| 1. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 2. |
- Doubek, Jonathan P., et al.
(författare)
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The extent and variability of storm-induced temperature changes in lakes measured with long-term and high-frequency data
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:5, s. 1979-1992
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Tidskriftsartikel (refereegranskat)abstract
- The intensity and frequency of storms are projected to increase in many regions of the world because of climate change. Storms can alter environmental conditions in many ecosystems. In lakes and reservoirs, storms can reduce epilimnetic temperatures from wind-induced mixing with colder hypolimnetic waters, direct precipitation to the lake's surface, and watershed runoff. We analyzed 18 long-term and high-frequency lake datasets from 11 countries to assess the magnitude of wind- vs. rainstorm-induced changes in epilimnetic temperature. We found small day-to-day epilimnetic temperature decreases in response to strong wind and heavy rain during stratified conditions. Day-to-day epilimnetic temperature decreased, on average, by 0.28 degrees C during the strongest windstorms (storm mean daily wind speed among lakes: 6.7 +/- 2.7 m s(-1), 1 SD) and by 0.15 degrees C after the heaviest rainstorms (storm mean daily rainfall: 21.3 +/- 9.0 mm). The largest decreases in epilimnetic temperature were observed >= 2 d after sustained strong wind or heavy rain (top 5(th) percentile of wind and rain events for each lake) in shallow and medium-depth lakes. The smallest decreases occurred in deep lakes. Epilimnetic temperature change from windstorms, but not rainstorms, was negatively correlated with maximum lake depth. However, even the largest storm-induced mean epilimnetic temperature decreases were typically <2 degrees C. Day-to-day temperature change, in the absence of storms, often exceeded storm-induced temperature changes. Because storm-induced temperature changes to lake surface waters were minimal, changes in other limnological variables (e.g., nutrient concentrations or light) from storms may have larger impacts on biological communities than temperature changes.
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| 3. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: 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, ). 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 (I-2 = 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.
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