Nevin Manimala

J Clin Oncol. 2022 Sep 2:JCO2200710. doi: 10.1200/JCO.22.00710. Online ahead of print.

ABSTRACT

PURPOSE: Secondary myeloid neoplasms (sMNs) remain the most serious long-term complications in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). However, sMNs lack specific predictors, dedicated surveillance measures, and early therapeutic interventions.

PATIENTS AND METHODS: We studied a multicenter, retrospective cohort of 1,008 patients (median follow-up 8.6 years) with AA and PNH to assess clinical and molecular determinants of clonal evolution.

RESULTS: Although none of the patients transplanted upfront (n = 117) developed clonal complications (either sMN or secondary PNH), the 10-year cumulative incidence of sMN in nontransplanted cases was 11.6%. In severe AA, older age at presentation and lack of response to immunosuppressive therapy were independently associated with increased risk of sMN, whereas untreated patients had the highest risk among nonsevere cases. The elapsed time from AA to sMN was 4.5 years. sMN developed in 94 patients. The 5-year overall survival reached 40% and was independently associated with bone marrow blasts at sMN onset. Myelodysplastic syndrome with high-risk phenotypes, del7/7q, and ASXL1, SETBP1, RUNX1, and RAS pathway gene mutations were the most frequent characteristics. Cross-sectional studies of clonal dynamics from baseline to evolution revealed that PIGA/human leukocyte antigen lesions decreased over time, being replaced by clones with myeloid hits. PIGA and BCOR/L1 mutation carriers had a lower risk of sMN progression, whereas myeloid driver lesions marked the group with a higher risk.

CONCLUSION: The risk of sMN in AA is associated with disease severity, lack of response to treatment, and patients’ age. sMNs display high-risk morphological, karyotypic, and molecular features. The landscape of acquired somatic mutations is complex and incompletely understood and should be considered with caution in medical management.

PMID:36054881 | DOI:10.1200/JCO.22.00710

Int J Biostat. 2022 Sep 5. doi: 10.1515/ijb-2022-0056. Online ahead of print.

ABSTRACT

In this paper, we review some important early developments on causal inference in medical statistics and epidemiology that were inspired by questions in oncology. We examine two classical examples from the literature and point to a current area of ongoing methodological development, namely the estimation of optimal adaptive treatment strategies. While causal approaches to analysis have become more routine in oncology research, many exciting challenges and open problems remain, particularly in the context of censored outcomes.

PMID:36054829 | DOI:10.1515/ijb-2022-0056

Glob Chang Biol. 2022 Aug 23. doi: 10.1111/gcb.16404. Online ahead of print.

ABSTRACT

Large-scale reforestation can potentially bring both benefits and risks to the water cycle, which needs to be better quantified under future climates to inform reforestation decisions. We identified 477 water-insecure basins worldwide accounting for 44.6% (380.2 Mha) of the global reforestation potential. As many of these basins are in the Asia-Pacific, we used regional coupled land-climate modelling for the period 2041-2070 to reveal that reforestation increases evapotranspiration and precipitation for most water-insecure regions over the Asia-Pacific. This resulted in a statistically-significant increase in water yield (p < 0.05) for the Loess Plateau-North China Plain, Yangtze Plain, Southeast China and Irrawaddy regions. Precipitation feedback was influenced by the degree of initial moisture limitation affecting soil moisture response and thus evapotranspiration, as well as precipitation advection from other reforested regions and moisture transport away from the local region. Reforestation also reduces the probability of extremely dry months in most of the water-insecure regions. However, some regions experience non-significant declines in net water yield due to heightened evapotranspiration outstripping increases in precipitation, or declines in soil moisture and advected precipitation.

PMID:36054815 | DOI:10.1111/gcb.16404

Nephrol Nurs J. 2022 Jul-Aug;49(4):351-358.

ABSTRACT

This project examined the effect of an educational intervention on blood pressure control among minority patients with chronic kidney disease (CKD). Adherence to a low-sodium diet is crucial for blood pressure control. It is also vital to assess food insecurity to improve diet adherence, especially among high-risk underrepresented populations. Participants were recruited from a public hospital renal clinic. Knowledge and food access was assessed using CKD and food insecurity questionnaires. Food frequency and 24-hour 3-day food diaries were completed and analyzed. Eighteen patients were enrolled (Black, non-Hispanic = 66.6%, Hispanic = 27.7%, uninsured = 33.3%, and Medicaid recipients = 27.7%). Eighty-nine percent of participants screened positive for food insecurity and received vouchers for healthy food from a food depository. Paired t tests showed statistically significant increase in knowledge (p < 0.00) and self-efficacy, and systolic blood pressure improved post-intervention. This study suggests that Black non-Hispanic and Hispanic patients with CKD have limited access to healthy food and consume higher sodium. Patient education, screening for food insecurity, and access to a food depository enhanced adherence to low sodium diet and improved blood pressure control.

PMID:36054808

Geriatr Gerontol Int. 2022 Aug 30. doi: 10.1111/ggi.14469. Online ahead of print.

ABSTRACT

AIM: To compare the predictive abilities of the FRAIL scale (FS), frailty screening questionnaire (FSQ) and clinical frailty scale (CFS) for adverse outcomes in older adults in the emergency department.

METHODS: In total, 317 older adults aged ≥65 years attending emergency department was screened for frailty using the FS, FSQ and CFS. Outcome measures included all-cause 28-day mortality and intensive care unit readmission. Cox proportional hazards model was used for survival comparison. Logistic regression was used to analyze risk factors for readmissions. In addition, we calculated the C-statistic, net reclassification improvement and integrated discrimination improvement to evaluate the predictive value of three scales.

RESULTS: The prevalence of frailty was 55.2% (FS), 47.0% (FSQ) and 69.4% (CFS). Cox regression and logistic regression analysis revealed that frailty screening by FS, FSQ and CFS was an independent risk factor for all-cause 28-day mortality and 30- and 90-day readmission after adjustment. Incorporation of FS, FSQ and CFS into a basic model with other risk factors significantly improved C-statistic. For all-cause 28-day mortality, the model including FS had the highest C-statistic from 0.786 (95% confidence interval: 0.706-0.865) to 0.854 (95% confidence interval: 0.802-0.907) and the improvements in risk prediction were also confirmed by category-free net reclassification improvement and integrated discrimination improvement, suggesting FS was significantly better than CFS and FSQ. The three tools had a low predictive ability for readmission (all C-statistics <0.7).

CONCLUSIONS: All three frailty scales showed a predictive ability for 28-day mortality and readmission but FS may be the most valid tool in the emergency department. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2022; ••: ••-••.

PMID:36054799 | DOI:10.1111/ggi.14469

Res Synth Methods. 2022 Aug 10. doi: 10.1002/jrsm.1597. Online ahead of print.

ABSTRACT

Meta-analysis allows researchers to combine evidence from multiple studies, making it a powerful tool for synthesizing information on the safety profiles of new medical interventions. There is a critical need to identify subgroups at high risk of experiencing treatment-related toxicities. However, this remains quite challenging from a statistical perspective as there are a variety of clinical risk factors that may be relevant for different types of adverse events, and adverse events of interest may be rare or incompletely reported. We frame this challenge as a variable selection problem and propose a Bayesian hierarchical model which incorporates a horseshoe prior on the interaction terms to identify high-risk groups. Our proposed model is motivated by a meta-analysis of adverse events in cancer immunotherapy, and our results uncover key factors driving the risk of specific types of treatment-related adverse events.

PMID:36054779 | DOI:10.1002/jrsm.1597

Pharm Stat. 2022 Aug 31. doi: 10.1002/pst.2263. Online ahead of print.

ABSTRACT

In pre-clinical oncology studies, tumor-bearing animals are treated and observed over a period of time in order to measure and compare the efficacy of one or more cancer-intervention therapies along with a placebo/standard of care group. A data analysis is typically carried out by modeling and comparing tumor volumes, functions of tumor volumes, or survival. Data analysis on tumor volumes is complicated because animals under observation may be euthanized prior to the end of the study for one or more reasons, such as when an animal’s tumor volume exceeds an upper threshold. In such a case, the tumor volume is missing not-at-random for the time remaining in the study. To work around the non-random missingness issue, several statistical methods have been proposed in the literature, including the rate of change in log tumor volume and partial area under the curve. In this work, an examination and comparison of the test size and statistical power of these and other popular methods for the analysis of tumor volume data is performed through realistic Monte Carlo computer simulations. The performance, advantages, and drawbacks of popular statistical methods for animal oncology studies are reported. The recommended methods are applied to a real data set.

PMID:36054773 | DOI:10.1002/pst.2263

Int J Cancer. 2022 Aug 19. doi: 10.1002/ijc.34252. Online ahead of print.

ABSTRACT

The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales “fatigue severity,” “reduced motivation” and “reduced activity,” respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For “fatigue severity,” associations appeared mainly driven by intraindividual associations, while for “reduced motivation” stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.

PMID:36054767 | DOI:10.1002/ijc.34252

J Am Geriatr Soc. 2022 Aug 29. doi: 10.1111/jgs.18013. Online ahead of print.

ABSTRACT

BACKGROUND: As the Department of Veterans Affairs (VA) healthcare system seeks to expand access to comprehensive geriatric assessments, evidence-based models of care are needed to support community-dwelling older persons. We evaluated the VA Geriatric Resources for Assessment and Care of Elders (VA-GRACE) program’s effect on mortality and readmissions, as well as patient, caregiver, and staff satisfaction.

METHODS: This retrospective cohort included patients admitted to the Richard L. Roudebush VA hospital (2010-2019) who received VA-GRACE services post-discharge and usual care controls who were potentially eligible for VA-GRACE but did not receive services. The VA-GRACE program provided home-based comprehensive, multi-disciplinary geriatrics assessment, and ongoing care. Primary outcomes included 90-day and 1-year all-cause readmissions and mortality, and patient, caregiver, and staff satisfaction. We used propensity score modeling with overlapping weighting to adjust for differences in characteristics between groups.

RESULTS: VA-GRACE patients (N = 683) were older than controls (N = 4313) (mean age 78.3 ± 8.2 standard deviation vs. 72.2 ± 6.9 years; p < 0.001) and had greater comorbidity (median Charlson Comorbidity Index 3 vs. 0; p < 0.001). VA-GRACE patients had higher 90-day readmissions (adjusted odds ratio [aOR] 1.55 [95%CI 1.01-2.38]) and higher 1-year readmissions (aOR 1.74 [95%CI 1.22-2.48]). However, VA-GRACE patients had lower 90-day mortality (aOR 0.31 [95%CI 0.11-0.92]), but no statistically significant difference in 1-year mortality was observed (aOR 0.88 [95%CI 0.55-1.41]). Patients and caregivers reported that VA-GRACE home visits reduced travel burden and the program linked Veterans and caregivers to needed resources. Primary care providers reported that the VA-GRACE team helped to reduce their workload, improved medication management for their patients, and provided a view into patients’ daily living situation.

CONCLUSIONS: The VA-GRACE program provides comprehensive geriatric assessments and care to high-risk, community-dwelling older persons with high rates of satisfaction from patients, caregivers, and providers. Widespread deployment of programs like VA-GRACE will be required to support Veterans aging in place.

PMID:36054760 | DOI:10.1111/jgs.18013

Am J Hum Biol. 2022 Aug 26:e23793. doi: 10.1002/ajhb.23793. Online ahead of print.

ABSTRACT

OBJECTIVES: Sexual dimorphism in deciduous tooth crown size is often used to identify sex in sub-adults from archeological sites and forensic settings. Yet sexual dimorphism in deciduous dental attributes is less well documented than in permanent teeth. This analysis was conducted to document variation in sexual dimorphism within and between a global sample of populations.

METHODS: Mean deciduous tooth crown size was culled from published literature, yielding a sample of 37 groups. Mean mesiodistal (MD) and buccolingual (BL) crown dimensions are the basis for computing percent sexual dimorphism [(M/F-1) * 100]. Three analyses were conducted: (1) a statistical analysis of mean % sex dimorphism (%SD) within and between populations, (2) an evaluation of rank-ordered %SD by tooth, and (3) an assessment of intergroup patterns in degree of sexual dimorphism. Univariate tests of significance, correlation and regression, and multivariate cluster analysis were used.

RESULTS: Mean %SD is low overall (1.77) for 26 groups and the level of dimorphism is not significantly different for MD (1.68) and BL (1.72) dimensions. The most sexual dimorphic deciduous teeth include incisor, canine and molar tooth types, while in the permanent dentition canines are consistently most sexual dimorphic. Global variation in sexual dimorphism of deciduous tooth size is low with little inter-ethnic variation.

CONCLUSIONS: Sexual dimorphism in crown size is lower and more variably expressed than in permanent teeth. Differences may relate to developmental, chromosomal, and hormonal factors. Degree of sexual dimorphism is not associated with ethnicity in this global sample.

PMID:36054733 | DOI:10.1002/ajhb.23793