| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- 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.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Coelho, Teresa, et al.
(författare)
-
Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy
- 2023
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 330:15, s. 1448-1458
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis.Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy.Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group.Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60).Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights.Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P <.001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group.Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo.Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.
|
|
| 8. |
- Goisis, Alice, et al.
(författare)
-
Birth outcomes following assisted reproductive technology conception among same-sex lesbian couples vs natural conception and assisted reproductive technology conception among heterosexual couples
- 2023
-
Ingår i: Journal of the American Medical Association (JAMA). - 0098-7484 .- 1538-3598. ; 329:13, s. 1117-1119
-
Tidskriftsartikel (refereegranskat)abstract
- Higher rates of adverse birth outcomes have been consistently reported among children conceived via assisted reproductive technology (ART) compared with children conceived through natural conception. Higher rates of multiple births in ART pregnancies partially explain the increased risk. It remains unclear to what extent the remaining difference can be attributed to the reproductive technology or to factors related to infertility, which is associated with an elevated risk of poorer birth outcomes. Same-sex lesbian couples undergo ART treatments generally without experiencing infertility. To distinguish the effects of reproductive treatment and infertility, we compared birth outcomes in ART pregnancies among same-sex lesbian couples vs natural conceptions and ART pregnancies among heterosexual couples.Methods: In Sweden, same-sex lesbian couples have been eligible to receive publicly funded ART treatments with donated sperm since 2005. This study included all births in Sweden from 2007 to 2018. Using pseudonymized personal identifiers, the Swedish National Quality Registry for Assisted Reproduction, which includes all ART treatments (in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI], and intrauterine insemination [IUI]), was linked to the medical birth register and the total population registers, which include information on birth outcomes and sociodemographic characteristics. We focused on first live births for ART and naturally conceived births because 97.3% of ART births among same-sex lesbian couples were first births. We analyzed 4 outcomes: birth weight (continuous), gestational age (continuous), low birth weight (binary, <2500 g), and preterm delivery (binary, <37 weeks of gestation). We estimated linear models on the continuous outcomes and linear probability models on the binary outcomes comparing ART-conceived births among same-sex lesbian couples (reference category) with ART births and naturally conceived births among heterosexual couples. For each outcome, we estimated unadjusted and adjusted (controlling for child sex, multiplicity, and maternal age at birth) models. We also estimated differences focusing on children conceived via IVF/ICSI because 99.4% of ART births among heterosexual couples were conceived via IVF/ICSI compared with 63.3% in same-sex couples, as same-sex couples often start treatments with IUI, which has a lower chance of success regardless of subfertility.Analyses were conducted using R version 4.1.1 (R Foundation). Statistical significance was set at P < .05 (2-sided). This study was approved by the Regional Ethical Review Board of Stockholm. Informed consent was not required for pseudonymized data.Results: During the study period, there were 868 ART births among same-sex lesbian couples, 23 488 ART births among heterosexual couples, and 456 898 naturally conceived births. ART-conceived births from same-sex and heterosexual couples showed a higher proportion of multiplicity (5.8% and 7.5%, respectively) than naturally conceived births (2.1%) (Table 1). Couples who conceived naturally had significantly lower birth weight and gestational age and similar risk of low birth weight and preterm delivery compared with same-sex couples who conceived via ART (Table 2). For example, birth weight was 3429.5 g in naturally conceived births vs 3460.2 g in same-sex ART births (adjusted difference, −76.2 g [95% CI, −113 to −39.3 g]; P < .001; low birth weight, 4.9% vs 6.7%, adjusted difference, 0.28 [95% CI, −1.11 to 1.66] percentage points; P = .70). Heterosexual couples who conceived via ART had statistically significantly lower birth weight and gestational age than same-sex couples (eg, birth weight: 3342.9 g vs 3460.2 g; adjusted difference, −97.4 g [95% CI, −134.8 to −59.9 g]; P < .001). Percentages of low birth weight and preterm birth were higher in ART conceptions among heterosexual couples vs same-sex couples but did not reach statistical significance (eg, low birth weight: 8.9% vs 6.7%; adjusted difference, 1.23 [95% CI, −0.17 to 2.65] percentage points; P = .09). The results were qualitatively similar when only considering IVF/ICSI-conceived children (Table 2).Discussion: This study demonstrated that same-sex lesbian couples undergoing ART had more favorable or similar birth outcomes to heterosexual couples who conceived naturally or underwent ART to conceive, suggesting that infertility-related factors rather than reproductive treatments contribute to higher rates of adverse birth outcomes in ART pregnancies. Limitations of the study include that the presence of infertility factors was not directly assessed and the relatively small sample size of same-sex couples reduced the statistical power of the study, particularly in the binary outcomes analyses.
|
|
| 9. |
|
|
| 10. |
- Griffin, TC
(författare)
-
Making Ends Meet
- 2024
-
Ingår i: JAMA. - 1538-3598. ; 331:10, s. 827-828
-
Tidskriftsartikel (refereegranskat)
|
|
