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- Barbateskovic, Marija, et al.
(författare)
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A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions
- 2021
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 135, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.
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- Munch, Marie W., et al.
(författare)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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- Fahmy, Nagia, et al.
(författare)
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A novel homozygous p.Ser69Pro SOD1 mutation causes severe young-onset ALS with decreased enzyme activity
- 2023
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Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 270, s. 1770-1773
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Tidskriftsartikel (refereegranskat)abstract
- Background: The dose–effect of various SOD1 mutations on SOD1 enzymatic activity offers valuable insights into ALS pathogenesis with possible therapeutic implications. Homozygous SOD1 mutations, yet scarce, are of special interest. We report a novel homozygous SOD1 mutation with decreased enzymatic activity and severe early onset ALS phenotype.Methods: Whole exome sequencing and targeted screening of commonly implicated genes were conducted. Repeat-primed PCR and fragment length analysis were used for C9orf72. Bi-directional Sanger sequencing was used for SOD1 and other genes. SOD1 activity was measured by direct spectrophotometry. Serum neurofilament light chain level was measured by the ELLA immunoassay system.Results: The homozygous patient for a novel SOD1 variant p.Ser69Pro showed poor SOD1 enzymatic activity (16% of controls) and an early onset ALS phenotype predominantly affecting lower motor neurons with rapid involvement of the trunk, upper limbs and bulbar muscles. The asymptomatic heterozygous relatives had at least 68% of normal enzyme activity. Level of serum neurofilament light chain was much higher (148 pg/ml) in the patient than the relatives who had normal levels (6–10 pg/ml).Conclusion: This novel mutation adds knowledge to the ALS genotype–phenotype spectrum and supports the strong dose–effect of SOD1 mutations associated with severely decreased enzymatic activity.
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- Feiner, Nathalie, et al.
(författare)
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Enhanced locomotor performance on familiar surfaces is uncoupled from morphological plasticity in Anolis lizards
- 2020
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Ingår i: Journal of Experimental Zoology Part A: Ecological and Integrative Physiology. - : Wiley. - 2471-5638 .- 2471-5646. ; 333:5, s. 284-294
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Tidskriftsartikel (refereegranskat)abstract
- The radiation of Anolis lizards in the Caribbean is associated with a diversification of the functional match between morphology, habitat use, and locomotor performance. It has been hypothesized that the microhabitat a lizard is reared in can achieve a similar fit of form and function within a species. This predicts that plasticity in the locomotor apparatus is accompanied by changes in perching behavior or improved locomotor performance. To test this, we raised juveniles of two species (Anolis sagrei and Anolis carolinensis) on either broad or narrow surfaces and examined perching behavior and locomotor performance as well as the shape of the pectoral and pelvic girdles, limb length, and thickness of the long bones. Perching behavior was not affected by the habitat surface experienced during ontogeny. However, individuals raised on broad surfaces showed better locomotor performance on broad surfaces, and the magnitude of the effect was as large as the difference between the two species. Both species showed modifications of pectoral and pelvic shape, but only A. carolinensis developed longer limbs on broad surfaces. However, these morphological adjustments induced by physical activity did not explain why lizards raised on broad surfaces performed better. Thus, it appears that early-life experiences can affect both the morphology of the locomotor apparatus and locomotor performance in Anolis lizards, without the two being functionally connected.
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- Feiner, Nathalie, et al.
(författare)
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Plasticity and evolutionary convergence in the locomotor skeleton of greater antillean anolis lizards
- 2020
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Ingår i: eLife. - 2050-084X. ; 9, s. 1-47
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Tidskriftsartikel (refereegranskat)abstract
- Plasticity can put evolution on repeat if development causes species to generate similar morphologies in similar environments. Anolis lizards offer the opportunity to put this role of developmental plasticity to the test. Following colonization of the four Greater Antillean islands, Anolis lizards independently and repeatedly evolved six ecomorphs adapted to manoeuvring different microhabitats. By quantifying the morphology of the locomotor skeleton of 95 species, we demonstrate that ecomorphs on different islands have diverged along similar trajectories. However, microhabitat-induced morphological plasticity differed between species and did not consistently improve individual locomotor performance. Consistent with this decoupling between morphological plasticity and locomotor performance, highly plastic features did not show greater evolvability, and plastic responses to microhabitat were poorly aligned with evolutionary divergence between ecomorphs. The locomotor skeleton of Anolis may have evolved within a subset of possible morphologies that are highly accessible through genetic change, enabling adaptive convergence independently of plasticity.
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