Vanillin could prevent or reduce psoriatic skin inflammation

Small amounts of artificial vanilla extract, also known as vanillin, are in a wide range of products, from baked goods to perfumes. But vanillin's versatility doesn't stop there. In a recent mouse study reported in ACS' Journal of Agricultural and Food Chemistry, researchers report that this compound could also prevent or reduce psoriatic skin inflammation.

Psoriasis is an inflammatory skin disorder that affects about 125 million people worldwide, resulting in scaly red plaques that typically show up on the elbows, knees or scalp. Immune system proteins called interleukins (IL) 17 and 23 are known to be key players in the development of the condition. Interestingly, vanillin can have effects on different interleukins that are involved in other inflammatory conditions and diseases. So, Chien-Yun Hsiang and Tin-Yun Ho wanted to see if treatment with vanillin could prevent psoriatic symptoms.

The researchers induced psoriatic skin inflammation on groups of mice by putting a compound called imiquimod on their skin. In addition, the mice were orally given daily doses (0, 1, 5, 10, 50 or 100 milligrams/kilograms of body weight) of vanillin for seven days. Mice treated with 50- or 100-milligram/kilograms of body weight doses had reduced psoriatic symptoms compared to those receiving smaller or no doses of vanillin. In all mice treated with vanillin, IL-17 and IL-23 protein levels were decreased. The researchers say that vanillin was an effective compound against psoriatic skin inflammation in this animal model.

Vanillin could prevent or reduce psoriatic skin inflammation

Immune-boosting drug combination may hold promise for treating ovarian cancer

Johns Hopkins Kimmel Cancer Center researchers demonstrated that mice with ovarian cancer that received drugs to reactivate dormant genes along with other drugs that activate the immune system had a greater reduction of tumor burden and significantly longer survival than those that received any of the drugs alone.

The study already spurred a clinical trial in ovarian cancer patients. The investigators, led by graduate student Meredith Stone, Ph.D.; postdoctoral fellow Kate Chiappinelli, Ph.D.; and senior author Cynthia Zahnow, Ph.D., believe it could lead to a new way to attack ovarian cancer by strengthening the body's natural immune response against these tumors. It was published in the Dec. 4, 2017, issue of the Proceedings of the National Academy of Sciences.

Ovarian cancer is currently the leading cause of death from gynecological malignancies in the U.S. "We've taken two types of therapies that aren't very effective in ovarian cancer and put them together to make them better at revving up the immune system and attacking the tumor," says Zahnow, associate professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Zahnow says that a class of immunotherapy drugs known as checkpoint inhibitors, currently being studied at the Bloomberg~Kimmel Institute for Cancer Immunotherapy, helps the immune system recognize cancers and fight them off. The drugs have shown success in treating melanoma, nonsmall cell lung cancer and renal cell cancers, but they have had only modest effects on ovarian cancer.

Similarly, another class of drugs known as epigenetic therapies has been used to treat some types of cancer by turning on genes that have been silenced-- either by the presence of chemical tags, known as methyl groups, or by being wound too tightly around protein spools, known as histones--but these drugs haven't been effective against ovarian cancer either.

Zahnow and her colleagues became inspired to investigate a new way to treat ovarian cancer by two recent publications from their group that showed epigenetic drugs turn on immune signaling in ovarian, breast and colon cancer cells (Li et al., Oncotarget 2014). These immune genes are activated when epigenetic therapy turns on segments of ancient retroviruses that activate type 1 interferon signaling in the cells (Chiappinelli et al., Cell 2015). Stone, Chiappinelli and Zahnow wanted to know if this increase in immune signaling could lead to the recruitment of tumor killing immune cells to the cancer.

Zahnow and her colleagues worked with a mouse model of the disease in which mouse ovarian cancer cells are injected into the animals' abdomens to mimic human disease. These cells eventually develop into hundreds of small tumors, which cause fluid to collect within the abdomen, a condition known as ascites. Floating in this fluid is a milieu of both cancer and immune cells, offering a convenient way to keep tabs on both the tumor and the animals' immune response.

The researchers started by pretreating the ovarian cancer cells outside of the animal in a culture dish with a DNA methyltransferase inhibitor (a drug that knocks methyl groups from DNA) called 5-azacytidine (AZA). After injecting these cells into mice, the researchers found that animals receiving the pretreated cells had significantly decreased ascites or tumor burden and significantly more cancer-fighting immune cells in the ascites fluid compared to those injected with untreated cells. These cells also had increased activity in a variety of genes related to immune response. Pretreating these cells with histone deacetylase inhibitors (HDACis), which help DNA uncoil from histones, didn't affect the animals' ascites or boost their immune response.

These early findings suggested that changes in gene activity induced by AZA cause the tumor cells themselves to summon immune cells to their location. In addition, when the researchers transplanted untreated cells into mice and treated the animals with both AZA and an HDACi, significantly more immune cells were in the ascites fluid, suggesting that the HDACi was acting on the animals' immune systems. These mice also had decreased ascites, lower tumor burden and longer survival than mice that received just AZA.

When the researchers treated the mice with both AZA and an HDACi, along with an immune checkpoint inhibitor, they got the greatest response--the highest decreases in ascites and tumor burden, and the longest survival. Further experiments using immunocompromised mice showed that the immune system is pivotal to the action of these drugs, rather than the drugs themselves acting directly to kill tumor cells.

"We think that AZA and the HDACis are bringing the soldiers, or immune cells, to the battle. But the checkpoint inhibitor is giving them the weapons to fight," says Zahnow, who also collaborated with epigenetics scientist Stephen Baylin, M.D., on this project.

The preclinical data generated through this study is already being used to help patients with ovarian cancer through an ongoing clinical trial to test the effectiveness of combining AZA and a checkpoint inhibitor. Future trials may add an HDACi to determine if it affects outcomes.

"Combining epigenetic therapy and a checkpoint blocker leads to the greatest reduction in tumor burden and increase in survival in our mouse model and may hold the greatest promise for our patients," says Zahnow.

Ref : https://www.hopkinsmedicine.org/news/media/releases/combination_strategy_could_hold_promise_for_ovarian_cancer

Immune-boosting drug combination may hold promise for treating ovarian cancer

FDA Approves Kaléo’s Auvi-Q (Epinephrine Injection, USP) 0.1 mg Auto-Injector for Life-Threatening Allergic Reactions in Infants and Small Children

In continuation of my update on epinephrine

Kaléo, a privately-held pharmaceutical company,  announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental New Drug Application (sNDA) for Auvi-Q (epinephrine injection, USP) 0.1 mg, the first and only epinephrine auto-injector (EAI) specifically designed for the treatment of life-threatening allergic reactions, including anaphylaxis, in infants and small children weighing 16.5 to 33 pounds (7.5 to 15 kilograms) who are at risk for or have a history of serious allergic reactions.

The sNDA for the Auvi-Q 0.1 mg Auto-injector was granted Priority Review by the FDA, an expedited regulatory pathway reserved for products that may provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to available therapies.

Auvi-Q is a compact epinephrine auto-injector with industry-first features, including a voice prompt system that guides a user with step-by-step instructions through the delivery process, and a needle that automatically retracts following administration. The new 0.1 mg-dose epinephrine auto-injector has a shorter needle length and lower dose of epinephrine than current FDA approved 0.15 mg and 0.3 mg epinephrine auto-injectors.

Children are increasingly being treated for anaphylaxis. There was a 129.8 percent increase in emergency room visits for anaphylaxis among children four years old and younger between 2005 and 2014.[i] According to a study published in Allergy, Asthma & Clinical Immunology, 43 percent of children weighing 16.5 pounds (7.5 kilograms) to 33 pounds (15 kilograms) treated with a 0.15 mg EAI having a standard 12.7 mm needle length are at risk of having the needle strike the bone, therefore potentially impacting the administration of epinephrine during a life-threatening emergency.[ii] The needle length in Auvi-Q 0.1 mg was specifically designed for use with infants and small children to help mitigate this safety concern.

“Today’s decision by the FDA to approve the Auvi-Q 0.1 mg Auto-injector is exciting for all of us in the life-threatening allergy community who have been working for many years to fulfill this unmet medical need,” said Spencer Williamson, President and CEO of kaléo. “As a company that focuses on patients first, and providing potentially life-saving treatments, we are particularly glad we will be able to help caregivers by providing an EAI that was specifically designed with an appropriate dose and needle length for infants and children (16.5 to 33 pounds) in order to maximize the potential for a safe administration of epinephrine.”

“The approval of Auvi-Q 0.1 mg will help achieve our goal of working to fulfill unmet medical needs,” said Eric S. Edwards, MD, PhD, Vice President of Innovation and Research & Development at kaléo. “We developed the Auvi-Q 0.1 mg EAI to deliver a dose of epinephrine appropriate to infants and small children weighing 16.5 – 33 pounds, with a shorter needle length to help mitigate the risk of striking bone which could potentially cause injury or interfere with the delivery of epinephrine.”

Only Auvi-Q 0.1 mg has a dose and needle length designed specifically for treating anaphylaxis in infants and small children weighing 16.5 – 33 pounds. Auvi-Q 0.1 mg includes the innovative AUVI-Q electronic voice instruction system as well as visual cues to help guide users step-by-step through the administration.

“The approval of an epinephrine auto-injector specifically designed for infants and small children is timely, especially given the recent changes to guidelines recommending that certain high-risk infants, as young as four to six months old, be introduced to peanut-containing foods,” said Eleanor Garrow-Holding[1], President and CEO of the Food Allergy & Anaphylaxis Connection Team (FAACT). “We are pleased that the pediatric allergy healthcare community and parents of infants and small children with life-threatening allergies will have the ability to obtain an FDA-approved epinephrine auto-injector in the event of an allergic emergency. We look forward to the availability of Auvi-Q 0.1 mg.”

“Until now, healthcare practitioners and caregivers to infants and small children have not had an epinephrine auto-injector with an appropriate dose of epinephrine available to them, potentially causing some delay in the administration of epinephrine in a life-threatening allergic emergency,” said Dr. Vivian Hernandez-Trujillo[1], a pediatric allergist, and fellow of the American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; and American Academy of Pediatrics specializing in the management of life-threatening allergies and anaphylaxis. “Having an epinephrine auto-injector with a needle length and dose specifically designed for infants and small children should help alleviate concerns around hitting the bone or injecting too much epinephrine.”

Identical twin brothers, Evan and Eric Edwards, the inventors of Auvi-Q, know what it is like to live with life-threatening allergies, both as patients and parents of food-allergic children. Their goal was to develop an epinephrine auto-injector that contained innovative features, such as a voice instruction system that helps guide patients and caregivers step-by-step through the injection process. Evan and Eric Edwards believe and trust in Auvi-Q, not only for themselves, but also for their children and other families who may have to depend on it to administer epinephrine during an allergic emergency.

FDA Approves Kaléo’s Auvi-Q (Epinephrine Injection, USP) 0.1 mg Auto-Injector for Life-Threatening Allergic Reactions in Infants and Small Children

FDA Approves Sublocade (buprenorphine) Once-Monthly Injection for Opioid Use Disorder

In continuation of my update on Sublocade (buprenorphine)

The U.S. Food and Drug Administration today approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.

Buprenorphine for the treatment of OUD is currently approved to administer as a tablet or film that dissolves in the mouth, or as an implant. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade at a meeting held last month.

"Given the scale of the opioid crisis, with millions of Americans already affected, the FDA is committed to expanding access to treatments that can help people pursue lives of sobriety. Everyone who seeks treatment for opioid use disorder deserves the opportunity to be offered the treatment best suited to the needs of each individual patient, in combination with counseling and psychosocial support, as part of a comprehensive recovery plan,” said FDA Commissioner Scott Gottlieb, M.D. “As part of our ongoing work in supporting the treatment of those suffering from addiction to opioids, the FDA plans to issue guidance to expedite the development of new addiction treatment options. We’ll continue to pursue efforts to promote more widespread use of existing, safe and effective FDA-approved therapies to treat addiction.”

Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis.

OUD is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress and includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition.

MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with OUD. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their OUD cut their risk of death from all causes in half.

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film (absorbed under the tongue). Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group.

The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose).

Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.

FDA Approves Sublocade (buprenorphine) Once-Monthly Injection for Opioid Use Disorder

Benzodiazepines linked to increased risk of death among Alzheimer’s disease patients

Benzodiazepine and related drug use is associated with a 40 per cent increase in mortality among persons with Alzheimer's disease, according to a new study from the University of Eastern Finland. The findings were published in the International Journal of Geriatric Psychiatry.

The study found that the risk of death was increased right from the initiation of benzodiazepine and related drug use. The increased risk of death may result from the adverse events of these drugs, including fall-related injuries, such as hip fractures, as well as pneumonia and stroke.

The study was based on the register-based MEDALZ (Medication Use and Alzheimer's Disease) cohort, which includes all persons diagnosed with Alzheimer's disease in Finland during 2005-2011. Persons who had used benzodiazepines and related drugs previously were excluded from this study, and therefore, the study population consisted of 10,380 new users of these drugs. They were compared with 20,760 persons who did not use these drugs.

Although several treatment guidelines state that non-pharmacological options are the first-line treatment of anxiety, agitation and insomnia in persons with dementia, benzodiazepines and related drugs are frequently used in the treatment of these symptoms. If benzodiazepine and related drug use is necessary, these drugs are recommended for short-term use only. These new results encourage more consideration for benzodiazepine and related drug use in persons with dementia.

Ref : https://www.uef.fi/en/-/bentsodiatsepiinit-lisaavat-kuolleisuutta-alzheimerin-tautia-sairastavilla

Benzodiazepines linked to increased risk of death among Alzheimer’s disease patients

Study: Alectinib 600 mg more effective than standard therapy in Asian ALK positive NSCLC patients

In continuation of my update on crizotinib and alectinib

 and  

A subanalysis of the phase III ALEX study has shown that alectinib 600 mg twice daily is more effective than standard of care crizotinib in Asian patients with anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC), researchers report at the ESMO Asia 2017 Congress.

The J-ALEX study demonstrated that alectinib 300 mg twice daily improved progression-free survival compared to crizotinib in Japanese patients with ALK positive NSCLC. (3) The ALEX study subsequently showed improvement in progression-free survival with alectinib 600 mg twice daily compared to crizotinib in a global population of ALK positive NSCLC patients. (4)

This subanalysis of the ALEX study investigated the efficacy and safety of alectinib 600 mg twice daily compared to crizotinib in Asian versus non-Asian patients with ALK positive NSCLC. As previously reported, the ALEX study included 303 patients who were randomised in a 1:1 ratio to receive alectinib or standard of care crizotinib. There were 69 Asian patients in each treatment group. The primary endpoint was progression-free survival.

A distinguishing feature of the study was that all patients underwent magnetic resonance imaging (MRI) of the brain every six months, regardless of whether or not they had brain metastases at the start of the study. The time to progression in the brain was measured and compared between the two treatment groups.

"Around 50% of NSCLC patients with ALK mutations will develop brain metastases so it is very important to demonstrate the efficacy of alectinib in the brain," said lead author Professor Tony S.K. Mok, Chairman, Department of Clinical Oncology, The Chinese University of Hong Kong.

The subanalysis showed similar efficacy and safety with alectinib in Asian and non-Asian patients. Progression-free survival was longer with alectinib compared to crizotinib in Asian and non-Asian populations, with hazard ratios (HRs) of 0.46 and 0.49, respectively. Alectinib reduced central nervous system (CNS) progression compared to crizotinib in the Asian and non-Asian groups, with cause-specific HRs of 0.21 and 0.16, respectively. Median overall survival was not reached in either subgroup.

Response rates to alectinib and crizotinib were 81.2% versus 76.8%, respectively, for the Asian subgroup and 84.3% versus 74.4%, respectively, for the non-Asian subgroup.

The rates of nausea, vomiting, and grade III toxicities overall were lower with alectinib compared to crizotinib, and similar between the Asian and non-Asian subgroups. Liver toxicity due to alectinib was slightly higher in the Asian compared to the non-Asian subgroup.

Mok said: "Alectinib 600 mg twice daily was similarly effective in Asian and non-Asian patients in the ALEX study in terms of progression-free survival, CNS progression, and response rate. The rates of toxicities were also comparable. The findings suggest that 600 mg should be the standard dose of alectinib across Asia."

Commenting on the research, Dr Pilar Garrido, Head of the Thoracic Tumour Section, Medical Oncology Department, Ramón y Cajal University Hospital, Madrid, Spain, said: "ALK rearrangements emerged as important therapeutic targets in NSCLC in 2007, defining a distinct molecular subset of tumours. Around 5% of NSCLC patients harbour ALK mutations and are highly sensitive to ALK tyrosine kinase inhibitors, which efficiently induce apoptosis. Patients wih advanced ALK positive NSCLC have a high lifetime risk of CNS metastases and a high frequency of brain metastases at diagnosis, with the CNS being the most common site of disease progression."

Benzodiazepines linked to increased risk of death among Alzheimer’s disease patients

Benzodiazepine and related drug use is associated with a 40 per cent increase in mortality among persons with Alzheimer's disease, according to a new study from the University of Eastern Finland. The findings were published in the International Journal of Geriatric Psychiatry.

The study found that the risk of death was increased right from the initiation of benzodiazepine and related drug use. The increased risk of death may result from the adverse events of these drugs, including fall-related injuries, such as hip fractures, as well as pneumonia and stroke.

The study was based on the register-based MEDALZ (Medication Use and Alzheimer's Disease) cohort, which includes all persons diagnosed with Alzheimer's disease in Finland during 2005-2011. Persons who had used benzodiazepines and related drugs previously were excluded from this study, and therefore, the study population consisted of 10,380 new users of these drugs. They were compared with 20,760 persons who did not use these drugs.

Although several treatment guidelines state that non-pharmacological options are the first-line treatment of anxiety, agitation and insomnia in persons with dementia, benzodiazepines and related drugs are frequently used in the treatment of these symptoms. If benzodiazepine and related drug use is necessary, these drugs are recommended for short-term use only. These new results encourage more consideration for benzodiazepine and related drug use in persons with dementia.

Ref : https://www.uef.fi/en/-/bentsodiatsepiinit-lisaavat-kuolleisuutta-alzheimerin-tautia-sairastavilla

Benzodiazepines linked to increased risk of death among Alzheimer’s disease patients

Moderate coffee consumption more likely to provide beneficial health outcomes

In continuation of my update on coffee

Drinking coffee is "more likely to benefit health than to harm it" for a range of health outcomes, say researchers in The BMJ today.

They bring together evidence from over 200 studies and find that drinking three to four cups of coffee a day is associated with a lower risk of death and getting heart disease compared with drinking no coffee. Coffee drinking is also associated with lower risk of some cancers, diabetes, liver disease and dementia.

However, they say drinking coffee in pregnancy may be associated with harms, and may be linked to a very small increased risk of fracture in women.

The included studies used mainly observational data, providing lower quality evidence, so no firm conclusions can be drawn about cause and effect, but their findings back up other recent reviews and studies of coffee intake. As such, they say, excluding pregnancy and women at risk of fracture, "coffee drinking appears safe within usual patterns of consumption" and they suggest that coffee could be safely tested in randomised trials.

Coffee is one of the most commonly consumed beverages worldwide and could have positive health benefits. But existing evidence is of lower quality from observational research and randomized controlled trials are needed to strengthen the evidence of benefits.

To better understand the effects of coffee consumption on health, a team led by Dr Robin Poole, Specialist Registrar in Public Health at the University of Southampton, with collaborators from the University of Edinburgh, carried out an umbrella review of 201 studies that had aggregated data from observational research and 17 studies that had aggregated data from clinical trials across all countries and all settings.

Umbrella reviews synthesize previous meta-analyses and provide a high-level summary of research on a particular topic

Drinking coffee was consistently associated with a lower risk of death from all causes and from heart disease, with the largest reduction in relative risk of death at three cups a day, compared with non-coffee drinkers. Increasing consumption to above three cups a day was not associated with harm, but the beneficial effect was less pronounced.

Coffee was also associated with a lower risk of several cancers, including prostate, endometrial, skin and liver cancer, as well as type 2 diabetes, gallstones and gout. The greatest benefit was seen for liver conditions, such as cirrhosis of the liver.

Finally, there seemed to be beneficial associations between coffee consumption and Parkinson's disease, depression and Alzheimer's disease.

There was less evidence for the effects of drinking decaffeinated coffee but it had similar benefits for a number of outcomes.

Many of the included studies may have adjusted for factors that may be associated with both the health outcome and with coffee drinking, such as smoking. This was not comprehensive and varied from study to study. The authors can therefore not rule out the effect of such factors on the apparent harmful or beneficial associations.

The authors conclude that coffee drinking "seems safe within usual patterns of consumption, except during pregnancy and in women at increased risk of fracture." And they call for robust randomized controlled trials "to understand whether the key observed associations are causal."

In a linked editorial, Eliseo Guallar at the Johns Hopkins Bloomberg School of Public Health says, although we can be reassured that coffee intake is generally safe, doctors should not recommend drinking coffee to prevent disease - and people should not start drinking coffee for health reasons.

As this study shows, some people may be at higher risk of adverse effects, he writes, and there is "substantial uncertainty" about the effects of higher levels of intake. Finally, coffee is often consumed with products rich in refined sugars and unhealthy fats, "and these may independently contribute to adverse health outcomes," he adds.

However, even with these caveats, "moderate coffee consumption seems remarkably safe, and it can be incorporated as part of a healthy diet by most of the adult population," he concludes.

Ref : http://www.bmj.com/content/359/bmj.j5356

Moderate coffee consumption more likely to provide beneficial health outcomes

FDA Expands Approval of Sprycel (dasatinib) to Include Treatment of Children with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase

In continuation of my update on Sprycel(dasatinib)

Bristol-Myers Squibb Company (NYSE:BMY) announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel(dasatinib) tablets to include the treatment of children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP). This approval for Sprycel in pediatric patients with Ph+ CML in chronic phase was granted under priority review, and the indication received orphan drug designation from the FDA. The safety and efficacy of Sprycel in pediatric patients was evaluated in two pediatric studies of 97 patients with CP-CML: an open-label, non-randomized, dose-ranging trial (NCT00306202) and an open-label, non-randomized, single-arm trial (NCT00777036). Among the 97 patients in the two studies, 51 patients (exclusively from the single-arm trial) had newly diagnosed CP-CML, and 46 patients (17 from the dose-ranging trial and 29 from the single-arm trial) were resistant or intolerant to previous treatment with imatinib.

Sprycel is associated with the following Warnings and Precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity and effects on growth and development in pediatric patients.¹.

“While chronic myeloid leukemia is rare in children, accounting for less than three percent of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,”^2,3 said Vickie Buenger, President, Coalition Against Childhood Cancer. “The FDA’s decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”

“Our decision to pursue an expanded indication for Sprycel is indicative of our commitment to exploring pediatric applications within our broad development program,” said Johanna Mercier, head, U.S. Commercial, Bristol-Myers Squibb. “We are pleased this option is now available for appropriate pediatric chronic phase CML patients and their physicians.”

As part of its commitment to children and adolescents with cancer, Bristol-Myers Squibb continues to explore pediatric applications for investigational oncology agents within its broad development program. In addition, Bristol-Myers Squibb supports organizations and initiatives focused on pediatric patients and their families.

Fat-busting ingredients in cinnamon

In continuation of my update on Cinnamon...

Researchers have found that certain ingredients in cinnamon can help burn fat in humans. They along with several other previous studies have noted that cinnamon – a common kitchen spice – contains cinnamaldehyde. This is an essential oil that gives the special flavor to cinnamon. In laboratory mice, cinnamaldehyde helps to protect against obesity as has been seen in previous studies.

This new study from the team of researchers at the University of Michigan reports that this oil can burn fat in humans as well. The study titled, “Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic reprogramming,” was published in the latest issue of the journal Metabolism.

The team found that this essential oil in cinnamon can activate thermogenesis. This means that it can activate the metabolism in the body that can burn the body fat to produce heat. There are several other metabolic benefits offered by cinnamon to the body. The gearing up of the metabolism also leads to starting off on a path to weight loss they explain. Lead author Jun Wu, research assistant professor at the Life Sciences Institute said that the benefits of cinnamaldehyde are a known one because of the studies that have been already conducted proving its effects on obesity. What was not known, Wu noted, was the effects cinnamaldehyde was having on metabolism. This was what prompted this study. Wu said, “…we wanted to figure out how -- what pathway might be involved, what it looked like in mice and what it looked like in human cells.”

For this objective Wu and colleagues tried to see the effects of cinnamaldehyde on several volunteers or participants who agreed to provide some of their body fat cells or tissues for laboratory studies. The volunteers had different body weights, and were of different or varied age groups and ethnicities. They found that use of this essential oil led to enhancement of certain genes in the adipocytes of fat cells. This led to increased lipid metabolism or break down of the fat. It also triggered thermogenesis or production of heat by breaking down the body fat. Till date however the team has tested this in human cells in the laboratory and not on humans as such.

Molecular look at the state of affairs showed that cinnamaldehyde could significantly activate “protein kinase A (PKA) signaling”. This caused increased workings of genes that can cause thermogenesis. This led to increased “HSL and PLIN1 in murine primary adipocytes.” There is an increased in genetic workings of proteins Ucp1 and Fgf21 which normally play a role in metabolism and its regulations. Dr. Wu explained that energy surplus and its storage in the adipocytes is a new phenomenon for humans with the abundance of food.

Wu explained that more studies on actual human subjects was necessary to prove that use of cinnamaldehyde indeed was beneficial and safe for consumption. Wu said he hopes that this spice that has been part of the human diet for centuries could offer protection against obesity that is becoming a rising epidemic worldwide. People generally enjoy this spice and if it is protective and beneficial, the chances that people would adopt this and stick to this therapy are higher.

Ref : http://www.metabolismjournal.com/article/S0026-0495(17)30212-3/fulltext

Fat-busting ingredients in cinnamon