Few randomized trials in preterm birth prevention meet predefined usefulness criteria

Funding Information: Funding: The study was funded by a grant from the Netherlands Organization for Health Research and Development (ZonMw Rubicon grand #452182306). The funder had no involvement in any phase of this study. Meta-Research Innovation Center at Stanford (METRICS), Stanford University is supported by a grant from the Laura and John Arnold Foundation. JvtH is supported by postdoctoral grant from the Netherlands Organization for Health Research and Development (Rubicon grand 452,182,306). C.A. is supported by postdoctoral grants from the Knut and Alice Wallenberg Foundation (K.A.W. 2019.0561), Uppsala University, and the Sweden-America Foundation. B.M. is supported by an NHMRC Investigator grant (GNT1176437). B.M. reports consultancy for Guerbet, has been a member of the ObsEva advisory board and holds Stock options for ObsEva. The work of J.I. has been supported by an unrestricted gift from Sue and Bob O'Donnell. J.I. is a team member of the editorial board of JCE. Publisher Copyright: © 2023 The AuthorsPeer reviewe

Assessing the usefulness of randomised trials in obstetrics and gynaecology

FUNDING INFORMATION The study was funded by a grant from the Netherlands Organization for Health Research and Development (ZonMw Rubicon grant #452182306). The funder had no involvement in any phase of this study.Non peer reviewedPublisher PD

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats

Causal and associational language in observational health research: a systematic evaluation

We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched and screened for 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, three reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as None (no causal implication) in 13.8%, Weak 34.2%, Moderate 33.2%, and Strong 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was “associate” (45.7%). Reviewer’s ratings of linking word roots were highly heterogeneous; over half of reviewers rated “association” as having at least some causal implication. This research undercuts the assumption that avoiding “causal” words leads to clarity of interpretation in medical research

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Anxious personality traits in pregnant women : Associations with postpartum depression, delivery complications and health care use

Anxious personality traits, including those encompassed by negative emotionality (neuroticism) and the tendency to worry about close relationships (attachment anxiety) during pregnancy were the focus of this thesis. The overall aim was to examine perinatal correlates of these characteris-tics in terms of psychiatric and obstetric health as well as antenatal care (ANC). Papers I-II were part of a large population-based project on pregnant women in Uppsala in 2009-2012 (n=2160). Papers III-IV adjoined participants from several projects in 2005-2011, on oral contraceptive use, infertility, induced abortion, premenstrual mood disorder, and perina-tal depression (n=2819). The participants reported on the Swedish universities Scales of Per-sonality for neuroticism (papers II-IV) and the Attachment Style Questionnaire (ASQ) for attachment anxiety (papers I-II). The participants also answered the Edinburgh Postnatal De-pression Scale on depressive symptoms (paper II). In paper III, information on obstetric com-plications for primiparous women with singleton pregnancies (n=1969) was extracted from Swedish national health registers. In paper IV, ANC use was derived from medical records of obstetric low-risk women residing in Uppsala (n=1052). The ASQ had similar psychometric properties in pregnant women (n=1631) as in previous reports (paper I). In non-depressed pregnant women (n=1431), the combination of neuroticism and attachment anxiety was the best risk indicator of postpartum depressive symptoms (paper II). Whereas high neuroticism was not related to obstetric complications (paper III), it was associated with higher use of ANC (paper IV). Summarized, this thesis illustrates how anxious personality traits may predispose for post-partum depression and higher use of ANC in the absence of obstetric complications. Future development of these findings should be to evaluate individual and societal benefits of a greater emphasis on psychological support in ANC

Anxious personality traits in pregnant women : Associations with postpartum depression, delivery complications and health care use

Anxious personality traits, including those encompassed by negative emotionality (neuroticism) and the tendency to worry about close relationships (attachment anxiety) during pregnancy were the focus of this thesis. The overall aim was to examine perinatal correlates of these characteris-tics in terms of psychiatric and obstetric health as well as antenatal care (ANC). Papers I-II were part of a large population-based project on pregnant women in Uppsala in 2009-2012 (n=2160). Papers III-IV adjoined participants from several projects in 2005-2011, on oral contraceptive use, infertility, induced abortion, premenstrual mood disorder, and perina-tal depression (n=2819). The participants reported on the Swedish universities Scales of Per-sonality for neuroticism (papers II-IV) and the Attachment Style Questionnaire (ASQ) for attachment anxiety (papers I-II). The participants also answered the Edinburgh Postnatal De-pression Scale on depressive symptoms (paper II). In paper III, information on obstetric com-plications for primiparous women with singleton pregnancies (n=1969) was extracted from Swedish national health registers. In paper IV, ANC use was derived from medical records of obstetric low-risk women residing in Uppsala (n=1052). The ASQ had similar psychometric properties in pregnant women (n=1631) as in previous reports (paper I). In non-depressed pregnant women (n=1431), the combination of neuroticism and attachment anxiety was the best risk indicator of postpartum depressive symptoms (paper II). Whereas high neuroticism was not related to obstetric complications (paper III), it was associated with higher use of ANC (paper IV). Summarized, this thesis illustrates how anxious personality traits may predispose for post-partum depression and higher use of ANC in the absence of obstetric complications. Future development of these findings should be to evaluate individual and societal benefits of a greater emphasis on psychological support in ANC

Anxious personality traits in pregnant women : Associations with postpartum depression, delivery complications and health care use

Anxious personality traits, including those encompassed by negative emotionality (neuroticism) and the tendency to worry about close relationships (attachment anxiety) during pregnancy were the focus of this thesis. The overall aim was to examine perinatal correlates of these characteris-tics in terms of psychiatric and obstetric health as well as antenatal care (ANC). Papers I-II were part of a large population-based project on pregnant women in Uppsala in 2009-2012 (n=2160). Papers III-IV adjoined participants from several projects in 2005-2011, on oral contraceptive use, infertility, induced abortion, premenstrual mood disorder, and perina-tal depression (n=2819). The participants reported on the Swedish universities Scales of Per-sonality for neuroticism (papers II-IV) and the Attachment Style Questionnaire (ASQ) for attachment anxiety (papers I-II). The participants also answered the Edinburgh Postnatal De-pression Scale on depressive symptoms (paper II). In paper III, information on obstetric com-plications for primiparous women with singleton pregnancies (n=1969) was extracted from Swedish national health registers. In paper IV, ANC use was derived from medical records of obstetric low-risk women residing in Uppsala (n=1052). The ASQ had similar psychometric properties in pregnant women (n=1631) as in previous reports (paper I). In non-depressed pregnant women (n=1431), the combination of neuroticism and attachment anxiety was the best risk indicator of postpartum depressive symptoms (paper II). Whereas high neuroticism was not related to obstetric complications (paper III), it was associated with higher use of ANC (paper IV). Summarized, this thesis illustrates how anxious personality traits may predispose for post-partum depression and higher use of ANC in the absence of obstetric complications. Future development of these findings should be to evaluate individual and societal benefits of a greater emphasis on psychological support in ANC