Ocean Pollution and Human Health

Although it may not be obvious to us in our day-to-day lives, the health of the ocean has significant consequences on human health. For example, 70% of the oxygen we breathe is generated by marine plants. Additionally, 97% of the Earth’s water supply is stored in our oceans. Finally, a huge 30% of the carbon emissions produced by human activity are absorbed by the ocean, demonstrating the two-way nature of the relationship between ocean health and human health. The ocean is vital to the health of humans, and we are vital to the health of the ocean.

Ocean Pollution. Image Credit: Rich Carey/Shutterstock.com

The link between ocean pollution and human health has been downplayed

Ocean pollution is far-reaching and prevailing across waters in all regions of the globe. While recent years have seen human interest in environmental issues peak, the situation of ocean pollution is not improving it is deteriorating. For many decades, scientists have collected evidence that demonstrates the serious impact ocean pollution has on human health. However, the full scope of this threat has not been widely grasped.

A recent project led by Philip Landrigan, the results of which were published in the journal Annals of Global Health in 2020, emphasizes the link between ocean pollution and human health by providing the very first comprehensive assessment of the multiple impacts of ocean pollution on human health.

Many factors contribute to ocean pollution. Humans produce many different kinds of waste, such as agricultural runoff, industrial waste, fertilizers, manufactured chemicals, pharmaceutical chemicals, pesticides, petroleum, plastics, sewage, toxic metals, and urban waste, a large portion of which end up in our oceans. Around 80% of these pollutants enter the ocean from land-based sources via rivers, runoff, deposition from the atmosphere, and dumping.

Here, we outline how distinct types of ocean pollution specifically impact human health.

Plastic pollution

Plastic takes hundreds of years to degrade, and even then, it is not fully decomposed, it remains in the environment in the form of microplastics. These tiny particles that can measure just a few nanometres are becoming more concentrated in our environment. Recent studies have shown that there is now 60 times more microplastic in the ocean than there was just 15 years ago. This presents a significant threat to human health as microplastics have been linked with cancer, reduced fertility, psychological illnesses, and birth defects. Plastics often contain a myriad of toxic chemicals that include neurotoxins, carcinogens, and endocrine disrupters.

A new technique was recently developed by researchers at Arizona State University that allows scientists to detect the presence of microplastics in human tissue. The results were alarming. The team showed that microplastics were detectable in 100% of the tissues sampled. This is concerning as it shows that microplastics are entering the human body and likely accumulating there, where, in greater quantities, they are more likely to cause harm.

Studies have shown that microplastics easily enter the food chain and accumulate in the food we eat, such as fish and shellfish. When we ingest seafood we are also ingesting large amounts of microplastics. Unless plastic pollution is addressed, this problem will likely worsen, with greater amounts of plastic waste ending up in the ocean each year. This may lead to an increase in the prevalence of diseases and illnesses linked with microplastic exposure.

Mercury pollution

Like plastic, mercury is also found in abundance in the ocean. Mercury pollution is most commonly attributed to the use of coal, both domestic and industrial use. Coal naturally contains mercury, when it burns mercury is released into the atmosphere where it eventually ends up in bodies of water and accumulates in the sea. Mercury is a neurotoxin that causes damage to the brain, nervous system, and other organs.

Therefore, mercury pollution presents a major threat to human health. The chemical is known to accumulate in fish that are higher up in the food chain, such as predatory fish like tuna and swordfish. When we eat these fish, mercury can then accumulate in our own bodies.

Mercury exposure has been shown to increase a person’s risk of dementia and heart disease. Additionally, in-utero exposure to the chemical has been shown to cause neurodevelopmental damage and has been shown to reduce IQ and increase the risk of developing autism, ADHD, and other learning disorders.

Coastal pollution

Numerous sources of pollution, such as agricultural runoff, industrial waste, pesticides, and sewage accumulate around the coast, contributing to the problem of coastal pollution. These pollutants cause increases in harmful algal blooms that produce toxins that accumulate in seafood. Studies have shown that ingestion of these toxins in humans can cause amnesia, dementia, paralysis, and even death.

This evidence highlights the important link between ocean health and human health. Humans contribute a significant amount of pollution to our oceans, which in turn negatively impacts human health in multiple ways. Implementing effective strategies to prevent and reduce ocean pollution will be key to protecting human health.

References:

  • Campanale, Massarelli, Savino, Locaputo and Uricchio, 2020. A Detailed Review Study on Potential Effects of Microplastics and Additives of Concern on Human Health. International Journal of Environmental Research and Public Health, 17(4), p.1212. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068600/
  • Landrigan, P., Stegeman, J., Fleming, L., Allemand, D., Anderson, D., Backer, L., Brucker-Davis, F., Chevalier, N., Corra, L., Czerucka, D., Bottein, M., Demeneix, B., Depledge, M., Deheyn, D., Dorman, C., Fénichel, P., Fisher, S., Gaill, F., Galgani, F., Gaze, W., Giuliano, L., Grandjean, P., Hahn, M., Hamdoun, A., Hess, P., Judson, B., Laborde, A., McGlade, J., Mu, J., Mustapha, A., Neira, M., Noble, R., Pedrotti, M., Reddy, C., Rocklöv, J., Scharler, U., Shanmugam, H., Taghian, G., Van de Water, J., Vezzulli, L., Weihe, P., Zeka, A., Raps, H. and Rampal, P., 2020. Human Health and Ocean Pollution. Annals of Global Health, 86(1), p.151. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731724/
  • Microplastic particles now discoverable in human organs. Damian Carrington. The Guardian. Available at: https://www.theguardian.com/environment/2020/aug/17/microplastic-particles-discovered-in-human-organs
  • Vethaak, A. and Legler, J., 2021. Microplastics and human health. Science, 371(6530), pp.672-674. https://science.sciencemag.org/content/371/6530/672

Last Updated: Jul 29, 2021

Sarah Moore

Written by

Sarah Moore

After studying Psychology and then Neuroscience, Sarah quickly found her enjoyment for researching and writing research papers; turning to a passion to connect ideas with people through writing.

Source: Read Full Article

tezepelumab

tezepelumab

Tezepelumab Granted Priority Review By U.S. FDA

THOUSAND OAKS, Calif., July 7, 2021 /PRNewswire/ — Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted a Biologics License Application (BLA) and granted Priority Review for tezepelumab in the treatment of asthma. Tezepelumab is being developed by Amgen in collaboration with AstraZeneca.

The FDA grants Priority Review to applications for medicines that offer significant advantages over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.1 The Prescription Drug User Fee Act goal date for a decision by the FDA is during the first quarter of 2022.

Despite recent advances in severe asthma, many patients may not qualify for or respond well to current biologic medicines.2-5 Patients with severe, uncontrolled asthma experience frequent exacerbations, significant limitations on lung function and a reduced quality of life.2,6,7

“Severe asthma is a challenging, complex disease for physicians and millions of patients and has a high unmet medical need,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “We are proud to advance an innovative, first-in-class monoclonal antibody that targets the top of the inflammatory cascade and represents a potentially transformative treatment option for a broad population of patients with severe asthma. We look forward to bringing tezepelumab to patients as quickly as possible.” 

The BLA was based on results from the PATHFINDER clinical trial program, including results from the pivotal NAVIGATOR Phase 3 trial in which tezepelumab demonstrated superiority across every primary and key secondary endpoint compared to placebo in a broad population of patients with uncontrolled asthma while receiving treatment with medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without oral corticosteroids (OCS).8 There were no clinically meaningful differences in safety results between the tezepelumab and placebo groups in the NAVIGATOR trial.8 The most frequently reported adverse events with tezepelumab were nasopharyngitis, upper respiratory tract infection and headache.8

Results from the NAVIGATOR Phase 3 trial were published in the New England Journal of Medicine in May 2021.

Tezepelumab was granted an FDA Breakthrough Therapy Designation for patients with severe asthma without an eosinophilic phenotype in September 2018.

About Severe Asthma

Globally, there are approximately 2.5 million patients with severe asthma who are uncontrolled or biologic eligible, with approximately 1 million in the U.S. Many patients with severe asthma have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control.2,6,9 Uncontrolled asthma occurs when symptoms persist despite treatment. Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.2,6,9 Patients with severe uncontrolled asthma have twice the risk of asthma-related hospitalizations.10,11 There is also a significant socio-economic burden, with these severe, uncontrolled asthma patients accounting for 50% of asthma-related costs.12

Multiple inflammatory pathways are involved in the pathogenesis of asthma.13-15 Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma.15 These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).16,17 However, many patients do not fit the criteria for eosinophilic or allergic asthma, may have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.17

About the NAVIGATOR and the PATHFINDER Clinical Trial Program
Building on the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program included two trials, NAVIGATOR8,18 and SOURCE.19,20 The program includes additional planned mechanistic and long-term safety trials.21

NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in 1,061 adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without OCS. NAVIGATOR met the primary endpoint with tezepelumab added to standard of care (SoC) demonstrating a statistically significant and clinically meaningful reduction in the annualized asthma exacerbation rate (AAER) over 52 weeks in the overall patient population, compared to placebo added to SoC. The trial also met the primary endpoint in the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER in that patient population. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells pstoper microliter.21,22

NAVIGATOR primary endpoints8

Endpoint

Timepoint

Annual Exacerbation Rate

Results

Tezepelumab added to SoC vs placebo added to SoC

Tezepelumab

Placebo

AAER – overall patient population

Over 52 weeks

0.93 (95% CI: 0.80, 1.07)

2.10 (95% CI: 1.84, 2.39)

56% reduction (95% CI: 47, 63; p<0.001)

AAER – baseline eosinophil counts < 300 cells/µL

Over 52 weeks

1.02 (95% CI: 0.84, 1.23)

1.73 (95% CI: 1.46, 2.05)

41% reduction (95% CI: 25, 54; p<0.001)

CI: confidence interval

NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma irrespective of eosinophils by targeting the thymic stromal lymphopoietin (TSLP). The U.S. Food and Drug Administration Breakthrough Therapy Designation was granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype.

SOURCE is a Phase 3 multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy. In the trial, patients were randomized to receive tezepelumab 210 mg every four weeks or placebo as add-on therapy, with patients maintained on their currently prescribed ICS plus LABA, with or without other asthma controller therapy.

Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue in DESTINATION, a Phase 3 extension trial assessing long-term safety and efficacy.23

About Tezepelumab
Tezepelumab is being developed by AstraZeneca in collaboration with Amgen (see AstraZeneca and Amgen collaboration below) as an investigational, potential first-in-class human monoclonal antibody that works on the primary source of inflammation: the airway epithelium, which is the first point of contact for viruses, allergens, pollutants and other environmental insults. Specifically, tezepelumab targets and blocks thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic and other types of airway inflammation associated with severe asthma.24,25

TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.24,25 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.24,26 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.24,26 By working at the top of the cascade, tezepelumab helps stop inflammation at the source and has the potential to treat a broad population of severe asthma patients.24,26

About the Amgen and AstraZeneca Collaboration
In 2020, Amgen and AstraZeneca updated the 2012 collaboration agreement for tezepelumab. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid-single-digit royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement in North America, Amgen and AstraZeneca will jointly commercialize tezepelumab; Amgen will record sales in the U.S. and AstraZeneca will record sales in Canada.  Outside the U.S., Amgen will record sales as collaboration revenue.

Amgen Inflammation
Amgen brings therapies to millions of people with inflammatory diseases, with a focus on serving unmet patient needs. For those with debilitating moderate to severe rheumatoid arthritis, psoriatic arthritis, moderate to severe plaque psoriasis, ankylosing spondylitis, asthma, and other chronic conditions, the suffering and needs are severe. Complex diseases of inflammation have defied simple solutions, and the breadth of inflammatory disease and the burden patients bear is not well understood.

For more than two decades, Amgen has been committed to advancing the science and the understanding around inflammation to address the unmet patient needs that exist and expanding our portfolio. We lead with science through discovery research that is disease-agnostic and biology-first, modality-second. In doing so, we have introduced and evolved novel therapies that have changed the lives of patients.

Our commitment to patients is reflected not only in where we have succeeded, but in where we have failed and opened new doors. Throughout, we have remained dedicated to the principle of leading with science, pursuing where pathways and promising discoveries in inflammation take us, and not relenting until innovative solutions for patients are found. It’s a commitment that extends beyond introducing novel therapies. We are focused on improving the entire patient journey.

About Amgen 
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or any collaboration to manufacture therapeutic antibodies against COVID-19), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), or the Five Prime Therapeutics, Inc. acquisition, as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems such as the ongoing COVID-19 pandemic on Amgen’s business, outcomes, progress, or effects relating to studies of Otezla as a potential treatment for COVID-19, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including its most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those Amgen projects. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for Amgen to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and Amgen expects similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints Amgen has selected. Amgen develops product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as Amgen may have believed at the time of entering into such relationship. Also, Amgen or others could identify safety, side effects or manufacturing problems with its products, including its devices, after they are on the market.

Amgen’s results may be affected by its ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing its products and global economic conditions. In addition, sales of Amgen’s products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, Amgen’s research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Amgen’s business may be impacted by government investigations, litigation and product liability claims. In addition, Amgen’s business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If Amgen fails to meet the compliance obligations in the corporate integrity agreement between Amgen and the U.S. government, Amgen could become subject to significant sanctions. Further, while Amgen routinely obtains patents for its products and technology, the protection offered by its patents and patent applications may be challenged, invalidated or circumvented by its competitors, or Amgen may fail to prevail in present and future intellectual property litigation. Amgen performs a substantial amount of its commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depends on third parties for a portion of its manufacturing activities, and limits on supply may constrain sales of certain of its current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for Amgen’s manufacturing activities, the distribution of Amgen’s products, the commercialization of Amgen’s product candidates, and Amgen’s clinical trial operations, and any such events may have a material adverse effect on Amgen’s product development, product sales, business and results of operations. Amgen relies on collaborations with third parties for the development of some of its product candidates and for the commercialization and sales of some of its commercial products. In addition, Amgen competes with other companies with respect to many of its marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for Amgen’s products are supplied by sole third-party suppliers. Certain of Amgen’s distributors, customers and payers have substantial purchasing leverage in their dealings with Amgen. The discovery of significant problems with a product similar to one of Amgen’s products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on its business and results of operations. Amgen’s efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology Amgen has acquired, may not be successful. A breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of Amgen’s systems and Amgen’s data. Amgen’s stock price may be volatile and may be affected by a number of events. Global economic conditions may magnify certain risks that affect our business. Amgen’s business performance could affect or limit the ability of the Amgen Board of Directors to declare a dividend or its ability to pay a dividend or repurchase its common stock. Amgen may not be able to access the capital and credit markets on terms that are favorable to it, or at all.

The scientific information discussed in this news release related to Amgen’s product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates.

Further, any scientific information discussed in this news release relating to new indications for Amgen’s products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses.

References

1.US Food and Drug Administration. Priority Review. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. [Last accessed: June 2021].
2.Wenzel S. Severe Asthma in Adults. Am J Respir Crit Care Med. 2005;172;149–60.
3.Peters SP, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. 2006;100:1139-51.
4.Hyland ME, et al. A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma. Explor Res Hypothesis Med. 2019;4:35–38.
5.Tran TN, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116:37–42.
6.Chung KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43: 343–73.
7.Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372.
8.Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809. DOI: 10.1056/NEJMoa2034975.
9.Kupczyk M, Wenzel S. U.S. and European severe asthma cohorts: what can they teach us about severe asthma? J Intern Med 2012;272:121–32.
10.Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 12; 24: 14009.
11.World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available at: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php  [Last accessed: April 2021].
12.Busse WW. Biological Treatments for Severe Asthma: A Major Advance in Asthma Care. Allergol Int 2019; 68: 158–66.
13.Godar M, Blanchetot C, de Haard H, et al. Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs. 2018; 10 (1): 34–45.
14.Rabe KF, Busse W, Pavord I, Castro M. Raising the clinical bar beyond current biologics in uncontrolled persistent asthma: translating emerging data in future clinical decisions. EMJ Allergy Immunol. 2018; 3: 60-9.
15.Peters MC, Mekonnen ZK, Yuan S, et al. Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma. J Allergy Clin Immunol. 2014; 133: 388–94.
16.Clinicaltrials.gov. Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SOURCE) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03406078. [Last accessed: April 2021].
17.Fahy JV. Type 2 inflammation in asthma–present in most, absent in many. Nat Rev Immunol. 2015; 15: 57-65.
18.Menzies-Gow A, et al. NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res. 2020;21:266.
19.Wechsler ME, et al. Oral corticosteroid-sparing effect of tezepelumab in adults with severe asthma. Am J Respir Crit Care Med. 2021;203:A1197.
20.Weschler ME, et al. SOURCE: A Phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of Tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma. Respir Res. 2020;21:264.
21.Diver S, et al. Effect of Tezepelumab on Airway Inflammation in Patients with Moderate-to-Severe Uncontrolled Asthma: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study (CASCADE). Am J Respir Crit Care Med. 2021;203:A1456.
22.Corren J, Bourdin A, Chupp G, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma grouped by baseline blood eosinophil count and fractional exhaled nitric oxide level: results from the NAVIGATOR phase 3 study. Am J Respir Crit Care Med. 2021;203:A1198.
23.Clinicaltrials.gov. Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma (DESTINATION) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03706079. [Last accessed: May 2021].
24.Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. N Engl J Med. 2017;377:936-946.
25.Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
26.Li Y, et al. Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of Severe Refractory Disease. J Immunol. 2018;200:2253–2262.

SOURCE Amgen
 

Posted: July 2021

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tezepelumab FDA Approval History

Source: Read Full Article

Antipsychotics and Heat Stroke

Antipsychotic medications can impairer the body’s ability to regulate its own temperature and hot weather can lead to hyperthermia (heat stroke).

Antipsychotic medications are used to treat psychosis in a variety of psychiatric conditions such as schizophrenia, bipolar disorder, major depression, personality disorder, and agitation in dementia. However, some antipsychotics are also used to treat unrelated issues such as persistent hiccups and problems with balance.

Heatstroke. Image Credit: Antonio Guillem/Shutterstock.com

Schizophrenia and Heat Intolerance

One study aimed to investigate body temperature differences in response to exercise in male schizophrenic patients receiving treatment compared to healthy controls. Interestingly, schizophrenic patients initially had much lower skin temperatures compared to healthy controls before commencing exercise, though core body temperature was not different.

Upon exercise, body temperature rose the fastest and highest in the patient group compared to the control group. Upon rest periods, the temperature fell the most in the control group compared to the patient group suggesting that the patient group had consistently higher temperature throughout.

Indeed, further case studies have also shown the link between antipsychotic medication and heat stroke. A 49-year-old man was admitted to hospital in the summer of 2004 suffering heat stroke and re-admitted a second time the same summer for heat exhaustion. This individual had schizophrenia and diabetes mellitus and was receiving antipsychotic medications including benzhexol, chlorpromazine, and zuclopenthixol decanoate. The conclusion by the physicians was that the heatstroke was due to the medications he was receiving rather than any of his conditions themselves.

Antipsychotics and Impaired Thermoregulation/Heat Intolerance

Heat exhaustion is caused by hyperthermia and is the most common heat-related health condition that is typically non-life threatening and can be managed at home. This tends to occur in people involved in physical activity outdoors during high temperatures. Symptoms are usually brief and include irritability, rapid pulse/heartbeat, rapid breathing, profuse perspiration (sweating), dizziness, nausea, and cramps.

Heatstroke is a serious medical emergency characterized by excessive body temperature >40C, and whist heat stroke can affect anyone, its risk is highly exacerbated in people with chronic conditions and comorbidities and those receiving antipsychotic medications. Symptoms can include confusion, lethargy, coma, and seizures with a rapid pulse/heartbeat.

So, what leads to hyperthermia and heat stroke in those receiving antipsychotic treatments? Many antipsychotic medications tend to have some degree of anticholinergic effects, and these can inhibit sweating and reduce heat elimination from the body. Normally this would not be too much of an issue, but when combined with high temperatures in the summer, this can lead to severely impaired heat loss mechanisms from the body leading to heatstroke.

What to do in Hot Weather

Many antipsychotic medications can impair thermoregulation, largely making individuals susceptible to hyperthermia and heat stroke in high temperatures. As such, individuals receiving antipsychotic medications should exercise extreme caution in hot weather to minimize the risk of both heat exhaustion and heatstroke.

Specific things that people can do to minimize heat exhaustion include:

  • Avoiding overexertion in warmer periods of the day
  • Application of sun cream/lotion
  • Increased intake of fluids to prevent dehydration – avoiding caffeine and alcohol
  • Dressing in lighter clothing – both color and fitting
  • Having regular food intake throughout the day to ensure adequate levels of sugar and salt

In summary, antipsychotic medications used to treat a variety of conditions can make individuals more susceptible to heat intolerance, heat exhaustion, and even heat stroke – especially in hotter weather. It is therefore advised that people receiving such medications exercise caution in the hot weather to minimize their risk of developing heat exhaustion.

References:

  • Kwok & Chan, 2005. Recurrent heat-related illnesses during antipsychotic treatment. Ann Pharmacother. 39(11):1940-2. https://pubmed.ncbi.nlm.nih.gov/16174785/
  • Hoffman et al, 2016. Heat stroke during long-term clozapine treatment: should we be concerned about hot weather? Trends Psychiatry Psychother. 38(1):56-9. https://pubmed.ncbi.nlm.nih.gov/27074342/
  • Hermesh et al, 2000. Heat intolerance in patients with chronic schizophrenia maintained with antipsychotic drugs. Am J Psychiatry. 157(8):1327-9. https://pubmed.ncbi.nlm.nih.gov/10910799/

Further Reading

  • All Brain Content
  • Human Brain Structure
  • The Impact of Climate Change on Brain Health
  • Language and the Human Brain
  • An Overview of Brain Development
More…

Last Updated: Jul 19, 2021

Written by

Dr. Osman Shabir

Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield.

Source: Read Full Article

Sun Safety: What Should you Know?

Although spending time outdoors has many benefits including reducing stress, offering options to be physically active, and access to vitamin D, exposing skin to the harmful rays of the sun can raise the risk of skin cancer. Most types of skin cancers result from exposure to ultraviolet (UV) light, which can penetrate to deep levels of the skin, damaging or killing skin cells. However, there are steps that can be taken to protect the skin from the damaging effects of the sun.

Reducing the risk

The most effective way to reduce the risk of skin damage and cancer is to minimize direct skin exposure to the sun:

  • Clothing: Wearing clothing made from a densely woven fabric that covers the skin (such as long-sleeved tops) offers some protection from UV light. Clothing in dark colors is more effective as darker colors absorb more UV light than lighter shades, reducing the amount of UV light that can reach the skin.
  • Hat: Wearing a hat with a wide brim that shades the face, ears, and neck offers the best protection.
  • Sunglasses: Sunglasses protect the thin, sensitive skin surrounding the eyes, but also the eyes themselves. They can mitigate against developing cataracts which can occur if the surface of the eye becomes burned. Reflected sunlight (from water or snow) is particularly dangerous to the eyes. Even when wearing sunglasses, looking directly at the sun should be avoided, as this can cause permanent damage to the eyes.
  • Shades: Avoiding direct sunlight by stays in the shade provides some protection from UV light, but sunscreen and protective clothing should still be worn.
  • Sunscreen: Liberally applying sunscreen with a high sun protection factor (SPF) is important but should not be considered sufficient alone. It is most effective when combined with other sun safety precautions. To be as effective as possible, it should be reapplied frequently and used within its expiration date.

Sun Safety. Image Credit: kordeo/Shutterstock.com

What is the sun protection factor (SPF)?

The sun protection factor (SPF) is one measure of the efficacy of a given sunscreen agent and relates to the degree to which a product protects the skin from the damaging effects of ultraviolet (UV) light. UV radiation has a wide spectrum and is divided into different types of radiation, including UVA and UVB radiation. Exposure to UVA remains constant and has a cumulative effect over time, degrading elastin and collagen, and reducing elasticity.

UVB exposure is increased during the summer months and causes acute skin changes such as sunburn and pigmentation, but also chronic changes such as photocarcinogenesis. Photocarcinogenesis is the result of biochemical changes which lead to skin cancer.

SPF is a measure of the amount of protection from UVB radiation that a sunscreen product offers, measured by the amount of UVB that it absorbs. In 2011, the United States Food and Drug Administration provided a clear formula to calculate SPF. SPF was defined as the dose of UVB required to produce one minimal erythema dose (MED; the lowest dose of UV light needed to cause reddening of the skin) after the application of a sunscreen product, divided by the UV light causing MED on untreated skin.

When applied, this formula shows that an SPF of 15 correlates with 93% UVB absorption, an SPF of 30 relates to 96.7% absorption and an SPF of 50 correlates with 98% UVB absorption.

In the United Kingdom, products also receive a star rating which measures the degree of protection from UVA radiation. Ranging from 0-5, stars indicate the proportion of UVA absorbed by the product compared to UVB. As this system awards stars according to the ratio of protection from both UVA and UVB (with 5 stars indicating that UVA and UVB protection is about the same), a low SPF product can be highly starred.

Therefore, it is important to select a product with both a high SPF and high star rating. A good level of sun protection is a sunscreen with an SPF of 30 and a minimum of 4 stars.

How to apply sunscreen

Sunscreen should be applied liberally. If it is applied too thinly, it may not offer the purported amount of SPF. It should be applied to all areas of exposed skin, ideally twice: 30 minutes before sun exposure, and again before exposure.

It should be reapplied frequently, approximately every two hours, and immediately after swimming, showering, sweating, or towel drying, even if it is labeled as water-resistant.

Top sun safety tips

  • Protect skin with clothing, including a hat, t-shirt, and sunglasses, and always choose a sunscreen product of at least SPF 30. Sunscreen should be applied generously and frequently.
  • Ensure that you never allow the skin to burn.
  • Spend time under shade during the middle part of the day when the sun is at its strongest.
  • Take extra care with children and keep babies and toddlers out of direct sunlight.

References:

  • Dale Wilson, B., Moon, S., & Armstrong, F. (2012). Comprehensive review of ultraviolet radiation and the current status on sunscreens. The Journal of clinical and aesthetic dermatology, 5(9), 18–23.
  • Latha, M. S., Martis, J., Shobha, V., Sham Shinde, R., Bangera, S., Krishnankutty, B., Bellary, S., Varughese, S., Rao, P., & Naveen Kumar, B. R. (2013). Sunscreening agents: a review. The Journal of clinical and aesthetic dermatology, 6(1), 16–26.
  • Ma, Y., & Yoo, J. (2021). History of sunscreen: An updated view. Journal of cosmetic dermatology, 20(4), 1044–1049. https://doi.org/10.1111/jocd.14004
  • Anon, (2019). Sun Safety. [online] Available at: https://www.cdc.gov/cancer/skin/basic_info/sun-safety.htm.
  • www.bad.org.uk. (n.d.). British Association of Dermatologists – Sunscreen Fact Sheet. [online] Available at: https://www.bad.org.uk/skin-cancer/sunscreen-fact-sheet.

Last Updated: Jun 18, 2021

Written by

Clare Knight

Since graduating from the University of Cardiff, Wales with first-class honors in Applied Psychology (BSc) in 2004, Clare has gained more than 15 years of experience in conducting and disseminating social justice and applied healthcare research.

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KHN’s ‘What the Health?’: The Return of the Public Option

Can’t see the audio player? Click here to listen on SoundCloud. You can also listen on on Spotify, Apple Podcasts, Stitcher, Pocket Casts or wherever you listen to podcasts.

The “public option” is back — both in Washington, D.C., and the states. President Joe Biden as a candidate supported the idea of a government-run or heavily regulated insurance plan that would compete with private insurance. But until now it has been more of a concept than a plan. Two top health leaders in Congress say they will try to put a plan together, while public options in various forms work their way through legislatures in Colorado and Nevada.

Meanwhile, bioethicists are debating whether the U.S. should be vaccinating low-risk adolescents against covid-19 while high-risk adults in other countries remain vulnerable.

This week’s panelists are Julie Rovner of KHN, Margot Sanger-Katz of The New York Times, Alice Miranda Ollstein of Politico and Rachana Pradhan of KHN.

Among the takeaways from this week’s podcast:

  • Sen. Patty Murray (D-Wash.) and Rep. Frank Pallone (D-N.J.), who each chair key health committees on Capitol Hill, have put out a request for ideas about the public option. The idea has been championed by many Democrats since it was excluded from the Affordable Care Act, and some lawmakers have introduced bills to set up such a program. The sound bites are appealing but creating such a program would be exceedingly complicated. Murray and Pallone’s initiative is an effort to start a detailed inquiry into what would be needed for a public option and where the political fault lines lie.
  • State efforts to set up public options are generally seen as much less effective than a national program would be.
  • Five Senate Republicans joined Democrats to support the confirmation of Chiquita Brooks-LaSure as administrator of the Centers for Medicare & Medicaid Services. Although the agency isn’t exactly considered a glamour post, it is one of the most influential jobs in government. By controlling spending and administration of both Medicare and Medicaid, as well as the ACA’s insurance marketplaces, the agency controls about a quarter of all federal spending.
  • Early reports of Biden’s first budget suggest that while he will not be putting dollars behind plans to lower Medicare eligibility or establish a government-run public insurance option on the ACA marketplaces, he will acknowledge that those options are goals he would like to see Congress pursue.
  • Biden is also expected to signal he wants federal funding bills to no longer include the Hyde Amendment, a long-standing federal policy to deny government funding for abortion in most cases. Many Democrats have complained that the provision keeps low-income women who have Medicaid insurance or federal workers who are covered through their jobs from securing an abortion if they need it. Republicans have argued that taxpayers shouldn’t have to finance abortion if they are morally opposed to it.
  • New federal data shows that more than 50% of adults have been vaccinated against covid. But the success of the U.S. inoculation campaign is raising questions about what Americans should be doing to help other countries. Some argue that vaccine supplies here should be given to countries that are struggling before many lower-risk people in this country — including children — get their shots.
  • New reports are casting suspicions on the assumption that covid came from a natural transmission from animal to human in China and suggest it may be tied to a viral research lab in Wuhan, China. This could have implications for research protocols in the future and U.S.-Chinese relations on health studies and other issues.

Plus, for extra credit, the panelists recommend their favorite health policy stories of the week they think you should read, too:

Julie Rovner: The New York Times’ “Covid Killed His Father. Then Came $1 Million in Medical Bills,” by Sarah Kliff

Alice Miranda Ollstein: HuffPost’s “Can America Close the COVID Vaccine Race Gap?” by Jonathan Cohn

Margot Sanger-Katz: KHN’s “Corporations Encourage Employee Vaccination but Stop Short of Mandates,” by Anna Almendrala

Rachana Pradhan: The Wall Street Journal’s “Intelligence on Sick Staff at Wuhan Lab Fuels Debate on Covid-19 Origin,” by Michael R. Gordon, Warren P. Strobel and Drew Hinshaw

To hear all our podcasts, click here.

And subscribe to KHN’s What the Health? on Spotify, iTunes, Stitcher, Pocket Casts or wherever you listen to podcasts.

Source: Read Full Article

ublituximab

ublituximab

TG Therapeutics Announces FDA Acceptance of Biologics License Application for Ublituximab in Combination with Ukoniq (umbralisib) as a Treatment for Patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

NEW YORK, May 25, 2021 (GLOBE NEWSWIRE) — TG Therapeutics, Inc. (NASDAQ: TGTX), today announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for ublituximab, the Company’s investigational glycoengineered anti-CD20 monoclonal antibody, in combination with UKONIQ® (umbralisib), the Company’s once-daily, oral, inhibitor of PI3K-delta and CK1-epsilon, as a treatment for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of March 25, 2022. The FDA also notified the Company that it is not currently planning to hold an advisory committee meeting to discuss this application.

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, “We are extremely pleased that the ublituximab BLA has been accepted by the FDA. This is an important milestone for us as it brings us one step closer to our goal of providing a novel combination treatment option to patients with both treatment naive and relapsed or refractory CLL and SLL. We look forward to collaborating with the FDA throughout this review process.”

The BLA submission was based on the results of the UNITY-CLL trial, a global Phase 3 trial evaluating the combination of ublituximab plus UKONIQ (U2) compared to obinutuzumab plus chlorambucil in patients with treatment naive and relapsed or refractory CLL. The U.S. FDA previously granted Fast Track designation to the combination of ublituximab and UKONIQ for the treatment of adult patients with CLL and orphan drug designation for ublituximab in combination with UKONIQ for the treatment of CLL.

ABOUT UNITY-CLL PHASE 3 TRIAL
UNITY-CLL is a global Phase 3 randomized controlled clinical trial comparing the combination of ublituximab plus UKONIQ (umbralisib), or U2, to an active control arm of obinutuzumab plus chlorambucil in patients with both treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial randomized patients into four treatment arms: ublituximab single agent, UKONIQ single agent, ublituximab plus UKONIQ, and an active control arm of obinutuzumab plus chlorambucil. A prespecified interim analysis was conducted to assess the contribution of ublituximab and UKONIQ in the U2 combination arm and allowed for the termination of the single agent arms. Accordingly, the UNITY-CLL Phase 3 trial continued enrollment in a 1:1 ratio into the two combination arms: the investigational arm of U2 and the control arm of obinutuzumab plus chlorambucil. Approximately 420 subjects enrolled to the two combination arms and approximately 60% of patients were treatment-naïve and 40% were relapsed or refractory. The primary endpoint for this study was superior progression-free survival (PFS) for the U2 combination compared to the control arm. The trial met its primary endpoint and results were presented at the American Society of Hematology (ASH) Annual Meeting in December 2020. The UNITY-CLL Phase 3 trial is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA).

ABOUT CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. It is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States in 2020 and approximately 45,000 new cases globally in 2020.1,2 Although signs and symptoms of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of malignant cells.

ABOUT FAST TRACK
Fast Track is a program designed to expedite the development and review of drugs that treat serious conditions and that demonstrate the potential to address an unmet medical need. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy that may be potentially better than available therapy.

A drug that receives Fast Track designation is eligible for more frequent interactions with the FDA, priority review if relevant criteria are met, and rolling submission of the Biologics License Application or New Drug Application.

ABOUT ORPHAN DRUG DESIGNATION
Orphan drug designation is granted by the FDA to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain incentives which may include tax credits towards the cost of clinical trials and prescription drug user fee waivers. If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity.

ABOUT TG THERAPEUTICS, INC.
TG Therapeutics is a fully-integrated, commercial stage biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. In addition to an active research pipeline including five investigational medicines across these therapeutic areas, TG has received accelerated approval from the U.S. FDA for UKONIQ™ (umbralisib), for the treatment of adult patients with relapsed/refractory marginal zone lymphoma who have received at least one prior anti-CD20-based regimen and relapsed/refractory follicular lymphoma who have received at least three prior lines of systemic therapies. Currently, the Company has three programs in Phase 3 development for the treatment of patients with relapsing forms of multiple sclerosis (RMS) and patients with chronic lymphocytic leukemia (CLL) and several investigational medicines in Phase 1 clinical development. For more information, visit www.tgtherapeutics.com, and follow us on Twitter @TGTherapeutics and Linkedin.

UKONIQ® is a registered trademark of TG Therapeutics, Inc.

ABOUT UKONIQ® (umbralisib)
UKONIQ is the first and only oral inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. PI3K-delta is known to play an important role in supporting cell proliferation and survival, cell differentiation, intercellular trafficking and immunity and is expressed in both normal and malignant B-cells. CK1-epsilon is a regulator of oncoprotein translation and has been implicated in the pathogenesis of cancer cells, including lymphoid malignancies. 

UKONIQ is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen and for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

These indications are approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORANT SAFETY INFORMATION
Infections: Serious, including fatal, infections occurred in patients treated with UKONIQ. Grade 3 or higher infections occurred in 10% of 335 patients, with fatal infections occurring in <1% . The most frequent Grade ≥3 infections included pneumonia, sepsis, and urinary tract infection. Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) and consider prophylactic antivirals during treatment with UKONIQ to prevent CMV infection, including CMV reactivation. Monitor for any new or worsening signs and symptoms of infection, including suspected PJP or CMV, during treatment with UKONIQ. For Grade 3 or 4 infection, withhold UKONIQ until infection has resolved. Resume UKONIQ at the same or a reduced dose. Withhold UKONIQ in patients with suspected PJP of any grade and permanently discontinue in patients with confirmed PJP. For clinical CMV infection or viremia, withhold UKONIQ until infection or viremia resolves. If UKONIQ is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly.

Neutropenia: Serious neutropenia occurred in patients treated with UKONIQ. Grade 3 neutropenia developed in 9% of 335 patients and Grade 4 neutropenia developed in 9%. Monitor neutrophil counts at least every 2 weeks for the first 2 months of UKONIQ and at least weekly in patients with neutrophil count <1 x 109/L (Grade 3-4) neutropenia during treatment with UKONIQ. Consider supportive care as appropriate. Withhold, reduce dose, or discontinue UKONIQ depending on the severity and persistence of neutropenia.

Diarrhea or Non-Infectious Colitis: Serious diarrhea or non-infectious colitis occurred in patients treated with UKONIQ. Any grade diarrhea or colitis occurred in 53% of 335 patients and Grade 3 occurred in 9%. For patients with severe diarrhea (Grade 3, i.e., > 6 stools per day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, or peritoneal signs, withhold UKONIQ until resolved and provide supportive care with antidiarrheals or enteric acting steroids as appropriate. Upon resolution, resume UKONIQ at a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue UKONIQ. Discontinue UKONIQ for life-threatening diarrhea or colitis.

Hepatotoxicity: Serious hepatotoxicity occurred in patients treated with UKONIQ. Grade 3 and 4 transaminase elevations (ALT and/or AST) occurred in 8% and <1%, respectively, in 335 patients. Monitor hepatic function at baseline and during treatment with UKONIQ. For ALT/AST greater than 5 to less than 20 times ULN, withhold UKONIQ until return to less than 3 times ULN, then resume at a reduced dose. For ALT/AST elevation greater than 20 times ULN, discontinue UKONIQ.

Severe Cutaneous Reactions: Severe cutaneous reactions, including a fatal case of exfoliative dermatitis, occurred in patients treated with UKONIQ. Grade 3 cutaneous reactions occurred in 2% of 335 patients and included exfoliative dermatitis, erythema, and rash (primarily maculo-papular). Monitor patients for new or worsening cutaneous reactions. Review all concomitant medications and discontinue any potentially contributing medications. Withhold UKONIQ for severe (Grade 3) cutaneous reactions until resolution. Monitor at least weekly until resolved. Upon resolution, resume UKONIQ at a reduced dose. Discontinue UKONIQ if severe cutaneous reaction does not improve, worsens, or recurs. Discontinue UKONIQ for life-threatening cutaneous reactions or SJS, TEN, or DRESS of any grade. Provide supportive care as appropriate.

Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5: UKONIQ contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons, frequently in patients who also have aspirin hypersensitivity.

Embryo-fetal Toxicity: Based on findings in animals and its mechanism of action, UKONIQ can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males with female partners of reproductive potential to use effective contraception during treatment and for at least one month after the last dose.

Serious adverse reactions occurred in 18% of 221 patients who received UKONIQ. Serious adverse reactions that occurred in ≥2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). Permanent discontinuation of UKONIQ due to an adverse reaction occurred in 14% of patients. Dose reductions of UKONIQ due to an adverse reaction occurred in 11% of patients. Dosage interruptions of UKONIQ due to an adverse reaction occurred in 43% of patients.

The most common adverse reactions (>15%), including laboratory abnormalities, in 221 patients who received UKONIQ were increased creatinine (79%), diarrhea-colitis (58%, 2%), fatigue (41%), nausea (38%), neutropenia (33%), ALT increase (33%), AST increase (32%), musculoskeletal pain (27%), anemia (27%), thrombocytopenia (26%), upper respiratory tract infection (21%), vomiting (21%), abdominal pain (19%), decreased appetite (19%), and rash (18%).

Lactation: Because of the potential for serious adverse reactions from umbralisib in the breastfed child, advise women not to breastfeed during treatment with UKONIQ and for at least one month after the last dose.

Please visit www.tgtherapeutics.com/prescribing-information/uspi-ukon for full Prescribing Information and Medication Guide.

__________________________________________________
1 Cancer Stat Facts: Leukemia — Chronic Lymphocytic Leukemia (CLL). National Cancer Institute Surveillance, Epidemiology, and End Results Program website. https://seer.cancer.gov/statfacts/html/clyl.html. Accessed October 26, 2020.
2 EpiCast Report: Chronic Lymphocytic Leukemia – Epidemiology Forecast to 2025. Available at: https://store.globaldata.com/report/gdhcer164-17–epicast-report-chronic-lymphocytic-leukemia-epidemiology-forecast-to-2025/.

Cautionary Statement
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to the BLA submission of ublituximab in combination with UKONIQ® (umbralisib), the FDA review and potential approval of the BLA and the timing thereof, the potential benefits, safety and efficacy of ublituximab in combination with UKONIQ in CLL, the clinical development of our product candidates, and anticipated milestones. In addition to the risk factors identified from time to time in our reports filed with the U.S. Securities and Exchange Commission, factors that could cause our actual results to differ materially are the following: the risk that the FDA will not approve the BLA submission; the risk that fast track designation may not actually lead to a faster regulatory review or approval process; the risk that safety issues or trends will be observed in the UNITY-CLL study or in other studies that prevent approval of ublituximab in combination with UKONIQ; the risk that ublituximab in combination with UKONIQ, or any other product candidates, will not be commercially successful if approved; the risk that the differentiated tolerability profile for UKONIQ previously observed in clinical trials will not be reproduced in the UNITY-CLL trial or any other on-going studies; our ability to successfully and cost effectively complete preclinical and clinical trials; the uncertainties inherent in research and development; and the risk that the ongoing COVID-19 pandemic and associated government control measures have an adverse impact on our research and development plans or commercialization efforts. Further discussion about these and other risks and uncertainties can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2020, as updated by our subsequent Quarterly Reports on Form 10-Q, and in our other filings with the U.S. Securities and Exchange Commission.Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at www.tgtherapeutics.com. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only.

Source: TG Therapeutics

Posted: May 2021

Related Articles

  • TG Therapeutics Completes Rolling Submission of Biologics License Application to the U.S. Food and Drug Administration for Ublituximab in Combination with Ukoniq (umbralisib) as a Treatment for Patients with Chronic Lymphocytic Leukemia – March 29, 2021
  • TG Therapeutics Initiates Rolling Submission of Biologics License Application to U.S. Food and Drug Administration for Ublituximab in Combination with Umbralisib as a Treatment for Patients with Chronic Lymphocytic Leukemia – December 1, 2020

ublituximab FDA Approval History

Source: Read Full Article

COVID-19 and Sickle Cell Disease

Sickle cell disease (SCD) is a genetically inherited blood disorder characterized by the presence of sickled red blood cells (caused by a single mutation) that can get stuck in capillaries and cause clots. People with SCD must receive lifelong treatment and are at a heightened risk from clotting and tissue/organ ischemia. Viral infections (including influenza and COVID-19) can lead to complications in people with SCD.

Sickle Cell Disease (SCD). Image Credit: Kateryna Kon/Shutterstock.com

COVID-19 and SCD

People with SCD are classes as extremely clinically vulnerable (in the UK for example) due to being immunocompromised and are therefore strongly advised to be extremely cautious during the pandemic in adhering to the rules regarding shielding, social distancing, frequent handwashing & mask-wearing when out in public to minimize the risk of contracting COVID-19.

This is because the risk of adverse health effects and complications is greater in people with SCD. People with SCD have impaired immunity which can arise from functional hyposplenism and systemic vasculopathy – all increasing the risk of thrombosis (clotting) – which in itself is a common symptom and complication of COVID-19, especially in younger individuals.

Specific case studies have shown different outcomes depending on whether the SCD patient is of advanced age, has pre-existing comorbidities, or any SCD-related complications within 1-3 years or not. In general, people who have had SCD-related complications and crises close to contracting COVID-19 and/or have 1 or more comorbidities are at a far greater risk of developing more severe COVID-19, ICU admission, and in some cases, death. This is very much in line with influenza infection and disease severity, though the evidence for COVID-19 severity is recent and still emerging.

What is sickle-cell disease?

In one UK study, 6 out of 8 SCD patients with COVID-19 developed an SCD-related vaso-occlusive crisis (VOC) manifested clinically as varying degrees of pain in the body. All patients had hypoxemia and were given oxygen therapy to maintain oxygen SaO2>95%, analgesics for VOC pain, and antibiotics to prevent infection. The majority of these patients made a full recovery except 1 patient who had pre-existing comorbidities (previous stroke).

Another UK study saw 9 out of 10 SCD-COVID positive patients recovered without intensive treatment. 5 of the patients simply received oxygen and/or simple transfusions for their SCD, whilst the other 5 were supported at home without hospitalization and offered regular transfusions and hydroxyurea for their SCD. The one patient that died also suffered from severe asthma, lymphopenia, thrombocytopenia, and elevated C-reactive protein (CRP) which are all associated with poor COVID-19 outcome generally.

Young & Healthy SCD Patients vs Older & Comorbid Patients

Whilst these 2 limited case studies show that the majority of younger, otherwise healthy (non-comorbid) SCD patients undergoing regular treatment with manageable symptoms tend to recover fully – either at home with regular medications, or with some support in hospital. Where severe complications arise, it is primarily due to age, pre-existing comorbidity (such as previous stroke, clotting, asthma in addition to the common risk factors for severe COVID-19 such as diabetes, hypertension, and lung disease), or the development of a secondary infection. These tend to go on to develop acute chest syndrome (ACS) requiring intubation and transfusion. Whilst some will make full recoveries, unfortunately, a small subset will go on to die.

As the evidence of clinical features of COVID-19 in SCD patients is still fully emerging, there have been some interesting observations. In some cases, COVID-19 may trigger VOC in people with SCD without any noticeable respiratory symptoms, as well as the lack of a fever – both common symptoms otherwise in COVID-19. Furthermore, the incidence of ACS in SCD patients with COVID-19 is now thought to be lower than initially expected, thankfully.

However, this largely applies to younger otherwise healthy SCD individuals, and not those with other conditions, complications poorly managed SCD (delayed treatments), and age. Specific risk factors for more severe combined COVID-19 and SCD are elevated D-dimer and prothrombin levels as well as reduced levels of fibrinogen. Thus, serum-based diagnostic tools should be used routinely to prognose the likelihood of severe disease, and harsher treatment strategies can be used earlier on.

In another study, 75% of 66 SCD patients with COVID-19 required hospitalization of which 7 (10%) died. Those more likely to be hospitalized had pre-existing kidney disease and ACS developed in 60% of those hospitalized (including those that died). The most common symptomatic presentation was that of VOC pain. Of all those that required hospitalization and subsequently died, all of them had pulmonary hypertension, congestive heart failure, chronic kidney disease, and stroke as comorbidities, as well as being over the age of 50. Furthermore, all deaths occurred in patients not taking hydroxyurea or any other SCDdisease-modifying treatment.

COVID-19 Vaccine. Image Credit: siam.pukkato/Shutterstock.com

SCD and COVID-19 Vaccination

As patients with SCD are classed as clinically vulnerable, patients must be vaccinated at the earliest possible opportunity to minimize the risk of contracting COVID-19, and more importantly, reducing the overall risk of severe disease and death. The two main mRNA vaccines; Pfizer and Moderna, have been shown to be extremely safe and effective in the vast majority of people, including those with SCD.

Recently, the Oxford-Astra Zeneca and Johnson & Johnson vaccines have been in the news for their supposed links to increased clotting. However, these events are incredibly rare, and the benefits of vaccination far outweigh the risks associated with vaccination or COVID-19 itself, and therefore even people with SCD are strongly encouraged to get these vaccines, though it can be advisable to talk to your GP or healthcare professional beforehand if you are still unsure.

In summary, patients with SCD who develop COVID-19 are at an increased risk of moderate to severe disease, especially those that are older and those that have pre-existing underlying health conditions (comorbidities).

Sources:

  • Menapace & Thein, 2020. COVID-19 and sickle cell disease. Haematologica. 105(11):2501-2504. https://pubmed.ncbi.nlm.nih.gov/33131239/
  • McCloskey et al, 2020. COVID-19 infection and sickle cell disease: a UK centre experience. Br J Haematol. 190(2):e57-e58. https://pubmed.ncbi.nlm.nih.gov/32369606/
  • Chakravorty et al, 2020. COVID-19 in patients with sickle cell disease – a case series from a UK Tertiary Hospital. Haematologica. 105(11):2691-2693. https://pubmed.ncbi.nlm.nih.gov/33131264/
  • Minniti et al, 2021. Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection. Blood Adv. 5(1):207-215. https://pubmed.ncbi.nlm.nih.gov/33570644/
  • Hussain et al, 2020. COVID-19 infection in patients with sickle cell disease. Br J Haematol. 189(5):851-852. https://pubmed.ncbi.nlm.nih.gov/32314798/

Further Reading

  • All Sickle Cell Disease Content
  • Understanding Sickle Cell Disease
  • What is Sickle-Cell Disease?
  • Sickle-Cell Disease Classification
  • Sickle-Cell Disease Diagnosis
More…

Last Updated: May 25, 2021

Written by

Dr. Osman Shabir

Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield.

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The Genetics of Asthma

Asthma is a chronic condition characterized by lung airway inflammation that is caused by both genetic and environmental factors.

Asthma is a chronic inflammatory condition affecting the airways of the lungs that is caused by increased airway responsiveness and reversible airway obstruction. This leads to symptoms of chest tightness, wheezing, coughing, and shortness of breath.

When these symptoms occur (usually suddenly), it is known as an asthma attack. Reliever inhalers (normally blue) can be used as effective and quick emergency treatments to combat asthma attacks. However, if emergency inhalers are not available, or medical attention is not immediately sought, asthma attacks can be life-threatening and 3 people die every day in the UK due to untreated asthma attacks.

The worldwide prevalence of asthma has been increasing and continues to rise across the world. More specifically, asthma rates in urban areas are increasing more than in rural areas. Many of the causes of asthma may be attributed to environmental factors such as smoking, air pollution, climate change, but also increasing evidence points towards specific genetic factors that may directly cause asthma in families or predispose individuals to later-onset asthma – especially in combination with environmental factors.

Image Credit: Lightspring/Shutterstock.com

Genetics of asthma

Almost half of all people affected by asthma have a genetic susceptibility – either inherited genetic mutations or single nucleotide polymorphisms (SNPs) which increase the risk of developing asthma especially in combination with certain environmental factors.

For example, people with no family history of asthma have a 5% risk of developing asthma. Having a sibling or a parent with asthma increases this risk to 25%, having both parents with asthma increases this risk to 50%, and having a monozygotic twin increases the risk to 75%. This clearly illustrates a strong genetic basis for asthma risk. The latter also highlights that asthma is not a purely genetic disease and the environment plays an important role in determining asthma risk too (otherwise the risk would be 100% with a monozygotic twin).

Where genes play a strong role as compared to the environment would be primarily in early-onset asthma. Having a family history of asthma usually results in earlier onset disease thus genes may be implicated in the age at onset of disease. Furthermore, the severity of the disease may also be uniform in families e.g., more severe asthmatic parent leading to a severely asthmatic child. Specific genes may increase the risk of allergic asthma (most common) whereas others are involved in non-allergic asthma (rarer but tends to be more severe and usually occurs later in life).

Genes involved in asthma

Most genes implicated in asthma are related to inflammation/modulation of the immune system, or to do with lung physiology. To date, over 100 such genes have been identified – with more being identified each year. These genes include specific cytokines (inflammation/immunity), Toll-like receptors, major histocompatibility complexes (MHC), receptors, cysteine leukotriene metabolic pathway, airway hyperresponsiveness, lung function as well as some other genes.

What is asthma?

Specific genes commonly implicated in asthma include:

  • ORMDL3 (ORMDL Sphingolipid Biosynthesis Regulator 3) is a gene that is strongly associated with early-onset asthma – leading to high levels of IgE.
  • HLA-DQ(A1/B1) is the αβ heterodimer of type MHC class II found on antigen-presenting cells, involved in autoimmune conditions including coeliac disease and diabetes mellitus type 1. Mutations within this gene are involved in late-onset asthma.
  • ADAM33 (A Disintegrin and Metalloproteinase 33) is expressed strongly in bronchial smooth muscle cells and lung fibroblasts and is involved in airway hyperresponsiveness and decreased lung function.
  • Filaggrin is a gene involved in the maintenance of skin barriers and mutations are typically involved in atopic dermatitis & ichthyosis Vulgaris. Having mutations in this gene usually increases the risk of skin conditions, but also increases the risk of asthma and hay fever on top of those.
  • Other commonly implicated genes include (non-exhaustive list):
    • IL1RL1 – Interleukin 1 Receptor Like 1 (receptor)
    • IL33 – Interleukin-33 (cytokine)
    • SMAD3 – SMAD Family Member 3 (intracellular signal transducer protein)
    • IL2RB – Interleukin 2 Receptor Subunit B (receptor subunit)
    • SPINK5 – Serine Peptidase Inhibitor Kazal Type 5 (multidomain serine protease inhibitor)
    • VDR – Vitamin D Receptor (receptor)
    • DPP10 – Dipeptidyl Peptidase Like 10 (membrane protein)
    • PHF11 – Ph.D. Finger Protein 11 (Ph.D. type zinc finger)
    • HLA-G – Human Leukocyte Antigen G (MHC)
    • IL13 – Interleukin-13 (cytokine)
    • GPR15 – G Protein-Coupled Receptor 15 (receptor)
    • TLR2/4/6/9/10 – Toll-Like Receptors 2, 4, 6, 9 & 10 (receptors)

Many of these genes are involved in inflammation, immunity, and lung function. Mutations or polymorphisms to any of these genes compromise their normal function thus leading to dysregulated immune/inflammatory responses (i.e., exaggerated response), or remodeling of the airways decreasing lung function, or increasing hyperresponsiveness.

Collectively they contribute either to causing earlier-onset asthma, or predisposing adults to developing asthma later in life in combination with certain environmental factors (such as smoking, air pollution, dust mites, or pollen) or combination with other conditions such as dermatitis.

In summary, asthma is a complex multifactorial condition that has many causes – both environmental and genetic. Having a family history of asthma increases the risk of asthma thus suggesting a strong genetic basis. Certain genes may only predispose individuals to asthma (later-onset/environmentally triggered), however, other genes may be directly causative of asthma – particularly early-onset or that which is more severe (typically running in families). Knowing what genes cause asthma or increase the risk of asthma is important in the development of novel therapies and treatments.

References

  • Huo & Zhang, 2018. Genetic Mechanisms of Asthma and the Implications for Drug Repositioning. Genes (Basel). 9(5):237. https://pubmed.ncbi.nlm.nih.gov/29751569/
  • Thomsen, 2015. Genetics of asthma: an introduction for the clinician. Eur Clin Respir J. 16;2. https://pubmed.ncbi.nlm.nih.gov/26557257/
  • Jindal, 2015. Genetic basis of asthma. Indian J Med Res. 142(6):640-3. https://pubmed.ncbi.nlm.nih.gov/26831411/

Further Reading

  • All Asthma Content
  • Asthma
  • Childhood Asthma
  • Signs of Asthma Attack
  • Asthma Symptoms
More…

Last Updated: May 4, 2021

Written by

Dr. Osman Shabir

Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield.

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Women seeking help for unmet needs often overdue for cervical cancer screenings

More than half of cervical cancer cases in the United States occur in women who have not had timely Pap smears and/or HPV tests — screenings that allow for detection of precancerous or cancerous cells on the cervix. Encouraging low-income women in particular to participate in such screenings likely would improve cancer detection and save lives, but health-care professionals have been uncertain of how best to improve patient adherence to screenings and follow-ups involving abnormal results.

Women with low incomes sometimes skip Pap smears and other cancer prevention screenings because they are focused on more pressing needs such as housing, food and other necessary expenses. So, researchers at Washington University School of Medicine in St. Louis evaluated efforts to help such women obtain cervical cancer screenings.

The scientists studied a group of female callers in Missouri seeking assistance from a free and confidential phone service that helps people find basic resources. The researchers determined that many female callers were due for cervical cancer screenings but most did not schedule one, even with the support of a health navigator, an individual trained to help people access medical care. Their findings indicate a new, more involved approach is needed to achieve such screenings and, ultimately, lower the number of women treated for advanced cancer.

“Reasons for inadequate screening are many and often deeply rooted to social and structural determinants of health that drive health inequities,” said first author Lindsay Kuroki, MD, an assistant professor of obstetrics & gynecology. “We wanted to determine the need for cervical cancer screening among women seeking assistance with unmet basic needs and to assess different methods of encouraging callers to seek Pap screening. Connecting underserved women to cervical cancer-screening services and assisting them with barriers to access medical care can improve health equity and reduce cancer disparities.“

The findings are available online in the American Journal of Obstetrics & Gynecology.

Participants were recruited from June 2010 through June 2012 from among callers to United Way 2-1-1 Missouri, a telephone helpline for local health and social service resources. Most callers seek help with basic needs such as food, utility bills, shelter and unexpected expenses.

Of 932 callers, 211 were referred for cervical cancer screenings. Callers were randomized to one of three conditions: phone call only; phone call and a print reminder; or a phone call and a personal navigator. The researchers looked at how many women contacted a clinic to schedule a Pap test one month after receiving a referral.

Patients in need of Pap screening had multiple cervical cancer risk factors. These women had a mean age of 48.2 years, were predominantly non-white, poor and unemployed, not married, and actively smoking. Nearly all (94.7%) female callers, regardless of their need for Pap testing, had at least one unmet basic need, with callers reporting an average of two unmet needs.

Women in the group that was assigned health navigators reported higher rates of contacting Pap services (29.6%) than those given phone calls only (15.1%), or phone calls and tailored print reminders (13.4%). Health navigators tripled the likelihood that women made contact with Pap services, and this remained true even among women with multiple unmet needs. Nevertheless, only 41 of 211 (19.4%) women who were overdue for Pap testing and received a referral contacted the referred clinic to schedule cervical cancer screenings.

The scientists said future research is necessary to understand how unmet basic needs pose barriers to cervical screening and how effective interventions to meet basic needs may lead to improved access to cancer prevention services. Some of these interventions might include immediate help such as assisting women with transportation and childcare. Other interventions might focus on redesigning health systems and influencing social policy to provide women at risk for cervical cancer with secure homes free of hunger and tobacco.

“Women contacting 2-1-1 are likely to have health needs that greatly exceed those of the general population, in addition to lacking financial resources and social support required to seek cervical cancer screening,” said senior author Matthew Kreuter, PhD, the Kahn Family Professor of Public Health at the Brown School. “Continuing this line of research is critical to improving outcomes for low-income, medically underserved populations. No woman should die from a preventable cancer.”

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Shocking New Facts Reveal why You Should ALWAYS Sleep at Work

It’s time to put the myth to sleep. The Spanish didn’t really invent siestas as we know them, they just perfected the practice. The word siesta has its origins from the Latin word sexta. In days gone past, the Romans stopped to eat and rest in the sixth hour of the day.

The Spanish have historically had peculiar working hours, with time, they managed to slot in a couple of hours to nap in their daily routines. Their culture supports a practice called presenteeism, which translates to spending more work hours to give the impression of being busy and committed to the workplace. Traditionally, most companies believed that spending more hours at work meant improved productivity. Whilst this is not necessarily always the case, the introduction of afternoon siestas between 2-5pm did allow them to rejuvenate and carry on with their daily activities.

Power Naps

For the siesta to survive in the new age, many things need to be taken into consideration. The sleeping culture of big cities needs to be revised in order to ensure compatibility with the workforce.

There have already been a few initiatives among the Spanish populace to save siesta sessions. Last year sleep pods were tried out in Madrid’s Atocha train station to offer a temporary lunch break relief for tired office work.

An app known as SiestAPP has also been developed to help users refresh and revitalize. The app works by letting users grab some precious 40 winks and then waking them up just in time to get back to work.

In the New Age, people are paid by the Hour, Napping in the Afternoon may thus not make sense for most employers

Downtime

When we take breaks and/or sleep, the brain engages in mundane but important activities. Scientists have always suspected that when one is not actively engaged in a learning experience, the brain strives to amalgamate new data. It is during this time that memory gets stored up and the brain gets to subconsciously rehearse new skills by etching them into the brain tissue.

Most students can give testimony to the fact that after a late night out studying, they were able to recall most of the things learnt in the morning after a good night of sleep. Musicians practicing instruments also experience this same phenomenon. In essence, a good sleep session is an essential component of memory.

Psychology

Psychologists have established that taking breaks and vacations can have real advantages for most people. A vacation takes the mind out of focus on particular issues and helps it concentrate on new things.

Taking a quick shower on a hot day can have the same benefits as a good sleep session. By distracting the mind and giving it a new pre-occupation, different parts of the brain responsible for creativity and memory are triggered. This can have a great benefit in how we are able to execute work much more efficiently afterward.

Siestas allow the brain to switch off for a while and take inventory of the day’s happenings whilst preparing us for future functionality with improved effectiveness

Hobbits

In Tolkien’s Middle Earth magnum opus, the Hobbits are known to partake in two breakfasts, the first and the second. The same way pre-industrial Europe was known to have a first and second sleep session typically divided by an hour of crepuscular activity. Numerous studies have shown that taking naps helps the brain sharpen concentration and improve productivity at workplaces.

A good downtime session can significantly help improve the attention span of people

While there are a couple of forward-thinking companies in the US that allow workers to take naps at the office, most still don’t cater for such needs. A good alternative for those unable to take naps at the office space because of their bosses would be to spend some time outdoors exploring. By taking our minds off work and school for short periods, we’re able to prepare the brain for intensive information processing later in the day.

A good downtime session can help improve the attention span of individuals too. Sleep and meditation are considered to be some great ways to help the mind focus on issues we deem important when we’re feeling a bit fatigued. A nap a day, keeps the productivity at an all-time high. It’s the miracle cure that seems too good to be true, yet still, it is.

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