Levothyroxine Sodium

The annual meeting of the Radiological Society of North America was held from Dec. 1 to 5 in Chicago, drawing participants from around the world, including radiologists, radiation oncologists, physicists in medicine, radiologic technologists, and other health care professionals. The conference featured scientific papers from a number of subspecialties covering the newest trends in radiological research, as well as education and informatics exhibits. In an observational study, Elena Ghotbi, M.D., of the Johns Hopkins University School of Medicine in Baltimore, and colleagues identified an association between bone loss and levothyroxine, the second most commonly prescribed medication among older adults in the United States. The association did not include an increased prevalence of clinically significant low bone density, such as rates of osteoporosis. The authors aimed to determine if levothyroxine use and higher thyroid hormone levels within the reference range were associated with higher bone loss with normal thyroid function. Data from the prospective, observational, Baltimore Longitudinal Study of Aging were evaluated. During a median follow-up of 6.3 years, the researchers found that levothyroxine use was associated with greater loss of total body bone mass and bone density, even in participants with thyroid-stimulating hormone (TSH) levels within the normal range and when accounting for baseline TSH and other risk factors. Data also indicated that levothyroxine may be prescribed in some older adults when it is not truly indicated. However, to establish causality and clarify the potential long-term musculoskeletal risks of levothyroxine use in this population, further research, including randomized trials, is necessary, according to the authors. "While it is too early to draw clinical conclusions based on these preliminary observational findings, the study raises important questions. For instance, thyroid hormone is sometimes initiated in patients who do not have hypothyroidism, such as for managing symptoms despite normal hormone levels," Ghotbi said. "Patients with concerns should consider discussing their diagnosis and treatment goals with their health care provider to ensure the appropriateness of their therapy." Press Release In another study, Kevin C. Yu, of the Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues found that concussions are related to reduced cortical excitability in the frontal cortex, which is associated with worse cognitive function. The authors collected preseason and postseason resting-state magnetoencephalography data to identify the impacts of concussions on aperiodic activity. The Post-Concussive Symptom Inventory, a clinical evaluation tool for concussions, was used to correlate preseason and postseason physical, cognitive, and behavioral symptoms. The researchers found that concussion reduces cortical excitability in parts of the brain important for cognitive function, like attention. These concussion-related changes in cortical excitability were also associated with worse cognitive symptoms. "We believe these findings are important, both because they provide insight into the mechanisms and clinical implications of concussion in the adolescent brain, and because they may inform recommendations for clinical monitoring and intervention strategies for individuals with head trauma," Yu said. "This study highlights the importance of monitoring the brain signaling of adolescents carefully after any head injury and taking concussion seriously. It also underscores the importance of protective measures in sports and ensuring that young adults take the necessary time to fully recover before returning to play." Press Release Mahsa Dolatshahi, M.D., of the Mallinckrodt Institute of Radiology at the Washington University School of Medicine in St. Louis, and colleagues found that visceral adipose tissue, or deep belly fat -- but not other types of fat -- plays a role in the hallmark pathologies of Alzheimer disease. The authors evaluated 80 cognitively normal middle-aged individuals who underwent brain positron emission tomography, body magnetic resonance imaging (MRI), metabolic assessment, and blood lipid level evaluation. The researchers found that visceral adiposity mediated the link between high body mass index (BMI) and amyloid deposition in the brain, and is likely linked to early tau pathology, independent of BMI. While high BMI, as the classic definition of obesity, is important, it is not the whole story, as other types of fat or muscle mass are not particularly linked to these pathologies, the authors note. They stress that modification of visceral adiposity, coupled with dyslipidemia, should be the focus of interventions for brain health-related outcomes. The effect of visceral fat on amyloid accumulation is partly mediated by lower high-density lipoprotein. "The impacts on clinical practice for now are mostly limited to suggestions at preventive levels for modifying excess body fat," Dolatshahi said. "We need more longitudinal and interventional studies to understand the effects of different lifestyle and social determinants in visceral adiposity and brain health." Press Release Marianne Nabbout, M.D., of the University of Arkansas for Medical Sciences in Little Rock, and colleagues found that one episode of electronic cigarette inhalation can have an acute and measurable effect on vascular beds. The researchers aimed to demonstrate the acute effects of tobacco smoking and nicotinized and nonnicotinized e-cigarette vaping on vascular function among healthy smokers and vapers using quantitative MRI. Study participants underwent two MRI exams, one before and one after each of the following smoking/vaping episodes: tobacco cigarette, e-cigarette aerosol with nicotine, and e-cigarette aerosol without nicotine. Following nicotinized and nonnicotinized e-cigarette vaping challenges, baseline venous oxygen saturation significantly decreased in the superficial femoral vein, which suggests an immediate decrease in the uptake of oxygen by the lungs following e-cigarette smoking. In the superficial femoral artery, the time of forward flow (the duration of monophasic waveform during reactive hyperemia that occurs due to decreased microvascular resistance) was significantly decreased following both nicotinized and nonnicotinized e-cigarette vaping challenges. Following inhalation of each type of vaping or smoking, there was a significant decrease seen in the resting blood flow velocity in the superficial femoral artery. The hyperemic index (at the superficial femoral artery) was significantly decreased following nicotinized e-cigarette vaping. "These observations may suggest depressed hyperemia in the femoral artery following induced ischemia via cuff occlusion at the level of the upper thigh," Nabbout said. "The reason we saw significant effects following nonnicotinized electronic cigarette vaping may be due to the presence of harmful constituents other than nicotine. The study is ongoing to acquire more data. The larger the sample size, the more likely we are to detect statistically significant effects." Press Release Keegan Staab, of the University of Iowa in Iowa City, and colleagues identified a link between lung function and brain function in patients with long COVID that could lead to a better understanding of the mechanisms responsible for the persistent dyspnea and cognitive symptoms observed after COVID-19 infection. The researchers aimed to gain insight into the link between pulmonary MRI gas exchange, structural and functional brain MRI, and cognition among patients with long COVID. They found that pulmonary gas exchange measured using hyperpolarized xenon MRI was related to cognitive function assessed using the National Institutes of Health Toolbox and brain perfusion measured via MRI. "Previous work has attributed perceived cognitive deficits to psychological distress rather than an underlying disease process," Staab said. "Our data provide evidence that this may not be the case and could be caused by underlying physiological and persistent lung abnormalities." Press Release RSNA: Opportunistic Assessment of Aortic Calcium Predicts MACE MONDAY, Dec. 9, 2024 -- A fully automated algorithm to quantify aortic artery calcification on computed tomography scans performed for other clinical purposes can predict the risk for subsequent major adverse cardiovascular events, according to a study presented at the annual meeting of the Radiological Society of North America, held from Dec. 1 to 5 in Chicago. Read Full Text RSNA: Genicular Artery Embolization Effective, Safe for Knee Osteoarthritis FRIDAY, Dec. 6, 2024 -- Genicular artery embolization is effective and safe for reducing osteoarthritis symptoms among patients with knee osteoarthritis that is refractory to conservative therapy, according to a study presented at the annual meeting of the Radiological Society of North America, held from Dec. 1 to 5 in Chicago. Read Full Text RSNA: Obesity, VAT Linked to Measures of Amyloid Burden in Midlife WEDNESDAY, Dec. 4, 2024 -- Obesity and visceral fat are associated with measures of amyloid burden in the brain among cognitively normal midlife individuals, according to a study presented at the annual meeting of the Radiological Society of North America, held from Dec. 1 to 5 in Chicago. Read Full Text RSNA: Silicosis Often Missed in Engineered Stone Countertop Workers TUESDAY, Dec. 3, 2024 -- Few primary clinicians or radiologists recognize silicosis among engineered stone countertop workers, according to a study presented at the annual meeting of the Radiological Society of North America, held from Dec. 1 to 5 in Chicago. Read Full Text RSNA: Levothyroxine Tied to Bone Loss Over Time in Older Adults MONDAY, Nov. 25, 2024 -- Levothyroxine use is associated with longitudinal loss of bone mass and density in older adults, according to a study scheduled to be presented at the annual meeting of the Radiological Society of North America, held from Dec. 1 to 5 in Chicago. Read Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

虽然K药的销售表现让人瞩目，2022年销售额突破了200亿美元，但依然没有撼动药王的地位。虽然修美乐已经接近生命周期的终点，但仍以212.4亿美元的销售额成功卫冕。截止目前，修美乐已累计为雅培/艾伯维创造了2100亿美元的销售收入，尽管受专利悬崖影响而未来销售额持续下滑，但总累计销售额依然有望突破2500亿美元。然而，如此吸金的品种，却是在并购交易中白菜价捡到的，为什么雅培偏偏是这一个幸运的宠儿？在此，笔者就跟广大读者聊聊其背后的故事。 一、故事从失意的雅培说起 20 世纪80 年代，因为布局康复产品和积极对外合作，雅培得到了很好的发展，但在90 年代初期，雅培的制药业务除了丙戊酸钠，依然没有特别像样的产品，在1990年的全球药品销售额排名中，雅培排在15名以外，处方药销售额还不到20亿美元。尽管如此，公司发展创新药的决心很坚定，从20世纪80年代开始，雅培的研发投入一直稳步增长，1990年的研发投入达到了5.7亿美元，与默沙东、百时美施贵宝等当时的美国一线制药巨头相差无几。随着研发投入的逐渐增大，雅培在20世纪90年代陆续收获了几个非常有潜力的产品：1991年，新一代红霉素类抗生素Biaxin（克拉霉素）获批上市，1994年吸入麻醉剂七氟烷又获得FDA 批准，1997年抗病毒药Norvir（利托那韦）成功推出，尤其是克拉霉素还成为一个“重磅炸弹”药物。除此以外，与武田联合开发的Lupron（亮丙瑞林）和Prevacid（兰索拉唑）持续走俏，每年销售额高达20亿美元。 虽然新药研发取得了不错的成绩，但销售额并没有实现像20世纪80年代一样的高速增长，一方面是七八十年代推出的产品专利陆续到期，另一方面是研发不再像80年代那么高产，除此以外，武田在1997年宣布要在美国自建营销管线，不再续签下一个十年的产品代销合同，这将让雅培每年丧失高达20 亿美元的销售额。增长乏力，股票低迷，雅培公司面临着被对手吞并的危险。为了摆脱窘境，雅培走向了兼并之路。 1999年，诊断部门的高级副总裁Miles D. White 接管了帅印。White是一位能够放开手脚做事情的人，在他的带领下，雅培之前“求稳图存”的发展模式彻底被改变。还在领导权的过渡期，White就以2.34亿美元的价格收购了诊断设备制造商Murex Technologies，进一步加强雅培的诊断部门。尽管White 是放开手脚做事情的人，但也并非为追求规模一味地兼并，在兼并的同时也强调拆分，以实现资金平衡，业务稳步发展。通过几次医疗和诊断业务的并购，雅培的诊断和医疗用品的销售额在1999年达到52.5亿美元，加之国际业务高速发展，总营收达到132亿美元，相比1990年的62亿美元翻了2倍多。 虽然总销售额实现了高速增长，但是制药业务的境地却异常尴尬，出于武田不再续签合同的原因，雅培90年代的药品销售额并没有大幅上涨，1999年总销售额仅为24亿美元。为了加强制药业务，White也在积极寻找合适的标的。1999年6月，雅培宣布以价值73 亿美元股票为代价，向载药巨头ALZA 发起收购邀约，但遗憾的是这笔交易因雅培的股票暴跌而告吹。收购ALZA失败之后，White又迅速把目光转向了化工巨头BASF，最终在2000年以69亿美元的价格拿下BASF的制药部门Knoll。 二、无意中捡到药王 因为雅培收购BASF的制药部门，药王修美乐（阿达木单抗）终于可以出场了。修美乐是一种靶向作用于肿瘤坏死因子α（TNF-α）的单克隆抗体，也是人类历史上首个全人源化的单克隆抗体。因为阿达木单抗的出现，雅培/艾伯维的命运彻底被改写。 70年代以后，因为三次石油危机，很多化工巨头都大规模布局了制药业务，BASF作为化工界的“扛把子”自然也有一个相当体量的制药部门，即Knoll pharm。Knoll的产品线中拥有左甲状腺素钠（Synthroid）、西布曲明（Meridia）、妥洛特罗贴剂（Hokunalin Patch）等产品，1999年的药品销售额达25亿欧元，规模不比雅培的制药部门小。不过当时的Knoll因为左甲状腺素钠在美国长期受官司困扰，BASF在1999年不得不支付1.35亿美元的和解费。因为和解诉讼，BASF才浮现出剥离Knoll的想法。另外，当时制药业与化工业的差异越来越大，化工巨头老套的运作思路已经显得力不从心，很多化工巨头都剥离了自己的制药业务，这更加坚定了BASF剥离Knoll的决心。 当时的Knoll与雅培的特点很像，都是擅长做成熟药品的公司，创新药研发并没有被集团寄予厚望。但就这么一家公司，他们早在1993年就开始与Cambridge Antibody Technology Group（CAT）合作。当时的CAT处于初创阶段，财务状况非常拮据，Knoll在1993-1994年间给了CAT很大的帮助。虽然当时的Knoll对TNF-α抗体比较感兴趣，但阿达木单抗直到1997年才被筛选出来，随后Knoll顺理成章地获得了阿达木单抗的全球开发权益。 起初，人们对阿达木单抗的期待只是拿下类风湿性关节炎的适应症，虽然当时治疗类风湿性关节炎的药品不多，但市场也很小，阿达木单抗并没有被给予厚望，所以在收购中，阿达木单抗并不是估值的重点。1999年，阿达木单抗开始启动2期试验，但2期研究还没有结束，BASF因为左甲状腺素钠的官司而欲急着脱手Knoll。2000年，雅培将这个年销售额达25亿欧元的公司，仅用了69亿美元的代价就收入了囊中，阿达木单抗纯属意外的收获。直到2002年，阿达木单抗治疗类风湿性关节炎的3期临床试验才结束，当时雷曼兄弟的分析师们预测该产品在美国的销售额峰值只有6亿美元，美国以外地区仅为3亿美元，美林证券的悲观分析师更是一语惊人，他们预测修美乐在2010年的销售额仅为3100万英镑，另外，荷兰银行分析师为修美乐给出的2007年销售额预测值也只有3.9亿美元…… 虽然分析师们普遍不看好，但并没有影响White持续开发阿达木单抗的决心，雅培在收购Knoll以后的几年里，先后又从CAT获得了克罗恩病、银屑病等多个自免疫疾病的开发授权。2002年底，修美乐如期获得了FDA批准，但这个全人源化单克隆抗体的销售表现，远远超过了众多分析师的预测，2005年的销售额就已经达到了14亿美元。随后的几年里，阿达木单抗的适应症不断增多，销售表现也不断刷新着人们的认知，并在2011年达到79.3亿美元。 三、最年轻的前三大制药巨头 随着阿达木单抗销售额的快速增长，雅培又收购了Kos Pharma和Solvay（苏威制药）来扩充产品管线，使得雅培很快就进入了全球前十大制药巨头的行列。然而，雅培是一家长期做成熟产品业务的公司，很多“老人”只会做健康品、康复用药、诊断用品和奶粉的生意，他们对高投入，高风险的创新药并不看好。一方面，修美乐虽然销售表现在不断刷新人们的认知，但销售额难以持续增长，而且该产品将在2016年面临专利悬崖，而且雅培创新乏力，研发管线空虚，届时市盈率必将下滑；另一方面，创新药和成熟产品是完全不同的操盘手法，虽然雅培的模式一直在效仿强生，但业务表现远不及强生，因为企业文化和管理矩阵的差异，强生模式并不适用于雅培，雅培两大截然不同的业务都需要专业的管理。 为了避免再次出现80年代后期的管理层纷争，雅培选择了拆分。通过拆分创新药业务，保守派和革新派都能得到满足，两大业务也能得到最专业的管理，同时股东还能从差异化的业务中最大获利，何乐而不为？早在2011年，雅培内部就有人提出要剥离创新药业务，当时也引起了很多媒体的不解。但该新闻最终在2013年成为了现实，雅培将创新药业务剥离除了成为了独立的子公司艾伯维，然后再独立上市。 当时的艾伯维虽然有修美乐撑起门楣，但产品管线非常空虚，而且创新药研发一直处于屡败屡战中挣扎。拆分之后的艾伯维，虽然得到了全部品牌药管线，但分摊到更债务，而雅培则获得更多现金，故起初艾伯维的市盈率不及雅培。但幸运的是，修美乐并没有人们预想的那么短命，虽然2016年开始面临专利悬崖，但生物仿制药仅在欧洲市场出现，美国市场则可延迟到2023年，而且销售额还屡创新高，2021年和2022年的销售额分别高达206.9和212.4亿美元。随着修美乐销售额的持续增长，艾伯维终于用重金砸出了一条像样的产品管线。 雅培/艾伯维市盈率变化（平均） 随着修美乐销售额的持续增长，艾伯维成为了最大的赢家，不但建立起了像样的产品管线，而且还兼并了艾尔建，成功挤入了世界前三大制药巨头的行列，2022年的总销售额高达580.5亿美元，净利润高达144.6亿美元，成为仅次于辉瑞的全球第二大巨头，也是全球最年轻的top 3制药巨头。 三、必然与偶然 看到修美乐今天的成就，不知道BASF有没有哭晕在厕所，但无论如何历史不能重演。虽然制药业是从化工业中衍生出来的，但随着生命科学的不断发展，制药业务的与化工业务的边界变得越来越清晰，制药业不仅要求源源不断的创新，还要拥有强大的疾病认识、理解和管理能力，这是化工巨头们“玩不转”了的根本原因。除了BASF，很多化工巨头也曾屡屡与药王擦肩而过。杜邦在出售制药业务时，把阿哌沙班以白菜价转给了百时美施贵宝，阿克苏诺贝尔也在卖制药业务时，把K药以白菜价卖给了先灵葆雅……这一系列的结果看似偶然，实则是必然，因为化工巨头对疾病认识、理解和管理能力的欠缺，让他们无法对创新药的发展趋势有精准的预判，因为缺乏强大的研发技术，让他们丧失了慧眼识珠的能力。 所以，术业有专攻，多元化并不一定是好事，尤其是那些天马行空的多元化。多元化虽然可以让企业销售额增加，分摊某个业务不可预期性所带来的销售额波动风险，但多元化的缺点也很突出，包括运营成本升高，资源被分散，决策效率降低，现金流压力大，冒然进入不熟悉的多元化领域容易错选产品，错误用人，让企业深陷泥潭，最终丧失了重大的发展机遇。雅培/艾伯维、BASF、杜邦和阿克苏诺贝尔的拆分案例希望广大读者对多元化有进一步的理解。 从另一个角度，有抛必须有接，只有经常交易的人，才能捡到宝…… 药事纵横征稿启事