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Nevin Manimala Statistics

Recurrent venous thromboembolism and major bleeding in patients with localised, locally advanced or metastatic cancer: an analysis of the Caravaggio study

Eur J Cancer. 2022 Feb 27;165:136-145. doi: 10.1016/j.ejca.2022.01.023. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear.

METHODS: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation.

RESULTS: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ratio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The efficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study.

CONCLUSIONS: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding.

PMID:35235870 | DOI:10.1016/j.ejca.2022.01.023

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Nevin Manimala Statistics

Tailoring Pain Interference Measurement in People with Cancer: A Feasibility Study

J Pain Symptom Manage. 2022 Feb 27:S0885-3924(22)00416-X. doi: 10.1016/j.jpainsymman.2022.02.334. Online ahead of print.

ABSTRACT

CONTEXT: Most patient-reported outcomes (PRO) are not directly tailored to an individual patient’s values, partially because tailored PROs require clinical interviews or are difficult to use in statistical analyses.

OBJECTIVES: This study tested a method for tailoring pain PROs, Precision PROs, that can be implemented and analyzed using standard statistical tests.

METHODS: People with cancer and pain (n=231) completed an online survey and then a second survey (n=161) one to two weeks later. Participants reviewed the PROMIS pain interference item bank, chose the four items most important to their quality of life and then completed those items. Kappas compared choices between the two surveys. Participants completed measures of pain intensity, physical function, and a standard pain interference measure.

RESULTS: All participants were able to select four items that were personally meaningful. Only one item (enjoyment of life) was chosen by more than half the sample (50.6%). Kappas for item choice were in the moderate to nearly perfect range for 32 of 35 items. The majority of the sample (59%) preferred tailoring their own PRO questions to completing a previously determined, non-patient-specific PRO. The Precision PRO scores had similar associations with pain intensity and physical function as the standard pain interference measure.

CONCLUSIONS: The Precision PRO approach was feasible, more preferred by patients, and showed consistency over a short timeframe. This approach could be used to make PRO assessment in clinical care and clinical trials more patient-centered. Additional research is needed to determine the generalizability of this approach to other outcomes and populations.

PMID:35235855 | DOI:10.1016/j.jpainsymman.2022.02.334

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Nevin Manimala Statistics

Quality of life and quality of care as experienced by patients with advanced cancer and their relatives: A multicentre observational cohort study (eQuiPe)

Eur J Cancer. 2022 Feb 27;165:125-135. doi: 10.1016/j.ejca.2022.01.039. Online ahead of print.

ABSTRACT

AIM: This study aims to assess the quality of life and quality of care as experienced by patients with advanced cancer and their relatives while taking their interdependency into account.

METHODS: A prospective multicentre observational study (eQuiPe study) was conducted. Quality of life scores (EORTC QLQ-C30) was compared to a matched normative population and logistic regression analyses were conducted to assess the relation between high emotional functioning (EF, measured with the EORTC QLQ-C30) and experienced quality of care (IN-PATSAT32, CQ-index PC).

RESULTS: In total, 1103 (65%) patients and 831 (71%) relatives completed the baseline questionnaire, including 699 unique patient-relative couples. Patients experienced lower EF than the normative population (78 versus 87, p < .001). Compared to patients, relatives reported clinically relevantly lower EF (69 versus 78, p < .001). Being more satisfied with care in general (p < .05) and clarity about the key health-care provider (p < .05) was positively associated with high EF in patients. For relatives, experienced continuity of care (p < .01) and information for the patient (p < .05) were positively associated with high EF. The EF of patients (p < .001) and relatives (p < .001) were positively associated with each other and continuity of care as perceived by relatives was positively associated with high EF in patients (p < .01).

CONCLUSIONS: Patients with advanced cancer reported low levels of EF but their relatives reported even lower levels of EF. Experienced integrated organisation and satisfaction with care were positively related to EF. The interdependent relation between patients’ and relatives’ EF and their care experiences suggests that a family-centred approach can optimise palliative cancer care.

TRIAL REGISTRATION: The eQuiPe study is registered as NTR6584 in the Netherlands Trial Register.

PMID:35235869 | DOI:10.1016/j.ejca.2022.01.039

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Nevin Manimala Statistics

Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis

Cell Rep. 2022 Mar 1;38(9):110444. doi: 10.1016/j.celrep.2022.110444.

ABSTRACT

Accumulation of senescent cells affects organismal aging and the prevalence of age-associated disease. Emerging evidence suggests that activation of autophagy protects against age-associated diseases and promotes longevity, but the roles and regulatory mechanisms of autophagy in cellular senescence are not well understood. Here, we identify the transcription factor, MondoA, as a regulator of cellular senescence, autophagy, and mitochondrial homeostasis. MondoA protects against cellular senescence by activating autophagy partly through the suppression of an autophagy-negative regulator, Rubicon. In addition, we identify peroxiredoxin 3 (Prdx3) as another downstream regulator of MondoA essential for mitochondrial homeostasis and autophagy. Rubicon and Prdx3 work independently to regulate senescence. Furthermore, we find that MondoA knockout mice have exacerbated senescence during ischemic acute kidney injury (AKI), and a decrease of MondoA in the nucleus is correlated with human aging and ischemic AKI. Our results suggest that decline of MondoA worsens senescence and age-associated disease.

PMID:35235784 | DOI:10.1016/j.celrep.2022.110444

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Nevin Manimala Statistics

Be-7 and Pb-210 in fallout and aerosols in 2000-2016 in central Europe – Deposition velocity and dependence on meteorological parameters

Sci Total Environ. 2022 Feb 27:154205. doi: 10.1016/j.scitotenv.2022.154205. Online ahead of print.

ABSTRACT

The main aim of this research was to determine the transport and deposition velocities of 7Be and 210Pb based on a vast database containing the results of measurements of 7Be and 210Pb in fallout and aerosol samples carried out at several stations located throughout Poland in the period from 2000 to 2016. The monthly deposition flux of 7Be and 210Pb showed an unequivocal downward trend but was also subject to seasonal changes, with maximum values in the summer period. The same patterns were found in the case of the deposition rate, the average values of which were 0.7 cm s-1 for 7Be and 0.5 cm s-1 for 210Pb. A strong, statistically significant dependence of the deposition rate on the amount of dust was demonstrated, whereby a 10 μg m-3 decrease in dust increases the 7Be deposition rate by 0.1 cm s-1. Reduction of the concentration of carrier particles reduces the share of dry deposition in favour of precipitation convection, which is much more significant for the transport of both isotopes to the surface. Study of the effect of meteorological parameters showed that the concentrations of 7Be in fallout and aerosol samples and 210Pb in fallout increase with increasing temperature, indicating a significant share of convection processes in isotope transport. The concentrations of 210Pb in aerosols did not show any significant statistical changes over time. Their maximum values were observed in the winter period, indicating an additional source of this isotope related to combustion processes in the heating season. The studies confirmed the dominant role of convective precipitation and large-scale precipitation processes in the elution of 7Be from the atmosphere by showing the monthly deposition of this isotope to be strongly dependent on the total precipitation (r = 0.618).

PMID:35235848 | DOI:10.1016/j.scitotenv.2022.154205

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Nevin Manimala Statistics

“Taste typicality” is a foundational and multi-modal dimension of ordinary aesthetic experience

Curr Biol. 2022 Feb 26:S0960-9822(22)00261-5. doi: 10.1016/j.cub.2022.02.039. Online ahead of print.

ABSTRACT

Aesthetic experience seems both regular and idiosyncratic. On one hand, there are powerful regularities in what we tend to find attractive versus unattractive (e.g., beaches versus mud puddles).1-4 On the other hand, our tastes also vary dramatically from person to person:5-8 what one of us finds beautiful, another might find distasteful. What is the nature of such differences? They may in part be arbitrary-e.g., reflecting specific past judgments (such as liking red towels over blue ones because they were once cheaper). However, they may also in part be systematic-reflecting deeper differences in perception and/or cognition. We assessed the systematicity of aesthetic taste by exploring its typicality for the first time across seeing and hearing. Observers rated the aesthetic appeal of ordinary scenes and objects (e.g., beaches, buildings, and books) and environmental sounds (e.g., doorbells, dripping, and dialtones). We then measured “taste typicality” (separately for each modality) in terms of the similarity between each individual’s aesthetic preferences and the population’s average. The data revealed two primary patterns. First, taste typicality was not arbitrary but rather was correlated to a moderate degree across seeing and hearing: people who have typical taste for images also tend to have typical taste for sounds. Second, taste typicality captured most of the explainable variance in people’s impressions, showing that it is the primary dimension along which aesthetic tastes systematically vary.

PMID:35235766 | DOI:10.1016/j.cub.2022.02.039

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Nevin Manimala Statistics

Gomisin J attenuates cerebral ischemia/reperfusion injury by inducing anti-apoptotic, anti-inflammatory, and antioxidant effects in rats

Bioengineered. 2022 Mar;13(3):6908-6918. doi: 10.1080/21655979.2022.2026709.

ABSTRACT

Ischemic stroke is one of the leading causes of morbidity and mortality in humans. Cerebral ischemia-reperfusion (CIR) injury serves as a leading cause of stroke. Schisandra chinensis is a well-known Chinese traditional medicine. In this study, we explored the role of Gomisin J (GJ), a compound of S. chinensis, in CIR using a middle cerebral artery occlusion/reperfusion rat model and the possible mechanisms. We identified that GJ reduced neurological scores, cerebral infarction, and water content in the I/R rat brain. Importantly, GJ rescued I/R treatment-reduced neuron survival in the hippocampus, inhibited apoptosis of ischemic tissues in I/R rats, increased B-cell lymphoma-extra-large (Bcl-XL) expression, and reduced the levels of cleaved caspase-3, Bax, cyclooxygenase-2, nuclear factor kappa-B, and nitric oxide in I/R rat brain tissues. Furthermore, GJ treatment enhanced nuclear factor E2 related factor 2 (Nrf2) translocation, heme oxygenase-1 (HO-1) expression, superoxide dismutase and glutathione peroxidase activities, and glutathione level. Overall, GJ treatment GJ attenuates CIR injury by inducing anti-apoptotic, antioxidant, and anti-inflammatory effects in vivo.

PMID:35235758 | DOI:10.1080/21655979.2022.2026709

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Nevin Manimala Statistics

Measurement-Based Care for Psychotic Disorders in the Veterans Health Administration: Current Practices and Future Directions

J Clin Psychiatry. 2022 Mar 1;83(2):21m14274. doi: 10.4088/JCP.21m14274.

ABSTRACT

Objective: Measurement-based care (MBC) improves patient outcomes. However, there has been minimal focus on MBC for psychotic disorders. This study examines the use of patient-reported outcome measures (PROMs) in the Veterans Health Administration (VHA) to characterize their use among Veterans with psychotic disorders and to inform candidate measures for psychosis-related MBC.

Methods: Data on Veterans with and without ICD-10 psychotic disorders and at least 1 PROM during fiscal years (FYs) 2016-2019 (FY16-FY19) were collected. The sample included 3,935,504 PROM administrations among 1,192,897 Veterans. Included PROMs spanned multiple symptom and non-symptom domains. Percentages of total PROM administrations were calculated by aggregating across time and diagnosis. Facility-level statistics were also calculated. Absolute change in the percentage of unique Veterans administered a particular and repeated PROMs over time were calculated.

Results: The core PROMs for VHA MBC (Patient Health Questionnaire-9 [PHQ-9], General Anxiety Disorder-7 Scale, PTSD Checklist-5, and Brief Addiction Monitor) accounted for the majority of PROMs for Veterans with (88.18%) and without (92.56%) psychotic disorders. The PHQ-9 accounted for the largest proportion (psychotic disorder: 45.89%; other diagnosis: 46.70%). The absolute changes in percentages of repeated PROM administration were similar over time across groups.

Conclusions: The use of PROMs in VHA mental health care increased during FY16-FY19 for Veterans with and without psychosis. The rates of PROM use were similar for both groups, and PROM use predominately consisted of the core measures. While the similar rates of PROM administration are encouraging, these findings highlight the need for psychosis-specific measures to tailor MBC for Veterans with these diagnoses.

PMID:35235719 | DOI:10.4088/JCP.21m14274

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Nevin Manimala Statistics

A Bayesian perspective on Biogen’s aducanumab trial

Alzheimers Dement. 2022 Mar 2. doi: 10.1002/alz.12615. Online ahead of print.

ABSTRACT

This perspective is a companion to a recent editorial on the use of Bayesian analysis in clinical research. We aim to introduce and highlight the relevance and advantages that Bayesian inference offers to clinical trials using the data on the amyloid antibody aducanumab presented at a Food and Drug Administration hearing in November 2020 as an applied example. We apply Bayesian analysis of model plausibility and effect sizes based on simulated data of the two phase 3 trials of aducanumab in prodromal and mild dementia stages of Alzheimer’s disease (AD). Bayesian analysis can quantify evidence in favor of, or against, the presence of an effect (i.e., provide evidence of absence), as well as assess the strength of the effect. This is in contrast to the binary conclusions provided by frequentist tests.

PMID:35235700 | DOI:10.1002/alz.12615

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Nevin Manimala Statistics

Differences in the temporal scale of reproductive investment across the slow-fast continuum in a passerine

Ecol Lett. 2022 Mar 2. doi: 10.1111/ele.13982. Online ahead of print.

ABSTRACT

Life-history strategies differ with respect to investment in current versus ‘future’ reproduction, but when is this future? Under the novel ‘temporality in reproductive investment hypothesis’, we postulate variation should exist in the time frame over which reproductive costs are paid. Slow-paced individuals should pay reproductive costs over short (e.g. inter-annual) time scales to prevent reproductive costs accumulating, whereas fast-paced individuals should allow costs to accumulate (i.e. senescence). Using Fourier transforms, we quantify adjustments in clutch size with age, across four populations of blue tits (Cyanistes caeruleus). Fast populations had more prevalent and stronger long-term changes in reproductive investment, whereas slower populations had more prevalent short-term adjustments. Inter-annual environmental variation partly accounted for short-, but not long-term changes in reproductive investment. Our study reveals individuals differ in when they pay the cost of reproduction and that failure to partition this variation across different temporal scales and environments could underestimate reproductive trade-offs.

PMID:35235709 | DOI:10.1111/ele.13982