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https://www.readbyqxmd.com/read/29667952/useful-pharmacodynamic-endpoints-in-children-selection-measurement-and-next-steps
#1
REVIEW
Lauren E Kelly, Yashwant Sinha, Charlotte I S Barker, Joseph F Standing, Martin Offringa
Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools...
April 18, 2018: Pediatric Research
https://www.readbyqxmd.com/read/29667562/caregiver-perceptions-of-a-fruit-and-vegetable-prescription-programme-for-low-income-paediatric-patients
#2
Amy Saxe-Custack, Heather Claire Lofton, Mona Hanna-Attisha, Colleen Victor, Gwendolyn Reyes, Tiffany Ceja, Jenny LaChance
OBJECTIVE: The physical and social environments that surround children should support good health. However, challenges with food security and access prevent many children from consuming a healthy diet, which is critical to proper growth and development. The present study sought to gain a better understanding of primary care initiatives to address these issues in a low-income setting. DESIGN: Following the relocation of a paediatric clinic to a farmers' market building and the implementation of a fruit and vegetable prescription programme, researchers conducted thirty-two semi-structured interviews with caregivers...
April 18, 2018: Public Health Nutrition
https://www.readbyqxmd.com/read/29667443/implications-of-structural-and-functional-brain-changes-in-amyotrophic-lateral-sclerosis
#3
Thanuja Dharmadasa, William Huynh, Jun Tsugawa, Yoshimitsu Shimatani, Yan Ma, Matthew C Kiernan
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes progressive muscle weakness and disability, eventually leading to death. Heterogeneity of disease has become a major barrier to understanding key clinical questions such as prognosis and disease spread, and has disadvantaged clinical trials in search of therapeutic intervention. Patterns of disease have been explored through recent advances in neuroimaging, elucidating structural, molecular and functional changes. Unique brain signatures have emerged that have lent a greater understanding of critical disease mechanisms, offering opportunities to improve diagnosis, guide prognosis, and establish candidate biomarkers to direct future therapeutic strategies...
April 19, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29667327/novel-west-syndrome-candidate-genes-in-a-chinese-cohort
#4
Jing Peng, Ying Wang, Fang He, Chen Chen, Li-Wen Wu, Li-Fen Yang, Yu-Ping Ma, Wen Zhang, Zi-Qing Shi, Chao Chen, Kun Xia, Hui Guo, Fei Yin, Nan Pang
AIMS: West syndrome (WS) is a classic form of early infantile epileptic encephalopathy (EIEE) characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on electroencephalography. Genetic defects play a critical role in the pathology of WS, and 54 EIEE genes have been identified till date. This study was designed to uncover new candidate genes for West syndrome. METHODS: In this study, we recruited 56 Chinese families with WS of unknown etiology...
April 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29667230/nephropreventing-effect-of-hypoxia-inducible-factor-1%C3%AE-in-a-rat-model-of-ischemic-reperfusion-acute-kidney-injury
#5
Huiling Wang, Nanmei Liu, Rui Li, Jun Tian, Weifeng Hu, Jinyuan Zhang
Acute kidney injury (AKI) often occurs in 5% hospitalized patients and in 50% sepsis patients with acute renal dysfunction. However, there is no safe and effective therapeutic strategies until now. Hypoxia condition is closely related to renal injuries and function under AKI. As HIF-1α is critical for cellular response to hypoxia, we investigated the protective effect of HIF-1α in a rat AKI model. We found that HIF-1 α injection improved the survival of rat with AKI, and the level of Cr and BUN was also increased...
April 17, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29667175/first-line-drugs-for-hypertension
#6
REVIEW
James M Wright, Vijaya M Musini, Rupam Gill
BACKGROUND: This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question. OBJECTIVES: To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment...
April 18, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29667019/what-is-new-in-heart-failure-management-in-2017-update-on-acc-aha-heart-failure-guidelines
#7
REVIEW
Biykem Bozkurt
PURPOSE OF REVIEW: The goal of this paper is to provide a summary of the new recommendations in the most recent 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. The intent is to provide the background and the supporting evidence for the recommendations and to provide practical guidance for management strategies in treatment of heart failure patients...
April 17, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29666958/ictal-interictal-continuum-patterns
#8
REVIEW
Gamaleldin M Osman, Davi F Araújo, Carolina B Maciel
PURPOSE OF REVIEW: To present data available on the epidemiology and significance of rhythmic and periodic patterns that lie on the ictal interictal continuum and propose an algorithm for the clinical approach to patients exhibiting these patterns. RECENT FINDINGS: There is accumulating evidence on the prognostic implications of various rhythmic and periodic patterns in the critically ill population. These patterns are not only associated with increased seizure risk but have also been associated with worse outcome and increased long-term risk of epilepsy in recent studies...
April 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29666944/macrophages-play-an-essential-role-in-trauma-induced-sterile-inflammation-and-tissue-repair
#9
REVIEW
Moritz Peiseler, Paul Kubes
Severe trauma is accompanied by a profound activation of the immune system. Patients with polytrauma develop systemic inflammatory response syndrome (SIRS) and often sepsis, which contributes substantially to high mortality of this condition. On a cellular level, necrosis and loss of plasma membrane integrity lead to the release of endogenous "damage-associated molecular patterns" (DAMPs) as danger signals, which in turn activate innate immune cells. Inflammation that occurs in the absence of invading pathogens has been termed sterile inflammation and trauma with tissue damage represents an acute form of sterile inflammation...
April 17, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/29666943/the-gtn-patch-a-simple-and-effective-new-approach-to-cardioprotection
#10
Derek M Yellon, Zhenhe He, Rayomand Khambata, Amrita Ahluwalia, Sean M Davidson
There remains a significant un-met need to reduce the extent of myocardial injury caused by ischaemia and reperfusion injury in patients experiencing an ST-elevation MI. Although nitric oxide is central to many cardioprotective strategies currently undergoing investigation, cardioprotection from the delivery of nitrates/nitrites has been inconsistently observed. The route of administration appears to be a critical variable. The glyceryl trinitrate (GTN) patch is commonly used as a simple and practical means of delivering nitric oxide to patients with ischaemic heart disease, but whether acute cardioprotection can be achieved by application of a GTN patch has not been investigated before...
April 17, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29666934/quo-vadis-do-immunotherapies-have-a-role-in-glioblastoma
#11
REVIEW
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29666811/immune-checkpoint-pathways-in-non-small-cell-lung-cancer
#12
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcello Cruz, Nisha Mohindra, Victoria Villaflor, Francis J Giles
Immunotherapy has evolved at a phenomenal pace in cancer therapeutics. This has primarily been fueled by the much perceived necessity to procure an alternative to current standard of care chemotherapy agents, owing to several concerns such as treatment-related toxicity and poor long-term survival associated with the same. The knowledge of various mechanisms involved in regulation of immune response to cancer cells has served a fundamental role in identifying key molecules through which immune cell activity may be modulated...
March 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666810/the-8-th-tnm-edition-for-lung-cancer-a-critical-analysis
#13
REVIEW
Paul E Van Schil, Ramon Rami-Porta, Hisao Asamura
The 8th edition of the tumor, node and metastasis (TNM) classification provides several new categories and for the first time, some prospective data are included. The T (tumor) descriptor is further subdivided with 1 cm increments for T1 and T2 disease. For metastatic disease (M descriptor) the new M1b category comprises patients with only one metastasis in one distant organ, whereas M1c implies multiple distant metastases in one or several organs. There are no changes regarding the nodal map and N component but new categories are suggested for further analysis, subdividing the N1 and N2 descriptors into involvement of single or multiple lymph node stations...
March 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666801/current-therapeutic-landscape-for-advanced-gastroesophageal-cancers
#14
REVIEW
Anthony Lopez, Kazuto Harada, Dilsa Mizrak Kaya, Jaffer A Ajani
Treatment of advanced gastroesophageal cancers remains challenging for clinicians, patients, and caregivers alike. Despite considerable research, the therapeutic armamentarium is restricted and hardly personalized. In the first-line setting, trastuzumab with a fluoropyrimidine and platinum agent is the standard-of-care in patients with HER2-positive tumor. For the others, a platinum-based doublet (preferably with oxaliplatin) is recommended. Three-drug cytotoxic regimens should be reserved for exceptional cases where patients have good performance status...
February 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666712/eustachian-valve-endocarditis-echocardiographic-diagnosis-in-a-critical-care-patient
#15
Mariana Alves, Rita Faria, António Messias, Carlos Meneses-Oliveira
Eustachian valve endocarditis is rare. A literature review revealed that only 29 cases have been reported and, among them, there is only one mention of an intensive care unit (ICU) admission. We present an 82-year-old man without previous medical records who presented with septic shock with multiple organ dysfunction. The patient was admitted to the ICU and deteriorated with combined shock (septic + cardiogenic). A second ultrasound screen detected a prominent Eustachian valve with mobile multilobulated vegetation attached...
2018: Case Reports in Critical Care
https://www.readbyqxmd.com/read/29666604/the-association-of-sj%C3%A3-gren-syndrome-and-autoimmune-thyroid-disorders
#16
REVIEW
Chiara Baldini, Francesco Ferro, Marta Mosca, Poupak Fallahi, Alessandro Antonelli
Sjögren's syndrome (SS) and autoimmune thyroid diseases (AITD) may frequently coexist in clinical practice, resulting in a complex overlapping disorder that represents a particular example of the expression of heterogeneity in patients with autoimmune disorders. Objective of this review was to describe the prevalence of the SS-AITD association in the most recent literature, exploring in particular to what extent the presence of AITD might influence the clinical expression of SS and vice versa . Moreover, we summarized some of the proposed genetic, biologic, and molecular mechanisms implied in the pathogenesis of AITD-SS association...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29666554/effect-of-different-pre-analytical-conditions-on-plasma-lactate-concentration
#17
Ivana Rako, Ana Mlinaric, Monika Dozelencic, Gordana Fressl Juros, Dunja Rogic
Introduction: Plasma lactate is a frequently used and important parameter for medical decision making. To setup a pre-analytical algorithm, we aimed to investigate the influence of different test tube additives, aliquoting, ice storage and haemolysis on plasma lactate concentrations for possible sparing critically ill (ICU) patients of additional blood drawing. Materials and methods: In our study (N = 177), lactate concentration and haemolysis index (HI) were measured in aliquoted (AHP) and unaliquoted (HP) Li-heparin, NaF/K3 EDTA and NaF/KOX plasma, centrifuged within 15 minutes after venipuncture, on Cobas c501 analyzer...
June 15, 2018: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/29666405/mediators-of-the-effects-of-gender-on-uric-acid-nephrolithiasis-a-novel-application-of-structural-equation-modeling
#18
Hao-Wei Chen, Yu-Chen Chen, Frances M Yang, Wen-Jeng Wu, Ching-Chia Li, Yong-Yuan Chang, Yii-Her Chou
Numerous epidemiological studies have shown that male patients with uric acid nephrolithiasis outnumber female patients. To our knowledge, no research exists evaluating the reasons gender affects the development of uric acid nephrolithiasis. We hereby used a novel application of structural equation modeling to analyze the mediators of the effects of gender on uric acid nephrolithiasis. In 1,098 patients with nephrolithiasis between 2012 and 2016, male gender was found to have a statistically significant positive indirect effect on the development of uric acid nephrolithiasis, which was mediated by lower urine pH (estimate: 0...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666295/lung-ultrasound-prior-to-spontaneous-breathing-trial-is-not-helpful-in-weaning-the-decision-making-process
#19
Ana Carolina P Antonio, Marli M Knorst, Cassiano Teixeira
BACKGROUND: Lung ultrasound is increasingly becoming a diagnostic tool in the critical care setting. B-pattern on a lung ultrasound is an artifact composed of multiple B-lines and correlates with interstitial edema. A randomized controlled trial concluded that bedside thoracic ultrasound could predict postextubation distress through changes in lung aeration during a weaning procedure; however, it could not screen patients before performance of a spontaneous breathing trial (SBT). METHODS: We conducted a 2-year, prospective, multicenter, observational study in 2 adult medical-surgical ICUs in southern Brazil...
April 17, 2018: Respiratory Care
https://www.readbyqxmd.com/read/29666281/pathogenic-effects-of-ifit2-and-interferon-%C3%AE-during-fatal-systemic-candida-albicans-infection
#20
Marcin Stawowczyk, Shamoon Naseem, Valeria Montoya, Darren P Baker, James Konopka, Nancy C Reich
A balanced immune response to infection is essential to prevent the pathology and tissue damage that can occur from an unregulated or hyperactive host defense. Interferons (IFNs) are critical mediators of the innate defense to infection, and in this study we evaluated the contribution of a specific gene coding for IFIT2 induced by type I IFNs in a murine model of disseminated Candida albicans Invasive candidiasis is a frequent challenge during immunosuppression or surgical medical interventions, and C. albicans is a common culprit that leads to high rates of mortality...
April 17, 2018: MBio
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