Category: Statistics

Cancer Treat Rev. 2021 Mar 30;97:102202. doi: 10.1016/j.ctrv.2021.102202. Online ahead of print.

ABSTRACT

BACKGROUND: The real impact of bevacizumab maintenance as single agent in metastatic colorectal cancer (mCRC) remains unclear. SAKK-41/06 and PRODIGE-9 failed to demonstrate the non-inferiority and superiority of bevacizumab versus no maintenance, respectively, while AIO-KRK-0207 showed the non-inferiority of maintenance bevacizumab versus bevacizumab and fluoropyrimidines for time to strategy failure.

METHODS: Bibliography electronic databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials) were searched for English published clinical trials prospectively randomizing mCRC patients to receive bevacizumab maintenance or not after first-line chemotherapy plus bevacizumab. Individual patients’ data (IPD) were provided by investigators for all included trials. Primary end-points were progression-free survival (PFS) and overall survival (OS), both from the start of induction and maintenance. Univariate and multivariate analyses for PFS and OS were performed.

RESULTS: Three phase III studies – PRODIGE-9, AIO-KRK-0207 and SAKK-41/06 – were included. Considering the different timing of randomization, IPD of patients not progressed during induction and starting maintenance phase entered the analysis. 909 patients were included, 457 (50%) received bevacizumab maintenance. Median PFS from induction start was 9.6 and 8.9 months in bevacizumab group versus no maintenance group, respectively (HR 0.78; 95%CI: 0.68-0.89; p < 0.0001). Subgroups analysis for PFS showed a significant interaction according for RAS status (p = 0.048), with a maintenance benefit limited to RAS wild-type patients. No difference in terms of OS was observed.

CONCLUSIONS: Despite the statistically significant PFS improvement for bevacizumab maintenance, the absolute benefit appears limited. Subgroup analysis shows a differential effect of bevacizumab maintenance in favor of RAS wild-type patients. Considering these results, maintenance therapy with fluoropyrimidine with or without bevacizumab remains the first option. Single agent bevacizumab maintenance can be considered in selected cases, such as cumulative toxicity or patient’s refusal, in particular for RAS wild-type patients.

PMID:33838596 | DOI:10.1016/j.ctrv.2021.102202

J Affect Disord. 2021 Mar 31;287:406-416. doi: 10.1016/j.jad.2021.03.083. Online ahead of print.

ABSTRACT

BACKGROUND: Stressful life events as important stressors have gradually been recognized as the potential etiology that may lead to adverse birth outcomes such as preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). However, researches on this topic have shown relatively inconsistent results. This systematic review and meta-analysis was performed to synthesize available data on the association between prenatal stressful life events and increased risks of PTB, LBW, and SGA.

METHODS: Electronic databases were searched from their inception until September 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to assess the association between prenatal stressful life events and PTB, LBW, and SGA using random effects models. In addition, subgroup analyses, cumulative meta-analyses, sensitivity analyses, and publication bias diagnosis were conducted. STATA 14.0 was applied for statistical analyses.

RESULTS: Totally 31 cohort studies involving 5,665,998 pregnant women were included. Prenatal stressful life events were associated with a 20% higher risk of PTB (RR = 1.20, 95%CI = 1.10-1.32), a 23% increased risk for LBW (RR = 1.23, 95%CI = 1.10-1.39), and a 14% higher risk of SGA (RR = 1.14, 95%CI = 1.08-1.20). Sensitivity analysis indicated the results were stable.

CONCLUSIONS: Findings indicated that pregnant women experiencing prenatal stressful life events were at increased risk of PTB, LBW, and SGA. This information provided additional supports that pregnant women experiencing prenatal stressful life events would benefit from receiving assessment and management in prenatal care services.

PMID:33838476 | DOI:10.1016/j.jad.2021.03.083

Neuroimage Clin. 2021 Mar 29;30:102647. doi: 10.1016/j.nicl.2021.102647. Online ahead of print.

ABSTRACT

Children with hearing loss (CHL) exhibit delays in language function relative to children with normal hearing (CNH). However, evidence on whether these delays extend into other cognitive domains such as working memory is mixed, with some studies showing decrements in CHL and others showing CHL performing at the level of CNH. Despite the growing literature investigating the impact of hearing loss on cognitive and language development, studies of the neural dynamics that underlie these cognitive processes are notably absent. This study sought to identify the oscillatory neural responses serving verbal working memory processing in CHL compared to CNH. To this end, participants with and without hearing loss performed a verbal working memory task during magnetoencephalography. Neural oscillatory responses associated with working memory encoding and maintenance were imaged separately, and these responses were statistically evaluated between CHL and CNH. While CHL performed as well on the task as CNH, CHL exhibited significantly elevated alpha-beta activity in the right frontal and precentral cortices during encoding relative to CNH. In contrast, CHL showed elevated alpha maintenance-related activity in the right precentral and parieto-occipital cortices. Crucially, right superior frontal encoding activity and right parieto-occipital maintenance activity correlated with language ability across groups. These data suggest that CHL may utilize compensatory right-hemispheric activity to achieve verbal working memory function at the level of CNH. Neural behavior in these regions may impact language function during crucial developmental ages.

PMID:33838545 | DOI:10.1016/j.nicl.2021.102647

Neuroimage Clin. 2021 Mar 29;30:102650. doi: 10.1016/j.nicl.2021.102650. Online ahead of print.

ABSTRACT

BACKGROUND: Infants born preterm are at increased risk of neurological complications resulting in significant morbidity and mortality. The exact mechanism and the impact of antenatal factors has not been fully elucidated, although antenatal infection/inflammation has been implicated in both the aetiology of preterm birth and subsequent neurological sequelae. It is therefore hypothesized that processes driving preterm birth are affecting brain development in utero. This study aims to compare MRI derived regional brain volumes in fetuses that deliver < 32 weeks with fetuses that subsequently deliver at term.

METHODS: Women at high risk of preterm birth, with gestation 19.4-32 weeks were recruited prospectively. A control group was obtained from existing study datasets. Fetal MRI was performed on a 1.5 T or 3 T MRI scanner: T2-weighted images were obtained of the fetal brain. 3D brain volumetric datsets were produced using slice to volume reconstruction and regional segmentations were produced using multi-atlas approaches for supratentorial brain tissue, lateral ventricles, cerebellum cerebral cortex and extra-cerebrospinal fluid (eCSF). Statistical comparison of control and high-risk for preterm delivery fetuses was performed by creating normal ranges for each parameter from the control datasets and then calculating gestation adjusted z scores. Groups were compared using t-tests.

RESULTS: Fetal image datasets from 24 pregnancies with delivery < 32 weeks and 87 control pregnancies that delivered > 37 weeks were included. Median gestation at MRI of the preterm group was 26.8 weeks (range 19.4-31.4) and control group 26.2 weeks (range 21.7-31.9). No difference was found in supra-tentorial brain volume, ventricular volume or cerebellar volume but the eCSF and cerebral cortex volumes were smaller in fetuses that delivered preterm (p < 0.001 in both cases).

CONCLUSION: Fetuses that deliver preterm have a reduction in cortical and eCSF volumes. This is a novel finding and needs further investigation. If alterations in brain development are commencing antenatally in fetuses that subsequently deliver preterm, this may present a window for in utero therapy in the future.

PMID:33838546 | DOI:10.1016/j.nicl.2021.102650

Soc Sci Med. 2021 Apr 3;277:113893. doi: 10.1016/j.socscimed.2021.113893. Online ahead of print.

ABSTRACT

INTRODUCTION: Lolland-Falster is a rural area in south-eastern Denmark that scores unfavourable in health surveys and has the lowest life expectancy in the country. To determine the origin of poor health in Lolland-Falster, we investigated impact on mortality of long-term population movements.

METHODS: We used data from the Danish Central Population Register 1968-2017 to track movements in and out of Lolland-Falster. This enabled us to calculate mortality based on tenure of residence. Poisson regression adjusted for sex, 5-year age-groups, and calendar year; separately for men and women; and ages <30, 30-64 and ≥ 65 years; was reported as mortality rate ratios (MRR) with 95% confidence intervals (95% CI).

RESULTS: Until 1988, mortality in Lolland-Falster was fairly similar to that in the rest of Denmark. Hereafter, mortality rates drifted apart. In 2008-2017, MRR of the total Lolland-Falster population was 1.21 (95% CI: 1.19-1.23). In each 10-year calendar period, people recently in-migrating constituted about one fourth of the population. MRRs of the in-migrating population increased over time from 1.17 (95% CI: 1.08-1.26) in 1968-1977, to 1.82 (95% CI: 1.75-1.89) in 2008-2017. Persons aged 30-64 constituted the largest in-migrating group and had highest excess mortality, MRR 2.34 (95% CI: 2.19-2.50) in 2008-2017.

CONCLUSION: Long-term selective in-migration of vulnerable persons was behind the gradual build-up of the currently high mortality in Lolland-Falster compared to the rest of Denmark. In particular, people of working age in-migrating to Lolland-Falster contributed to this disparity.

PMID:33838450 | DOI:10.1016/j.socscimed.2021.113893

Cancer Epidemiol. 2021 Apr 7;72:101935. doi: 10.1016/j.canep.2021.101935. Online ahead of print.

ABSTRACT

BACKGROUND: Accurate forecasts of cancer incidence, with appropriate estimates of uncertainty, are crucial for planners and policy makers to ensure resource availability and prioritize interventions. We used Bayesian age-period-cohort (APC) models to project the future incidence of cancer in Australia.

METHODS: Bayesian APC models were fitted to counts of cancer diagnoses in Australia from 1982 to 2016 and projected to 2031 for seven key cancer types: breast, colorectal, liver, lung, non-Hodgkin lymphoma, melanoma and stomach. Aggregate cancer data from population-based cancer registries were sourced from the Australian Institute of Health and Welfare.

RESULTS: Over the projection period, total counts for these cancer types increased on average by 3 % annually to 100 385 diagnoses in 2031, which is a 50 % increase over 2016 numbers, although there is considerable uncertainty in this estimate. Counts for each cancer type and sex increased over the projection period, whereas decreases in the age-standardized incidence rates (ASRs) were projected for stomach, colorectal and male lung cancers. Large increases in ASRs were projected for liver and female lung cancer. Increases in the percentage of colorectal cancer diagnoses among younger age groups were projected. Retrospective one-step-ahead projections indicated both the incidence and its uncertainty were successfully forecast.

CONCLUSIONS: Increases in the projected incidence counts of key cancer types are in part attributable to the increasing and ageing population. The projected increases in ASRs for some cancer types should increase motivation to reduce sedentary behaviour, poor diet, overweight and undermanagement of infections. The Bayesian paradigm provides useful measures of the uncertainty associated with these projections.

PMID:33838461 | DOI:10.1016/j.canep.2021.101935

Am J Emerg Med. 2021 Apr 5;48:33-37. doi: 10.1016/j.ajem.2021.03.090. Online ahead of print.

ABSTRACT

INTRODUCTION: Due to the high mortality and spread rates of coronavirus disease 2019 (COVID-19), there are currently serious challenges in emergency department management. As such, we investigated whether the blood urea nitrogen (BUN)/albumin ratio (BAR) predicts mortality in the COVID-19 patients in the emergency department.

METHODS: A total of 602 COVID-19 patients who were brought to the emergency department within the period from March to September 2020 were included in the study. The BUN level, albumin level, BAR, age, gender, and in-hospital mortality status of the patients were recorded. The patients were grouped by in-hospital mortality. Statistical comparison was conducted between the groups.

RESULTS: Of the patients who were included in the study, 312(51.8%) were male, and their median age was 63 years (49-73). There was in-hospital mortality in 96(15.9%) patients. The median BUN and BAR values of the patients in the non-survivor group were significantly higher than those in the survivor group (BUN: 24.76 [17.38-38.31] and 14.43 [10.84-20.42], respectively [p < 0.001]; BAR: 6.7 [4.7-10.1] and 3.4 [2.5-5.2], respectively [p < 0.001]). The mean albumin value in the non-survivor group was significantly lower than that in the survivor group (3.60 ± 0.58 and 4.13 ± 0.51, respectively; p < 0.001). The area-under-the-curve (AUC) and odds ratio values obtained by BAR to predict in-hospital COVID-19 mortality were higher than the values obtained by BUN and albumin (AUC of BAR, BUN, and albumin: 0.809, 0.771, and 0.765, respectively; odds ratio of BAR>3.9, BUN>16.05, and albumin<4.01: 10.448, 7.048, and 6.482, respectively).

CONCLUSION: The BUN, albumin, and BAR levels were found to be reliable predictors of in-hospital mortality in COVID-19 patients, but BAR was found to be a more reliable predictor than the BUN and albumin levels.

PMID:33838471 | DOI:10.1016/j.ajem.2021.03.090

J Surg Res. 2021 Apr 7;264:230-235. doi: 10.1016/j.jss.2021.02.035. Online ahead of print.

ABSTRACT

BACKGROUND: Central neck dissection (CND) remains a controversial intervention for papillary thyroid carcinoma (PTC) patients with clinically negative nodes (cN0) in the central compartment. Proponents state that CND in cN0 patients prevents locoregional recurrence, while opponents deem that the risks of complications outweigh any potential benefit. Thus, there remains conflicting results amongst studies assessing oncologic and surgical outcomes in cN0 PTC patients who undergo CND. To provide clarity to this controversy, we sought to evaluate the efficacy, safety, and oncologic impact of CND in cN0 PTC patients at our institution.

MATERIALS AND METHODS: Six hundred and ninety-five patients with PTC who underwent thyroidectomy at our institution between 1998 and 2018 were identified using an institutional cancer registry and supplemental electronic medical record queries. Patients were stratified by whether or not they underwent CND; identified as CND(+) or CND(-), respectively. Patients were also stratified by whether or not they received adjuvant radioactive iodine (RAI) therapy. Patient demographics, pathologic results, as well as surgical and oncologic outcomes were reviewed. Standard statistical analyses were performed using ANOVA and/or t-test and chi-squared tests as appropriate.

RESULTS: Among the 695 patients with PTC, 492 (70.8%) had clinically and radiographically node negative disease (cN0). The mean age was 50 ± 1 years old and 368 (74.8%) were female. Of those with cN0 PTC, 61 patients (12.4%) underwent CND. CND(+) patients were found to have higher preoperative thyroid stimulating hormone (TSH) values, 2.8 ± 0.8 versus 1.5 ± 0.2 mU/L (P = 0.028) compared to CND(-) patients. CND did not significantly decrease disease recurrence, development of distant metastatic disease (P = 0.105) or persistence of disease (P = 0.069) at time of mean follow-up of 38 ± 3 months compared to CND(-) patients. However, surgical morbidity rates were significantly higher in CND(+) patients; including transient hypocalcemia (36.1% versus 14.4%; P < 0.001), transient recurrent laryngeal nerve (RLN) injury (19.7% vers us 7.0%; P < 0.001), and permanent RLN injury (3.3% versus 0.7%; P < 0.001).

CONCLUSIONS: The majority of patients at our institution with cN0 PTC did not undergo CND. This data suggests that CND was not associated with improvements in oncologic outcomes during the short-term follow-up period and led to increased postoperative morbidity. Therefore, we conclude that CND should not be routinely performed for patients with cN0 PTC.

PMID:33838407 | DOI:10.1016/j.jss.2021.02.035

Chemosphere. 2021 Apr 3;278:130484. doi: 10.1016/j.chemosphere.2021.130484. Online ahead of print.

ABSTRACT

Aluminium (Al), not essential for biological activities, accumulates in the tissues. It exerts toxic effects on the nervous system, inducing in humans’ irreversible cognitive impairment. In this study, a cluster sampling method was used to observe the cognitive function of long-term occupational Al-exposed workers in a large Al factory, and determine the expression of peripheral blood tumour necrosis factor receptor 1 (TNFR1), receptor-interacting protein 1 (RIP1), and RIP3. TNF-alpha, expressed in blood macrophages and microglia, with its receptors TNFR1, TR1 and TR3, enhances the necroptosis of neurons. Additionally, the relationship between the expression of TNFR1, RIP1, and RIP3 in the peripheral blood of long-term occupational Al-exposed workers and changes in their cognitive function was explored. The differences in the distributions of clock drawing test (CDT) scores among the three groups were statistically significant (P < 0.05). The results of correlation analysis showed that RIP1 and RIP3 protein contents were negatively correlated with mini-mental state examination (MMSE) and CDT scores (P < 0.05). Plasma Al content was positively correlated with other biological indicators (P < 0.05), and negatively correlated with MMSE and CDT scores (P < 0.05). Results showed that RIP3 protein had an incomplete mediation effect between plasma Al content and cognitive function. This suggests that Al may affect cognitive function by influencing the expression of TNFR1, RIP1, and RIP3 in the nervous system.

PMID:33838418 | DOI:10.1016/j.chemosphere.2021.130484

Clin Imaging. 2021 Mar 31;78:171-178. doi: 10.1016/j.clinimag.2021.03.026. Online ahead of print.

ABSTRACT

OBJECTIVE: To review MRI findings of pure lobular neoplasia (LN) on MRI guided biopsy, evaluate surgical and clinical outcomes, and assess imaging findings predictive of upgrade to malignancy.

METHODS: HIPAA compliant, IRB-approved retrospective review of our MRI-guided breast biopsy database from October 2008-January 2015. Biopsies yielding atypical lobular hyperplasia or lobular carcinoma in situ were included in the analysis; all biopsy slides were reviewed by a dedicated breast pathologist. Imaging indications, MRI findings, and histopathology were reviewed. Statistical analysis was performed using the two-tailed Fisher exact-test and the t-test, and 95% CIs were determined. A p < 0.05 was considered statistically significant.

RESULTS: Database search yielded 943 biopsies in 785 patients of which 65/943 (6.9%) reported LN as the highest risk pathologic lesion. Of 65 cases, 32 were found to have LN as the dominant finding on pathology and constituted the study population. All 32 findings were mammographically and sonographically occult. Three of 32 (9.3%) cases of lobular neoplasia were upgraded to malignancy, all LCIS (one pleomorphic and two classical). The most common MRI finding was focal, heterogenous non-mass enhancement with low T2 signal. No clinical features or imaging findings were predictive of upgrade to malignancy.

CONCLUSION: Incidence of pure lobular neoplasia on MRI guided biopsy is low, with comparatively low incidence of upgrade to malignancy. No imaging or clinical features are predictive of upgrade on surgical excision, therefore, prudent radiologic-pathologic correlation is necessary.

PMID:33838434 | DOI:10.1016/j.clinimag.2021.03.026