Developing more generalizable prediction models from pooled studies and large clustered data sets

Prediction models often yield inaccurate predictions for new individuals. Large data sets from pooled studies or electronic healthcare records may alleviate this with an increased sample size and variability in sample characteristics. However, existing strategies for prediction model development generally do not account for heterogeneity in predictor-outcome associations between different settings and populations. This limits the generalizability of developed models (even from large, combined, clustered data sets) and necessitates local revisions.
We aim to develop methodology for producing prediction models that require less tailoring to different settings and populations. We adopt internal-external cross-validation to assess and reduce heterogeneity in models’ predictive performance during the development. We propose a predictor selection algorithm that optimizes the (weighted) average performance while minimizing its variability across the hold-out clusters (or studies).
Predictors are added iteratively until the estimated generalizability is optimized. We illustrate this by developing a model for predicting the risk of atrial fibrillation and updating an existing one for diagnosing deep vein thrombosis, using individual participant data from 20 cohorts (N = 10 873) and 11 diagnostic studies (N = 10 014), respectively. Meta-analysis of calibration and discrimination performance in each hold-out cluster shows that trade-offs between average and heterogeneity of performance occurred. Our methodology enables the assessment of heterogeneity of prediction model performance during model development in multiple or clustered data sets, thereby informing researchers on predictor selection to improve the generalizability to different settings and populations, and reduce the need for model tailoring. Our methodology has been implemented in the R package metamisc.

The Next Set of COVID-19 Vaccines: Leveraging New Development Platforms to Increase Access for More People Around the World

The approval of the coronavirus disease 2019 (COVID-19) mRNA vaccines brought much optimism to efforts to end the pandemic. A recombinant adenovirus vaccine recently received emergency use authorization, and several other vaccines are likely to follow. These vaccines all use relatively new vaccine production platforms to produce the severe acute respiratory syndrome coronavirus 2 Spike protein. This review discusses how these platforms work, what advantages they offer, and the gaps that remain in public health efforts to control the COVID-19 pandemic. (Clin Ther. 2021;XX:XXX-XXX) © 2021 Elsevier HS Journals, Inc.
Keywords: COVID; SARS-CoV-2; baculovirus; recombinant adenovirus; vaccines.

Involvement of two or moresets of lacrimal glands and/or major salivary glands is related to greater systemic disease activity due to multi-organ involvement in IgG4-related dacryoadenitis/sialadenitis

Objectives: In IgG4-related dacryoadenitis and/or sialadenitis (IgG4-DS), involvement of two or more sets of lacrimal glands (LGs) and/or major salivary glands (MSGs) is regarded as a specific finding with diagnostic significance. This study aimed to clarify the influence of this factor on the overall clinical picture of IgG4-DS.
Methods: We retrospectively reviewed the medical records of 130 patients with IgG4-related disease, 97 of whom were diagnosed with IgG4-DS. We determined their clinical features according to the presence/absence of involvement of ≥2 sets of LGs and/or MSGs and compared the results with those obtained in 33 DS-limited patients.
Results: The IgG4-DS patients comprised 60 men and 37 women (median age 65 years). The median serum IgG4 level at diagnosis was 548 mg/dL. The patients with involvement of ≥2 sets (n = 44) had significantly more affected organs, lower serum C3 and C4 levels, and a tendency to have higher serum IgG levels and IgG4-RD responder index than did those without it (n = 53). In the 33 DS-limited patients, these two groups had no significant differences in clinical features.
Conclusions: Involvement of ≥2 sets of LGs and/or MSGs suggests greater systemic disease activity mainly reflected by involvement of more organs.
Keywords: IgG4-related dacryoadenitis and sialadenitis; IgG4-related disease; disease activity; two sets.

The Frequent Network Neighborhood Mapping of the human hippocampus shows much more frequent neighbor sets in males than in females.

In the study of the human connectome, the vertices and the edges of the network of the human brain are analyzed: the vertices of the graphs are the anatomically identified gray matter areas of the subjects; this set is exactly the same for all the subjects. The edges of the graphs correspond to the axonal fibers, connecting these areas. In the biological applications of graph theory, it happens very rarely that scientists examine numerous large graphs on the very same, labeled vertex set.
Exactly this is the case in the study of the connectomes. Because of the particularity of these sets of graphs, novel, robust methods need to be developed for their analysis.
Here we introduce the new method of the Frequent Network Neighborhood Mapping for the connectome, which serves as a robust identification of the neighborhoods of given vertices of special interest in the graph. We apply the novel method for mapping the neighborhoods of the human hippocampus and discover strong statistical asymmetries between the connectomes of the sexes, computed from the Human Connectome Project. We analyze 413 braingraphs, each with 463 nodes. We show that the hippocampi of men have much more significantly frequent neighbor sets than women; therefore, in a sense, the connections of the hippocampi are more regularly distributed in men and more varied in women. Our results are in contrast to the volumetric studies of the human hippocampus, where it was shown that the relative volume of the hippocampus is the same in men and women.

A relatively higher intraocular pressure set at the end of vitrectomy is associated with a more stable and rapid visual recovery for patients with vitreous haemorrhage.

To compare structural and functional improvements in patients with vitreous haemorrhage (VH) with different IOPs re-established at the end of pars plana vitrectomy (PPV).It is a prospective, randomized, comparative, interventional study. Ninety-five patients with nonclearing VH were randomized to receive PPV with normalized IOPs of 15 mmHg (Group I: 32 eyes), 25 mmHg (Group II: 32 eyes) and 35 mmHg (Group III: 31 eyes) at the end of surgery. The grade of vitreous opacity and best-corrected visual acuity (BCVA) on postoperative day 1, week 1, month 1 and month 3 were compared with a mixed model for repeated measures analysis.
All 3 groups achieved significant improvement on postoperatively in BCVA (p < 0.01) and vitreous opacity (p < 0.01) compared with the baseline. The group difference was significant at the end of week 1 and showed a trend of higher IOP set at the end of PPV with better anatomical (p < 0.01) and visual recovery (p < 0.01). However, at postoperative month 1 and month 3, equivalent anatomical (month 1: p = 0.56; month 3: p = 0.36) and visual outcomes (month 1: p = 0.16; month 3: p = 0.88) were obtained in the 3 groups.

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The average effect of IOP on BCVA (group II versus group III: effect size (ES): 0.41, p < 0.01; group I versus group III: ES: 0.66, p < 0.01) and vitreous opacity (group II versus group III: ES: 0.70, p < 0.01; group I versus group III: ES:1.09, p < 0.01) over the course of the study period was statistically significant. The only postoperative complication was recurrent VH in two patients allocating in group I and II, respectively.A relatively higher IOP set at the end of vitrectomy resulted in a more stable and rapid recovery with fewer complications in patients with non-complex VH.

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