Publications by authors named "Rachel Hughes"

34 Publications

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma.

Adv Ther 2021 Sep 24. Epub 2021 Sep 24.

Evidence Synthesis, Modeling, and Communication Group, Evidera, The Ark, 201 Talgarth Rd, Hammersmith, London, W6 8BJ, UK.

Introduction: Single-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678).

Methods: At the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH).

Results: Belamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3-4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001).

Conclusion: Single-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.
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http://dx.doi.org/10.1007/s12325-021-01884-7DOI Listing
September 2021

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial.

Brain Stimul 2021 Sep-Oct;14(5):1095-1105. Epub 2021 Jul 29.

Epworth Centre for Innovation in Mental Health, Epworth Healthcare and Department of Psychiatry, Monash University, Camberwell, Victoria, Australia.

Introduction: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established.

Methods: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300 patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4.

Results: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p = 0.180) or remission (p = 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub- and supra-threshold intensities were not significantly different (p = 0.319). Linear mixed model analysis showed a significant effect of time (p < 0.01), but not rTMS type (p = 0.680).

Conclusion: This is the largest accelerated bilateral TBS study to date and provides evidence that it is effective and safe in treating TRD. The accelerated application of TBS was not associated with more rapid antidepressant effects. Bilateral sequential TBS did not have superior antidepressant effect to unilateral 10 Hz rTMS. There was no significant difference in antidepressant efficacy between sub- and supra-threshold accelerated bilateral TBS.
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http://dx.doi.org/10.1016/j.brs.2021.07.018DOI Listing
July 2021

Network meta-analysis of eribulin versus other chemotherapies used as second- or later-line treatment in locally advanced or metastatic breast cancer.

BMC Cancer 2021 Jun 30;21(1):758. Epub 2021 Jun 30.

Evidence Synthesis, Modeling & Communication, Evidera, San Francisco, CA, USA.

Background: Eribulin mesylate (ERI; Halaven®) is a microtubule inhibitor approved in the United States for metastatic breast cancer patients with at least two prior chemotherapy regimens for metastatic breast cancer, and in the European Union in locally advanced breast cancer or metastatic breast cancer patients who progressed after at least one chemotherapy for advanced disease. This network meta-analysis compared the efficacy and safety of ERI versus other chemotherapies in this setting.

Methods: Systematic searches conducted in MEDLINE, Embase, and the Cochrane Central Register of Clinical Trials identified randomized controlled trials of locally advanced breast cancer/metastatic breast cancer chemotherapies in second- or later-line settings. Efficacy assessment included pre-specified subgroup analysis of breast cancer subtypes. Included studies were assessed for quality using the Centre for Reviews and Dissemination tool. Bayesian network meta-analysis estimated primary outcomes of overall survival and progression-free survival using fixed-effect models. Comparators included: capecitabine (CAP), gemcitabine (GEM), ixabepilone (IXA), utidelone (UTI), treatment by physician's choice (TPC), and vinorelbine (VIN).

Results: The network meta-analysis included seven trials. Results showed that second- or later-line patients treated with ERI had statistically longer overall survival versus TPC (hazard ratio [HR]: 0.81; credible interval [CrI]: 0.66-0.99) or GEM+VIN (0.62; 0.42-0.90) and statistically longer progression-free survival versus TPC (0.76; 0.64-0.90), but statistically shorter progression-free survival versus CAP+IXA (1.40; 1.17-1.67) and CAP+UTI (1.61; 1.23-2.12). In triple negative breast cancer, ERI had statistically longer overall survival versus CAP (0.70; 0.54-0.90); no statistical differences in progression-free survival were observed in triple negative breast cancer.

Conclusions: This network meta-analysis suggests that ERI may provide an overall survival benefit in the overall locally advanced breast cancer/metastatic breast cancer populations and triple negative breast cancer subgroup compared to standard treatments. These findings support the use of ERI in second- or later-line treatment of patients with locally advanced breast cancer/metastatic breast cancer.
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http://dx.doi.org/10.1186/s12885-021-08446-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244131PMC
June 2021

Epidemiological and clinical burden associated with plexiform neurofibromas in pediatric neurofibromatosis type-1 (NF-1): a systematic literature review.

Neurol Sci 2021 Jun 18. Epub 2021 Jun 18.

AstraZeneca, Gaithersburg, MD, 20871, USA.

Purpose: Patients with neurofibromatosis type-1 (NF-1) and associated plexiform neurofibromas (PNs) often have a high burden of illness owing to debilitating symptoms of these tumors and limited management options. To investigate this complex disease, a systematic literature review (SLR) was conducted on the epidemiology of pediatric NF-1 and associated PNs, the burden of illness, and outcomes of surgical resection of these tumors.

Methods: Searches of MEDLINE and Embase (from database inception to October 2019) and conference proceedings (2017-2019) were performed to identify relevant studies. The review methodology was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: Twenty studies were identified. Evidence confirmed NF-1 is rare but that occurrence may differ geographically. Only limited data on the birth incidence of NF-1 were identified. Prevalence estimates for pediatric NF-1 varied from one per 960 individuals (aged 17 years) to one per 5681 children (aged < 16 years) across five large registry/surveillance studies (each involving > 19,000 individuals). The prevalence of associated PNs was 0-29.6%. PNs carried increased mortality risk in pediatric NF-1 in both studies that explored this potential association. Patients with PNs reported high use of analgesics. The complication rate post-surgery for PNs was around 17-19%. The recurrence rate (18-68%) was dependent on the extent of excision achieved during surgery.

Conclusions: Data suggest NF-1 is a rare disease with increased morbidity and mortality in children with associated PNs. Surgical outcomes for PNs are often poor. These findings suggest significant unmet needs in patients with NF-1-associated PNs.
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http://dx.doi.org/10.1007/s10072-021-05361-5DOI Listing
June 2021

Integration of teaming therapy and mixed-reality simulation as remote learning modality for couple and family therapy graduate training programs.

J Marital Fam Ther 2021 Apr 21;47(2):392-407. Epub 2021 Feb 21.

Couple and Family Therapy Department, Antioch University Seattle, Seattle, WA, USA.

In response to COVID-19, a couple and family therapy (CFT) graduate training program integrated a teaming therapy model with virtual technology using mixed-reality simulation software. By utilizing teaming therapy--a model with strong roots in systemic theory and practice-- combined with cutting-edge simulation technology, this distance learning modality provides distinctly relational therapy supervision and training for students at a time when their internships sites are struggling to offer remote clinical services due to the pandemic. This integrative framework offers a high degree of both realism and safety, allowing experiential learning to be appropriately scaffolded for optimum creativity and engagement in an online setting. This paper describes the conceptual, systemic basis for the learning modality, steps for implementation, benefits of the model, and the authors plan for further evaluation.
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http://dx.doi.org/10.1111/jmft.12494DOI Listing
April 2021

Dimensions of Craving Interact with Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment.

Brain Sci 2021 Jan 6;11(1). Epub 2021 Jan 6.

VA Palo Alto Health Care System, Mental Illness Research, Education, and Clinical Center (MIRECC), Palo Alto, CA 94304, USA.

(1) Background: Alcohol use disorder (AUD) is associated with poor medical, psychological, and psychosocial outcomes and approximately 60% of individuals with AUD relapse six months after treatment. Craving is a core aspect of AUD and associated with high risk of relapse. One promising avenue to improve outcomes may be in understanding the relationship between genotype, craving, and treatment outcomes. (2) Methods: To this end, we assessed craving, recent drinking history, and impulsivity in 70 individuals with AUD undergoing a standard course of treatment at a regional Veteran Affairs (VA) medical center. Saliva samples were collected to determine genotype. In this prospective observational study, participants were followed for six months to determine who went on to relapse after treatment. (3) Results: Results revealed a significant interaction between craving and catechol--methyltransferse () genotype in predicting relapse. Post hoc exploratory analyses indicated that Met/Met homozygotes reported the highest levels of craving, and craving was associated with recent drinking history. Among Val/Val homozygotes, who had higher rates of relapse, craving was associated with impulsivity. (4) Conclusions: These associations highlight that specific profiles of psychological and biological factors may be important in understanding which individuals are at highest risk of relapse following treatment. Future studies that build on these findings are warranted.
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http://dx.doi.org/10.3390/brainsci11010062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825287PMC
January 2021

Correction to: Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis: Systematic Literature Review and Network Meta-Analysis.

Dermatol Ther (Heidelb) 2020 Dec;10(6):1441-1444

Global Biometrics and Data Management (Statistics), Pfizer Inc., Groton, USA.

The authors would like to replace 2 small sections of the published manuscript that refer to a qualitative review of safety data for included studies (together with an associated safety table), to provide some further clarifications on these safety data and to include some quantitative updates for rates.
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http://dx.doi.org/10.1007/s13555-020-00452-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649182PMC
December 2020

Shame, self-discrepancies, and adjustment after acquired brain injury.

Brain Inj 2020 07 2;34(8):1061-1067. Epub 2020 Jul 2.

Brain Injury Rehabilitation Trust , York, UK.

Objectives: To explore the relationship between shame and self-discrepancies and the extent that these factors predict adjustment after an acquired brain injury (ABI).

Method: 62 participants with an ABI completed the following self-report qualitative questionnaires: the Hospital Anxiety and Depression Scale, the Quality of Life after Brain Injury Scale, the Internalized Shame Scale, and the Head Injury Semantic Differential Scale - III. Data was analyzed using correlations, repeated ANOVA, and multiple regression models.

Results: A significant self-discrepancy was found between the present self and the pre-injury self, with the present self-being rated more negatively. This self-discrepancy was found to be positively correlated to shame, and these two variables were found to predict adjustment (emotional distress and quality of life).

Conclusions: Shame and self-discrepancies both appear to play a crucial role in adjustment following an ABI. However, the relationship between shame and self-discrepancies needs more consideration to understand how these variables may interact to predict adjustment.
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http://dx.doi.org/10.1080/02699052.2020.1776395DOI Listing
July 2020

Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis: Systematic Literature Review and Network Meta-Analysis.

Dermatol Ther (Heidelb) 2020 Aug 20;10(4):681-694. Epub 2020 May 20.

Global Biometrics and Data Management (Statistics), Pfizer Inc., Groton, USA.

Introduction: There is a need to compare efficacy and safety profiles of crisaborole ointment, 2%, versus other topical treatments across randomized clinical trials (RCTs). We performed this review/network meta-analysis to evaluate the comparative efficacy and safety of crisaborole versus other topical pharmacologic therapies for mild-to-moderate atopic dermatitis (AD) among patients aged ≥ 2 years.

Methods: Searches were conducted in MEDLINE, Embase, the Cochrane Collection Central Register of Clinical Trials, and the Database of Abstracts of Reviews of Effects using Ovid to identify English language articles reporting RCTs of topical anti-inflammatory agents in patients aged ≥ 2 years with mild-to-moderate AD published between inception and 10 March 2020. This review used a prespecified protocol with eligibility criteria for population, interventions, comparisons, outcomes, and study design. Efficacy was evaluated using the Investigator's Static Global Assessment (ISGA) of clear (0) or almost clear (1) and expressed by hazard ratios (HR) with 95% credible intervals.

Results: Patients treated with crisaborole or tacrolimus ointment, 0.1% or 0.03%, versus vehicle alone were significantly more likely to achieve ISGA 0/1 at 28-42 days, with the greatest point estimate observed for the crisaborole comparison (hazard ratio: 2.07; 95% credible interval 1.76 to - 2.36; probability HR above 1 [p better]: 100.0%). Patients were also more likely to achieve ISGA 0/1 with crisaborole than with pimecrolimus cream, 1% (HR: 1.62; 95% credible interval 1.04-2.48; p better: 98.3%). While network meta-analysis for safety was not feasible because of data limitations, crisaborole pivotal studies (AD-301/AD-302) showed crisaborole was well tolerated.

Conclusions: Crisaborole was shown to be superior to vehicle and pimecrolimus and comparable to tacrolimus, 0.1% or 0.03%, with respect to ISGA 0/1 at 28-42 days in patients aged ≥ 2 years with mild-to-moderate AD. This evaluation of comparative efficacy of crisaborole further supports use of crisaborole as an effective therapeutic option in this population.
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http://dx.doi.org/10.1007/s13555-020-00389-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367970PMC
August 2020

Peer support groups after acquired brain injury: a systematic review.

Brain Inj 2020 06 18;34(7):847-856. Epub 2020 May 18.

Brain Injury Rehabilitation Trust , York, UK.

Background: Peer support groups can be a way to obtain support, problem solve, and widen social networks. However, there has been no systematic literature review examining the evidence for the use of peer support groups after an acquired brain injury (ABI).

Objective: This review sought to systematically evaluate the evidence for (1) the psychosocial effectiveness, and (2) the experience of peer support groups in adults who had experienced ABI's.

Methods: The systematic literature search was conducted across the following four databases: PsycINFO, PsycARTICLES, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) in October 2019. The mixed methods appraisal tool was used to examine the quality of the research.

Results: 13 papers were included in this review. Limited evidence was found for the psychosocial effectiveness of peer support groups in ABI, although the experience of partaking in a peer support group was largely found to be positive. The benefits and helping factors of taking part in a peer support group can be summarized as: being connected, interacting with others, and providing and receiving support.

Conclusions: The findings of this review suggest that peer support groups could be a promising intervention to support individuals and promote adjustment following an ABI.
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http://dx.doi.org/10.1080/02699052.2020.1762002DOI Listing
June 2020

Alterations of Brain Signal Oscillations in Older Individuals with HIV Infection and Parkinson's Disease.

J Neuroimmune Pharmacol 2021 06 14;16(2):289-305. Epub 2020 Apr 14.

Neuroscience Program, Biosciences Division, Center for Health Sciences, SRI International, Menlo Park, CA, USA.

More than 30 years after the human immunodeficiency virus (HIV) epidemic, HIV patients are now aging due to the advances of antiretroviral therapy. With immunosenescence and the susceptibility of dopamine-rich basal ganglia regions to HIV-related injury, older HIV patients may show neurofunctional deficits similar to patients with Parkinson's disease (PD). We examined the amplitudes of low frequency fluctuations (ALFF) across different frequency bands of the BOLD signal in 30 older HIV-infected individuals, 33 older healthy controls, and 36 PD patients. Participants underwent resting-state fMRI, neuropsychological testing, and a clinical motor exam. HIV patients mainly showed abnormalities in cortical ALFF with reduced prefrontal amplitudes and enhanced sensorimotor and inferior temporal amplitudes. Frontal hypoactivation was overlapping for HIV and PD groups and different from controls. PD patients further exhibited reduced pallidum amplitudes compared to the other groups. In the HIV group, lower pallidum amplitudes were associated with lower CD4 nadir and CD4 T cell counts. Abnormalities in ALFF dynamics were largely associated with cognitive and motor functioning in HIV and PD groups. The disruption of neurofunctional frequency dynamics in subcortical-cortical circuits could contribute to the development of cognitive and motor dysfunction and serve as a biomarker for monitoring disease progression with immunosenescence. Graphical Abstract.
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http://dx.doi.org/10.1007/s11481-020-09914-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554056PMC
June 2021

Reasons for voriconazole prophylaxis discontinuation in allogeneic hematopoietic cell transplant recipients: A real-life paradigm.

Med Mycol 2020 Nov;58(8):1029-1036

Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

We sought to describe the clinical experience of voriconazole as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant recipients (allo-HCTr). This was a single-center retrospective study of adult allo-HCTr (1 January 2014 to 31 December 2016) who received ≥two doses of voriconazole-AFP. Voriconazole-AFP was started on day +7 post-HCT and continued at least through day +60 post-HCT, or longer as clinically indicated. We reviewed the rate, reasons, and risk factors of voriconazole-AFP discontinuation until day-100 post-HCT. A total of 327 patients were included. Voriconazole-AFP was continued for a median of 69 days (mean: 57.9; range 1, 100): for a median of 90 days (mean :84; range 2, 100) in 180/327 (55%) in the standard-of-care (SOC) group and 20 days (mean :25.6 ; range 1, 89; P-value < .001) in 147/327 (45%) patients in the early-discontinuation-group. Early-voriconazole-AFP discontinuation was due to adverse events, drug interactions, insurance coverage, and other reasons in 101/147 (68.7%), 27 (18.4%), 13 (8.8%), and 6 (4.1%) patients, respectively. Early-voriconazole-AFP discontinuation occurred in 73/327 (22.3%) patients due to hepatotoxicity. Important predictors for early-voriconazole-AFP discontinuation included: graft-versus-host disease grade ≥2 (odds ratio [OR]: 1.9, P-value: .02), alanine-aminotransferase ≥75 IU/ml on voriconazole-administration day-14 (OR: 5.6, P-value: .02) and total bilirubin ≥1.3 mg/dl on voriconazole-administration day-7 (OR: 3.0, P-value: .03). There were 13 proven/probable invasive fungal infections by day-180 post-HCT (8/147, 5.4%, and 5/180, 2.8% in the early-discontinuation and SOC-groups, respectively; log-rank:0.13). By day-180 post HCT, 23/147 (15.6%) and 14/180 (7.8%) patients in the early-discontinuation and SOC-groups had died, respectively (log-rank:0.03). Voriconazole-AFP was discontinued in up to 45% of allo-HCTr. Hepatotoxicity during the first 2 weeks post-HCT is a significant predictor of early-voriconazole-AFP discontinuation.
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http://dx.doi.org/10.1093/mmy/myaa008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657092PMC
November 2020

Genetic Influences of the Microbiota on the Life Span of Drosophila melanogaster.

Appl Environ Microbiol 2020 05 5;86(10). Epub 2020 May 5.

Department of Plant & Wildlife Sciences, Brigham Young University, Provo, Utah, USA

To better understand how associated microorganisms ("microbiota") influence organismal aging, we focused on the model organism We conducted a metagenome-wide association (MGWA) as a screen to identify bacterial genes associated with variation in the life span. The results of the MGWA predicted that bacterial cysteine and methionine metabolism genes influence fruit fly longevity. A mutant analysis, in which flies were inoculated with strains bearing mutations in various methionine cycle genes, confirmed a role for some methionine cycle genes in extending or shortening fruit fly life span. Initially, we predicted these genes might influence longevity by mimicking or opposing methionine restriction, an established mechanism for life span extension in fruit flies. However, follow-up transcriptome sequencing (RNA-seq) and metabolomic experiments were generally inconsistent with this conclusion and instead implicated glucose and vitamin B metabolism in these influences. We then tested if bacteria could influence life span through methionine restriction using a different set of bacterial strains. Flies reared with a bacterial strain that ectopically expressed bacterial transsulfuration genes and lowered the methionine content of the fly diet also extended female life span. Taken together, the microbial influences shown here overlap with established host genetic mechanisms for aging and therefore suggest overlapping roles for host and microbial metabolism genes in organismal aging. Associated microorganisms ("microbiota") are intimately connected to the behavior and physiology of their animal hosts, and defining the mechanisms of these interactions is an urgent imperative. This study focuses on how microorganisms influence the life span of a model host, the fruit fly First, we performed a screen that suggested a strong influence of bacterial methionine metabolism on host life span. Follow-up analyses of gene expression and metabolite abundance identified stronger roles for vitamin B and glucose than methionine metabolism among the tested mutants, possibly suggesting a more limited role for bacterial methionine metabolism genes in host life span effects. In a parallel set of experiments, we created a distinct bacterial strain that expressed life span-extending methionine metabolism genes and showed that this strain can extend fly life span. Therefore, this work identifies specific bacterial genes that influence host life span, including in ways that are consistent with the expectations of methionine restriction.
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http://dx.doi.org/10.1128/AEM.00305-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205492PMC
May 2020

Deep phenotyping of peripheral tissue facilitates mechanistic disease stratification in sporadic Parkinson's disease.

Prog Neurobiol 2020 04 11;187:101772. Epub 2020 Feb 11.

Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK. Electronic address:

Mechanistic disease stratification will be crucial to develop a precision medicine approach for future disease modifying therapy in sporadic Parkinson's disease (sPD). Mitochondrial and lysosomal dysfunction are key mechanisms in the pathogenesis of sPD and therefore promising targets for therapeutic intervention. We investigated mitochondrial and lysosomal function in skin fibroblasts of 100 sPD patients and 50 age-matched controls. A combination of cellular assays, RNA-seq based pathway analysis and genotyping was applied. Distinct subgroups with mitochondrial (mito-sPD) or lysosomal (lyso-sPD) dysfunction were identified. Mitochondrial dysfunction correlated with reduction in complex I and IV protein levels. RNA-seq based pathway analysis revealed marked activation of the lysosomal pathway with enrichment for lysosomal disease gene variants in lyso-sPD. Conversion of fibroblasts to induced neuronal progenitor cells and subsequent differentiation into tyrosine hydroxylase positive neurons confirmed and further enhanced both mitochondrial and lysosomal abnormalities. Treatment with ursodeoxycholic acid improved mitochondrial membrane potential and intracellular ATP levels even in sPD patient fibroblast lines with comparatively mild mitochondrial dysfunction. The results of our study suggest that in-depth phenotyping and focussed assessment of putative neuroprotective compounds in peripheral tissue are a promising approach towards disease stratification and precision medicine in sPD.
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http://dx.doi.org/10.1016/j.pneurobio.2020.101772DOI Listing
April 2020

The microbiota influences the Drosophila melanogaster life history strategy.

Mol Ecol 2020 02 3;29(3):639-653. Epub 2020 Jan 3.

Department of Plant and Wildlife Sciences, Brigham Young University, Provo, UT, USA.

Organisms are locally adapted when members of a population have a fitness advantage in one location relative to conspecifics in other geographies. For example, across latitudinal gradients, some organisms may trade off between traits that maximize fitness components in one, but not both, of somatic maintenance or reproductive output. Latitudinal gradients in life history strategies are traditionally attributed to environmental selection on an animal's genotype, without any consideration of the possible impact of associated microorganisms ("microbiota") on life history traits. Here, we show in Drosophila melanogaster, a key model for studying local adaptation and life history strategy, that excluding the microbiota from definitions of local adaptation is a major shortfall. First, we reveal that an isogenic fly line reared with different bacteria varies the investment in early reproduction versus somatic maintenance. Next, we show that in wild fruit flies, the abundance of these same bacteria was correlated with the latitude and life history strategy of the flies, suggesting geographic specificity of the microbiota composition. Variation in microbiota composition of locally adapted D. melanogaster could be attributed to both the wild environment and host genetic selection. Finally, by eliminating or manipulating the microbiota of fly lines collected across a latitudinal gradient, we reveal that host genotype contributes to latitude-specific life history traits independent of the microbiota and that variation in the microbiota can suppress or reverse the differences between locally adapted fly lines. Together, these findings establish the microbiota composition of a model animal as an essential consideration in local adaptation.
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http://dx.doi.org/10.1111/mec.15344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507235PMC
February 2020

C9orf72 expansion within astrocytes reduces metabolic flexibility in amyotrophic lateral sclerosis.

Brain 2019 12;142(12):3771-3790

Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, 385 Glossop Road, Sheffield S10 2HQ, UK.

It is important to understand how the disease process affects the metabolic pathways in amyotrophic lateral sclerosis and whether these pathways can be manipulated to ameliorate disease progression. To analyse the basis of the metabolic defect in amyotrophic lateral sclerosis we used a phenotypic metabolic profiling approach. Using fibroblasts and reprogrammed induced astrocytes from C9orf72 and sporadic amyotrophic lateral sclerosis cases we measured the production rate of reduced nicotinamide adenine dinucleotides (NADH) from 91 potential energy substrates simultaneously. Our screening approach identified that C9orf72 and sporadic amyotrophic lateral sclerosis induced astrocytes have distinct metabolic profiles compared to controls and displayed a loss of metabolic flexibility that was not observed in fibroblast models. This loss of metabolic flexibility, involving defects in adenosine, fructose and glycogen metabolism, as well as disruptions in the membrane transport of mitochondrial specific energy substrates, contributed to increased starvation induced toxicity in C9orf72 induced astrocytes. A reduction in glycogen metabolism was attributed to loss of glycogen phosphorylase and phosphoglucomutase at the protein level in both C9orf72 induced astrocytes and induced neurons. In addition, we found alterations in the levels of fructose metabolism enzymes and a reduction in the methylglyoxal removal enzyme GLO1 in both C9orf72 and sporadic models of disease. Our data show that metabolic flexibility is important in the CNS in times of bioenergetic stress.
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http://dx.doi.org/10.1093/brain/awz302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906594PMC
December 2019

Microbiome composition shapes rapid genomic adaptation of .

Proc Natl Acad Sci U S A 2019 10 16;116(40):20025-20032. Epub 2019 Sep 16.

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.

Population genomic data has revealed patterns of genetic variation associated with adaptation in many taxa. Yet understanding the adaptive process that drives such patterns is challenging; it requires disentangling the ecological agents of selection, determining the relevant timescales over which evolution occurs, and elucidating the genetic architecture of adaptation. Doing so for the adaptation of hosts to their microbiome is of particular interest with growing recognition of the importance and complexity of host-microbe interactions. Here, we track the pace and genomic architecture of adaptation to an experimental microbiome manipulation in replicate populations of in field mesocosms. Shifts in microbiome composition altered population dynamics and led to divergence between treatments in allele frequencies, with regions showing strong divergence found on all chromosomes. Moreover, at divergent loci previously associated with adaptation across natural populations, we found that the more common allele in fly populations experimentally enriched for a certain microbial group was also more common in natural populations with high relative abundance of that microbial group. These results suggest that microbiomes may be an agent of selection that shapes the pattern and process of adaptation and, more broadly, that variation in a single ecological factor within a complex environment can drive rapid, polygenic adaptation over short timescales.
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http://dx.doi.org/10.1073/pnas.1907787116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778213PMC
October 2019

Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson's disease.

Neurosci Biobehav Rev 2019 08 24;103:305-315. Epub 2019 May 24.

Department of Psychology, Palo Alto University, 1791 Arastradero Rd, Palo Alto, CA, 94304, USA; Neuroscience Program, Center for Health Sciences, Bioscience Division, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025, USA. Electronic address:

Recent evidence has advanced our understanding of the function of sleep to include removal of neurotoxic protein aggregates via the glymphatic system. However, most research on the glymphatic system utilizes animal models, and the function of waste clearance processes in humans remains unclear. Understanding glymphatic function offers new insight into the development of neurodegenerative diseases that result from toxic protein inclusions, particularly those characterized by neuropathological sleep dysfunction, like Parkinson's disease (PD). In PD, we propose that glymphatic flow may be compromised due to the combined neurotoxic effects of alpha-synuclein protein aggregates and deteriorated dopaminergic neurons that are linked to altered REM sleep, circadian rhythms, and clock gene dysfunction. This review highlights the importance of understanding the functional role of glymphatic system disturbance in neurodegenerative disorders and the subsequent clinical and neuropathological effects on disease progression. Future research initiatives utilizing noninvasive brain imaging methods in human subjects with PD are warranted, as in vivo identification of functional biomarkers in glymphatic system functioning may improve clinical diagnosis and treatment of PD.
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http://dx.doi.org/10.1016/j.neubiorev.2019.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692229PMC
August 2019

Bacterial Methionine Metabolism Genes Influence Drosophila melanogaster Starvation Resistance.

Appl Environ Microbiol 2018 09 17;84(17). Epub 2018 Aug 17.

Department of Plant & Wildlife Sciences, Brigham Young University, Provo, Utah, USA

Animal-associated microorganisms (microbiota) dramatically influence the nutritional and physiological traits of their hosts. To expand our understanding of such influences, we predicted bacterial genes that influence a quantitative animal trait by a comparative genomic approach, and we extended these predictions via mutant analysis. We focused on starvation resistance (SR). We first confirmed that SR responds to the microbiota by demonstrating that bacterium-free flies have greater SR than flies bearing a standard 5-species microbial community, and we extended this analysis by revealing the species-specific influences of 38 genome-sequenced bacterial species on SR. A subsequent metagenome-wide association analysis predicted bacterial genes with potential influence on SR, among which were significant enrichments in bacterial genes for the metabolism of sulfur-containing amino acids and B vitamins. Dietary supplementation experiments established that the addition of methionine, but not B vitamins, to the diets significantly lowered SR in a way that was additive, but not interactive, with the microbiota. A direct role for bacterial methionine metabolism genes in SR was subsequently confirmed by analysis of flies that were reared individually with distinct methionine cycle mutants. The correlated responses of SR to bacterial methionine metabolism mutants and dietary modification are consistent with the established finding that bacteria can influence fly phenotypes through dietary modification, although we do not provide explicit evidence of this conclusion. Taken together, this work reveals that SR is a microbiota-responsive trait, and specific bacterial genes underlie these influences. Extending descriptive studies of animal-associated microorganisms (microbiota) to define causal mechanistic bases for their influence on animal traits is an emerging imperative. In this study, we reveal that starvation resistance (SR), a model quantitative trait in animal genetics, responds to the presence and identity of the microbiota. Using a predictive analysis, we reveal that the amino acid methionine has a key influence on SR and show that bacterial methionine metabolism mutants alter normal patterns of SR in flies bearing the bacteria. Our data further suggest that these effects are additive, and we propose the untested hypothesis that, similar to bacterial effects on fruit fly triacylglyceride deposition, the bacterial influence may be through dietary modification. Together, these findings expand our understanding of the bacterial genetic basis for influence on a nutritionally relevant trait of a model animal host.
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http://dx.doi.org/10.1128/AEM.00662-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102978PMC
September 2018

Texting as a Means of Reducing Pediatric Adolescent Psychiatric Emergency Encounters Wait Times.

Pediatr Emerg Care 2018 Jul;34(7):524-529

St Louis Children's Hospital, St Louis, MO.

Rationale: There is no universal system to facilitate communication between emergency rooms (ERs) and pediatric mental health providers, which leads to long wait times. This project tested the concept that a group texting application (GroupMe) could improve communication between providers and could reduce wait times by allowing frontline workers to contact multiple providers simultaneously.

Methods: We compared total wait times or overall length of service of 906 ER encounters before and 921 encounters after the GroupMe texting application was implemented. To reduce differences between preintervention and postintervention time points, we utilized propensity score matching to generate a matched group of controls (total sample n = 831 ER encounters before and n = 831 ER encounters after).

Results: Although there were no differences in total wait times when using the GroupMe application, there was a significant decrease in wait times after patients were diagnosed in ER by psychiatric provider both before (mean difference, 96.4 minutes saved; t = 2.23; P < 0.05) and after propensity score matching (mean difference, 88.0 minutes saved; t = 2.48; P < 0.05) for disposition type and acuity level.

Conclusions: Use of a group texting application has the potential to improve communication and wait times. However, its ability to reduce overall wait times is hampered when the limited availability of pediatric psychiatry providers results in delays in diagnosis and treatment decisions.
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http://dx.doi.org/10.1097/PEC.0000000000001546DOI Listing
July 2018

A Metagenome-Wide Association Study and Arrayed Mutant Library Confirm Lipopolysaccharide Genes Are Necessary for Association with .

G3 (Bethesda) 2018 03 28;8(4):1119-1127. Epub 2018 Mar 28.

Plant and Wildlife Sciences Department, Brigham Young University, Provo Utah 84602

A metagenome wide association (MGWA) study of bacterial host association determinants in predicted that LPS biosynthesis genes are significantly associated with host colonization. We were unable to create site-directed mutants for each of the predicted genes in , so we created an arrayed transposon insertion library using DsW_054 isolated from Creation of the DsW_054 gene knock-out library was performed by combinatorial mapping and Illumina sequencing of random transposon insertion mutants. Transposon insertion locations for 6,418 mutants were successfully mapped, including hits within 63% of annotated genes in the DsW_054 genome. For 45/45 members of the library, insertion sites were verified by arbitrary PCR and Sanger sequencing. Mutants with insertions in four different LPS biosynthesis genes were selected from the library to validate the MGWA predictions. Insertion mutations in two genes biosynthetically upstream of Lipid-A formation, and , show significant differences in host association, whereas mutations in two genes encoding LPS biosynthesis functions downstream of Lipid-A biosynthesis had no effect. These results suggest an impact of bacterial cell surface molecules on the bacterial capacity for host association. Also, the transposon insertion mutant library will be a useful resource for ongoing research on the genetic basis for traits.
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http://dx.doi.org/10.1534/g3.117.300530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873903PMC
March 2018

Where's the LGBT in integrated care research? A systematic review.

Fam Syst Health 2017 Sep 14;35(3):308-319. Epub 2017 Aug 14.

Department of Family and Community Medicine, Saint Louis University.

Introduction: Lesbian, gay, bisexual, and transgender (LGBT) individuals experience more negative health outcomes compared with their heterosexual peers. The health disparities are often related to family and social rejection of the LGBT individuals. Integrated care, and Medical Family Therapy in particular, may aid in addressing the systemic nature of the negative health outcomes.

Method: To better understand the current state of the integrated care literature on addressing the health needs of LGBT individuals, a systematic review of the research literature was conducted from January 2000 to January 2016 for articles including integrated health care interventions for LGBT populations. Independent reviewers coded identified articles.

Results: Only 8 research articles met criteria for inclusion out of the 2,553 initially identified articles in the search. Results indicated a lack of integrated care research on health care and health needs of LGBT individuals, and none of the articles addressed the use of family or systemic-level interventions.

Discussion: Implications for future research and the need for better education training are discussed. (PsycINFO Database Record
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http://dx.doi.org/10.1037/fsh0000290DOI Listing
September 2017

Advance Care Planning Discussions with Adolescent and Young Adult Cancer Patients Admitted to a Community Palliative Care Service: A Retrospective Case-Note Audit.

J Adolesc Young Adult Oncol 2018 02 2;7(1):112-119. Epub 2017 Aug 2.

3 Rural Clinical School of Western Australia (Albany), University of Western Australia , Albany, Western Australia .

Purpose: Adolescents and young adults (AYA) with cancer are a cohort requiring specialized healthcare models to address unique cognitive and physical challenges. Advance care planning (ACP) discussions likely warrant age-appropriate adaptation, yet, there is little Australian research data available to inform best practice for this group. The goal of this work is to inform future models of ACP discussions for AYA.

Methods: Retrospective medical record audit of AYA patients and an adult comparison group, diagnosed with a malignancy and referred to a community hospice service, in Western Australia, in the period between January 1, 2012 and December 1, 2015. Information was collected regarding end-of-life care discussions, documentation of agreed plan of care, and care received.

Results: Twenty-seven AYA and 37 adult medical records were reviewed. Eighteen (66.7%) AYA patients died at home, compared with 19 (51.4%) adults (p = 0.028). Desire to pursue all available oncological therapies, including clinical trials, was documented for 14 (51.9%) AYA patients compared with 9 (24.3%) of the adult group (p = 0.02). Eleven AYA patients (40.7%) received chemotherapy during the last month of life compared with two (5.4%) adults (p = 0.001).

Conclusions: The results indicate that end-of-life care preferences for this unique cohort may differ from those of the adult population and need to be captured and understood. An ACP document incorporating a discussion regarding goals of care, preferred location of care, preference for place of death, and consent to future intervention, including cardiopulmonary resuscitation and prompts for review, could assist in pursuing this objective.
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http://dx.doi.org/10.1089/jayao.2017.0032DOI Listing
February 2018

Evaluation of the safety of iron dextran with parenteral nutrition in the paediatric inpatient setting.

Nutr Diet 2017 Nov 7;74(5):471-475. Epub 2017 Jul 7.

Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Aim: Practitioners often avoid administering iron dextran in parenteral nutrition (PN) for hospitalised children because of the concern for anaphylaxis. The primary aim of the present study was to determine the risk of anaphylaxis associated with exposure to PN containing iron dextran in the inpatient setting.

Methods: Charts were reviewed for all children admitted to The Children's Hospital of Philadelphia from January 1, 2011 to December 30, 2013 who received PN containing low molecular weight (LMW) iron dextran. Subject characteristics, primary diagnoses and PN orders were evaluated. The pharmacy adverse events database was queried for adverse drug reactions.

Results: Over three years, 89 subjects received PN containing a maintenance dose of LMW iron dextran with a total of 2774 days of exposure. Subjects ranged from two months to 21 years of age and received between 1 and 196 days of PN containing iron dextran. The mean dose of iron dextran in children decreased as the weight category increased from <5 kg (0.21 ± 0.05 mg/kg/day) to ≥40 kg (1.9 ± 0.5 mg/day; P-value for trend <0.005). No anaphylactic reactions occurred in any subjects.

Conclusions: PN containing a maintenance dose of LMW iron dextran can be safely administered to hospitalised children, and further studies are need to evaluate the potential to prevent iron deficiency anaemia and the need for additional IV iron infusions.
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http://dx.doi.org/10.1111/1747-0080.12355DOI Listing
November 2017

Do Patient-Centered Medical Homes Improve Health Behaviors, Outcomes, and Experiences of Low-Income Patients? A Systematic Review and Meta-Analysis.

Health Serv Res 2018 06 3;53(3):1777-1798. Epub 2017 Jul 3.

Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO.

Objectives: To examine: (1) what elements of patient-centered medical homes (PCMHs) are typically provided to low-income populations, (2) whether PCMHs improve health behaviors, experiences, and outcomes for low-income groups.

Data Sources/study Setting: Existing literature on PCMH utilization among health care organizations serving low-income populations.

Study Design: Systematic review and meta-analysis.

Data Collection/extraction Methods: We obtained papers through existing systematic and literature reviews and via PubMed, Web of Science, and the TRIP databases, which examined PCMHs serving low-income populations. A total of 434 studies were reviewed. Thirty-three articles met eligibility criteria.

Principal Findings: Patient-centered medical home interventions usually were composed of five of the six recommended components. Overall positive effect of PCMH interventions was d = 0.247 (range -0.965 to 1.42). PCMH patients had better clinical outcomes (d = 0.395), higher adherence (0.392), and lower utilization of emergency rooms (d = -0.248), but there were apparent limitations in study quality.

Conclusions: Evidence shows that the PCMH model can increase health outcomes among low-income populations. However, limitations to quality include no assessment for confounding variables. Implications are discussed.
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http://dx.doi.org/10.1111/1475-6773.12737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980195PMC
June 2018

Persistent Complications of Child Sexual Abuse: Sexually Compulsive Behaviors, Attachment, and Emotions.

J Child Sex Abus 2017 Feb-Mar;26(2):140-157

a Family and Community, Medicine School of Medicine , Saint Louis University , St. Louis , Missouri , USA.

Child sexual abuse has the potential to cause distress for the victim across the lifespan. Romantic relationships may be particularly difficult for victims of child sexual abuse. This retrospective study examined differences in adult romantic attachment, sexually compulsive behaviors, and emotion regulation by history of child sexual abuse in a large, nonclinical sample. Those with a history of child sexual abuse reported more attachment anxiety in romantic relationships and engaged in more sexually compulsive behaviors. Overall, males displayed more sexually compulsive behaviors than females regardless of history of sexual abuse. Males with a history of sexual abuse displayed the greatest number of sexually compulsive behaviors. Surprisingly, no differences were observed in emotion regulation or attachment avoidant behaviors by history of child sexual abuse. Future research should seek to replicate current findings and examine emotion regulation difficulties experienced as a result of trauma.
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http://dx.doi.org/10.1080/10538712.2016.1269144DOI Listing
July 2017

Rapid Recovery Pathway After Spinal Fusion for Idiopathic Scoliosis.

Pediatrics 2016 04 23;137(4). Epub 2016 Mar 23.

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is associated with significant pain and prolonged hospitalization. There is evidence that early mobilization and multimodal analgesia can accelerate functional recovery and reduced length of stay (LOS). Using these principles, we implemented a quality improvement initiative to enable earlier functional recovery in our AIS-PSF population.

Methods: We designed and implemented a standardized rapid recovery pathway (RRP) with evidence-based management recommendations for children aged 10 to 21 years undergoing PSF for AIS. Our primary outcome, functional recovery, was assessed using statistical process control charts for LOS and average daily pain scores. Our process measures were medication adherence and order set utilization. The balancing measure was 30-day readmission rate.

Results: We included 322 patients from January 1, 2011 to June 30, 2015 with 134 (42%) serving as historical controls, 104 (32%) representing our transition population, and 84 (26%) serving as our RRP population. Baseline average LOS was 5.7 days and decreased to 4 days after RRP implementation. Average daily pain scores remained stable with improvement on postoperative day 0 (3.8 vs 4.9 days) and 1 (3.8 vs 5 days) after RRP implementation. In the second quarter of 2015, gabapentin (91%) and ketorolac (95%) use became routine and order set utilization was 100%. Readmission rates did not increase as a result of this pathway.

Conclusions: Implementation of a standardized RRP with multimodal pain management and early mobilization strategies resulted in reduced LOS without an increase in reported pain scores or readmissions.
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http://dx.doi.org/10.1542/peds.2015-1568DOI Listing
April 2016

Prevalence and Intensity of Pain and Other Physical and Psychological Symptoms in Adolescents and Young Adults Diagnosed with Cancer on Referral to a Palliative Care Service.

J Adolesc Young Adult Oncol 2015 Jun;4(2):70-5

1 ONTrac at Peter Mac, Victorian Adolescent and Young Adult Oncology Service, Peter MacCallum Cancer Centre , East Melbourne, Victoria, Australia .

Purpose: While adolescent and young adult (AYA) oncology is recognized as a distinct specialty, there remains a paucity of literature documenting symptomatology in this cohort. This study aimed to identify the prevalence, severity, and mechanism of pain and other symptoms in AYA patients referred to a palliative care service in a specialist Australian cancer center.

Methods: A retrospective design analyzed the case file data of 33 eligible AYA patients aged 15-25 years old at diagnosis and two randomly selected control groups of patients >25 years old: unmatched and matched for diagnosis and sex. All cases were referred to the palliative care service between July 2009 and June 2012. Descriptive statistics, analysis of Edmonton Symptom Assessment Scale (ESAS) and Edmonton Classification System of Cancer Pain (ECS-CP) data, and non-parametric tests were performed.

Results: The most common malignancies among the AYA patients were sarcoma and hematological cancers. All AYA patients reported pain syndrome on the ECS-CP compared with 85% of the matched controls (p=0.018). An age group effect was found for mechanisms of pain (p=0.035). A trend toward more neuropathic pain among AYA cases was also found (59% vs. 39%). The most common ESAS symptoms in AYAs were pain (91%), diminished well-being (76%), fatigue (75%), and decreased appetite (67%).

Conclusion: AYA cancer patients appear to experience a unique symptom profile with high symptom prevalence and complexity. Further research is warranted to identify determinants and inform integration of supportive and palliative care services for this unique patient cohort.
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http://dx.doi.org/10.1089/jayao.2014.0015DOI Listing
June 2015

Sequential injection analysis with chemiluminescence detection for rapid monitoring of commercial Calendula officinalis extractions.

Phytochem Anal 2015 Nov-Dec;26(6):454-60. Epub 2015 Jul 29.

Flinders University, School of Chemical and Physical Sciences, Bedford Park, South Australia, 5042, Australia.

Introduction: Plant extracts containing high levels of antioxidants are desirable due to their reported health benefits. Most techniques capable of determining the antioxidant activity of plant extracts are unsuitable for rapid at-line analysis as they require extensive sample preparation and/or long analysis times. Therefore, analytical techniques capable of real-time or pseudo real-time at-line monitoring of plant extractions, and determination of extraction endpoints, would be useful to manufacturers of antioxidant-rich plant extracts.

Objectives: To develop a reliable method for the rapid at-line extraction monitoring of antioxidants in plant extracts.

Materials And Methods: Calendula officinalis extracts were prepared from dried flowers and analysed for antioxidant activity using sequential injection analysis (SIA) with chemiluminescence (CL) detection. The intensity of CL emission from the reaction of acidic potassium permanganate with antioxidants within the extract was used as the analytical signal. The SIA-CL method was applied to monitor the extraction of C. officinalis over the course of a batch extraction to determine the extraction endpoint. Results were compared with those from ultra high performance liquid chromatography (UHPLC).

Results: Pseudo real-time, at-line monitoring showed the level of antioxidants in a batch extract of Calendula officinalis plateaued after 100 min of extraction. These results correlated well with those of an offline UHPLC study.

Conclusion: SIA-CL was found to be a suitable method for pseudo real-time monitoring of plant extractions and determination of extraction endpoints with respect to antioxidant concentrations. The method was applied at-line in the manufacturing industry.
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http://dx.doi.org/10.1002/pca.2580DOI Listing
August 2016
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