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Phase II, double blind, placebo controlled, multi-site study to evaluate the safety, feasibility and desirability of conducting a phase III study of anamorelin for anorexia in people with small cell lung cancer: A study protocol (LUANA trial).
Sousa, MS, Martin, P, Johnson, MJ, Lind, M, Maddocks, M, Bullock, A, Agar, M, Chang, S, Kochovska, S, Kinchin, I, et al
PloS one. 2023;(5):e0285850
Abstract
Anorexia is experienced by most people with lung cancer during the course of their disease and treatment. Anorexia reduces response to chemotherapy and the ability of patients to cope with, and complete their treatment leading to greater morbidity, poorer prognosis and outcomes. Despite the significant importance of cancer-related anorexia, current therapies are limited, have marginal benefits and unwarranted side effects. In this multi-site, randomised, double blind, placebo controlled, phase II trial, participants will be randomly assigned (1:1) to receive once-daily oral dosing of 100mg of anamorelin HCl or matched placebo for 12 weeks. Participants can then opt into an extension phase to receive blinded intervention for another 12 weeks (weeks 13-24) at the same dose and frequency. Adults (≥18 years) with small cell lung cancer (SCLC); newly diagnosed with planned systemic therapy OR with first recurrence of disease following a documented disease-free interval ≥6 months, AND with anorexia (i.e., ≤ 37 points on the 12-item Functional Assessment of Anorexia Cachexia Treatment (FAACT A/CS) scale) will be invited to participate. Primary outcomes are safety, desirability and feasibility outcomes related to participant recruitment, adherence to interventions, and completion of study tools to inform the design of a robust Phase III effectiveness trial. Secondary outcomes are the effects of study interventions on body weight and composition, functional status, nutritional intake, biochemistry, fatigue, harms, survival and quality of life. Primary and secondary efficacy analysis will be conducted at 12 weeks. Additional exploratory efficacy and safety analyses will also be conducted at 24 weeks to collect data over longer treatment duration. The feasibility of economic evaluations in Phase III trial will be assessed, including the indicative costs and benefits of anamorelin for SCLC to the healthcare system and society, the choice of methods for data collection and the future evaluation design. Trial registration. The trial has been registered with the Australian New Zealand Clinical Trials Registry [ACTRN12622000129785] and approved by the South Western Sydney Local Health District Human Research Ethics Committee [2021/ETH11339]. https://clin.larvol.com/trial-detail/ACTRN12622000129785.
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A review of portable quantitative and semi-quantitative devices for measurement of vitamin A in biological samples.
Huey, SL, Krisher, JT, Morgan, D, Mkambula, P, Gannon, BM, Mbuya, MNN, Mehta, S
Current research in biotechnology. 2022;:253-274
Abstract
BACKGROUND We catalog and summarize evidence of the analytical performance of portable quantitative and semi-quantitative devices for the assessment of vitamin A status and vitamin A deficiency (VAD) in various biological samples-including whole blood, plasma, serum, and milk-in addition to VAD determination by functional indicators such as pupillary response. METHODS We searched the literature for published research articles, patents, and information from manufacturers of mobile devices, particularly those appropriate for low-resource settings. The included devices were required to be portable (lightweight and ideally not needing a power outlet) and to measure vitamin A as well as define VAD. Eligible studies compared a portable device to a reference standard of high-performance liquid chromatography for blood and milk, or a Goldmann-Weekers dark adaptometer for eyes/vision. Where available, identified devices were compared with reference methods across several performance criteria. When possible, we compared the device's performance reported in published studies against the stated performance criteria from the manufacturers' websites. RESULTS We catalogued 25 portable devices for measuring vitamin A and/or VAD via biological samples. We also identified 18 comparison studies (plus associated reports) assessing nine methods: the iCheck Fluoro, iCheck Carotene, CRAFTi, Tidbit with or without the HYPER filtration system, custom field-friendly immunoassays, and microfluidic assays for blood; the iCheck Fluoro and iCheck Carotene for milk; and the Scotopic Sensitivity Tester-1 for eye function. CONCLUSIONS The iCheck Fluoro and iCheck Carotene are commercially available for use and are acceptable for measuring vitamin A in blood and milk samples, according to the available validation data. Many of the other identified devices, including other portable fluorometers, photometers, immunoassays, microfluidics-based devices, and dark adaptometers, were proofs of concept and not yet commercially available. Furthermore, none of these other devices included manufacturer-described device performance criteria to compare with descriptions from experimental studies. Several gaps remain, including studies comparing the other portable devices against a reference standard, particularly for functional indicators of vitamin A status/deficiency; available manufacturer-reported device performance criteria against which to compare future results of investigations; and more comprehensive reporting of validation metrics including sensitivity, specificity, precision, and Bland-Altman analysis.
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Impact of COVID-19 on the Onset and Progression of Alzheimer's Disease and Related Dementias: A Roadmap for Future Research.
Gordon, MN, Heneka, MT, Le Page, LM, Limberger, C, Morgan, D, Tenner, AJ, Terrando, N, Willette, AA, Willette, SA
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;(5):1038-1046
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Abstract
COVID-19 causes lasting neurological symptoms in some survivors. Like other infections, COVID-19 may increase risk of cognitive impairment. This perspective highlights four knowledge gaps about COVID-19 that need to be filled to avoid this possible health issue. The first is the need to identify the COVID-19 symptoms, genetic polymorphisms and treatment decisions associated with risk of cognitive impairment. The second is the absence of model systems in which to test hypotheses relating infection to cognition. The third is the need for consortia for studying both existing and new longitudinal cohorts in which to monitor long term consequences of COVID-19 infection. A final knowledge gap discussed is the impact of the isolation and lack of social services brought about by quarantine/lockdowns on people living with dementia and their caregivers. Research into these areas may lead to interventions that reduce the overall risk of cognitive decline for COVID-19 survivors.
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Primary immunodeficiency and the microbiome.
Al-Nesf, MA, Morgan, D, Mohamed-Ali, V
Current opinion in pediatrics. 2021;(6):633-638
Abstract
PURPOSE OF REVIEW The current understanding of the relationship of the microbiota to clinical manifestation in patients with primary immunodeficiency, specifically the inflammatory processes caused by or that result in microbial dysbiosis, and their potential therapeutic options in primary immunodeficiency diseases (PID), is the basis of this review. RECENT FINDINGS PIDs are heterogeneous diseases with variable presentations, genetic backgrounds, complications, and severity. The immune-mediators may be extrinsic, such as therapeutic regimens that patients are on, including immunoglobin, biologics, antibiotics and diet, or intrinsic, like cytokines, microRNA and microbiome. The microbiome in PID, in particular, appears to play a crucial role in helping the host's immune system maintain hemostatic control in the intestine. Many of the clinical manifestations and complications of PID may be attributed to inflammatory and immune dysregulatory processes connected to the imbalances of the diet-microbiota-host-immunity axis, as shown by data pointing to the loss of microbial diversity, dysbiosis, in PID. SUMMARY The gut microbiome is a promising area of study in PID. Although the connection of the microbiome to humoral immunodeficiency is evident, the possibility of utilizing the association of humoral and cellular immunodeficiency and the microbiome for therapeutic benefit is still under investigation.
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Efficacy of ulipristal acetate in women with fibroid induced menorrhagia: A systematic review and meta-analysis.
Kounidas, G, Kastora, SL, Barnott, E, Black, L, Robinson-Burke, T, Gould, A, Morgan, D, Urquhart, G, Poobalan, A, Jack, A
Journal of gynecology obstetrics and human reproduction. 2021;(9):102173
Abstract
AIM: To evaluate the efficacy of UPA in women with fibroid induced menorrhagia. METHODS Embase, MEDLINE, CAB Abstracts, Cochrane Central Register of Controlled Trials, PsychInfo were searched up to 18th May 2020 and updated on 7th February 2021. Randomised controlled trials evaluating the efficacy of UPA in women with fibroid induced menorrhagia were included in the study. RESULTS Two authors independently reviewed and extracted the study data. Statistical heterogeneity was quantified using I2 statistics. Publication bias and data asymmetry was assessed by funnel plots. A meta-analysis was conducted where appropriate. Six studies were eligible for inclusion. UPA (5 mg and 10 mg) achieved statistically significant amenorrhoeic outcome when compared to placebo (p<0.00001). Increased adverse events (AE) profile was observed in the higher UPA dose, however, did not reach statistical significance. CONCLUSIONS This review demonstrates the efficacy of UPA in achieving amenorrhoea in women with fibroid induced menorrhagia. However, the favourable dose of UPA remains inconclusive when AE profile is taken into account. Evidence remains obscure regarding liver damage and further research is warranted to attain a conclusive outcome.
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Immediate and long-term consequences of COVID-19 infections for the development of neurological disease.
Heneka, MT, Golenbock, D, Latz, E, Morgan, D, Brown, R
Alzheimer's research & therapy. 2020;12(1):69
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Plain language summary
Covid-19 may cause brain dysfunction evidenced by symptoms individuals experience once they have contracted the disease. Loss of smell, taste and confusion have all been reported by patients and a number of severe cases have reported incidences of stroke. These are all of concern, as Covid-19 can severely affect the elderly who ordinarily are the most likely to suffer from brain disorders. This small review paper of 27 studies stated that there are four possible ways in which Covid-19 may affect the brain, which put Covid-19 sufferers at an increased risk of long-term brain disorders. This was supported by findings, which showed one third of Covid-19 patients leave hospital with evidence of brain dysfunction. Inflammation was heavily reviewed by the authors as a possible causal factor. It was concluded that patients who survive Covid-19 infection are at an increased risk for developing brain disorders such as Alzheimer's disease, however it was acknowledged that further studies are required. Clinicians could use this study to understand the possible need for both short-term and long-term monitoring of brain function in individuals who have survived Covid-19, especially if they are elderly.
Abstract
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.
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Circulating Antibodies against Epstein-Barr Virus (EBV) and p53 in EBV-Positive and -Negative Gastric Cancer.
Camargo, MC, Kim, KM, Matsuo, K, Torres, J, Liao, LM, Morgan, D, Michel, A, Waterboer, T, Song, M, Gulley, ML, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020;(2):414-419
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BACKGROUND Epstein-Barr virus (EBV)-positive gastric cancers have clinicopathologic differences from EBV-negative tumors and lack TP53 mutation. Serologic profiles may inform viral contribution to carcinogenesis. METHODS We compared humoral responses of EBV-positive (n = 67) and EBV-negative (n = 137) patients with gastric cancer from the International EBV-Gastric Cancer Consortium. Serum antibodies against four EBV proteins, nuclear (EBNA), viral capsid (VCA), early-diffuse (EA-D), and Zta replication activator (ZEBRA), and to p53 were assessed by multiplex assays. OR of antibody level tertiles (T1-T3) were adjusted by logistic regression. We also conducted a meta-analysis of reported anti-p53 seropositivity in gastric cancer. RESULTS Consistent with EBV's ubiquity, 99% of patients were seropositive for anti-EBNA and 98% for anti-VCA, without difference by tumor EBV status. Seropositivity varied between patients with EBV-positive and EBV-negative tumors for anti-EA-D (97% vs. 67%, respectively, P < 0.001) and anti-ZEBRA (97% vs. 85%, respectively, P = 0.009). Adjusted ORs (vs. T1) for patients with EBV-positive versus EBV-negative tumors were significantly elevated for higher antibodies against EBNA (2.6 for T2 and 13 for T3), VCA (1.8 for T2 and 2.4 for T3), EA-D (6.0 for T2 and 44 for T3), and ZEBRA (4.6 for T2 and 12 for T3). Antibodies to p53 were inversely associated with EBV positivity (3% vs. 15%; adjusted OR = 0.16, P = 0.021). Anti-p53 prevalence from the literature was 15%. CONCLUSIONS These serologic patterns suggest viral reactivation in EBV-positive cancers and identify variation of p53 seropositivity by subtype. IMPACT Anti-EBV and anti-p53 antibodies are differentially associated with tumor EBV positivity. Serology may identify EBV-positive gastric cancer for targeted therapies.
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AGA Technical Review on Gastric Intestinal Metaplasia-Natural History and Clinical Outcomes.
Gawron, AJ, Shah, SC, Altayar, O, Davitkov, P, Morgan, D, Turner, K, Mustafa, RA
Gastroenterology. 2020;(3):705-731.e5
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A comparison of compliance in the estimation of body fluid status using daily fluid balance charting and body weight changes during continuous renal replacement therapy.
Davies, H, Leslie, GD, Morgan, D, Dobb, GJ
Australian critical care : official journal of the Confederation of Australian Critical Care Nurses. 2019;(2):83-89
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From Disease to Health: Physical Therapy Health Promotion Practices for Secondary Prevention in Adult and Pediatric Neurologic Populations.
Quinn, L, Morgan, D
Journal of neurologic physical therapy : JNPT. 2017;(Suppl 3 IV STEP Spec Iss):S46-S54
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Abstract
BACKGROUND AND PURPOSE Over the last decade there has been a substantial increase in efforts to better understand how targeted physical activity and exercise interventions can be used to minimize secondary consequences arising from neurological damage in both adult and pediatric populations. This article offers an overview of contemporary research that addresses mediators of functional and neuroplastic adaptations associated with physical activity and exercise. We emphasize the important role that physical therapists can play to increase participation and improve well-being in adults and children with neurological disorders. We further highlight potential strategies to foster translation of evidence-based findings for use by clinicians and consumers. SUMMARY OF KEY POINTS Engagement in physical activity can serve as a powerful promoter of health and well-being in adults and youth with neurologic disease, and has the potential to alter the course of disease processes. Physical therapists can play a key role in promoting fitness and wellness by encouraging active living, providing early diagnosis of disease and prescribing targeted activity interventions to improve fitness and participation, and helping individuals overcome personal and environmental barriers to an active lifestyle. RECOMMENDATIONS FOR CLINICAL PRACTICE Physical therapists must adopt a model of rehabilitation that emphasizes secondary prevention in adults and youth with neurologic diseases. Physical therapists have a unique role in developing forward-thinking approaches in using innovative health and wellness strategies to promote positive changes in activity and exercise behaviors.