Accurate identification of patients likely to achieve long-progression-free survival (PFS) after chemoimmunotherapy is essential given the availability of less toxic alternatives, such as ibrutinib. ...Fludarabine, cyclophosphamide, and rituximab (FCR) achieved a high response rate, but continued relapses were seen in initial reports. We reviewed the original 300 patient phase 2 FCR study to identify long-term disease-free survivors. Minimal residual disease (MRD) was assessed posttreatment by a polymerase chain reaction-based ligase chain reaction assay (sensitivity 0.01%). At the median follow-up of 12.8 years, PFS was 30.9% (median PFS, 6.4 years). The 12.8-year PFS was 53.9% for patients with mutated immunoglobulin heavy chain variable (IGHV) gene (IGHV-M) and 8.7% for patients with unmutated IGHV (IGHV-UM). 50.7% of patients with IGHV-M achieved MRD-negativity posttreatment; of these, PFS was 79.8% at 12.8 years. A plateau was seen on the PFS curve in patients with IGHV-M, with no relapses beyond 10.4 years in 42 patients (total follow-up 105.4 patient-years). On multivariable analysis, IGHV-UM (hazard ratio, 3.37 2.18-5.21; P < .001) and del(17p) by conventional karyotyping (hazard ratio, 7.96 1.02-61.92; P = .048) were significantly associated with inferior PFS. Fifteen patients with IGHV-M had 4-color MRD flow cytometry (sensitivity 0.01%) performed in peripheral blood, at a median of 12.8 years posttreatment (range, 9.5-14.7). All were MRD-negative. The high rate of very long-term PFS in patients with IGHV-M after FCR argues for the continued use of chemoimmunotherapy in this patient subgroup outside clinical trials; alternative strategies may be preferred in patients with IGHV-UM, to limit long-term toxicity.
•FCR-treated chronic lymphocytic leukemia patients with mutated IGHV gene achieve long-term PFS, with a plateau on the PFS curve.•MRD-negativity posttreatment is highly predictive of long-term PFS, particularly in patients with mutated IGHV gene.
The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role was in immune defense, where its ...ROS production leads to the destruction of pathogens by the immune cells. NOX from phagocytes catalyzes, via one-electron trans-membrane transfer to molecular oxygen, the production of the superoxide anion. Over the years, six human homologs of the catalytic subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the NOX2/gp91
component present in the phagocyte NADPH oxidase assembly itself, the homologs are now referred to as the NOX family of NADPH oxidases. NOX are complex multidomain proteins with varying requirements for assembly with combinations of other proteins for activity. The recent structural insights acquired on both prokaryotic and eukaryotic NOX open new perspectives for the understanding of the molecular mechanisms inherent to NOX regulation and ROS production (superoxide or hydrogen peroxide). This new structural information will certainly inform new investigations of human disease. As specialized ROS producers, NOX enzymes participate in numerous crucial physiological processes, including host defense, the post-translational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. These diversities of physiological context will be discussed in this review. We also discuss NOX misregulation, which can contribute to a wide range of severe pathologies, such as atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, or neurodegenerative diseases, giving this family of membrane proteins a strong therapeutic interest.
•SARS-CoV-2 viral loads peak from upper respiratory tract samples around symptom onset.•Viral loads from sputum samples may be higher than upper respiratory tract samples.•Viral loads appear to be ...similar between asymptomatic and symptomatic patients.•The prolonged virus detection in stool samples has unclear clinical significance.•Patients may not be infectious for the entire duration of virus detection.
To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity.
A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020.
We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance.
No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus.
There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
Update of the Healthy Eating Index: HEI-2015 Krebs-Smith, Susan M.; Pannucci, TusaRebecca E.; Subar, Amy F. ...
Journal of the Academy of Nutrition and Dietetics,
September 2018, 2018-09-00, 20180901, Letnik:
118, Številka:
9
Journal Article
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The Healthy Eating Index (HEI) is a measure for assessing whether a set of foods aligns with the Dietary Guidelines for Americans (DGA). An updated HEI is released to correspond to each new edition ...of the DGA, and this article introduces the latest version, which reflects the 2015-2020 DGA. The HEI-2015 components are the same as in the HEI-2010, except Saturated Fat and Added Sugars replace Empty Calories, with the result being 13 components. The 2015-2020 DGA include explicit recommendations to limit intakes of both Added Sugars and Saturated Fats to <10% of energy. HEI-2015 does not account for excessive energy from alcohol within a separate component, but continues to account for all energy from alcohol within total energy (the denominator for most components). All other components remain the same as for HEI-2010, except for a change in the allocation of legumes. Previous versions of the HEI accounted for legumes in either the two vegetable or the two protein foods components, whereas HEI-2015 counts legumes toward all four components. Weighting approaches are similar to those of previous versions, and scoring standards were maintained, refined, or developed to increase consistency across components; better ensure face validity; follow precedent; cover a range of intakes; and, when applicable, ensure the DGA level corresponds to a score >7 out of 10. HEI-2015 component scores can be examined collectively using radar graphs to reveal a pattern of diet quality and summed to represent overall diet quality.
Update of the Healthy Eating Index: HEI-2010 Guenther, Patricia M., PhD, RD; Casavale, Kellie O., PhD, RD; Reedy, Jill, PhD, RD ...
Journal of the Academy of Nutrition and Dietetics,
04/2013, Letnik:
113, Številka:
4
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Abstract The Healthy Eating Index (HEI) is a measure of diet quality in terms of conformance with federal dietary guidance. Publication of the 2010 Dietary Guidelines for Americans prompted an ...interagency working group to update the HEI. The HEI-2010 retains several features of the 2005 version: (a) it has 12 components, many unchanged, including nine adequacy and three moderation components; (b) it uses a density approach to set standards, eg, per 1,000 calories or as a percentage of calories; and (c) it employs least-restrictive standards; ie, those that are easiest to achieve among recommendations that vary by energy level, sex, and/or age. Changes to the index include: (a) the Greens and Beans component replaces Dark Green and Orange Vegetables and Legumes; (b) Seafood and Plant Proteins has been added to capture specific choices from the protein group; (c) Fatty Acids, a ratio of polyunsaturated and monounsaturated to saturated fatty acids, replaces Oils and Saturated Fat to acknowledge the recommendation to replace saturated fat with monounsaturated and polyunsaturated fatty acids; and (d) a moderation component, Refined Grains, replaces the adequacy component, Total Grains, to assess overconsumption. The HEI-2010 captures the key recommendations of the 2010 Dietary Guidelines and, like earlier versions, will be used to assess the diet quality of the US population and subpopulations, evaluate interventions, research dietary patterns, and evaluate various aspects of the food environment.
Evaluation of the Healthy Eating Index-2015 Reedy, Jill; Lerman, Jennifer L.; Krebs-Smith, Susan M. ...
Journal of the Academy of Nutrition and Dietetics,
September 2018, 2018-09-00, 20180901, Letnik:
118, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The Healthy Eating Index (HEI), a diet quality index that measures alignment with the Dietary Guidelines for Americans, was updated with the 2015-2020 Dietary Guidelines for Americans.
To evaluate ...the psychometric properties of the HEI-2015, eight questions were examined: five relevant to construct validity, two related to reliability, and one to assess criterion validity.
Three data sources were used: exemplary menus (n=4), National Health and Nutrition Examination Survey 2011-2012 (N=7,935), and the National Institutes of Health-AARP (formally known as the American Association of Retired Persons) Diet and Health Study (N=422,928).
Exemplary menus: Scores were calculated using the population ratio method. National Health and Nutrition Examination Survey 2011-2012: Means and standard errors were estimated using the Markov Chain Monte Carlo approach. Analyses were stratified to compare groups (with t tests and analysis of variance). Principal components analysis examined the number of dimensions. Pearson correlations were estimated between components, energy, and Cronbach’s coefficient alpha. National Institutes of Health-AARP Diet and Health Study: Adjusted Cox proportional hazards models were used to examine scores and mortality outcomes.
For construct validity, the HEI-2015 yielded high scores for exemplary menus as four menus received high scores (87.8 to 100). The mean score for National Health and Nutrition Examination Survey was 56.6, and the first to 99th percentile were 32.6 to 81.2, respectively, supporting sufficient variation. Among smokers, the mean score was significantly lower than among nonsmokers (53.3 and 59.7, respectively) (P<0.01), demonstrating differentiation between groups. The correlation between diet quality and diet quantity was low (all <0.25) supporting these elements being independent. The components demonstrated multidimensionality when examined with a scree plot (at least four dimensions). For reliability, most of the intercorrelations among the components were low to moderate (0.01 to 0.49) with a few exceptions, and the standardized Cronbach’s alpha was .67. For criterion validity, the highest vs the lowest quintile of HEI-2015 scores were associated with a 13% to 23% decreased risk of all-cause, cancer, and cardiovascular disease mortality.
The results demonstrated evidence supportive of construct validity, reliability, and criterion validity. The HEI-2015 can be used to examine diet quality relative to the 2015-2020 Dietary Guidelines for Americans.
There is a rising prevalence of multimorbidity, particularly in older patients, and a need for evidence-based medicines management interventions for this population. The Supporting Prescribing in ...Older Adults with Multimorbidity in Irish Primary Care (SPPiRE) trial aimed to investigate the effect of a general practitioner (GP)-delivered, individualised medication review in reducing polypharmacy and potentially inappropriate prescriptions (PIPs) in community-dwelling older patients with multimorbidity in primary care.
We conducted a cluster randomised controlled trial (RCT) set in 51 GP practices throughout the Republic of Ireland. A total of 404 patients, aged ≥65 years with complex multimorbidity, defined as being prescribed ≥15 regular medicines, were recruited from April 2017 and followed up until October 2020. Furthermore, 26 intervention GP practices received access to the SPPiRE website where they completed an educational module and used a template for an individualised patient medication review that identified PIP, opportunities for deprescribing, and patient priorities for care. A total of 25 control GP practices delivered usual care. An independent blinded pharmacist assessed primary outcome measures that were the number of medicines and the proportion of patients with any PIP (from a predefined list of 34 indicators based predominantly on the STOPP/START version 2 criteria). We performed an intention-to-treat analysis using multilevel modelling. Recruited participants had substantial disease and treatment burden at baseline with a mean of 17.37 (standard deviation SD 3.50) medicines. At 6-month follow-up, both intervention and control groups had reductions in the numbers of medicines with a small but significantly greater reduction in the intervention group (incidence rate ratio IRR 0.95, 95% confidence interval CI: 0.899 to 0.999, p = 0.045). There was no significant effect on the odds of having at least 1 PIP in the intervention versus control group (odds ratio OR 0.39, 95% CI: 0.140 to 1.064, p = 0.066). Adverse events recorded included mortality, emergency department (ED) presentations, and adverse drug withdrawal events (ADWEs), and there was no evidence of harm. Less than 2% of drug withdrawals in the intervention group led to a reported ADWE. Due to the inability to electronically extract data, primary outcomes were measured at just 2 time points, and this is the main limitation of this work.
The SPPiRE intervention resulted in a small but significant reduction in the number of medicines but no evidence of a clear effect on PIP. This reduction in significant polypharmacy may have more of an impact at a population rather than individual patient level.
ISRCTN Registry ISRCTN12752680.
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