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1.
Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?
Kooman, JP, Usvyat, LA, Dekker, MJE, Maddux, DW, Raimann, JG, van der Sande, FM, Ye, X, Wang, Y, Kotanko, P
Blood purification. 2019;(1-3):171-184
Abstract
Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.
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2.
Personalized treatment selection using data from crossover designs with carry-over effects.
Siriwardhana, C, Kulasekera, KB, Datta, S
Statistics in medicine. 2019;(28):5391-5412
Abstract
In this work, we propose a semiparametric method for estimating the optimal treatment for a given patient based on individual covariate information for that patient when data from a crossover design are available. Here, we assume there are carry-over effects for patients switching from one treatment to another. For the K treatment (K ≥ 2) scenario, we show that nonparametric estimation of carry-over effects can have the undesirable property that comparison of treatment means can only be done using independent outcome measurements from different groups of patients rather than using available joint measurements for each patient. To overcome this barrier, we compare probabilities of outcome variable of each treatment dominating outcome variables for all other treatments conditional on patient-specific scores constructed from patient covariates. We suggest single-index models as appropriate models connecting outcome variables to covariates and our empirical investigations show that frequencies of correct treatment assignments are highly accurate. The proposed method is also rather robust against departures from a single-index model structure. We also conduct a real data analysis to show the applicability of the proposed procedure.
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3.
Health Effects of an Individualized Lifestyle Intervention for People with Psychotic Disorders in Psychiatric Outpatient Services: A Two Year Follow-up.
Blomqvist, M, Ivarsson, A, Carlsson, IM, Sandgren, A, Jormfeldt, H
Issues in mental health nursing. 2019;(10):839-850
Abstract
People with psychotic disorders experience to a great extent avoidable physical illnesses and early mortality. The aim of the study was to investigate the potential effects for this group of participating in a lifestyle intervention. A multi-component nurse-led lifestyle intervention using quasi-experimental design was performed. Changes in biomedical and clinical measurements, self-reported health, symptoms of illness and health behavior were investigated. Multilevel modeling was used to statistically test differences in changes over time. Statistically significant changes were found in physical activity, HbA1c and waist circumference. A lifestyle intervention for people with severe mental illness can be beneficial for increasing physical activity.
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4.
Innovations in personalised diabetes care and risk management.
Nijpels, G, Beulens, JW, van der Heijden, AA, Elders, PJ
European journal of preventive cardiology. 2019;(2_suppl):125-132
Abstract
Type 2 diabetes is associated with an increased risk of developing macro and microvascular complications. Nevertheless, there is substantial heterogeneity between people with type 2 diabetes in their risk of developing such complications. Personalised medicine for people with type 2 diabetes may aid in efficient and tailored diabetes care for those at increased risk of developing such complications. Recently, progress has been made in the development of personalised diabetes care in several areas. Particularly for the risk prediction of cardiovascular disease, retinopathy and nephropathy, innovative methods have been developed for prediction and tailored monitoring or treatment to prevent such complications. For other complications or subpopulations of people with type 2 diabetes, such as the frail elderly, efforts are currently ongoing to develop such methods. In this review, we discuss the recent developments in innovations of personalised diabetes care for different complications and subpopulations of people with type 2 diabetes, their performance and modes of application in clinical practice.
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5.
Review article: biological mechanisms for symptom causation by individual FODMAP subgroups - the case for a more personalised approach to dietary restriction.
Wang, XJ, Camilleri, M, Vanner, S, Tuck, C
Alimentary pharmacology & therapeutics. 2019;(5):517-529
Abstract
BACKGROUND Due to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates-fructans, galacto-oligosaccharides, lactose, excess fructose and polyols-are thought to trigger gastrointestinal symptoms and are referred to collectively as "FODMAPs". AIMS To examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustment METHODS Recent literature was analysed via search databases including Medline, PubMed and Scopus. RESULTS Lactose, fructans and galacto-oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation. CONCLUSIONS While some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised "bottom-up" approach to the low-FODMAP diet, such as dietary restriction relevant to the patients' ethnicity, symptom profile and usual dietary intake.
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6.
The Importance of School-based Healthy Living Initiatives: Introducing the Health and Wellness Academy Concept.
Strieter, L, Laddu, DR, Sainsbury, J, Arena, R
Progress in cardiovascular diseases. 2019;(1):68-73
Abstract
Over the last 15 years, the number of school and community based health-intervention programs in the United States has grown. Many of these programs aim to prevent non-communicable chronic disease diagnoses (e.g., obesity, cardiovascular disease and type-2 diabetes). The Department of Physical Therapy in the College of Applied Health Sciences (CAHS) at the University of Illinois at Chicago (UIC) created a school-based wellness program (SBWP) that focuses on nutrition and physical activity, providing tailored experiences that motivate adolescents to make healthier lifestyle choices. The SBWP began as a camp for children in the surrounding neighborhoods and implemented healthy living practices utilizing students from Departments in the CAHS. From this camp, the Health and Wellness Academy (HWA) evolved. This paper provides a review of school-based initiatives and introduces the UIC HWA, an innovative and reproducible approach that can bring positive environmental change by improving health outcomes for children and their families.
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7.
[Development of Stratified and Personalized Medicine Based on Pharmacogenomic and Pharmacokinetic Analyses].
Hirai, K
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2019;(10):1253-1258
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Abstract
To administer optimal and safe pharmacotherapy, development of stratified and personalized therapy is imperative. Pharmacogenomics (PGx) is useful in elucidating factors causing individual differences in drug efficacy and the emergence of adverse effects. It also helps design accurate drug administration methods by evaluating the effects of patient-related factors, such as genetic factors, that influence pharmacokinetics (PK) and pharmacodynamics (PD). In addition, selection of appropriate therapeutic agents requires the implementation of precision medicine allowing accurate disease diagnosis. To establish precision medicine, it is necessary to uncover the association of pathophysiological factors, which are represented as endotype or genotype, with the pathology of several phenotypes. This review describes two aspects related to realization of individualized medicine, namely the effectiveness of PK/PD/PGx studies and the stratification of pathological conditions. First, we conducted a PK/PD/PGx study with the aim to individualize warfarin treatment. In this study, we elucidated the effect of CYP4F2 polymorphisms associated with vitamin K metabolism by measuring the blood concentrations of warfarin and vitamin K. Then, to develop precision medicine for asthma and chronic obstructive pulmonary disease (COPD), we analyzed not only clinical symptoms but also pathological biomarkers and genes associated with inflammation. The findings may contribute toward better understanding of the pathological conditions of asthma, COPD, and asthma-COPD overlap.
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Microfluidic Chip Method for Multi-SNPs Genotyping in Individual Risk Assessment of Micronutrient Deficiency.
Zhang, CH, Huo, JS, Chen, S, Xu, YC, Sun, J, Huang, J
Biomedical and environmental sciences : BES. 2019;(6):471-475
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An exploratory pilot study with copeptin as a biomarker for individualizing treatment for nocturnal polyuria.
Bruneel, E, Goessaert, AS, Denys, MA, Juul, KV, Nørgaard, JP, Everaert, K
Lower urinary tract symptoms. 2019;(1):43-47
Abstract
OBJECTIVE The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). METHODS In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile. A random blood sample was obtained during the day for measurement of plasma copeptin concentrations, osmolality, and serum sodium and creatinine concentrations. The effect of the use of different definitions for NP was evaluated. RESULTS The median age of the study participants was 61 years, and 48% were female. Copeptin was significantly correlated with urinary and plasma osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively; P < .001 for all). Study participants were divided into 3 groups: controls (n = 51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin concentrations were significantly lower in subjects with global polyuria than in those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P = .008 and .005). There was no significant difference in random daytime copeptin concentrations between the NP and control groups (P = .972). The results differed when other definitions for NP were used (e.g. NPi33 or NUP10). CONCLUSIONS We could not confirm our hypothesis that patients with NP have lower copeptin concentrations, although random blood sampling is not ideal. Further research is required to determine the use of copeptin in NP, perhaps in the identification of the desmopressin response.
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10.
DERIVING PRIMARY CANCER CELL CULTURES FOR PERSONALIZED THERAPY.
Esparza-López, J, Martínez-Aguilar, JF, Ibarra-Sánchez, MJ
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2019;(6):369-380
Abstract
Cancer is the second-leading cause of death in the world, accounting for one out of six deaths. Consequently, there is an urgent need for new and more effective therapeutic options as well as drug screening methods. Immortal, "stable" cancer cell lines have been employed since the past century to assess drug response but face several disadvantages. They often accumulate new genetic aberrations due to long-term culture and lack the indisputable heterogeneity of solid tumors, therefore, compromising the recapitulation of molecular features from parental tumors. Primary cancer cells have emerged as an attractive alternative to commercial cell lines since they can preserve such properties more closely. Here, we provide an overview of the basic concepts underlying generation and characterization of primary cell cultures from tumor samples. We emphasize the advantages and disadvantages of using these types of cancer cell cultures, and we make a comparison with other types of cultures used for personalized therapy. Finally, we consider the use of primary cancer cell cultures in personalized therapy as a means to improve drug response prediction and therapeutic outcomes.