Absolute vs. relative effects-implications for subgroup analyses.
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ABSTRACT:
SUBMITTER: Andersen LW
PROVIDER: S-EPMC7802340 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Absolute vs. relative effects-implications for subgroup analyses.
Trials 20210111 1
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Project description:Methods for extending-generalizing or transporting-inferences from a randomized trial to a target population involve conditioning on a large set of covariates that is sufficient for rendering the randomized and nonrandomized groups exchangeable. Yet, decision makers are often interested in examining treatment effects in subgroups of the target population defined in terms of only a few discrete covariates. Here, we propose methods for estimating subgroup-specific potential outcome means and average treatment effects in generalizability and transportability analyses, using outcome model--based (g-formula), weighting, and augmented weighting estimators. We consider estimating subgroup-specific average treatment effects in the target population and its nonrandomized subset, and we provide methods that are appropriate both for nested and non-nested trial designs. As an illustration, we apply the methods to data from the Coronary Artery Surgery Study (North America, 1975-1996) to compare the effect of surgery plus medical therapy versus medical therapy alone for chronic coronary artery disease in subgroups defined by history of myocardial infarction.
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Project description:ImportanceAmong patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy.ObjectiveTo quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes.Design, setting, and participantsThis cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden.ExposuresNew use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels.Main outcomes and measuresProgression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users.ResultsThe study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76).Conclusions and relevanceIn this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.
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Project description:In the phase 3 trial Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy, apixaban was noninferior to enoxaparin, overlapped and followed by warfarin, in the treatment of venous thromboembolism (VTE) with significantly less bleeding; in a real-world evaluation, risks for bleeding and recurrent VTE were lower with apixaban vs warfarin plus parenteral anticoagulant (PAC) bridge therapy. The present study extends this research by comparing outcomes over time and within selected subgroups. A retrospective observational cohort design and 4 US private health care claims databases were used. Study population included patients who initiated outpatient treatment with apixaban or warfarin (plus PAC bridge therapy) for VTE. Major bleeding, clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE were compared during the 180-day follow-up period, at selected follow-up time points (days 21, 90, 180), and within subgroups (pulmonary embolism [PE] with or without deep vein thrombosis [DVT], DVT only, provoked VTE, unprovoked VTE) using multivariable shared frailty models. Study population consisted of 20 561 apixaban patients and 35 080 warfarin patients; baseline characteristics were comparable. Overall, at selected follow-up time points, and within the aforementioned subgroups, adjusted risks were lower among apixaban vs warfarin patients: major bleeding, by 27% to 39%, CRNM bleeding, by 17% to 28%, and recurrent VTE, by 25% to 39% (all P ≤ .01). In this real-world study of VTE patients, risks of bleeding and recurrent VTE were lower among apixaban (vs warfarin) patients during the 180-day follow-up period, at selected follow-up time points, and within subgroups defined by index VTE episode.
| S-EPMC6988406 | biostudies-literature
Project description:The literature on relative age position effects is rather inconsistent. In this study we examined intra-classroom age position (or relative age) effects on Dutch adolescents' school progress and performance (as rated by teachers), physical development, temperamental development (fear and frustration), and depressive symptoms, all adjusted for age at the time of measurement. Data were derived from three waves of Tracking Adolescents' Individuals Lives Survey (TRAILS) of 2230 Dutch adolescents (baseline mean age 11.1, SD = 0.6, 51% girls). Albeit relative age predicted school progress (grade retention ORs = 0.83 for each month, skipped grade OR = 1.47, both p<.001), our key observation is the absence of substantial developmental differences as a result of relative age position in Dutch adolescents with a normative school trajectory, in contrast to most literature. For adolescents who had repeated a grade inverse relative age effects were observed, in terms of physical development and school performance, as well as on depressive symptoms, favoring the relatively young. Cross-cultural differences in relative age effect may be partly explained by the decision threshold for grade retention.
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Project description:BackgroundTo investigate whether quantifying both the absolute and relative intensity of physical activity (PA) improves understanding of age, sex, and occupation-related differences in PA in healthy adults aged 20-89.MethodsIn the cross-sectional COmPLETE study, participants (N = 460, 48% women, age 55 [IQR 37, 71]) wore accelerometers for up to 14 days and underwent cardiopulmonary exercise testing. Average acceleration (AvAcc) and distribution of intensity (IG) of PA across the day were expressed in absolute terms (_ABS) and relative (_REL) to the acceleration at the individual´s maximum intensity, predicted from cardiorespiratory fitness.ResultsAfter initial increases, AvAcc_ABS and IG_ABS continuously declined beyond age 40-45, whereas AvAcc_REL and IG_REL increased until stabilising at age ~ 70 and declining at age ~ 60, respectively. Cardiorespiratory fitness constantly declined. Women had trivially higher AvAcc_ABS and moderately higher AvAcc_REL, but not IG_ABS and IG_REL, than men. Occupations involving at least moderate PA showed higher AvAcc_ABS and AvAcc_REL, but not IG_ABS and IG_REL indicating longer periods of low-intensity PA, compared to sitting/standing occupations.ConclusionsDistinct age trajectories of absolute and relative metrics as well as cardiorespiratory fitness suggest that the age-related decline in the latter preceded that of PA. Women's higher AvAcc_ABS and AvAcc_REL relate to more low-intensity PA combined with lower cardiorespiratory fitness rather than more health-enhancing higher-intensity PA. Finally, the intensity profile of occupational PA may provide insight into why occupational PA appears to lack a prophylactic association with health. Quantifying both the absolute and relative intensity of accelerometer-assessed PA provides greater insight than either alone.Trial registrationOn clinicaltrials.gov (NCT03986892). Retrospectively registered 14 June 2019.
| S-EPMC11884089 | biostudies-literature
Project description:The absolute abundance of bacterial taxa in human host-associated environments plays a critical role in reproductive and gastrointestinal health. However, obtaining the absolute abundance of many bacterial species is typically prohibitively expensive. In contrast, relative abundance data for many species are comparatively cheap and easy to collect (e.g., with universal primers for the 16S rRNA gene). In this paper, we propose a method to jointly model relative abundance data for many taxa and absolute abundance data for a subset of taxa. Our method provides point and interval estimates for the absolute abundance of all taxa. Crucially, our proposal accounts for differences in the efficiency of taxon detection in the relative and absolute abundance data. We show that modeling taxon-specific efficiencies substantially reduces the estimation error for absolute abundance, and controls the coverage of interval estimators. We demonstrate the performance of our proposed method via a simulation study, a study of the effect of HIV acquisition on microbial abundances, and a sensitivity study where we jackknife the taxa with observed absolute abundances.
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Project description:BackgroundThe magnitude of socioeconomic health inequalities differs across age groups. It is less clear whether socioeconomic health inequalities differ across age groups by other factors that are known to affect the relation between socioeconomic position and health, like the indicator of socioeconomic position, the health outcome, gender, and as to whether socioeconomic health inequalities are measured in absolute or in relative terms. The aim is to investigate whether absolute and relative socioeconomic health inequalities differ across age groups by indicator of socioeconomic position, health outcome and gender.MethodsThe study sample was derived from the baseline measurement of the LifeLines Cohort Study and consisted of 95,432 participants. Socioeconomic position was measured as educational level and household income. Physical and mental health were measured with the RAND-36. Age concerned eleven 5-years age groups. Absolute inequalities were examined by comparing means. Relative inequalities were examined by comparing Gini-coefficients. Analyses were performed for both health outcomes by both educational level and household income. Analyses were performed for all age groups, and stratified by gender.ResultsAbsolute and relative socioeconomic health inequalities differed across age groups by indicator of socioeconomic position, health outcome, and gender. Absolute inequalities were most pronounced for mental health by household income. They were larger in younger than older age groups. Relative inequalities were most pronounced for physical health by educational level. Gini-coefficients were largest in young age groups and smallest in older age groups.ConclusionsAbsolute and relative socioeconomic health inequalities differed cross-sectionally across age groups by indicator of socioeconomic position, health outcome and gender. Researchers should critically consider the implications of choosing a specific age group, in addition to the indicator of socioeconomic position and health outcome, as findings on socioeconomic health inequalities may differ between them.
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Project description:ObjectiveStreptozotocin (STZ) is the most widely used diabetogenic agent in animal models of islet transplantation. However, the immunomodifying effects of STZ and the ensuing hyperglycemia on lymphocyte subsets, particularly on T regulatory cells (Tregs), remain poorly understood.Research design and methodsThis study evaluated how STZ-induced diabetes affects adaptive immunity and the consequences thereof on allograft rejection in murine models of islet and skin transplantation. The respective toxicity of STZ and hyperglycemia on lymphocyte subsets was tested in vitro. The effect of hyperglycemia was assessed independently of STZ in vivo by the removal of transplanted syngeneic islets, using an insulin pump, and with rat insulin promoter diphtheria toxin receptor transgenic mice.ResultsEarly lymphopenia in both blood and spleen was demonstrated after STZ administration. Direct toxicity of STZ on lymphocytes, particularly on CD8(+) cells and B cells, was shown in vitro. Hyperglycemia also correlated with blood and spleen lymphopenia in vivo but was not lymphotoxic in vitro. Independently of hyperglycemia, STZ led to a relative increase of Tregs in vivo, with the latter retaining their suppressive capacity in vitro. The higher frequency of Tregs was associated with Treg proliferation in the blood, but not in the spleen, and higher blood levels of transforming growth factor-β. Finally, STZ administration delayed islet and skin allograft rejection compared with naive mice.ConclusionsThese data highlight the direct and indirect immunosuppressive effects of STZ and acute hyperglycemia, respectively. Thus, these results have important implications for the future development of tolerance-based protocols and their translation from the laboratory to the clinic.
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Project description:Does serial learning result in specific associations between pairs of items, or does it result in a cognitive map based on relations of all items? In 2 experiments, we trained human participants to learn various lists of photographic images. We then tested the participants on new lists of photographic images. These new lists were constructed by selecting only 1 image from each list learned during training. In Experiment 1, participants were trained to choose the earlier (experimenter defined) item when presented with adjacent pairs of items on each of 5 different 5-item lists. Participants were then tested on derived lists, in which each item retained its original ordinal position, even though each of the presented pairs was novel. Participants performed above chance on all of the derived lists. In Experiment 2, a different group of participants received the same training as those of Experiment 1, but the ordinal positions of items were systematically changed on each derived list. The response accuracy for Experiment 2 varied inversely with the degree to which an item's original ordinal position was changed. These results can be explained by a model in which participants learned to make both positional inferences about the absolute rank of each stimulus, and transitive inferences about the relative ranks of pairs of stimuli. These inferences enhanced response accuracy when ordinal position was maintained, but not when it was changed. Our results demonstrate quantitatively that, in addition to item-item associations that participants acquire while learning a list of arbitrary items, they form a cognitive map that represents both experienced and inferred relationships. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Project description:There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1).
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