Nevin Manimala

Alzheimers Dement. 2022 Apr 22. doi: 10.1002/alz.12663. Online ahead of print.

ABSTRACT

INTRODUCTION: We examined whether German claims data are suitable for dementia risk prediction, how machine learning (ML) compares to classical regression, and what the important predictors for dementia risk are.

METHODS: We analyzed data from the largest German health insurance company, including 117,895 dementia-free people age 65+. Follow-up was 10 years. Predictors were: 23 age-related diseases, 212 medical prescriptions, 87 surgery codes, as well as age and sex. Statistical methods included logistic regression (LR), gradient boosting (GBM), and random forests (RFs).

RESULTS: Discriminatory power was moderate for LR (C-statistic = 0.714; 95% confidence interval [CI] = 0.708-0.720) and GBM (C-statistic = 0.707; 95% CI = 0.700-0.713) and lower for RF (C-statistic = 0.636; 95% CI = 0.628-0.643). GBM had the best model calibration. We identified antipsychotic medications and cerebrovascular disease but also a less-established specific antibacterial medical prescription as important predictors.

DISCUSSION: Our models from German claims data have acceptable accuracy and may provide cost-effective decision support for early dementia screening.

PMID:35451562 | DOI:10.1002/alz.12663

Hum Brain Mapp. 2022 Apr 22. doi: 10.1002/hbm.25878. Online ahead of print.

ABSTRACT

One important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, structural, or functional magnetic resonance imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within-parcel to between-parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the distance-controlled boundary coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting-state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task-based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting-state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi-modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct.

PMID:35451538 | DOI:10.1002/hbm.25878

Genet Epidemiol. 2022 Apr 22. doi: 10.1002/gepi.22453. Online ahead of print.

ABSTRACT

Genetic association studies of child health outcomes often employ family-based study designs. One of the most popular family-based designs is the case-parent trio design that considers the smallest possible nuclear family consisting of two parents and their affected child. This trio design is particularly advantageous for studying relatively rare disorders because it is less prone to type 1 error inflation due to population stratification compared to population-based study designs (e.g., case-control studies). However, obtaining genetic data from both parents is difficult, from a practical perspective, and many large studies predominantly measure genetic variants in mother-child dyads. While some statistical methods for analyzing parent-child dyad data (most commonly involving mother-child pairs) exist, it is not clear if they provide the same advantage as trio methods in protecting against population stratification, or if a specific dyad design (e.g., case-mother dyads vs. case-mother/control-mother dyads) is more advantageous. In this article, we review existing statistical methods for analyzing genome-wide marker data on dyads and perform extensive simulation experiments to benchmark their type I errors and statistical power under different scenarios. We extend our evaluation to existing methods for analyzing a combination of case-parent trios and dyads together. We apply these methods on genotyped and imputed data from multiethnic mother-child pairs only, case-parent trios only or combinations of both dyads and trios from the Gene, Environment Association Studies consortium (GENEVA), where each family was ascertained through a child affected by nonsyndromic cleft lip with or without cleft palate. Results from the GENEVA study corroborate the findings from our simulation experiments. Finally, we provide recommendations for using statistical genetic association methods for dyads.

PMID:35451532 | DOI:10.1002/gepi.22453

J Adv Nurs. 2022 Apr 22. doi: 10.1111/jan.15239. Online ahead of print.

ABSTRACT

AIMS: This review aims to examine updated evidence to evaluate the effectiveness of caregiver-mediated exercise interventions on basic and extended activities of daily living (ADL), anxiety and depression of post-stroke rehabilitation individuals.

DESIGN: A systematic review and meta-analysis.

DATA SOURCES: Six electronic databases, including CINAHL, CENTRAL, Embase, PubMed, PsycINFO and Scopus, grey literature and trial registry were searched from inception until February 2021.

METHODS: Only randomized controlled trials written in English were included. Meta-analyses were conducted for basic and extended ADL, anxiety and depression outcomes using RevMan software. Overall quality of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation framework.

RESULTS: A total of 11 randomized controlled trials comprising 2120 participants were identified, with 10 trials meta-analysed. Meta-analyses indicated statistically significant effects favouring caregiver-mediated exercise interventions for basic ADL. Subgroup analyses revealed significant effects for exercise-only interventions mediated by caregivers for basic ADL. No significant effects were found for extended ADL, anxiety and depression for stroke survivors.

CONCLUSION: Caregiver-mediated exercise interventions appear to have beneficial impacts on basic ADL for stroke survivors, suggesting caregiver-mediated exercise interventions as a potentially feasible way to improve functional independence.

IMPACT: Caregiver-mediated intervention with exercises as a major component could be a promising approach to augment stroke rehabilitation. Future research should include high-quality studies with focus on specific intervention components or to explore caregiver outcomes.

PMID:35451521 | DOI:10.1111/jan.15239

J Periodontol. 2022 Apr 22. doi: 10.1002/JPER.21-0615. Online ahead of print.

ABSTRACT

BACKGROUND: This cross-sectional study assessed the role of gingival landmarks (GLs) and cutting points (CPs) for gingival phenotype (GP) determination.

METHODS: Six maxillary anterior teeth (70 subjects) were evaluated using soft tissue cone-beam computed tomography (ST-CBCT). Gingival thickness was measured at different GLs: (1) tissue zone (gingival margin (GM), 1 and 2 mm apical to GM, cementoenamel junction, above the bone crest); (2) bone zone (buccal bone crest (BBC), 1, 2, and 3 mm apical to BBC). Cutting points of 0.6, 0.8, 1.0, 1.2, and 1.5 mm were used to discriminate between thin and thick GP. The clinical determination of GP was made based on transparency of the periodontal probe (TRAN).

RESULTS: The prevalence of thin and thick GP depended on the GL and CP. Considering the CP (1 mm), thin GP at the tissue zone ranged from 99% at the GM to 10.2% above the bone crest. In the bone zone, thick GP ranged from 28% at the BBC to 6% at 3 mm apical to the BBC. The predictability of a correct assessment of GP by TRAN compared to ST-CBCT was influenced by the GLs and CPs. A slight agreement (kappa < 0.2) and low accuracy (area under the curve < 0.7) were found between methods.

CONCLUSION: The determination of thin and thick gingival phenotypes is related to the gingival landmarks and cutting points. Further studies are required for a well-defined treatment protocol considering different gingival landmarks in tissue and bone zones. An ST-CBCT may be useful for this purpose. This article is protected by copyright. All rights reserved.

PMID:35451505 | DOI:10.1002/JPER.21-0615

Acta Obstet Gynecol Scand. 2022 Apr 22. doi: 10.1111/aogs.14366. Online ahead of print.

ABSTRACT

Traditional null hypothesis significance testing (NHST) incorporating the critical level of significance of 0.05 has become the cornerstone of decision-making in health care, and nowhere less so than in obstetric and gynecological research. However, such practice is controversial. In particular, it was never intended for clinical significance to be inferred from statistical significance. The inference of clinical importance based on statistical significance (p < 0.05), and lack of clinical significance otherwise (p ≥ 0.05) represents misunderstanding of the original purpose of NHST. Furthermore, the limitations of NHST-sensitivity to sample size, plus type I and II errors-are frequently ignored. Therefore, decision-making based on NHST has the potential for recurrent false claims about the effectiveness of interventions or importance of exposure to risk factors, or dismissal of important ones. This commentary presents the history behind NHST along with the limitations that modern-day NHST presents, and suggests that a statistics reform regarding NHST be considered.

PMID:35451497 | DOI:10.1111/aogs.14366

Metallomics. 2022 Apr 22:mfac028. doi: 10.1093/mtomcs/mfac028. Online ahead of print.

ABSTRACT

Hemodialysis (HD) represents a life-sustaining treatment for patients with end stage renal disease. However, it is associated with several complications, including anemia. Erythropoiesis stimulating agents (ESA) are often administered to HD patients with renal anemia, but a relevant proportion of them fail to respond to the therapy. Since trace metals are involved in several biological processes and their blood levels can be altered by hemodialysis, we study the possible association between serum trace metal concentrations and ratios with the administration and response to ESA. For this study, data and sample information of 110 HD patients were downloaded from the UC San-Diego Metabolomics Workbench public repository (PR000565). The blood serum levels (and ratios) of antimony, cadmium, copper, manganese, molybdenum, nickel, selenium, tin and zinc were studied applying an omics statistical approach. The Random Forest model was able to discriminate HD dependent patients treated and not treated with ESA, with an accuracy of 71.7% (95% CI 71.5-71.9%). Logistic regression analysis identifies alterations of Mn, Mo, Cd, Sn, and several of their ratios as characteristic of patients treated with ESA. Moreover, patients with scarce response to ESA showed to be characterized by reduced Mn to Ni and Mn to Sb ratios. In conclusion, our results show that trace metals, in particular manganese, play a role in the mechanisms underlying human response to ESA, and if further confirmed, the re-equilibration of their physiological levels could contribute to a better management of HD patients hopefully reducing their morbidity and mortality.

PMID:35451491 | DOI:10.1093/mtomcs/mfac028

J Nutr. 2022 Apr 22:nxac093. doi: 10.1093/jn/nxac093. Online ahead of print.

ABSTRACT

BACKGROUND: Diet therapy may bridge the therapeutic gap in ulcerative colitis (UC).

OBJECTIVES: The novel 4-SURE diet (4-strategies-to-SUlfide-REduction), designed to modulate colonic fermentation and influence production of excess hydrogen sulfide, was examined in a feasibility study for tolerability, clinical efficacy and effects on microbial end-points.

DESIGN: Adults ≥ 18 years old with mild to moderately active UC were advised to increase intake of fermentable fibers, restrict total and sulfur-containing proteins and avoid specific food additives for 8-weeks. The primary outcome was tolerability of diet (100-mm visual analogue scale (VAS) with 100-mm being intolerable). Secondary exploratory outcomes were self-reported adherence (always adherent ≥ 76-100%), clinical and endoscopic response (reduction in partial Mayo ≥ 2 and Mayo endoscopic sub-score ≥ 1), modulation of fecal characteristics including markers of protein and carbohydrate fermentation, and food-related quality of life (IBD-FRQoL-29). Primary analysis was by intention to treat, performed using paired t and Wilcoxon signed-rank statistical tests.

RESULTS: 28 adults with UC, mean age 42 (range 22-72) years, 15 female, 3 proctitis, 14 left-sided and 11 extensive, were studied. Prescribed dietary targets were achieved overall. The diet was well tolerated (VAS: 19 mm; 95% CI 7, 31 mm) with 95% frequently or always adherent. Clinical response occurred in 13/28 (46%) and endoscopic improvement in 10/28 (36%). Two (7%) worsened. Fecal excretion of short-chain fatty acids (SCFA) increased by 69% (p < 0.0001) while the proportion of branched-chain to SCFA were suppressed by 27% (-1.34%; 95% CI: -2.28, -0.40; p = 0.007). FRQoL improved by 10 points (95% CI: 4, 16; p < 0.001).

CONCLUSIONS: The 4-SURE dietary strategy is considered tolerable and an acceptable diet by adults with mild to moderately active UC. The dietary teachings achieved the prescribed dietary and fecal targets. Given signals of therapeutic efficacy, further evaluation of this diet is warranted in a placebo-controlled trial. Trial registration number: Australian New Zealand Clinical Trials Registry ACTRN12619000063112.

PMID:35451489 | DOI:10.1093/jn/nxac093

Nephrol Dial Transplant. 2022 Apr 22:gfac157. doi: 10.1093/ndt/gfac157. Online ahead of print.

ABSTRACT

BACKGROUND: In FIGARO-DKD, finerenone reduced the risk of cardiovascular events in patients with type 2 diabetes (T2D) and stage 1-4 chronic kidney disease (CKD). In FIDELIO-DKD, finerenone improved kidney and cardiovascular outcomes in patients with advanced CKD. This analysis further explores kidney outcomes in FIGARO-DKD.

METHODS: FIGARO-DKD (NCT02545049) included patients with urine albumin-to-creatinine ratio (UACR) 30-<300 mg/g and estimated glomerular filtration rate (eGFR) 25-90 mL/min/1.73 m2 or UACR 300-5000 mg/g and eGFR ≥ 60 mL/min/1.73 m2. Outcomes included two composite kidney endpoints of kidney failure, renal death and with either a sustained decrease from baseline of ≥ 40% or ≥ 57% in eGFR for ≥ 4 weeks. Change in of albuminuria and eGFR slope were also analysed. Kidney and CV outcomes were evaluated by baseline UACR.

RESULTS: A lower incidence rate for the eGFR ≥ 40% kidney composite endpoint was observed with finerenone compared with placebo, but the between-group difference was not significant (HR = 0.87; 95%CI 0.76-1.01; P = 0.069). A greater treatment effect was observed on the eGFR ≥ 57% kidney composite endpoint (HR = 0.77; 95%CI 0.60-0.99; P = 0.041) with a 36% relative risk reduction for end-stage kidney disease. A larger magnitude of effect on kidney outcomes was observed with finerenone versus placebo for patients with severely increased albuminuria than with moderately increased albuminuria. Improvements in UACR, eGFR slope and cardiovascular risk were evident in both subgroups with finerenone.

CONCLUSIONS: The present analyses suggest that finerenone protects against kidney disease progression and cardiovascular events in patients with T2D and early- or late-stage CKD.

PMID:35451488 | DOI:10.1093/ndt/gfac157

Pain Med. 2022 Apr 22:pnac064. doi: 10.1093/pm/pnac064. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the current cutoff score and a recalibrated adaptation of the Veterans Health Administration (VHA) Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose (RIOSORD) in active duty service members.

DESIGN: Retrospective case-control.

SETTING: Military Health System.

SUBJECTS: Active duty service members dispensed ≥ 1 opioid prescription between January 1, 2018 and December 31, 2019.

METHODS: Service members with a documented opioid overdose were matched 1:10 to controls. An active duty-specific (AD) RIOSORD was constructed using the VHA RIOSORD components. Analyses examined the risk stratification and predictive characteristics of two RIOSORD versions (VHA and AD).

RESULTS: Cases (n = 95) were matched with 950 controls. Only 6 of the original 17 elements were retained in the AD RIOSORD. Long-acting or extended-release opioid prescriptions, antidepressant prescriptions, hospitalization, and emergency department visits were associated with overdose events. The VHA RIOSORD had fair performance (C-statistic 0.77, 95% CI 0.75, 0.79), while the AD RIOSORD did not demonstrate statistically significant performance improvement (C-statistic 0.78, 95% CI, 0.77, 0.80). The DoD selected cut point (VHA RIOSORD > 32) only identified 22 of 95 ORD outcomes (Sensitivity 0.23) while an AD-specific cut point (AD RIOSORD > 16) correctly identified 53 of 95 adverse events (Sensitivity 0.56).

CONCLUSION: Results highlight the need to continually recalibrate predictive models and to consider multiple measures of performance. Although both models had similar overall performance with respect to the C-statistic, an AD-specific index threshold improves sensitivity. The calibrated AD RIOSORD does not represent an end-state, but a bridge to a future model developed on a wider range of patient variables, taking into consideration features that capture both care received, and care that was not received.

PMID:35451483 | DOI:10.1093/pm/pnac064