65 research outputs found
Utilizing Large Electronic Medical Record Data Sets to Identify Novel Drug–Gene Interactions for Commonly Used Drugs
The transient response of ice volume to orbital forcing during the warm Late Pliocene
Examining the nature of ice sheet and sea level response to past episodes of enhanced greenhouse gas forcing may help constrain future sea level change. Here, for the first time, we present the transient nature of ice sheets and sea level during the late Pliocene. The transient ice sheet predictions are forced by multiple climate snapshots derived from a climate model set up with late Pliocene boundary conditions, forced with different orbital forcing scenarios appropriate to two Marine Isotope Stages (MISs), MIS KM5c, and K1. Our results indicate that during MIS KM5c both the Antarctic and Greenland ice sheets contributed to sea level rise relative to present and were relatively stable. Insolation forcing between the hemispheres was out of phase during MIS K1 and led to an asynchronous response of ice volume globally. Therefore, when variations of precession were high, inferring the behavior of ice sheets from benthic isotope or sea level records is complex
Methodological quality of 100 recent systematic reviews of health-related outcome measurement instruments:an overview of reviews
PURPOSE: Systematic reviews evaluating and comparing the measurement properties of outcome measurement instruments (OMIs) play an important role in OMI selection. Earlier overviews of review quality (2007, 2014) evidenced substantial concerns with regards to alignment to scientific standards. This overview aimed to investigate whether the quality of recent systematic reviews of OMIs lives up to the current scientific standards.METHODS: One hundred systematic reviews of OMIs published from June 1, 2021 onwards were randomly selected through a systematic literature search performed on March 17, 2022 in MEDLINE and EMBASE. The quality of systematic reviews was appraised by two independent reviewers. An updated data extraction form was informed by the earlier studies, and results were compared to these earlier studies' findings.RESULTS: A quarter of the reviews had an unclear research question or aim, and in 22% of the reviews the search strategy did not match the aim. Half of the reviews had an incomprehensive search strategy, because relevant search terms were not included. In 63% of the reviews (compared to 41% in 2014 and 30% in 2007) a risk of bias assessment was conducted. In 73% of the reviews (some) measurement properties were evaluated (58% in 2014 and 55% in 2007). In 60% of the reviews the data were (partly) synthesized (42% in 2014 and 7% in 2007); evaluation of measurement properties and data syntheses was not conducted separately for subscales in the majority. Certainty assessments of the quality of the total body of evidence were conducted in only 33% of reviews (not assessed in 2014 and 2007). The majority (58%) did not make any recommendations on which OMI (not) to use.CONCLUSION: Despite clear improvements in risk of bias assessments, measurement property evaluation and data synthesis, specifying the research question, conducting the search strategy and performing a certainty assessment remain poor. To ensure that systematic reviews of OMIs meet current scientific standards, more consistent conduct and reporting of systematic reviews of OMIs is needed.</p
Methodological quality of 100 recent systematic reviews of health-related outcome measurement instruments:an overview of reviews
Purpose: Systematic reviews evaluating and comparing the measurement properties of outcome measurement instruments (OMIs) play an important role in OMI selection. Earlier overviews of review quality (2007, 2014) evidenced substantial concerns with regards to alignment to scientific standards. This overview aimed to investigate whether the quality of recent systematic reviews of OMIs lives up to the current scientific standards.Methods: One hundred systematic reviews of OMIs published from June 1, 2021 onwards were randomly selected through a systematic literature search performed on March 17, 2022 in MEDLINE and EMBASE. The quality of systematic reviews was appraised by two independent reviewers. An updated data extraction form was informed by the earlier studies, and results were compared to these earlier studies’ findings.Results: A quarter of the reviews had an unclear research question or aim, and in 22% of the reviews the search strategy did not match the aim. Half of the reviews had an incomprehensive search strategy, because relevant search terms were not included. In 63% of the reviews (compared to 41% in 2014 and 30% in 2007) a risk of bias assessment was conducted. In 73% of the reviews (some) measurement properties were evaluated (58% in 2014 and 55% in 2007). In 60% of the reviews the data were (partly) synthesized (42% in 2014 and 7% in 2007); evaluation of measurement properties and data syntheses was not conducted separately for subscales in the majority. Certainty assessments of the quality of the total body of evidence were conducted in only 33% of reviews (not assessed in 2014 and 2007). The majority (58%) did not make any recommendations on which OMI (not) to use.Conclusion: Despite clear improvements in risk of bias assessments, measurement property evaluation and data synthesis, specifying the research question, conducting the search strategy and performing a certainty assessment remain poor. To ensure that systematic reviews of OMIs meet current scientific standards, more consistent conduct and reporting of systematic reviews of OMIs is needed
Methodological quality of 100 recent systematic reviews of health-related outcome measurement instruments:an overview of reviews
Purpose: Systematic reviews evaluating and comparing the measurement properties of outcome measurement instruments (OMIs) play an important role in OMI selection. Earlier overviews of review quality (2007, 2014) evidenced substantial concerns with regards to alignment to scientific standards. This overview aimed to investigate whether the quality of recent systematic reviews of OMIs lives up to the current scientific standards.Methods: One hundred systematic reviews of OMIs published from June 1, 2021 onwards were randomly selected through a systematic literature search performed on March 17, 2022 in MEDLINE and EMBASE. The quality of systematic reviews was appraised by two independent reviewers. An updated data extraction form was informed by the earlier studies, and results were compared to these earlier studies’ findings.Results: A quarter of the reviews had an unclear research question or aim, and in 22% of the reviews the search strategy did not match the aim. Half of the reviews had an incomprehensive search strategy, because relevant search terms were not included. In 63% of the reviews (compared to 41% in 2014 and 30% in 2007) a risk of bias assessment was conducted. In 73% of the reviews (some) measurement properties were evaluated (58% in 2014 and 55% in 2007). In 60% of the reviews the data were (partly) synthesized (42% in 2014 and 7% in 2007); evaluation of measurement properties and data syntheses was not conducted separately for subscales in the majority. Certainty assessments of the quality of the total body of evidence were conducted in only 33% of reviews (not assessed in 2014 and 2007). The majority (58%) did not make any recommendations on which OMI (not) to use.Conclusion: Despite clear improvements in risk of bias assessments, measurement property evaluation and data synthesis, specifying the research question, conducting the search strategy and performing a certainty assessment remain poor. To ensure that systematic reviews of OMIs meet current scientific standards, more consistent conduct and reporting of systematic reviews of OMIs is needed
Psychosis and the level of mood incongruence in Bipolar Disorder are related to genetic liability for Schizophrenia
Abstract Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features. Design Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls. Settings & Participants 4399 BDcases, mean [sd] age-at-interview 46[12] years, of which 2966 were woman (67%) from the BD Research Network (BDRN) were included in the final analyses, with data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland included for comparison. Exposure Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second
Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform. Main outcome measure Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS). Results Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)). Conclusion We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms
Predictors of patterns of change in health-related quality of life in older women over 7 years: evidence from a prospective cohort study.
BACKGROUND: the evaluation of the determinants of change over time in health-related quality of life (HR-QoL) in older people is limited. This study aims to identify patterns of change in HR-QoL over 7 years and their determinants using data from the British Women's Heart and Health Study, a representative sample of older women (n = 4286). METHODS: longitudinal latent class analysis was used to identify subpopulations of women with similar HR-QoL trajectories from 1999-2000 to 2007. HR-QoL was measured using the EQ-5D. Multivariate multinomial logistic regression was used to model the association of identified trajectories with baseline predictors after multiple imputation of missing data. RESULTS: four distinct EQ-5D trajectories were suggested: high (19% of women), high decline (22%), intermediate (42%) and low decline (16%). Prevalent arthritis (OR = 13.4; 95% CI: 8.8, 20.5), diabetes (OR = 4.6; 95% CI: 1.5, 14.2) and obesity (OR = 3.9; 95% CI: 2.5, 6.0) were the strongest predicting health conditions of adverse changes in HR-QoL and physical activity the strongest predicting lifestyle factor (OR = 2.8; 95% CI: 2.0, 3.9). CONCLUSIONS: findings suggest that older women without obesity or pre-existing health conditions who undertake more physical activity are more likely to experience high HR-QoL, reinforcing the importance of these factors for healthy ageing
Guideline for reporting systematic reviews of outcome measurement instruments (OMIs):PRISMA-COSMIN for OMIs 2024
PurposeAlthough comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measure- ment INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024.MethodsThe development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement.ResultsFrom the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥ 67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final check- list to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review’s title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts.ConclusionPRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding expla- nation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA- COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application
Guideline for reporting systematic reviews of outcome measurement instruments (OMIs):PRISMA-COSMIN for OMIs 2024
PurposeAlthough comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measure- ment INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024.MethodsThe development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement.ResultsFrom the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥ 67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final check- list to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review’s title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts.ConclusionPRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding expla- nation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA- COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application
A re-randomisation design for clinical trials
Background: Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies. Methods: For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used. Results: The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations. Conclusions: If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations
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