital care platforms have been introduced, but there is limited evidence for their efficacy compared with traditional face-to-face treatment modalities.Objective: To compare mean pain reduction among individuals with osteoarthritis (OA) of the knee or hip who underwent face-to-face vs digital first-line intervention.Design, Setting, and Participants: This registry-based cohort study included all persons with knee or hip osteoarthritis who participated in structured first-line treatment for osteoarthritis in a primary care setting in Sweden. Inclusion criteria were as follows: the treatment was delivered face-to-face or digitally between April 1, 2018, and December 31, 2019; patients provided 3-month follow-up data for pain; and patients had program adherence of at least 80%. Data analysis was conducted in March 2021.Exposures: Participants completed a 3-month intervention, including education and exercise for hip or knee osteoarthritis, with program adherence of 80% or higher, delivered face-to-face or by a digital application.Main Outcomes and Measures: Difference in change in joint pain (11-point numeric rating scale, with 0 indicating no pain and 10, the worst possible pain) between baseline and 3-month follow-up between the 2 intervention modalities. A minimal clinically important difference in pain change between groups was predefined as 1 point. Secondary outcomes were walking difficulties, health-related quality of life, willingness to undergo joint surgery, and fear avoidance behavior.Results: A total of 6946 participants (mean [SD] age, 67 [9] years; 4952 [71%] women; 4424 [64%] knee OA; 2504 [36%] hip OA) were included, with 4237 (61%) receiving face-to-face treatment and 2709 (39%) receiving digital treatment. Both the face-to-face (mean change, -1.10 [95% CI -1.17 to -1.02] points) and digital interventions (mean change, -1.87 [95% CI, -1.94 to -1.79] points) resulted in a clinically important pain reduction at 3 months. Participants in the digitally delivered intervention experienced a larger estimated improvement at 3 months (adjusted mean difference, -0.93 [95% CI, -1.04 to -0.81] points). Results of secondary outcomes were broadly consistent with main outcome.Conclusions and Relevance: This Swedish national registry-based cohort study showed that people with knee or hip OA participating in first-line intervention experienced clinically relevant improvements in pain, whether delivered face-to-face or digitally. The increased benefit of digital delivery compared with face-to-face delivery was of uncertain clinical importance.
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21.
  • Li, Lin, 1989-, et al. (författare)
  • Association Between Pharmacological Treatment of Attention-Deficit/Hyperactivity Disorder and Long-term Unemployment Among Working-Age Individuals in Sweden
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Adults with attention-deficit/hyperactivity disorder (ADHD) are at greater risk for unemployment. Pharmacological treatment is effective in reducing the core symptoms of ADHD, but whether it helps to reduce the unemployment rate among adult patients remains unclear.Objective: To investigate the association between use of ADHD medication and long-term unemployment in working-age adults with ADHD.Design, Setting, and Participants: Data for this population-based cohort study were extracted from Swedish national registers. Among 25 358 individuals with ADHD born from 1958 to 1978, 12 875 middle-aged adults among the workforce were included. The longitudinal cohort was followed up from January 1, 2008, to December 31, 2013. Data were analyzed from March 1, 2020, through May 31, 2021.Exposures: Use of medication for ADHD during the previous 2 years was the main exposure, as both categorical and continuous variables.Main Outcomes and Measures: Yearly accumulated unemployed days were derived from the Public Employment Service, and long-term unemployment was defined as 90 or more days of unemployment per year. Overall and sex-specific relative risks (RRs) with 95% CIs were estimated using generalized estimating equations.Results: Among 12 875 individuals with ADHD (5343 women [41.50%] and 7532 men [58.50%]; mean [SD] age, 37.9 [5.6] years), the use of ADHD medications during the previous 2 years was associated with a 10% lower risk of long-term unemployment in the following year (adjusted RR, 0.90 [95% CI, 0.87-0.95]). An association between use of ADHD medications and long-term unemployment was found among women (RR, 0.82 [95% CI, 0.76-0.89]) but not men (RR, 0.96 [95% CI, 0.91-1.01]). Longer treatment duration was associated with a lower risk of subsequent long-term unemployment among women (RR for use of 1-6 months, 0.86 [95% CI, 0.78-0.95]; RR for use of 18-24 months, 0.72 [95% CI, 0.58-0.90]; P < .001 for trend). Within-individual comparisons showed that the long-term unemployment rate was lower during periods of ADHD medication treatment compared with nontreatment periods (RR, 0.89; 95% CI, 0.85-0.94).Conclusions and Relevance: The findings of this cohort study suggest that the use of ADHD medication is associated with a lower risk of subsequent long-term unemployment for middle-aged women. These findings should be considered together with the existing knowledge of risks and benefits of ADHD medication when developing treatment plans for working-age adults.
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22.
  • Lin, E., et al. (författare)
  • Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:8
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD. OBJECTIVE To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016. EXPOSURES Treatment with GnRH agonists and PCa diagnosis were the primary exposures. MAIN OUTCOMES AND MEASURES Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association. RESULTS The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82). CONCLUSIONS AND RELEVANCE In this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.
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23.
  • Liu, Can, et al. (författare)
  • School Outcomes Among Children Following Death of a Parent
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: To better support children with the experience of parental death, it is crucial to understand whether parental death increases the risk of adverse school outcomes.Objectives: To examine whether parental death is associated with poorer school outcomes independent of factors unique to the family, and whether children of certain ages are particularly vulnerable to parental death.Design, Setting, and Participants: This population-based sibling cohort study used Swedish national register-based longitudinal data with linkage between family members. Register data were collected from January 1, 1990, to December 31, 2016. Data analyses were performed on July 14, 2021. The participants were all children born between 1991 and 2000 who lived in Sweden before turning age 17 years (N = 908 064).Exposure: Parental death before finishing compulsory school.Main Outcomes and Measures: Mean school grades (year-specific z scores) and ineligibility for upper secondary education on finishing compulsory school at age 15 to 16 years. Population-based cohort analyses were conducted to examine the association between parental death and school outcomes using conventional linear and Poisson regression models, after adjustment for demographic and parental socioeconomic and health indicators measured before childbirth. Second, using fixed-effect linear and Poisson regression models, children who experienced parental death before finishing compulsory school were compared with their siblings who experienced the death after. Third, the study explored the age-specific associations between parental death and school outcomes.Results: In the conventional population-based analyses, bereaved children (N = 22 634; 11 553 boys [51.0%]; 11 081 girls [49.0%]; mean [SD] age, 21.0 [2.8] years) had lower mean school grade z scores (adjusted β coefficient, -0.19; 95% CI, -0.21 to -0.18; P < .001) and a higher risk of ineligibility for upper secondary education than the nonbereaved children (adjusted risk ratio, 1.36; 95% CI, 1.32-1.41; P < .001). Within-sibling comparisons using fixed-effects models showed that experiencing parental death before finishing compulsory school was associated with lower mean school grade z scores (-0.06; 95% CI, -0.10 to -0.01; P = .02) but not with ineligibility for upper secondary education (adjusted risk ratio, 1.07; 95% CI, 0.93-1.23; P = .34). Independent of birth order, losing a parent at a younger age was associated with lower grades within a family.Conclusions and Relevance: In this cohort study, childhood parental death was associated with lower school grades after adjustment for familial confounders shared between siblings. Children who lost a parent may benefit from additional educational support that could reduce the risk of adverse socioeconomic trajectories later in life.
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24.
  • Lu, Donghao, et al. (författare)
  • Association Between Childhood Body Size and Premenstrual Disorders in Young Adulthood
  • 2022
  • Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: Emerging data suggest that more than two-thirds of premenstrual disorders (PMDs), including premenstrual syndrome and premenstrual dysphoric disorder, have symptom onset during the teen years. Adulthood adiposity has been associated with PMDs; however, the association with childhood and adolescent body size is unknown.OBJECTIVE: To examine the association between childhood and adolescent body size and risk of PMDs in young adulthood.DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 6524 US female participants from the Growing Up Today Study (1996-2013). Data were analyzed from February 26, 2020, to June 23, 2021. EXPOSURES Body mass index (BMI) was estimated using self-reported height and weight through adolescence and converted to BMI for age (z score).MAIN OUTCOMES AND MEASURES: In 2013, premenstrual symptoms and identified PMDs were assessed with a validated scale based on the Calendar of Premenstrual Experiences. The associations of BMI for age with PMDs and premenstrual symptoms were examined using log-binomial and linear regressions, respectively.RESULTS: Among 6524 participants (mean [SD] age, 26 [3.5] years; 6108 [93.6%] White), 1004 (15.4%) met the criteria for a PMD. Baseline BMI for age reported at a mean (SD) age of 12.7 (1.1) years was associated with increased risk of PMDs (confounding-adjusted relative risk, 1.09 per unit of z score; 95% Cl, 1.03-1.15) and higher burden of premenstrual symptoms (beta = 0.06; 95% CI, 0.04-0.08). Associations were particularly pronounced for premenstrual dysphoric disorder and for PMDs with symptom onset before 20 years of age and remained in the absence of psychiatric comorbidities, including depression, anxiety, and disordered eating behavior. When analyzing BMI change over time, individuals with high BMI throughout adolescence had a higher burden of premenstrual symptoms (beta = 0.17; 95% CI, 0.08-0.27) compared with those with normal BMI throughout adolescence. Individuals with high BMI early followed by a mild decrease later did not report higher premenstrual symptoms (beta = 0.06; 95% CI, 0.00-0.12).CONCLUSIONS AND RELEVANCE: In this cohort study, childhood body size was associated with PMD risk and premenstrual symptoms in young adulthood. These findings suggest that maintaining a normal body mass in childhood may be considered for lowering the burden of PMDs in adulthood.
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