Category: Statistics

Sci Rep. 2021 Apr 7;11(1):7647. doi: 10.1038/s41598-021-86716-y.

ABSTRACT

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G × E) interplay, we interacted layoffs from business closures-a plausibly exogenous environmental exposure-with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.

PMID:33828129 | DOI:10.1038/s41598-021-86716-y

Cancer Epidemiol Biomarkers Prev. 2021 Apr 7:cebp.1568.2020. doi: 10.1158/1055-9965.EPI-20-1568. Online ahead of print.

ABSTRACT

BACKGROUND: The role of progestogens in colorectal cancer development are poorly characterized. To address this, our group developed a highly sensitive assay to measure concentrations of seven markers of endogenous progestogen metabolism among postmenopausal women.

METHODS: The markers were measured in baseline serum collected from postmenopausal women in a case-cohort study within the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT). We followed women not using exogenous hormones at baseline (1992-1993) for up to twelve years: 187 women with incident colorectal cancer diagnosed during follow-up and a subcohort of 495 women selected on strata of age and clinical center. We used adjusted Cox regression models with robust variance to estimate risk for colorectal cancer (hazard ratios [HR], 95% confidence intervals [CI]).

RESULTS: High concentrations of pregnenolone and progesterone were not associated with colorectal cancer (quintile(Q)5 vs. Q1: pregnenolone HR 0.71, CI 0.40-1.25; progesterone HR 1.25, CI 0.71-2.22). A trend of increasing risk was suggested, but statistically imprecise across quintiles of 17-hydroxypregnenolone (Q2 to Q5 HRs 0.75 to 1.44, p-trend 0.06).

CONCLUSIONS: We used sensitive and reliable assays to measure multiple circulating markers of progestogen metabolism. Progestogens were generally unassociated with colorectal cancer risk in postmenopausal women.

IMPACT: Our findings are consistent with most prior research on circulating endogenous sex hormones, which taken together, suggest sex hormones may not be major drivers of colorectal carcinogenesis in postmenopausal women.

PMID:33827983 | DOI:10.1158/1055-9965.EPI-20-1568

Dent Mater J. 2021 Apr 7. doi: 10.4012/dmj.2020-293. Online ahead of print.

ABSTRACT

The effects of space setting values and restorative materials on the bonding of metal-free CAD/CAM onlay restoration were examined quantitatively and qualitatively. Seventy-two standardized MODB onlay cavities, prepared using human molars were restored under nine conditions, based on three space setting values, Increased (IC), Standard (SC, control), Decreased (DC), and three restorative block materials, resin-composites (RC), lithium disilicate glass-ceramics (LD), Feldspar ceramics (FC, control). All the restored specimens were subjected to cyclic loading and thereafter the microtensile bond strength (µ-TBS) was measured and analyzed statistically. The effect of space setting value on the µ-TBS varied with the restorative material. The bonding reliability of RC and the bonding durability of LD were significantly superior to FC. The bonding characteristics of RC under IC and DC were similar to those under SC. LD under DC and FC under IC were effective in obtaining an excellent bonding reliability relative to their SC.

PMID:33827999 | DOI:10.4012/dmj.2020-293

Sci Rep. 2021 Apr 7;11(1):7641. doi: 10.1038/s41598-021-87066-5.

ABSTRACT

This paper presents the assessment of water resource security in the Guizhou karst area, China. A mean impact value and back-propagation (MIV-BP) neural network was used to understand the influencing factors. Thirty-one indices involving five aspects, the water quality subsystem, water quantity subsystem, engineering water shortage subsystem, water resource vulnerability subsystem, and water resource carrying capacity subsystem, were selected to establish an evaluation index of water resource security. In addition, a genetic algorithm and back-propagation (GA-BP) neural network was constructed to assess the water resource security of Guizhou Province from 2001 to 2015. The results show that water resource security in Guizhou was at a moderate warning level from 2001 to 2006 and a critical safety level from 2007 to 2015, except in 2011 when a moderate warning level was reached. For protection and management of water resources in a karst area, the modes of development and utilization of water resources must be thoroughly understood, along with the impact of engineering water shortage. These results are a meaningful contribution to regional ecological restoration and socio-economic development and can promote better practices for future planning.

PMID:33828114 | DOI:10.1038/s41598-021-87066-5

mSphere. 2021 Apr 7;6(2):e01019-20. doi: 10.1128/mSphere.01019-20.

ABSTRACT

Shannon’s entropy is a popular alpha diversity metric because it estimates both richness and evenness in a single equation. However, since its value is dependent on both those parameters, there is theoretically an infinite number of richness/evenness value combinations translating into the same index score. By decoupling both components measured by Shannon’s entropy, two communities having identical indices can be differentiated by mapping richness and evenness coordinates on a scatter plot. In such graphs, confidence ellipses would allow testing significant differences between groups of samples. Multivariate statistical tests such as permutational multivariate analysis of variance (PERMANOVA) can be performed on distance matrices calculated from richness and evenness coordinates and detect statistically significant differences that would have remained unforeseen otherwise. Therefore, plotting richness and evenness on two-dimensional (2D) graphs gives a more thorough understanding of how alpha diversity differs between groups of samples.

PMID:33827912 | DOI:10.1128/mSphere.01019-20

Pediatrics. 2021 Apr 7:e20201634. doi: 10.1542/peds.2020-1634. Online ahead of print.

ABSTRACT

BACKGROUND: Clinicians commonly obtain endotracheal aspirate cultures (EACs) in the evaluation of suspected ventilator-associated infections. However, bacterial growth in EACs does not distinguish bacterial colonization from infection and may lead to overtreatment with antibiotics. We describe the development and impact of a clinical decision support algorithm to standardize the use of EACs from ventilated PICU patients.

METHODS: We monitored EAC use using a statistical process control chart. We compared the rate of EACs using Poisson regression and a quasi-experimental interrupted time series model and assessed clinical outcomes 1 year before and after introduction of the algorithm.

RESULTS: In the preintervention year, there were 557 EACs over 5092 ventilator days; after introduction of the algorithm, there were 234 EACs over 3654 ventilator days (an incident rate of 10.9 vs 6.5 per 100 ventilator days). There was a 41% decrease in the monthly rate of EACs (incidence rate ratio [IRR]: 0.59; 95% confidence interval [CI] 0.51-0.67; P < .001). The interrupted time series model revealed a preexisting 2% decline in the monthly culture rate (IRR: 0.98; 95% CI 0.97-1.0; P = .01), immediate 44% drop (IRR: 0.56; 95% CI 0.45-0.70; P = .02), and stable rate in the postintervention year (IRR: 1.03; 95% CI 0.99-1.07; P = .09). In-hospital mortality, hospital length of stay, 7-day readmissions, and All Patients Refined Diagnosis Related Group severity and mortality scores were stable. The estimated direct cost savings was $26 000 per year.

CONCLUSIONS: A clinical decision support algorithm standardizing EAC obtainment from ventilated PICU patients was associated with a sustained decline in the rate of EACs, without changes in mortality, readmissions, or length of stay.

PMID:33827937 | DOI:10.1542/peds.2020-1634

Neurology. 2021 Apr 7:10.1212/WNL.0000000000011933. doi: 10.1212/WNL.0000000000011933. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effects of rituximab on retinal atrophy in patients with relapsing-remitting multiple sclerosis (RRMS), we performed serial optical coherence tomography (OCT) scans among a cohort of RRMS patients on rituximab, and compared rates of ganglion cell+inner plexiform layer (GCIPL) atrophy to those observed among age- and sex-matched glatiramer acetate (GA)- and natalizumab-treated RRMS patients, and healthy controls (HCs).

METHODS: In this observational study, patients with RRMS treated with a single disease-modifying therapy, and HCs, were followed with serial OCT for a median duration of 2.8 years. Participants with uncontrolled hypertension, diabetes mellitus, or glaucoma, and eyes with optic neuritis ≤6 months prior to baseline OCT, or during follow-up, were excluded. Statistical analyses were performed using linear mixed-effects regression.

RESULTS: During the overall follow-up period, rates of GCIPL atrophy were -0.28±0.11µm/yr among rituximab-treated RRMS patients (n=35). This was similar to GA-treated (n=49; -0.33±0.05µm/yr; p=0.69) and natalizumab-treated patients (n=88; -0.17±0.10µm/yr; p=0.13), and faster than HCs (n=78; -0.15±0.03µm/yr; p=0.006). Rituximab-treated patients exhibited 0.55±0.23µm/yr faster rates of GCIPL atrophy during the first 12 months of treatment, relative to afterwards (n=25; p=0.02), during which period GCIPL atrophy rates were -0.14±0.13µm/yr.

CONCLUSIONS: Retinal atrophy in RRMS is modulated by rituximab. Greater attenuation of retinal atrophy may occur after 12 months of rituximab treatment, following which time GCIPL atrophy rates are similar to those observed among natalizumab-treated RRMS patients and HCs. Our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, though should be confirmed by larger studies.

CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the difference in rate of change of the ganglion cell+inner plexiform layer thickness in patients with RRMS, comparing rituximab to other DMTs.

PMID:33827962 | DOI:10.1212/WNL.0000000000011933

J Immunother Cancer. 2021 Apr;9(4):e002421. doi: 10.1136/jitc-2021-002421.

ABSTRACT

BACKGROUND: Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.

METHODS: We present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.

RESULTS: 950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.

CONCLUSION: In this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

PMID:33827906 | DOI:10.1136/jitc-2021-002421

BMJ Open. 2021 Apr 7;11(4):e046226. doi: 10.1136/bmjopen-2020-046226.

ABSTRACT

OBJECTIVE: This study aims to advance understanding of globally valid versus country-specific quality dimensions and indicators, as perceived by relevant stakeholders. It specifically addresses patient-level indicators for cataract surgery.

DESIGN: A mixed-methods case study comparing Singapore and The Netherlands SETTING: Singapore (2017-2019) and The Netherlands (2014-2015).

PARTICIPANTS: Stakeholder representatives of cataract care in Singapore and The Netherlands.

INTERVENTION: Based on the previously identified complete set of stakeholders in The Netherlands, we identified stakeholders of cataract care in Singapore. Stakeholder representatives then established a multi-stakeholder perspective on the quality of cataract care using a concept mapping approach. This yielded a multidimensional cluster map based on multivariate statistical analyses. Consensus-based quality dimensions were subsequently defined during a plenary session. Thereafter, Singaporean dimensions were matched with dimensions obtained in The Netherlands to identify commonalities and differences.

MAIN OUTCOME MEASURE: Health-services quality dimensions of cataract care.

RESULTS: 19 Singaporean stakeholders representing patients, general practitioners, ophthalmologists, nurses, care providers, researchers and clinical auditors defined health-services quality of cataract care using the following eight dimensions: clinical outcome, patient outcomes, surgical process, surgical safety, patient experience, access, cost and standards of care. Compared with the Dutch results, 61% of the indicators were allocated to dimensions of comparable names and compositions. Considerable differences also existed in the composition of some dimensions and the importance attached to indicators.

CONCLUSIONS AND RELEVANCE: This study on cataract care in Singapore and The Netherlands shows that cataract care quality measurement instruments can share a common international core. At the same time, it emphasises the importance of taking a country-specific multi-stakeholder approach to quality definition and measurement. Complementing an international core set with country-specific measures is required to ensure that the included dimensions and indicators adequately capture the country-specific quality views.

PMID:33827846 | DOI:10.1136/bmjopen-2020-046226

BMJ Open. 2021 Apr 7;11(4):e047121. doi: 10.1136/bmjopen-2020-047121.

ABSTRACT

OBJECTIVES: To develop a prognostic model to identify and quantify risk factors for mortality among patients admitted to the hospital with COVID-19.

DESIGN: Retrospective cohort study. Patients were randomly assigned to either training (80%) or test (20%) sets. The training set was used to fit a multivariable logistic regression. Predictors were ranked using variable importance metrics. Models were assessed by C-indices, Brier scores and calibration plots in the test set.

SETTING: Optum de-identified COVID-19 Electronic Health Record dataset including over 700 hospitals and 7000 clinics in the USA.

PARTICIPANTS: 17 086 patients hospitalised with COVID-19 between 20 February 2020 and 5 June 2020.

MAIN OUTCOME MEASURE: All-cause mortality while hospitalised.

RESULTS: The full model that included information on demographics, comorbidities, laboratory results, and vital signs had good discrimination (C-index=0.87) and was well calibrated, with some overpredictions for the most at-risk patients. Results were similar on the training and test sets, suggesting that there was little overfitting. Age was the most important risk factor. The performance of models that included all demographics and comorbidities (C-index=0.79) was only slightly better than a model that only included age (C-index=0.76). Across the study period, predicted mortality was 1.3% for patients aged 18 years old, 8.9% for 55 years old and 28.7% for 85 years old. Predicted mortality across all ages declined over the study period from 22.4% by March to 14.0% by May.

CONCLUSION: Age was the most important predictor of all-cause mortality, although vital signs and laboratory results added considerable prognostic information, with oxygen saturation, temperature, respiratory rate, lactate dehydrogenase and white cell count being among the most important predictors. Demographic and comorbidity factors did not improve model performance appreciably. The full model had good discrimination and was reasonably well calibrated, suggesting that it may be useful for assessment of prognosis.

PMID:33827848 | DOI:10.1136/bmjopen-2020-047121