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Lesley Uttley, Iñigo Bermejo, Shijie Ren, Marrissa Martyn-St James, Ruth Wong, David L Scott, Adam Young, Matt Stevenson
As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Pfizer) of tofacitinib (TOF; Xeljanz® ) to submit evidence of the drug's clinical and cost-effectiveness in the treatment of rheumatoid arthritis (RA) after the failure of conventional disease-modifying antirheumatic drugs (cDMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
March 15, 2018: PharmacoEconomics
Giuseppa Patti, Marta Giaccardi, Valeria Capra, Flavia Napoli, Giuliana Cangemi, Sara Notarnicola, Sara Guzzetti, Silvia Russo, Mohamad Maghnie, Natascia Di Iorgi
Context: There is little information on long-term natural history of Silver-Russell syndrome (SRS). Objective: To describe the phenotypes and the metabolic status in adults with SRS. Design: Clinical and metabolic evaluations in adults with a molecular diagnosis of SRS. Partecipants: 7Caucasian patients (aged 18 to 46 years, mean age 26.9 years) were studied. Two had chromosome 7 maternal uniparental disomy, 3 had 11p15 loss of methylation and 2 had 11p15 duplication...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Floriane Rudwill, Donal O'Gorman, Etienne Lefai, Isabelle Chery, Alexandre Zahariev, Sylvie Normand, Allan F Pagano, Angèle Chopard, Anthony Damiot, Claire Laurens, Leanne Hodson, Emmanuelle Canet-Soulas, Martina Heer, Petra Frings Meuthen, Judith Buehlmeier, Natalie Baecker, Laure Meiller, Guillemette Gauquelin-Koch, Stéphane Blanc, Chantal Simon, Audrey Bergouignan
Context: The effects of energy balanced bed-rest on metabolic flexibility has not been thoroughly examined. Objective: We investigated the effects of 21-days bed-rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We further hypothesized protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. Design & Setting: Randomized cross-over longitudinal study conducted at the German Aerospace Center, Cologne, Germany...
March 12, 2018: Journal of Clinical Endocrinology and Metabolism
Aldo Berti, Michelle Granville, Robert E Jacobson
A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65...
January 12, 2018: Curēus
Peter Nash, Philip J Mease, Iain B McInnes, Proton Rahman, Christopher T Ritchlin, Ricardo Blanco, Eva Dokoupilova, Mats Andersson, Radhika Kajekar, Shephard Mpofu, Luminita Pricop
BACKGROUND: The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( NCT01989468). METHODS: Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s...
March 15, 2018: Arthritis Research & Therapy
Babu Nageswararao Kanuri, Sanjay C Rebello, Priya Pathak, Hobby Agarwal, Jitendra S Kanshana, Deepika Awasthi, Anand P Gupta, Jiaur R Gayen, Kumaravelu Jagavelu, Madhu Dikshit
Oxidative stress due to enhanced production or reduced scavenging of reactive oxygen species (ROS) has been associated with diet (dyslipidemia) induced obesity and insulin resistance (IR). The present study was undertaken to assess the role of p47phox in IR using wild type (WT) and p47phox-/- mice, fed with different diets (HFD, LFD or Chow). Augmented body weight, glucose intolerance and reduced insulin sensitivity were observed in p47phox-/- mice fed with 45% HFD and 10% LFD. Further, body fat and circulating lipids was increased significantly with 5 weeks LFD feeding in p47phox-/- mice, while parameters of energy homeostasis were reduced as compared to WT mice...
March 16, 2018: Free Radical Research
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Krzysztof Karpowicz, Katarzyna Krych, Małgorzata Karpowicz, Witold Nowak, Piotr Gronek
The map of candidate genes that can potentially affect physical fitness becomes larger every year, and they are associated with such aspects as respiratory and cardiovascular stability; body build and composition - especially muscle mass and strength; carbohydrate and lipid metabolism; response to training; and exercise intolerance.The aim of this study was to analyze the relationship between the CA repeat polymorphism of the P1 promoter of the IGF1 gene and the structure of motor skills in the two groups of Polish young athletes in 2011-2013...
March 15, 2018: Acta Biochimica Polonica
Kotaro Nochioka, Yasuhiko Sakata, Hiroaki Shimokawa
Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system play crucial roles in heart failure with reduced ejection fraction (HFrEF). Clinical trials provide strong evidence of prognostic benefits for combination therapy with angiotensin-converting enzyme inhibitor (ACEI) and β-blocker in the treatment of HFrEF. Angiotensin receptor blocker (ARB) is not superior to ACEI in improving mortality and an alternative for patients who are intolerant to ACEI. Prognostic evidence for triple therapy which combined angiotensin receptor blocker (ARB) and ACEI in addition to β-blocker therapy, is still controversial in HFrEF...
March 15, 2018: Advances in Experimental Medicine and Biology
Janki Shah, Jonathon O Russell, Tina Waters, Alan H Kominsky, Douglas Trask
OBJECTIVES: Hypoglossal nerve stimulation (HNS) therapy is an emerging surgical treatment for select patients with obstructive sleep apnea (OSA). This study aims to compare outcomes in patients with moderate to severe OSA who underwent HNS surgery (Inspire Medical Systems) and those who underwent traditional airway reconstructive surgery, specifically uvulopalatopharyngoplasty (UPPP). METHODS: Patients who underwent HNS implantation (n = 20), all with moderate to severe OSA, inability to adhere to positive pressure therapy, and compliant with previously published inclusion criteria, were compared to a historical cohort that were intolerant of CPAP with similar inclusion criteria who all underwent UPPP (n = 20) with some also undergoing additional procedures such as septoplasty/turbinate reduction...
March 2, 2018: American Journal of Otolaryngology
Elizabeth B Burgener, Richard B Moss
PURPOSE OF REVIEW: The aim of this study was to describe the newest development in cystic fibrosis (CF) care, CF transmembrane conductance regulator (CFTR) modulator therapies. RECENT FINDINGS: Phase II results showing CFTR modulator triple therapies are more effective than current CFTR modulators. SUMMARY: CFTR modulator therapy targets the protein defective in CF and boosts its function, but the drug must match mutation pathobiology. Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients)...
March 13, 2018: Current Opinion in Pediatrics
P Cordero, J Li, J A Oben
Obesity is the pandemic of the 21st century. Obesity comorbidities, including hypertension, dyslipidaemia and glucose intolerance define metabolic syndrome, which increases mortality risk and decreases the quality of life. Compared with lifestyles (diet and physical activity) and pharmacological interventions, bariatric surgery is by far the most effective treatment for obesity and its comorbidities. This minimally invasive surgical treatment is based on an increase of satiety (by hormonal regulation and decreasing stomach volume) or a decrease in nutrient retention (gastric and/or intestinal resection)...
December 2017: Journal of the Royal College of Physicians of Edinburgh
Rajesh Kumari, Venus Dalal, Garima Kachhawa, Ipshita Sahoo, Rajesh Khadgawat, Reeta Mahey, Vidushi Kulshrestha, Perumal Vanamail, J B Sharma, Neerja Bhatla, Alka Kriplani
Background: Gestational diabetes mellitus (GDM) is defined as a carbohydrate intolerance first diagnosed in pregnancy and may be associated with adverse maternal and perinatal outcome. Aim: The aim of the study was to determine the maternal and perinatal outcome in GDM during pregnancy. Materials and Methods: It is a retrospective analysis of women diagnosed with GDM who got antenatal care and delivered in our hospital in previous 5 years...
January 2018: Indian Journal of Endocrinology and Metabolism
Margaret O Murphy, Joseph B Herald, Jacqueline Leachman, Alejandro Villasante Tezanos, Dianne M Cohn, Analia S Loria
.: Exposure to early life stress (ELS) is associated with behavioral-related alterations, increases in body mass index and higher systolic blood pressure in humans. Postnatal maternal separation and early weaning (MSEW) is a mouse model of neglect characterized by a long-term dysregulation of the neuroendocrine system. OBJECTIVES: Given the contribution of adrenal-derived hormones to the development of obesity, we hypothesized that exposure to MSEW could contribute to  the worsening of cardiometabolic function in response to chronic high-fat diet (HF) feeding by promoting adipose tissue expansion and insulin resistance...
February 23, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Ramesh Khadka, Wei Jun Tian, Hao Xin, Rakshya Koirala
To review literature addressing determination of the risk factor, early diagnosis and overall survival on outcome among patient of pancreatic cancer associated with diabetes mellitus from the perspective of pancreatic surgery. To identify recent guidelines, clinical pathogenesis, pathological classification, screening methodology and advances in surgical management. It identifies those clinical and surgical variables to predict excellent prognosis in respect of life style changes, ongoing advancement in therapeutic and surgical treatment and postoperative follow up...
March 10, 2018: International Journal of Surgery
Takehiro Kato, Katsumi Iizuka, Ken Takao, Yukio Horikawa, Tadahiro Kitamura, Jun Takeda
We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild-type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. A thirty percent sucrose diet feeding did not affect phenotypes in KO...
March 12, 2018: Nutrients
Miguel A Lanaspa, Ana Andres-Hernando, David J Orlicky, Christina Cicerchi, Cholsoon Jang, Nanxing Li, Tamara Milagres, Masanari Kuwabara, Michael F Wempe, Joshua D Rabinowitz, Richard J Johnson, Dean R Tolan
Increasing evidence suggests a role for excessive intake of fructose in the Western diet as a contributor to the current epidemics of metabolic syndrome and obesity. Hereditary fructose intolerance (HFI) is a difficult and potentially lethal orphan disease associated with impaired fructose metabolism. In HFI, the deficiency of a particular aldolase, aldolase B, results in the accumulation of intracellular phosphorylated fructose thus leading to phosphate sequestration and depletion, increased ATP turnover and a plethora of conditions leading to clinical manifestations including fatty liver, hyperuricemia, Fanconi syndrome and severe hypoglycemia...
March 13, 2018: Journal of Clinical Investigation
Long The Nguyen, Hui Chen, Crystal Mak, Amgad Zaky, Carol Pollock, Sonia Saad
Recent studies indicate that SIRT1, an important metabolic sensor and regulator of lifespan, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high-fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (SRT, 25mg/kg/2days i...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yoshiya Tanaka, Tsutomu Takeuchi, Masayoshi Harigai, Hisashi Yamanaka, Toshikazu Nakano, Koshiro Akagi, Yoshifumi Ukyo, Benjamin Hsu
Objective To evaluate the efficacy and safety of sirukumab, a human anti-interleukin 6 monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy. Methods This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed...
March 13, 2018: Modern Rheumatology
John W Wax, Amy W An, Nicole Kosier, Timothy E Quill
Voluntary stopping of eating and drinking (VSED) is a deliberate, self-initiated attempt to hasten death in the setting of suffering refractory to optimal palliative interventions or prolonged dying that a person finds intolerable. Individuals who consider VSED tend to be older, have a serious but not always imminently terminal illness, place a high value on independence, and have significant illness burden. VSED can theoretically be performed independent of clinician assistance and therefore avoids many of the ethical and legal concerns associated with physician-assisted dying or other palliative measures of last resort, However, VSED is an intense process fraught with new sources of somatic and emotional suffering for individuals and their caregivers, so VSED is best supervised by an experienced, well-informed clinician who can provide appropriate pre-intervention assessment, anticipatory guidance, medical treatment of symptoms, and emotional support...
March 2018: Journal of the American Geriatrics Society
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