Teen suicide: What parents need to know.

Teen suicide can be prevented. Know the risk factors, the warning signs and the steps you can take to protect your teen.

Is your teen at risk of suicide? While no teen is immune, there are factors that can make some adolescents more vulnerable than others. Understand how to tell if your teen might be suicidal and where to turn for help and treatment.

What makes teens vulnerable to suicide?

Most teens who attempt or commit suicide have a mental health condition or substance abuse problem. As a result, they have trouble coping with the stress of being a teen, such as dealing with rejection, failure, breakups and family turmoil. They might also be unable to see that they can turn their lives around — and that suicide is a permanent solution to a temporary problem.

What are the risk factors for teen suicide?

Factors that increase the risk of teen suicide include:

• Having a psychiatric disorder, such as depression
• A history of suicide attempts or a family history of suicidal behavior
• A family history of mood disorder
• A history of physical or sexual abuse
• Exposure to violence, such as being injured or threatened with a weapon

Other factors, when combined with the above, also can increase the risk of teen suicide, including:

• Access to means, such as firearms
• Loss or conflict with close friends or family members
• Use of alcohol or drugs
• Becoming pregnant
• Social isolation
• Exposure to suicide

What role do antidepressants play?

Some studies have shown a possible link between starting treatment with an antidepressant and an increased risk of suicide. The Food and Drug Administration (FDA) requires manufacturers of all antidepressants to include a warning stating that antidepressants might increase suicide risk in children, adolescents and young adults.

However, the link between antidepressants and suicidal thinking isn’t clear — and withholding appropriate treatment also increases the risk of suicide. To be safe, anyone who starts taking an antidepressant should be watched closely for signs of suicidal thinking.

What are the warning signs that a teen might be suicidal?

Warning signs of teen suicide might include:

• Talking about or hinting at suicide — for example, making statements such as “I’m going to kill myself,” or “I won’t be a problem for you much longer”
• Talking about or writing about death
• Increased use of alcohol or drugs
• Feeling purposeless or hopeless
• Withdrawing from social contact
• Mood swings
• Changing normal routine, including eating or sleeping patterns
• Acting recklessly or aggressively
• Giving away belongings or getting affairs in order when there is no other logical explanation for why this is being done
• Developing personality changes or being severely anxious or agitated
• Unexplained cuts or burns caused by self-injury

What should I do if I suspect my teen is suicidal?

If you think your teen is in immediate danger, take him or her to the emergency room or call 911, your local emergency number or a suicide hot line number — such as the National Suicide Prevention Lifeline at 800-273-TALK (800-273-8255).

If you suspect that your teen might be thinking about suicide, talk to him or her immediately. Don’t be afraid to use the word suicide. Talking about suicide won’t plant ideas in your teen’s head. Ask your teen to talk about his or her feelings and listen carefully. Don’t dismiss his or her problems or get angry. Instead, reassure your teen of your love. Remind your teen that he or she can work through whatever is going on — and that you’re willing to help.

Also, be sure to seek medical help for your teen. Ask your teen’s doctor to guide you. Teens who are feeling suicidal usually need to see a psychiatrist or psychologist experienced in diagnosing and treating children with mental health problems. The doctor will want to get an accurate picture of what’s going on from a variety of sources, such as the teen, parents or guardians, other people close to the teen, school reports, and previous medical or psychiatric evaluations.

What can I do to prevent teen suicide?

You can take steps to help protect your teen. For example:

• Address depression or anxiety. Don’t wait for your teen to come to you with his or her problems. If your teen is sad, anxious or appears to be struggling — ask what’s wrong and offer your help.
• Pay attention. If your teen is thinking about suicide, he or she is likely displaying some warning signs. Listen to what your child is saying and watch how he or she is acting. Never shrug off threats of suicide as teen melodrama.
• Share your feelings. Make sure your teen realizes that everyone feels sad sometimes — including you. Try to get him or her to see that things will get better.
• Discourage isolation. Encourage your teen to spend time with friends and family — rather than alone. If he or she says no, however, don’t push.
• Encourage physical activity. Even light physical activity can help reduce depression symptoms.
• Support the treatment plan. If your teen is undergoing treatment for suicidal behavior, remind him or her that it might take some time to feel better. Help your teen follow his or her doctor’s recommendations. Also, encourage your teen to participate in fun, low-stress activities that will help him or her rebuild confidence.
• Safely store firearms, alcohol and medications. Access to means can increase the risk of teen suicide.

Remember, teen suicide can be prevented. If you’re worried about your teen, talk to him or her and seek help right away.

Source: Mayo clinic newsletter

Metreleptin improved metabolic parameters in children with lipodystrophy.

Positive results from an NIH-supported analysis indicate an investigational recombinant analogue of human leptin has potential as a therapy for pediatric lipodystrophy, according to data presented at the 2013 Pediatric Academic Societies Annual Meeting.

The literature has established that lipodystrophy is known to cause metabolic abnormalities (ie, hypertriglyceridemia, insulin resistance, diabetes andsteatohepatitis), which tend to become severe through childhood and adolescence, and may be resistant to current treatment options.

Rebecca Brown, MD, assistant clinical investigator of the diabetes, endocrinology and obesity branch at the National Institute of Diabetes and Digestive and Kidney Diseases, and colleagues included pediatric patients in an ongoing, open-label study at the NIH (2000 to present).

According to abstract data, patients included in the study (n=39; nine male and 30 female; mean age, 11.9 years) had four subtypes of the disease: congenital generalized lipodystrophy (n=26, 67%), acquired generalized lipodystrophy (n=9, 23%), familial partial lipodystrophy (n=2, 5%), and acquired partial lipodystrophy (n=2, 5%).

On average, the researchers administered metreleptin 4.4 mg (Bristol-Myers Squibb and AstraZeneca) subcutaneously once or twice daily for a mean duration of 3.9 years.

Data indicate that baseline HbA1c (9.8%) decreased significantly to 7.7% after 12 months (–2.3; 95% CI, –3.2 to –1.4) in adolescent patients aged 12 to 18 years.

Triglycerides were notably high in the same group at baseline (1,378 mg/dL), but improved significantly to 385 mg/dL after 12 months (–44; 95% CI, –73 to –15), according to data.

Both age groups displayed significantly elevated mean alanine aminotransferase (ALT; ≤12 years: 193 U/L; adolescents: 105 U/L) and aspartate aminotransferase (AST; ≤12 years: 119 U/L; adolescents: 87 U/L) at baseline. However, ALT (≤12 years: 155 U/L; adolescents: 59 U/L) and AST (≤12 years: 90 U/L; adolescents: 57 U/L) decreased after metreleptin therapy, according to data.

“Metabolic disorders resulting from lipodystrophy can develop in childhood and adolescence and are exacerbated over time,” Brown said in a press release. “This new analysis supports the continued study of investigational metreleptin as a potential treatment option for pediatric patients with lipodystrophy.”

Overall, metreleptin was well tolerated, and the most common adverse events reported were decreased weight (n=3, 7.7%) and hypoglycemia (n=3, 7.7%), followed by fatigue (n=2, 5.1%) and nausea (n=2, 5.1%), the researchers wrote.

According to the press release, metreleptin has acquired orphan designation from the FDA, and the European Medicines Agency is evaluating the agent.

For more information:

Brown R. #3490.3. Presented at: Pediatric Academic Societies Annual Meeting; May 4-7, 2013; Washington.

Source: Endocrine today

 

 

 

Empagliflozin provided sustained glycemic control, weight loss in type 2 diabetes.

• The novel investigational sodium-glucose cotransporter 2 inhibitor empagliflozin demonstrated 90 weeks of sustained glycemic control and weight loss in patients with type 2 diabetes. Study researcher Thomas Hach, MD, a senior medical director at Boehringer Ingelheim, spoke withEndocrine Today about the data presented during a late-breaking session here.

“We feel there is an important obligation for us to understand patient benefits: to look at benefit-risks and to really understand which patients will benefit most or where there could possibly be limitations,” Hach said.

In active-control studies, Hach told Endocrine Today that he and colleagues saw comparable efficacy. They conducted a randomized, open-label, 78-week extension study on empagliflozin (Boehringer Ingelheim/Eli Lilly and Company).

They investigated empagliflozin 10 mg (n=81), 25 mg (n=82) or metformin (n=80) as monotherapy, or empagliflozin 10 mg (n=71), 25 mg (n=70) or sitagliptin (n=71; Januvia, Merck) as add-on to metformin in patients with type 2 diabetes who also completed one of two 12-week randomized control trials.

According to 90-week data, adjusted mean changes in HbA1c from baseline were: –0.51% (empagliflozin 10 mg), –0.60% (empagliflozin 25 mg) and –0.64% (metformin); and –0.61% (empagliflozin 10 mg), –0.74% (empagliflozin 25 mg) and –0.45% (sitagliptin).

Further data indicate adjusted mean changes in fasting plasma glucose were: –32.4 mg/dL (empagliflozin 10 mg), –28.1 mg/dL (empagliflozin 25 mg), and –25.9 mg/dL (metformin); –23.3 mg/dL (empagliflozin 10 mg), –31.8 mg/dL (empagliflozin 25 mg), and –11.7 mg/dL (sitagliptin).

Moreover, changes in weight were reported as: –2.1 kg (empagliflozin 10 mg), –1.9 kg (empagliflozin 25 mg), and –0.9 kg (metformin); –2.9 kg (empagliflozin 10 mg), –3.8 k (empagliflozin 25 mg), and –0.6 kg (sitagliptin).

“If I was still in clinical practice, I would look forward to having something new in my armamentarium. Unfortunately, there’s still a huge unmet need in diabetes,” Hach said.

The medication was well tolerated, and the most common adverse events associated with empagliflozin include urinary tract and genital infections. Hach said clinicians should use caution with elderly patients or those with renal impairment because those patients are more susceptible to adverse events.

In March, a new drug application for empagliflozin was submitted to the FDA. Further data will be presented at the American Diabetes Association Scientific Sessions in Chicago next month, Hach said. – by Samantha Costa

For more information:

Ferrannini E. Abstract #1102. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.

Source: Endocrine today

 

Valproate Anti-Seizure Products: Drug Safety Communication – Contraindicated for Pregnant Women for Prevention of Migraine Headaches

Including valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics

 

 

ISSUE: FDA is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant. Stronger warnings about use during pregnancy will be added to the drug labels, and valproate’s pregnancy category for migraine use will be changed from “D” (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to “X” (the risk of use in pregnant women clearly outweighs any possible benefit of the drug).

Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder.

BACKGROUND: Valproate products are approved for the treatment of certain types of epilepsy, the treatment of manic episodes associated with bipolar disorder, and the prevention of migraine headaches. They are also used off-label (for uses not approved by FDA) for other conditions, particularly other psychiatric conditions.

This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs. For additional details, see the Drug Safety Communication Data Summary section.

RECOMMENDATION: Valproate products should not be used in pregnant women for prevention of migraine headaches and should be used in pregnant women with epilepsy or bipolar disorder only if other treatments have failed to provide adequate symptom control or are otherwise unacceptable.

Women who are pregnant and taking a valproate medication should not stop their medication but should talk to their health care professionals immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

Source: FDA

Novartis drug Ilaris® approved by FDA to treat active systemic juvenile idiopathic arthritis, a serious form of childhood arthritis.

• 
  Ilaris® (canakinumab) is the first interleukin-1 beta inhibitor for the treatment of SJIA and the only treatment approved specifically for SJIA that is given as a monthly subcutaneous injection[1]

 

• In Phase III studies, 84% of Ilaris-treated SJIA patients achieved significant improvement of systemic and arthritic symptoms (pediatric ACR30) after a single subcutaneous dose[1]

 

• SJIA is a rare, disabling autoinflammatory disease with limited treatment options[2]; Ilaris is being investigated in other inflammatory conditions, including several rare diseases for which approved treatment options do not exist

 

 Novartis announced today that the US Food and Drug Administration (FDA) has approved Ilaris^® (canakinumab) for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older. Ilaris is the first interleukin-1 beta (IL-1 beta) inhibitor approved for SJIAand the only treatment approved specifically for SJIA that is given as a once-monthly subcutaneous injection[1]. SJIA is a rare and disabling form of childhood arthritis characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood[2],[3].

 

This approval was based on two Phase III trials in SJIA patients, aged 2-19, showing significant improvement in the majority of Ilaris-treated patients[1]. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15[1]. In the open-label part of Study 2, 92 of 128 patients attempted “corticosteroid tapering”. Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids[1]. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75).

 

“In the US, this approval marks the second Ilaris indication for patients living with rare, autoinflammatory conditions,” said Timothy Wright, MD, Global Head of Development, Novartis Pharmaceuticals. “We are committed to studying Ilaris in other IL-1 beta mediated inflammatory diseases, including several rare diseases for which treatment options do not currently exist.”

 

SJIA affects 5-15 children per 100,000 in the United States,and is the most severe subtype of juvenile idiopathic arthritis[3]-[5]. Although the disease can be life-threatening, treatment options are limited. Corticosteroids are often used to treat symptoms and pain despite their long term use being associated with potentially serious adverse effects, including Cushing syndrome, growth suppression and osteoporosis[1],[6],[7].

 

Ilaris is being investigated in a number of rare autoinflammatory conditions, including Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and Hyper IgD Syndrome (HIDS). Ilaris is considered an investigational agent for these conditions at this point in time. As such, the role that Ilaris could play in treating these conditions and potential benefit to patients is still being determined.

 

About the Pivotal Phase III Studies

Study 1, a 4-week, randomized, double-blind, placebo-controlled study, involved 84 patients between the ages of 2 and 19 years with active SJIA[1],[2]. Patients were treated with either a single subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) (n=43) or placebo (n=41)[1]. The primary endpoint was the proportion of patients achieving the adapted pediatric American College of Rheumatology (ACR) 30 response criteria and resolution of fever from baseline at Day 15[1]. This means that patients had at least a 30% improvement in systemic and arthritic symptoms versus baseline. The study met its primary endpoint.

 

Study 2, a two-part study, had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II[1]. A total of 177 patients between the ages of 2 and 19 years with active SJIA were enrolled in the study[1]. Some of these patients had previously participated in the Study 1. In Part I, patients received a subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) every 4 weeks[1]. The primary endpoint of Part I was to assess whether treatment with Ilaris allowed successful tapering of corticosteroids in at least 25% of SJIA patients who entered the study using a corticosteroid.

 

In Part II of the study, patients were randomized to either continue receiving Ilaris, or to receive placebo every 4 weeks (“placebo-after-Ilaris group”), until a pre-specified number (37) of flare-events (“flares”) had occurred[1]. The primary endpoint of Part II was to demonstrate that the time to flare was longer with Ilaris than with placebo.

 

The primary endpoints for Study 1 and Study 2 were all met.

 

About Ilaris

Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body’s immune system defenses[1]. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases[8]. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation[1].

 

In addition to its approval for SJIA in the US, Ilaris is approved in the EU for the treatment of refractory gouty arthritis, and in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a rare, lifelong, genetic disorder with debilitating symptoms[1]. The approved indication may vary depending upon the individual country.

 

References:

1. Ilaris [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2013.
2. Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol 2006; 2(1):28-34.
3. Ramanan AV, Grom AA. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology (Oxford) 2005; 44(11):1350-3.
4. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features. Arthritis Care & Research 2011; 63(4):465-482.
5. Dewitt EM, Kimura Y, Beukelman T, et al. Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis. Arthritis Care & Research 2012; 64(7):1001-1010.
6. U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Cushing Syndrome. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000389.htm. Last accessed: 12/12/12.
7. Teitelbaum SL,Seton MP, Saag KG. Should Bisphosphonates be Used for Long-Term Treatment of Glucocorticoid-Induced Osteoporosis? Arthritis Rheum. 2011 February 63(2): 325-328. doi:10.1002/art.30135.
8. Martinon F, Petrilli V.  Gout-associated uric acid crystals activate the NALP3 inflammasome.Nature 2006; 440(9): 237-241.

 

Source: Novartis newsletter

Performance Enhancing Drugs: What Parents Need to Know.

In a frequently referenced 1997 Sports Illustrated article, aspiring Olympians were asked two questions; “If you were offered a banned performance-enhancing substance that guaranteed that you would win an Olympic medal and you could not be caught, would you take it?” Remarkably, 195 of 198 athletes said yes. The second question was: “Would you take banned performance-enhancing drugs with a guarantee that you will not be caught, you will win every competition for the next five years, but then will die from adverse effects of the substance?” More than 50 percent of the athletes said yes to this question as well.

Driven by the popularity of sports and athletes’ drive to succeed, the use of ergogenic (performance enhancing) drugs, or PEDs, is at all-time high in the United States today. Fifty-seven percent of high school students play on formal sports teams, and 1-3 million U.S. athletes nationally are taking some form of performance-enhancing drugs. Many of these athletes are youth who use these substances without knowledge of their risks and potential benefits.

Powerful dietary supplements and energy drinks have become part of the PED landscape for some athletes. These drinks and supplements can be found in vitamin and grocery stores and even gas stations. Young people are also using dietary supplements in combination with stimulant prescription medications, such as those used for attention-deficit hyperactivity disorder. Ritalin and other amphetamines are used at surprising rates by teenagers.

In addition to energy and dietary supplements, a growing number of non-elite athletes are using anabolic-androgenic steroids, or AAS, human growth hormones, or HGH, erythropoietin, or EPO and insulin.

A series in Sports Illustrated outlined the breadth of the problem, which encompasses not only players but also media personalities, police and paramilitary personnel and ordinary Americans who want to look, feel and live “at the top of their game.” Eighty percent of PED users are reported to be non-elite athletes.

The most common PEDs are anabolic steroids (eg. testosterone, androstanediol), creatine, stimulants (eg. amphetamine, ephedrine), Erythropoitetin, or EPO, and human growth hormone, or HGH. Although ephedra-based dietary supplements—which have also been used by athletes to reduce fatigue, lose weight and improve mental alertness—were banned by the U.S. Food and Drug Administration in 2004, their place is being taken by an increase in the use of drugs to treat ADHD among athletes.

What’s the appeal?
Athletes may have several reasons for using performance-enhancing drugs. An athlete may want to: build mass and strength of muscles and/or bones; decrease injury recovery time; increase delivery of oxygen to exercising tissues; mask pain; stimulate the body; relax; reduce weight or hide the use of other drugs.

Why are these drugs so appealing to athletes? Besides making muscles bigger, anabolic steroids may help athletes recover from a hard workout more quickly by reducing the muscle damage that occurs during the session. This enables athletes to work out harder and more frequently without overtraining. In addition, some athletes may like the aggressive feelings they get when they take the drugs.

Athletes face enormous pressure to excel in competition. They also know that winning can get them more than a gold medal. A star athlete can earn a lot of money and a lot of fame and athletes only have a short time to do their best work. Athletes know training is the best path to victory, but they also get the message that some drugs and other practices can boost their efforts and give them a shortcut, even as they risk their health and their athletic careers.

Are PEDs ever used for medical reasons? 
Anabolic steroids are used therapeutically in medicine to induce bone growth, stimulate appetite, induce male puberty and treat chronic wasting conditions, such as cancer and HIV/AIDS.

EPO is used in treating anemia resulting from chronic kidney disease and myelodysplasia from the treatment of cancer.

In children, HGH injections are approved for treating short stature of unknown cause as well as poor growth due to a number of medical causes.

In adults, approved uses of HGH include:

• Short bowel syndrome, a condition in which nutrients are not properly absorbed due to severe intestinal disease or the surgical removal of a large portion of the small intestine
• HGH deficiency due to rare pituitary tumors or their treatment
• Muscle-wasting disease associated with HIV/AIDS

What are the consequences of using PEDs improperly? 

Men may develop:

• Prominent breasts
• Baldness
• Shrunken testicles
• Infertility
• Impotence

Women may develop:

• A deeper voice
• An enlarged clitoris
• Increased body hair
• Baldness
• Infrequent or absent periods

Both men and women might experience:

• Severe acne
• Increased risk of tendinitis and tendon rupture
• Liver abnormalities and tumors
• Increased low-density lipoprotein, LDL cholesterol (the “bad” cholesterol)
• Decreased high-density lipoprotein, HDL cholesterol (the “good” cholesterol)
• High blood pressure/hypertension
• Heart and circulatory problems
• Prostate gland enlargement
• Aggressive behaviors, rage or violence
• Psychiatric disorders such as depression
• Drug dependence
• Infections or diseases such as HIV or hepatitis if you’re injecting the drugs
• Inhibited growth and development and risk of future health problems in teenagers

What symptoms could help identify someone who is abusing PEDs?

Possible red flags include:

• Behavioral, emotional or psychological changes — particularly increased aggressiveness (“roid rage”)
• Changes in body build, including muscle growth, rapid weight gain and development of the upper body
• Increased acne and facial bloating
• Needle marks in the buttocks or thighs
• Enlarged breasts in boys or smaller breasts in girls
• The bottom line… people who are abusing PEDs will not be themselves.

Is damage done from improper use of PEDs reversible? 

     In males, changes that can be reversed include reduced sperm production and shrinking of the testicles (testicular atrophy). Irreversible changes include male-pattern baldness and breast development (gynecomastia).

In the female body, anabolic steroids cause masculinization. Breast size and body fat decrease, the skin becomes coarse, the clitoris enlarges and the voice deepens. Women may experience excessive growth of body hair but lose scalp hair. With continued administration of steroids, some of these effects become irreversible.

Rising levels of testosterone and other sex hormones normally trigger the growth spurt that occurs during puberty and adolescence and provide the signals to stop growth as well. When a child or adolescent takes anabolic steroids, the resulting, artificially high, sex hormone levels can prematurely signal the bones to stop growing.

Steroid abuse has been associated with cardiovascular diseases, including heart attacks and strokes, even in athletes younger than 30.

Many abusers who inject anabolic steroids may use nonsterile injection techniques or share contaminated needles with other abusers. In addition, some steroid preparations are manufactured illegally under nonsterile conditions. These factors put abusers at risk for acquiring life-threatening viral infections, such as HIV and hepatitis B and C.

The most dangerous of the withdrawal symptoms from anabolic steroid use is depression because it sometimes leads to suicide attempts.

References:

http://www.resoundinghealth.com/casebook/show/206

http://www.dmos.com/articles/Honkamp_Youth_Athletes_Feb_08.pdf

http://www.mayoclinic.com/health/performance-enhancing-drugs/HQ01105

Hayashi, A, AAOS Now,” PED use: Legal, natural, and deadly”, Oct 2008
Schafer, M, Porucznik, M, AAOS Now, “If you’re not cheating, you’re not trying”, June 2008

Inhaled corticosteroids in severe COPD.

Guidelines and care pathways recommend inhaled corticosteroids (ICSs) over longacting bronchodilators in the treatment of patients with severe chronic obstructive pulmonary disease (COPD).1, 2 A Cochrane review3 about the safety and efficacy of combined ICSs and longacting β2 agonists (LABAs) in one inhaler versus LABAs alone for COPD was published in September, 2012. Although the analysis was based on a large database (14 studies, 11 794 people), the conclusions were unclear about prevention of exacerbations, hospital admission, and mortality. Furthermore, moderate-quality evidence suggested an increased risk of pneumonia with ICS—LABA combinations. The authors concluded that more information about the relative benefits and adverse event rates of ICS—LABA combinations versus LABAs alone would be useful and that head-to-head comparisons are needed.3

Fluticasone furoate is a new ICS and vilanterol a new LABA. Both drugs are given once daily. A single inhaler combination of these drugs improved forced expiratory volume in 1 s (FEV1) after a short duration of treatment.4 In The Lancet Respiratory Medicine, Mark T Dransfield and colleagues5 report the results of the first long-term study comparing fluticasone furoate and vilanterol with vilanterol alone for major outcomes of COPD (ie, moderate or severe exacerbations). Two pooled multinational randomised controlled trials (study 1 and study 2) of 3255 patients with severe COPD ran for 52 weeks. Mean FEV1 after bronchodilators was 44—46% of predicted values. Three doses of fluticasone furoate were tested—50 μg, 100 μg, and 200 μg—all in combination with 25 μg vilanterol. The primary efficacy endpoint was the yearly rate of moderate or severe exacerbations. The authors defined moderate exacerbations as worsening symptoms of COPD (≥2 consecutive days) necessitating treatment with oral corticosteroids or antibiotics, or both; severe exacerbations were similar events that necessitated admission to hospital.

Dransfield and coworkers’ study5 is of great interest because it is, to my knowledge, the first investigating the combination of fluticasone furoate and vilanterol for major outcomes of COPD, and because it attempts to answer the queries that arose from the Cochrane review.3 Pneumonia occurrence was recorded and confirmed with chest radiographs. The study was very carefully done, although an independent expert panel did not assess severe adverse events, which might have led to underestimation of pneumonia risk.

The effect of fluticasone furoate and vilanterol compared with that of vilanterol alone is not large. In study 1, no significant difference in exacerbation rate was noted between the 200/25 μg fluticasone furoate/vilanterol group and the vilanterol only group. In study 2 and the prespecified pooled analysis, exacerbation rates were significantly lower in all fluticasone furoate/vilanterol groups than in the vilanterol only group. The frequency of only moderate exacerbations was significantly lower with fluticasone furoate and vilanterol than with vilanterol alone. Hospital admissions were uncommon in the studies and did not differ significantly between treatment groups. Thus, the additive effect of fluticasone furoate could not be shown—results that accord with those of the Cochrane review3 and reinforce the strength of evidence.

The safety of ICSs in COPD is a serious problem, which was underscored by Dransfield and colleagues’ results.5 Pneumonia (confirmed by radiography) and fractures were reported more frequently with fluticasone furoate and vilanterol than with vilanterol alone in studies 1 and 2 and the pooled analysis. Furthermore, severe cases of pneumonia were more frequent in the fluticasone furoate/vilanterol groups than in the vilanterol group. Eight pneumonia-related deaths were reported during treatment, seven participants taking 200 μg fluticasone furoate and one taking 100 μg fluticasone furoate. One case of fatal pneumonia was reported after treatment in the vilanterol only group. The authors raised concerns about the 200/25 μg dose. However, mortality was not increased in any study group, according with the results of Dong and colleagues.

Patients and clinicians should assess the potential benefits and risks of ICSs in severe COPD. For a practising physician, establishing which patients need ICSs (and which do not) is crucial. Randomised controlled studies published so far cannot answer this question because their results are based on means from large groups of patients. The phenotypic characteristics of patients who benefit from ICSs and those of patients prone to pneumonia would be of interest. Dransfield and coworkers’ study might enable an analysis of practical interest. It shows that the debate about ICSs in patients with severe COPD is not yet over, and suggests that a personalised medicine approach is needed for such patients.

Source: lancet

 

 

 

Phase 3 study: Canagliflozin improved beta cell function.

An SGLT2 inhibitor recently approved by the FDA may improve measures of beta cell function in addition to glycemic control in patients already taking metformin plus sulfonylurea, according to phase 3 study results presented here at the AACE Annual Scientific and Clinical Congress.

“Despite the fact it doesn’t act directly on the beta cells, there is a lot of evidence from previous studies that SGLT2 inhibitors can improve beta-cell function,” David Polidori, PhD, of Janssen Research & Development, LLC, said here during a presentation.

Polidori and colleagues conducted a 26-week, randomized, double blind, placebo controlled study to evaluate canagliflozin (Invokana, Janssen) 100-mg and 300-mg compared with placebo as an add on to metformin plus sulfonylurea in patients with type 2 diabetes (n=469; mean age, 57 years). The mean baseline HbA1c level was 8.1%, BMI was 33 kg/m², and duration of diabetes was 9.6 years, according to data.

Of the 469 patients, 168 were administered a meal tolerance test at baseline and week 26. Their plasma glucose and serum C-peptide levels were measured seven times over a 3-hour period.

Polidori reported that at week 26, canagliflozin 100 mg significantly reduced HbA1c by –0.71% and 300 mg  by –0.92% compared with placebo (P<.001).

Further data indicate that the insulin secretion rates (ISR) vs. glucose relationship did not change with placebo. However, the relationship shifted upwards in both canagliflozin doses, Polidori said. This indicated an increase in ISR at each plasma glucose concentration, according to data.

Measures of beta cell function, including the ratio of C-peptide to glucose, were approximately 20% higher than baseline levels in both canagliflozin groups (P=.051 for 100 mg and P=.056 for 300 mg) but remained relatively unchanged in the placebo group. Mean beta cell glucose sensitivity was also increased by about 20% in both canagliflozin groups (P=.14 for 100 mg andP=.22 for 300 mg).

Additionally, mean ISR at 9 mM of glucose increased by about 50% to 60% in both canagliflozin groups (P=.02 for 100 mg and P=.007 for 300 mg), but remained relatively unchanged in the placebo group.

“Consistent with what we’ve seen in patients at earlier stages of diabetes and in some of the animal studies, both doses of canagliflozin improved the measures of beta cell function that we looked at in the meal tolerance test in these more advanced patients who were already inadequately controlled on dual therapy. This is promising,” Polidori said. “This is 26-week data and we’re certainly interested to see longer term data to see if this type of treatment can better prolong beta cell function and hopefully slow the rate of progression of type 2 diabetes.” – by Samantha Costa

Source: Endocrine Today

 

 

FDA Approves New Cholesterol-Cutting Combination Drug .

The FDA has approved a new ezetimibe-atorvastatin tablet (brand name, Liptruzet) for lowering cholesterol in patients with primary or mixed hyperlipidemia, and in those with homozygous familial hypercholesterolemia.

In a trial of some 620 patients, the once-daily tablet reduced LDL cholesterol by 53% at the lowest dose (10/10 mg) and 61% at the highest dose (10/80 mg). Common side effects include changes in liver function tests, muscle pain, memory loss, and tendon problems.

The combination treatment has not been shown to improve cardiovascular outcomes better than atorvastatin, which has some cardiologists questioning the FDA’s decision. Steven Nissen, chairman of cardiology at the Cleveland Clinic, says in Forbes that the agency seems to be “tone deaf” to concerns “about approving drugs with surrogate endpoints like cholesterol without evidence of a benefit for the disease [cardiologists] are truly trying to treat — cardiovascular disease.”

Source: Forbes 

 

 

 

Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea.

Abstract

Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting.

Source: JCO