Cures vs. Profits: Successes in Translational Research by ames Lyons-Weiler

445bda775171a63.jpg Author ames Lyons-Weiler
Isbn 9789814730143
File size 2.3MB
Year 2016
Pages 360
Language English
File format PDF
Category fitness


9846_9789814730136_TP.indd 1 8/3/16 11:14 AM b1816 MR SIA: FLY PAST b1816_FM This page intentionally left blank b1816_FM.indd vi 10/10/2014 1:12:39 PM World Scientific 9846_9789814730136_TP.indd 2 8/3/16 11:14 AM Published by World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore 596224 USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE Library of Congress Cataloging-in-Publication Data Names: Lyons-Weiler, James, author. Title: Cures vs. profits : successes in translational research / James Lyons-Weiler, Institute for Pure and Applied Knowledge, USA. Description: New Jersey : World Scientific, 2016. | Includes bibliographical references and index. Identifiers: LCCN 2015038339| ISBN 9789814730136 (hardcover : alk. paper) | ISBN 9814730130 (hardcover : alk. paper) | ISBN 9789814730143 (paperback : alk. paper) | ISBN 9814730149 (paperback : alk. paper) Subjects: LCSH: Medicine--Research--History. | Medicine--Research--Moral and ethical aspects. | Medical innovations--History. Classification: LCC R852 .L96 2016 | DDC 610.72--dc23 LC record available at British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Copyright © 2016 by World Scientific Publishing Co. Pte. Ltd. All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the publisher. For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher. Printed in Singapore SC - Cures vs. Profits.indd 1 7/12/2015 4:30:11 PM b2282 Cures vs. Profits: Successes in Translational Research “9x6” It is no measure of health to be well adjusted to a profoundly sick society. – Jiddu Krishnamurti The most dangerous man, to any government, is the man who is able to think things out for himself, without regard to the prevailing superstitions and taboos. Almost invariably he comes to the conclusion that the government he lives under is dishonest, insane and intolerable, and so, if he is romantic, he tries to change it. And if he is not romantic personally, he is apt to spread discontent among those who are. — HL Mencken The best doctor gives the least medicine. — Benjamin Franklin It is the responsibility of intellectuals to speak the truth and expose lies. — Noam Chomsky Scientists will save us all. — Johnny Gunther v b2282_FM.indd v 3/8/2016 10:45:22 AM b1816 MR SIA: FLY PAST b1816_FM This page intentionally left blank b1816_FM.indd vi 10/10/2014 1:12:39 PM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Contents Preface ix Abuses in Medicine Outrageous Acts of Pseudoscience Wait… Grapefruit is Bad for You? Hormone Receptor Status and Breast Cancer Treatment Chapter 5 Fecal Microbiota Transplantation Chapter 6 Overdiagnosis of ADHD: It’s Their Mind, Not Yours Chapter 7 Vaccination Programs: Eradication of Infectious Diseases Chapter 8 Chemosensitivity and Chemoresistance Assays in Cancer Chapter 9 A Very Special Kind of Brain Cancer Surgery Chapter 10 Genomics and Personalized Medicine Chapter 11 Robot-Guided Surgery Chapter 12 Hallmarks and Principles of Translational Research Success Chapter 13 Future Medicine 1: Early Detection and Cures for Alzheimer’s Disease Chapter 14 Future Medicine 2: Cancer Vaccines Chapter 15 The Future of Translational Research Postscript: Is Vaccination a Translational Success Story? 241 249 285 307 Index 317 Chapter 1 Chapter 2 Chapter 3 Chapter 4 1 9 17 37 55 63 123 165 183 187 221 231 vii b2282_FM.indd vii 3/8/2016 10:45:22 AM b1816 MR SIA: FLY PAST b1816_FM This page intentionally left blank b1816_FM.indd vi 10/10/2014 1:12:39 PM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Preface An era of progressive, enlightened biomedical research is needed, and these changes must begin with each individual realizing the potential benefits to humanity first, and the bottom line second. The history of medicine is filled with advances that have saved millions of lives and improved the outcome of diseases for millions more. From the invention of X-rays and the discovery of antibiotics to the creation of replacement organs in the lab from stem cells, these are translational successes. Someone had an idea, performed some type of research, and medical care was changed forever — to the betterment of humankind. This not a book about alternative medicine. Alternative medicine, by its very nature, is counterculture. It poses itself against the mainstream, positioning itself in opposition to “Big Pharma.” The positions in this book were formed as the result of my research on the history and recent events, including recent clinical studies, about topics which I thought important, not the other way around. While certain themes on that conflict emerge occasionally in this book, it is not a main theme, although it may prove informative to those on both “sides.” This is a book about successes in translational biomedical research in the face of what I call profit pressures. For example, whether a compound is effective against cancer, or not, is a scientific, empirical question, and if sufficient observational data existed to suggest that certain compounds might kill cancer cells, the compounds therein should be studied, unless prior knowledge of severe toxicity exists. The hurdles that might exist represent barriers to translation. Those hurdles may be found in the processes of science — or in the ix b2282_FM.indd ix 3/8/2016 10:45:22 AM b2282 x Cures vs. Profits: Successes in Translational Research “9x6” Cures vs. Profits: Successes in Translational Research numerous biases of business interests. They may also be found in a given people’s culture. If the compound exists naturally, it might face patent and exclusivity hurdles. If the compound is found in Cannabis, there may be additional cultural hurdles. Ethnobotanists often work with pharmaceutical companies to identify new compounds in plants; the popularity of Cannabis as a recreational drug, however, puts a spin on that plant as pro-Cannabis people want to popularize the drug as something that our government wants to keep from us. There may or may not be truth in such claims, but then, that kind of speculation is not the focus of this book. I start, and end, with the premise that profit alone should never be the primary objective for developing health care options. However, this is also not a book (entirely) about the influence of profit motives on research in academia. That topic is adroitly (and thoroughly) examined by Sheldon Krimsky, who reviews the changes in the operations and cultures within universities in response to the profit motive in his book Science in the Private Interest: Has the Lure of Profits Corrupted Biomedical Research? (Rowman and Littlefield Publishers). This book was written in response to my personal bouts of dread, grief and depression that resulted from my analysis of the international governmental, medical and scientific community’s late, misguided, and awkward response to the 2014 Ebola epidemic. The international events and fiascos surrounding that event are chronicled in my first book, Ebola: An Evolving Story (World Scientific). I was appalled by how wrong we (the collective we) got it, such that it proved difficult to tease out any sensible logic of how ignorance (of the biology of the virus), fear, belief, reason, superstition, dogma, culture, science, and political agendas all played a role in determining public policy. The notable exceptions were, in my view, Dr. Gavin MacGregor-Skinner and Doctors Without Borders. I was dismayed by the unintentional use of de facto concentration camps to isolate diagnosed and suspected ebolavirus disease patients. As the Ebola Treatment Units filled up, the Ebola Triage Camps became isolation camps, dooming many who did not have Ebola to contract the b2282_FM.indd x 3/8/2016 10:45:22 AM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Preface xi disease, and dooming nearly everyone in those camps to either beat the disease on their own, without treatment, or to die. My reaction was to write a second book, in search of silver lining in where we are and what we know in medicine as a result of (mostly) recent research. I started each chapter open-minded about the influences of profit pressures, competition vs. collaboration, remaining objective as long as possible with regard to the actors involved so as to discover, if possible, what some would call the truth. My goal was to provide a sober, logical look at any emergent issues. It did not take too long before I found the limits of knowledge imposing themselves, or, I should say, the limits we impose on what we think we can know via the ways we choose to go about the business of doing science in the name of medicine. In doing research on the very first chapter, I found myself deconstructing the gold standard of the design of the FDA’s sacred randomized clinical trial. I found that a change in how results from RCTs are interpreted may be in order. I have a high standard for science: Knowledge claims must be based on solid assumptions, using robust and reproducible measurements. I will grant that sounds ostentatious; however, it is not the first time in my career that I have developed improvements to the most popular methodologies for doing data analysis for biological and medical sciences. My “hit list” has included advances in methods for: understanding species diversity patterns; phylogenetic data analysis; studying molecular evolution; survival analysis in clinical trials; analysis of genomic data; analysis of proteomic data; identifying statistically significant prediction models using biomarkers; identifying significant differences between clinical groups with respect to survival; predicting the effects of integrating a diversity of methods into a coherent, cost-effective clinical diagnostic workflow; b2282_FM.indd xi 3/8/2016 10:45:22 AM b2282 xii Cures vs. Profits: Successes in Translational Research “9x6” Cures vs. Profits: Successes in Translational Research Next-Generation Sequence (NGS) variant calling; NGS gene expression studies; NGS methylation studies; Low-bias methods for identifying differentially expressed genes and proteins. I have a personal policy, however, and I have followed this policy throughout my career: My understandings of the flaws of the methods involved are made public only once I have found what I believe to be a suitable, demonstrably superior alternative. This was not the case for my assessments of progress in translational research in medicine. This time, I could remain biased, I allowed myself to seek the positive, but still analyze what I encountered with a cold, hard look at many topics in translational research with an open mind. By allowing myself a bias toward finding the silver linings, I would let the negative stories emerge in spite of my efforts to find good news in biomedical research. To that end, any discussion of successes in translational research requires working definitions, both of “translational research (Fig. 1)” and of “successes.” And any viable definition of the terms must capture Fig. 1 Typical view of translational research overview. Knowledge at one phase informs the next. A common view is “Bench to bedside and back,” with the effects in the clinical informing basic and pre-clinical phases. Translational research involves effort at each transition at overcoming pitfalls and hurdles that prevent movement from one phase to the next. Effort between Basic and Pre-clinical is considered T1 effort. Similarly, effort between clinical research and approved therapies is considered T2 effort. b2282_FM.indd xii 3/8/2016 10:45:22 AM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Preface xiii activities involved in the movement of knowledge, i.e., degree of understanding, from one phase to a more advanced phase. It should also address the type of knowledge, and for our purposes, the application of knowledge toward clinical impact. In biomedical research, this may mean improved understanding of the mechanism of a drug, or the molecular basis of a disease. Some measure of the degree of impact of scientific findings on personal and public health is necessary. Most of modern medicine is conducted in the reality of a climate of profit pressure — with significant opportunities for profit. I had to make a choice in setting out in this book: Do I look for examples of successes that include profit (win-win) or do I take an objective approach and provide an overall treatment regardless of, or in some cases, in spite of, profit pressures? Some advances, such as the allotransplantation of olfactory (bulbar) nerves to repair a man’s severed spinal cord — allowing him to walk again (Tabakow et al., 2014) — are easy to identify as successes, but even this clear example has its detractors (see Guest and Dietrich, 2015). Any ethical definition of a measure of the utility in clinical translational research must include, as the majority component, consideration of the effects on the reduction of human pain and suffering via improvements in clinical practices. I leave it to the reader to decide where I landed on the balance of that score, chapter by chapter. This book is meant to be a scholarly treatment that informs a conversation that has been going on in countries around the world, from people in all walks of life, regarding medicine, medical treatment, and medical research. Although medical doctors are at the core of that discussion, they are rarely overtly invited to participate. It would be impolitic to suggest to your physician that you suspect that their intentions are not to cure you of your diseases, but, rather, to keep you sick and on treatment so they may personally profit. The argument, more on point, goes something like this: Medical doctors and the pharmaceutical industry do not want cures for the diseases that afflict us; instead, they want treatments, because if there were cures, they could not profit. b2282_FM.indd xiii 3/8/2016 10:45:23 AM b2282 xiv Cures vs. Profits: Successes in Translational Research “9x6” Cures vs. Profits: Successes in Translational Research Combined with this is the secondary topic of how doctors do not treat diseases, rather, they treat symptoms, often not really knowing what ailment they are treating, and that they perform “diagnosis by treatment” — that is, trying treatments until the patient feels better. In effect, they use the patient in an unregistered clinical trial. These are serious charges being leveled at the medical community; they are trusted with our care, and trusted to reduce our pain and suffering. They are trusted with our very lives. And yet no one has brought the issue forward in a manner that might lead to change within the institutions of medicine and medical research within the US if and when these charges are supported by the facts. Books on closely related topics are often done to pitch so-called “alternative medicine,” and while such books may be somewhat effective at promoting their specific alternative agendas, they are written with an agenda, and not with the objectivity of a scientist. Anyone can find confirming instances to support their claim of what is wrong with a particular brand of modern medicine, thus seemingly bolstering their own alternative treatment. This is not science. It is arguing with statistics. Lining up many confirming instances is not science (Popper). By contrast, I have no particular agenda for this book other than to hopefully open up a dialog among all stakeholders in medicine with an eye on the positive. From the patient to the CEO, my goal is to help bring about changes in our practices and policies that might lead to a larger number of effective and safe medical treatment options for doctors and patients to choose from, thus reducing death due to disease. Most importantly to me personally, these options should reduce human pain and suffering. For some authors, it may be tempting to partake in the nonscientific near hysteria of people questioning the validity of western medicine. A counterculture exists in which suspicion, rumor, and idle speculation fan the flames of discontent. If I were to write a book in that vein, I could expect disdain from my colleagues, whose esteem I hold dear… but  I would expect to sell more books. No, this is no b2282_FM.indd xiv 3/8/2016 10:45:23 AM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Preface xv anti-medicine, anti-science book, either. It is instead an attempt to scrutinize objectively, and explain in simple, understandable terms, a number of important topics in medical research that I believe deserve a wider audience. For each topic, I began my research with an open mind. If, after my research, I have formulated an opinion, one way or the other, on a given topic, I say so. If I have reached a conclusion, I make it clear. Where I have not, I call for more research. Each individual medical doctor has taken the Hippocratic Oath, by which they pledged to “First, do no harm.” Violations of this oath occur on a regular basis. Via this oath and in our placing our lives, and our children’s lives, in their hands, medical doctors share a sacred social contract with the rest of humanity. We place our esteem in them, we give them influence on social matters and public health matters, and we bestow upon them great wealth. While many doctors deserve the respect, social status, and wealth that come with their position, those guilty of egregious instances of abuse should be tried, and if convicted, sentenced. Many Americans believe that for some doctors, the Hippocratic Oath is often made with some qualifiers in fine print, such as “First, do not harm (to profit).” It is not hard to see why; medicine is projected to become a trillion-dollar industry worldwide (Perkowski, 2014). The US is one of only two countries that permit, by law, direct-to-consumer marketing of pharmaceuticals (the other is New Zealand). This book is not about heroes in medicine. That said, some rough estimates of lives saved by advances in specific medical practices and procedures paint the picture of medicine in a more beautiful palette. The website Science Heroes, for example ( reports that blood transfusions are estimated to have saved over one billion people. Their list goes on to report 109 medical heroes, estimated to have saved billions of lives. (The website is a companion to the book Scientists Greater than Einstein (Woodward et al., 2009; Quill Driver Books). So where does the concern over undue profits fit in? While it is true that we are all treated with options that, from a pharmaceutical b2282_FM.indd xv 3/8/2016 10:45:23 AM b2282 xvi Cures vs. Profits: Successes in Translational Research “9x6” Cures vs. Profits: Successes in Translational Research corporation’s standpoint, were deemed potentially profitable, is this a mere fact of reality, or something else? Regardless of the nuances of motive, it means that many potentially effective drugs have not been brought to market. Why? Profitability is certainly a filter that has a homogenizing effect on medicine — our treatment options are much more limited than they could be. This seems to be a perfectly acceptable norm to many. On April 1, 2015, Anne De Groot, CEO of EpiVax, testified before the Blue Ribbon Study Panel on Biodefense at the Hudson Institute in Washington, D.C. Her focus was the need to prioritize innovative, nimble, responsive ways for dealing with existing and new biothreats. Former HHS Secretary Donna Shalala commented on the problems of balancing innovation and manufacturing at large capacities: Sec. Shalala: It’s one of those fundamental questions of what should government be doing, and when does it profit share. We’re talking about vaccines where the margins are smaller than other drugs. De Groot: We have also been able to look at existing vaccines and say ‘Wait a minute, we don’t think this is a good idea.’ There should be a place for us to say that where it’s going to be heard. And really, there’s no one I can talk to. My experience during H1N1 and during H7N9 is that the CDC doesn’t want to hear that. People do not want to hear that the vaccines that they are going to make (are not going to work). The H7N9 vaccine that we have today is the least effective vaccine that’s ever been made... We told you that in 2013 when sequence (of the virus) was published. We published a paper that the virus was a stealth virus, that new vaccines would be ineffective. Less than 10 months later, we were proven right. C-SPAN2 recorded a stream of the proceedings. Another CEO, Daniel Abdun-Nabi, of Emergent BioSolutions, also testified for the need to find a way to fund small companies like De Groot’s to be innovative, but offered that “she’s not going to manufacture.” According to a report in American Progress, Emergent BioSolutions b2282_FM.indd xvi 3/8/2016 10:45:23 AM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Preface xvii received some $1.3 billion from the US government to produce an anthrax vaccine, when it cost them only $250 million to manufacture the vaccine doses. The contrast between EpiVax’s focus and the focus of Emergent BioSolutions at the Blue Ribbon Panel was stark. EpiVax wants to reduce roadblocks and costs so the overall approach can be safe and effective. They are extremely good at predicting whether specific vaccines will likely be effective on emerging infectious diseases. In some ways, they are way ahead of the pack. In reality, they are one step behind. By the time they complete their analyses in response to a threat, the big wheel of the status quo has already started turning, and their input is seen as a distraction. This does not need to be so, of course. The big wheel could easily absorb a priori checks on the computed fit between antigen and antibodies, given the sequence, as first-step screen for existing vaccines likely to (or not to) work. The panel seemed focused on the status quo; Gov. Ridge discussed how government has “always worked this way,” and both he and Sec. Shalala acknowledge the need for some type of reform. They seemed to want somehow to keep the old system in place and add EpiVax’s ideas to the established large-contract process. After the testimony concluded, while the Blue Ribbon panelists were not aware, a microphone was left on which captured the conversation between former HHS Secretary Donna Shalala and Gov. Tom Ridge. Secretary Shalala: He (Daniel Abdun-Nabi) is making a fortune over there (at Emergent BioSolutions CEO). He’s figured out how to do it. She has not figured out a way to do that yet. Gov. Ridge: That was my take-away exactly. Whatever profit model is in play that would transform $250 million in investment into over $1 billion in profit seems par for the course. For others, such outcomes appear to be a necessary evil, but this is partly because we lack an obvious alternative means by which corporations b2282_FM.indd xvii 3/8/2016 10:45:23 AM b2282 xviii Cures vs. Profits: Successes in Translational Research “9x6” Cures vs. Profits: Successes in Translational Research can bring effective products forward. As health care costs skyrocket and Americans are asked to pay for their mandatory health insurance or face a fee, one wonders how the Ebola crisis might have been handled if even half of that $1 billion went into the development of a vaccine. The design of clinical trials is a key to success in medical research. As dry as that topic may be, it also part of the answer to why so few drugs are available to us. It is how medical research is done. Thus, the public should learn some details of how clinical trials are conducted. They should also learn of the limitations that are inherent to clinical trials, and find out whether alternatives to the gold standard might improve rates of discovery and translation, and if so, how. I, and many of my colleagues in research, would like to know that we are treated with options that are considered to be most effective, and safe, for each individual patient. There is, therefore, a movement afoot toward “personalized medicine,” which attempts to secure, based on information gleaned from individual patients, the best possible clinical route for that patient. Personalized medicine is juxtaposed as an alternative to population-based medicine, and yet the entire biomedical research paradigm is centered on population science. Seeing the tree for the forest can be challenging. But individualized medicine is a key to the success of the effective treatment of many of our most deadly diseases. There are thousands of promising pharmaceutical compounds on the shelves at pharmaceutical companies. These are known as “orphan drugs,” and they exist at a loss for companies. In fact, they are often pointed to as justification for the high cost of successful drugs. The argument goes like this: For every drug that actually makes it to market, there are a large number of other drugs that do not; we need to recoup the cost of those investments, too. While it is certainly true that pharma spends billions on R&D, they also spend billions on salaries and bonuses for executives. Also, it is not altogether clear that companies who experience losses due to poor or ineffective exploratory R&D are entitled to recoup their losses. Imagine an ice cream business stating that their high prices were due to all of the flavors they tried out while developing b2282_FM.indd xviii 3/8/2016 10:45:23 AM b2282 Cures vs. Profits: Successes in Translational Research “9x6” Preface xix their blockbuster flavors. The difference is the presumed added value in doing failed research because it could have benefited humanity. However, exactly how much of this failed effort is due to poor practices, or inefficiencies that resulted in profit-taking instead of re-investment, is unknown. Another complicating factor is a trend toward homogenization of health care options. While the capitalist in me appreciates an honestly earned financial incentive just like anyone else, there seems to be a missing financial mechanism that uses consumer demand; consumers are often not free to choose directly (they are rarely told all of the options), and this places the medical community as an arbiter in the economic cycle. On top of that sits a regulatory body that by its very nature restricts treatment options and has moved aggressively to restrict health claims for food products, even when studies strongly support those health claims. While idealists call for collaborative medical research on tough problems, there is a paradox of translation. The more valuable a new approach to medicine is, the more likely a research institution is to keep it a secret. This means that fewer people around the world can study the problem, and increase knowledge. The more ubiquitous a technique or new drug is, the less valuable it is to a single corporate entity, and while many more people can study it, it is less likely it is to be brought forward as a product. Further, as research is a massively parallelized endeavor, it seems likely that some parts of a solution to a medical issue may be known and owned by one entity, while another critical part may be known by others. I have been told by CEOs of some companies that these parts of knowledge often cannot be brought together thanks to the network of lawyers who protect their companies’ intellectual property. At the height of the Great Recession, I proposed an Intellectual Property Share Market (Lyons-Weiler, 2009) to allow investors to drive forward good ideas in biomedicine and other areas allowing the dollars to vote for the IP that might be brought forward. This idea exists in a less formal way via crowdsourced funding; however that approach b2282_FM.indd xix 3/8/2016 10:45:23 AM

Author ames Lyons-Weiler Isbn 9789814730143 File size 2.3MB Year 2016 Pages 360 Language English File format PDF Category Fitness Book Description: FacebookTwitterGoogle+TumblrDiggMySpaceShare Did you ever wonder whether doctors want cures, or just treatments? Did you know … Grapefruit can interact with over 100 drugs, but it may be useful for reducing blood pressure and for weight loss? ADHD over diagnosis is now recognized widely as a fact, and there are existing — and new ways — to avoid a misdiagnosis? Studies have been conducted demonstrating the utility of Omega 3 fatty acids, meditation, yoga, and melatonin for some important symptoms of ADHD, including executive functions? Vaccines have saved millions of lives in the last decade? But are the safe? Breast cancer rates are declining in the US, but have been steadily increasing in Japan? Doctors are getting better at predicting which chemotherapy will, and will not work, on certain cancers? There are vaccines against cancer? This book reviews recent key, hard-won successes and findings from recent biomedical research. Written by one of the most ardent defenders of the public trust in science, it provides an accessible, detailed look at successes in translational biomedical and clinical research. The author provides an optimistic, forward-looking view for the possibility of change for the public good, cutting through the controversy and gets to very core of each topic. The public can be optimistic about the future of medicine, but only if they learn the facts of these advances, and learn what their doctors should be expected to know. Highly referenced, and filled with interviews from experts and people directly involved in the research behind the new facts in each chapter, this book is a rich source of information on advances in biomedicine that you will want to share with your family & friends. Readership: Lay public, scientists, doctors, politicians, policy makers, public health workers, health care worker, investors.     Download (2.3MB) Cervical Cancer Screening in Developing Countries: Report of a WHO Consultation Crowdsourced Health: How What You Do on the Internet Will Improve Medicine Pediatric Cancer Survivors Serotonin and Melatonin: Their Functional Role in Plants, Food, Phytomedicine, and Human Health ACSM’s Complete Guide to Fitness & Health, 2nd Edition Load more posts

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