1 % esquizofrenia

Destacados:

"Nadie estamos libres de padecer esta enfermedad"

"A día de hoy, NADIE sabe lo que es la esquizofrenia"

"Tan pronto te sientes bien como te sientes fatal"

"Quienes realmente entienden la enfermedad, son los enfermos mismos"

"Parece que no hay nada que te motive, que te guste"

"Tienes miedos, pero en realidad, no dejan de ser sentimientos"

"La esquizofrenia es la dificultad de control de la propia voluntad"

"No hay personas enfermas, sino personas vulnerables"

"Las mujeres toleran mejor los tratamientos que los hombres"

"Es una enfermedad misteriosa, enigmática, conmovedora y que produce pánico"

A quien no está enfermo; a la sociedad

"La causa es genética, por una alteración familiar; pero también puede deberse

a factores ambientales, familiares y educacionales unidos. Probablemente ya haya 

una vulnerabilidad biologica"

"Puede deberse también a una desorganización social general,

es decir, que una sociedad sea LOCA"

"El miedo que tienen los enfermos es muy grande."

"A los enfermos les asusta, a veces, las relaciones que tienen con las personas"

"Muchas personas piensan que en el origen y el fondo de la esquizofrenia

hay unas vivencias de angustia brutales: ANGUSTIA PSICÓTICA"

"Los enfermos tienen miedo de lo que estan viendo y además, tienen miedo

de descontrolarse; precisamente porqué viven situaciones que no controlan"

"Los enfermos se aislan mucho del entorno.

Tienen miedo de poder hacer daño, mucho miedo"

"Los enfermos, en cuanto se ponen un poco

mal, enseguida tienen mucho miedo.

Les da mucho miedo la vida"

"La angustia se manifiesta de dos maneras: miedo a la muerte y miedo

a la locura. Son los 2 miedos más radicales de la realidad humana"

"El problema de la esquizofrenia es el miedo a uno mismo.

También el miedo a la locura de uno mismo"

"El miedo a uno mismo hace que se aisle

mucho mas del resto de las personas"

"Todos tenemos y nos sentimos reflejados a lo

que muestran los enfermos, pero a distinto nivel"

"A la sociedad le cuesta muchísimo ver comportamientos diferentes"

"Para los enfermos es muy duro ser rechazados"

"El esquizofrénico, generalmente, es una persona muy exigente consigo misma"

"Las familías transmiten la idea de que tienes que llegar a mucho, 

les exigen mucho o ser mucho; con padres muy autoritarios"

"Los enfermos tienen miedo a equivocarse, a fallar"

"Soy distante, desconfiado. Me da miedo abrirme a mi familia"

"En las familias esquizofrenógenas siempre hay dos niveles

de comunicación, el doble vínculo o el doble mensaje"

"Los factores familiares son lo no hablado, lo no dicho, sin embargo es sentido

y percibido. Bolsas de comunicación que no se tocan pero que están siempre presentes"

"Hay posibilidades de que la enfermedad destructure la familia"

"El enfermo es muy exigente"

"Los familiares, hagan lo que hagan no le ven mejor;

hagan lo que hagan no le ven más contento"

"Las familias buscan la curación, no importa el precio. No se creen al principio lo

que se les dice. Mientras estés en esa fase de negar, nunca llegarás a asumir"

"Los familiares, una vez el hijo ha sido diagnosticado con

esquizofrenia, superprotegen al hijo o lo rechazan"

"Las familias no veran cumplidos sus deseos de ver en el un ganador, una persona

que hace una vida normal, que crea una família..."

"Los esquizofrénicos pueden llegar a no responder de sus actos"

"Los esquizofrénicos piensan mucho, dan muchas vueltas a las cosas"

"Al principio piensas que las personas son malas, pero

al final te planteas que la mala debo de ser yo (enferma)"

"El 20% de la población reconoce tener delirios y alucinaciones"

"El ciudadano que sufre psicosis no es consciente de la enfermedad,

por lo que no va a ir voluntáriamente al médico"

"Se notan mucho las crisis por la desvariación del sueño, y estas

acaban desvariando el resto de los sentidos"

"Si el enfermo se aisla y se encierra en la habitación,

entra en un proceso delirante"

"El brote aparece de manera progresiva, o de la noche a la mañana"

"Algunos delirios son agradables. Puedo salvar el mundo, puedo con todo"

"La asociación de esquizofrenia con agresividad está lejísimos de la realidad"

"Estadísticamente, los enfermos esquizofrénicos son menos 

agresivos que la población general"

"Los casos puntuales de agresividad por parte

de esquizofrénicos son muy llamativos"

"El primer ingreso siempre resulta ser una situación traumática"

"Los esquizofrénicos se plantean el suicidio cuando están con muy baja autoestima

(has perdido el tiempo en tu vida, no sacas nada claro, que triste es mi vida,

la incomprensión de todo...)"

"La investigación viene financiada y pagada por la

indústria farmacológica"

"Una iniciativa psicosocial puede no llegar nunca. Algo que se ha

probado que funciona en un lugar, no se disemina"

"La farmacología ofrece de forma rápida una anulación de los síntomas,

que es lo que molesta al entorno. Se pueden tratar los síntomas sin tratar

la enfermedad (se puede hacer caminar a un cojo)"

"El delirio no se puede dejar extender, de ahí los fármacos que lo paralizan"

"Es más fácil dar una pastilla a un familiar y anularle, 

en vez de estar una hora hablando intentando saber

cuál es el problema que tienes"

"La intervención psicoterapéutica de los servicios públicos de salud

mental no se puede dar a todos los enfermos, pero la farmacológica sí"

"No se le habla a los pacientes de los efectos secundarios de

la medicación, temen que no se la puedan tomar"

"Si tu das un medicamento y das hora hasta dentro de 2-3 meses,

tu ya no puede controlar el efecto secundario, una vez el 

medicamento ha sido introducido"

"La medicación les ponen feo, les engordan, les deterioran,

la medicación les influye"

"Si no tienen mucho deseo, les cuesta eyacular o NO eyaculan"

"La menstruación en mujeres les va y viene cuando quiere"

"La medicación causa muchos efectos extrapiramidales,

moviendo mucho las manos y los pies"

"Las ganas de llorar te las impide en antidepresivo"

"Conducir un delirio hacia un acto creativo o hacia

algo donde pudiera salir (pintura, danza, escultura...), siempre

y cuando el enfermo tenga necesidad de expresión simbólica.

Pero deben estar dirigidos"

"De esta manera, el enfermo no tendría tanto miedo en delirar

ni en alucinar porqué el psicoanalista podría reconducir esos delirios

y alucinaciones"

"La burocracia en salud mental es terrible"

"La esquizofrenia es, por definición, crónica; pero se cura y recupera"

"El tratamiento en la esquizofrenia es tener esperanza. Nunca
perderla pero nunca hacerse grandes esperanzas"

"Un psiquiatra sólo no es capaz de tratar una esquizofrenia"

"Estamos lejos de tener cubiertas las necesidades de salud mental"

"La OMS/WHO advierte que la esquizofrenia augmentará y será uno
los problemas más graves del siglo XXI"

"Cada vez se diagnostíca más"

"Es más frecuente en urbes que en población rural"

"Es una enfermedad enormemente humana"

"Los esquizofrénicos son grandes luchadores ya 
que se sobreponen a enfermedades enormes"

"Les da mucho miedo el futuro"

"Se plantean el si no hubiesen existido"

What Is Xanax/Alprazolam?

Xanax (Alprazolam) is a commonly prescribed drug to help alleviate symptoms of anxiety and panic. It's manufactured by Pfizer Inc.

Xanax belongs to a class of drugs called benzodiazepines, which are central nervous system depressants that work by enhancing the effect of the neurotransmitter "gamma-aminobutyric acid" (GABA).

GABA is essentially the brain's tranquilizing neurotransmitter. Xanax binds to certain sites on the GABAA gamma-amino-butyric acid receptor, slowing down activity in the brain, producing a calming effect.

Xanax is a benzodiazepine with a very fast onset of action. Most people feel its effects kick-in within 20 minutes of ingestion - peak effects of the drug are normally achieved within an hour.

Initially approved by the US FDA in 1981 for the treatment of anxiety, Xanax became the first FDA-approved drug for panic disorder therapy in 1990.

Since its approval the drug has become one of the most prescribed, yet also one of the most misused benzodiazepines available - because of its high potential for abuse and dependence.

Medical uses of Xanax

Xanax is one of America's most popular anti-anxiety medications.

Xanax is primarily used to treat panic and anxiety disorders, such as social anxiety disorder (SAD) and generalized anxiety disorder (GAD). Xanax is also used to alleviate nausea after chemotherapy.

According to the FDA, "Demonstrations of the effectiveness of XANAX by systematic clinical study are limited to 4 months duration for anxiety disorder and 4 to 10 weeks duration for panic disorder."

Managing anxiety

The FDA has approved Xanax for short-term treatment of anxiety and for the management of certain anxiety disorders. Several high quality studies have demonstrated its efficacy in reducing anxiety.

A large-scale double blind study found that Xanax was effective in improving symptoms of anxiety in 151 anxious outpatients; the results of the study, published in the American Journal of Psychiatry, revealed that "alprazolam and diazepam produced similar clinical improvement, which was significantly larger than improvement produced by placebo and was clearly evident after only 1 week of treatment."

Panic disorder

Xanax is considered to be an effective medication for panic attacks. However, due to its potential for abuse it is not a first line treatment option. One study, published in the Journal of Clinical Psychopharmacology, concluded that "evidence fails to demonstrate alprazolam as superior to other benzodiazepines for the treatment of panic disorder."

A report in the Primary Care Companion Journal of Clinical Psychiatry noted that for treatment of panic disorder "four drug classes have similar efficacy (tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs], benzodiazepines, and monoamine oxidase inhibitors)."

The World Federation of Societies of Biological Psychiatry (WFSBP) only recommends the use of Xanax for the treatment of panic disorder when the patient shows no history of tolerance or dependence.

Precautions

Pregnant women should not take Xanax as it can cross the placenta and affect the fetus, increasing the risk of congenital abnormalities. In addition, taking Xanax during the last trimester of pregnancy can result in fetal drug dependence.

Doctors should be especially careful with patients who have a history of drug dependence when considering Xanax therapy.

Side effects of Xanax may include:

- Dry mouth
- Slurred speech
- Drowsiness
- Disinhibition
- Skin rash
- Constipation
- Hallucinations (very rare)

Dependence and withdrawal

Xanax - like all other benzodiazepines - binds to certain GABA receptors (called benzodiazepine receptors), prolonged use of the drug can eventually cause adaptive changes in these receptors, making them less sensitive to the drug's effect. When this occurs a higher dosage of Xanax is required for the same initial effect to be felt, increasing the risk of physical dependence and tolerance.

According to a paper published in the journal Addiction:

"Physiological dependence on benzodiazepines can occur following prolonged treatment with therapeutic doses, but it is not clear what proportion of patients are likely to experience a withdrawal syndrome."

"Withdrawal from normal dosage benzodiazepine treatment can result in a number of symptomatic patterns. The most common is a short-lived "rebound" anxiety and insomnia, coming on within 1-4 days of discontinuation, depending on the half-life of the particular drug. The second pattern is the full-blown withdrawal syndrome, usually lasting 10-14 days; finally, a third pattern may represent the return of anxiety symptoms which then persist until some form of treatment is instituted."

Signs and symptoms of Xanax dependence include:

- Being unable to cope without the medication
- Severe withdrawal symptoms in between doses
- Tolerance to the effects of the drug
- Unsuccessful attempts to stop taking the drug

Withdrawal symptoms include:

- Increased anxiety
- Depression
- Trouble sleeping
- Depersonalization
- Tremors
- Headache
- Muscle pains
- Hypersensitivity to touch
- Shakiness
- Twitching

It is important to taper off Xanax gradually, otherwise there is a risk of benzodiazepine withdrawal syndrome.

Source

Aemps: “La polémica sobre los equivalentes no existe en el plano clínico, sólo en el económico”

César Hernández García, jefe del departamento de Medicamentos de Uso Humano de la Agencia Española de Medicamentos y Productos Sanitarios (Aemps), ha afirmado este viernes que no existe una definición reglada de equivalentes, "ni tal vez sea necesaria", y eso no ha impedido que los médicos hayan trabajado siempre con criterios de alternativas terapéuticas en los tratamientos de cada paciente. "Si ahora hay un debate se debe a que detrás del intento de crear definiciones generales y categorías de erquivalentes está el precio y el propósito de condicionar el mercado", ha añadido.

Estas declaraciones fueron realizadas en una jornada que, con el título de ¿Existe la equivalencia terapéutica? La opinión de los expertos, han organizado en Madrid la Fundación Ad Qualitatem y PSN.

DEBATE ENTRE PROFESIONALES

Médicos, farmacéuticos de hospital, gestores y representantes de la industria han participado en el debate. "El problema no está en discutir si existen o no equivalentes terapéuticos ni qué organismo es el competente para definirlos, sino para qué se quieren una vez definidos", ha señalado Emili Esteve, director técnico de la patronal española de la industria innovadora, Farmaindustria. Porque, ha añadido, se puede estar induciendo un proceso en el que se reduzca la competencia entre medicamentos, se limite la prescripción de los médicos y se atienda con menos garantías a los pacientes. Esteve ha calificado de "muy importante" el cambio introducido en la Ley de Garantías, artículo 88, al señalar que cada decisión sobre medicamentos tomada por Sanidad será de aplicación en todo el territorio nacional, reduciendo la capacidad de las autonomías de aprobar iniciativas propias en la política de medicamentos.

Más pragmático se ha mostrado José Santiago Rabanal, gerente del Hospital Universitario de Cruces, Bilbao, que ha subrayado que en el Servicio Vasco de Salud hay una larga experiencia en trabajar con equivalentes y que éstos tienen una importante repercusión en la contención del gasto. Eso hay que tenerlo en cuenta, ha explicado, aunque también hay que admitir que "los tratamientos son de cada paciente y generalizar es complicado". En este sentido, José Luis Poveda, presidente de la Sociedad Española de Farmacia Hospitalaria (SEFH), ha afirmado en su intervención que los profesionales sanitarios han trabajado siempre con alternativas terapéuticas, que son instrumentos útiles y que tienen una indudable repercusión en el gasto por lo que debe usarse el sentido común, dejar el dogmatismo y abordar este asunto desde la clínica y la eficiencia, "como trabajan siempre los profesionales de la sanidad".

NO PARA LOS ONCOLÓGICOS

El más crítico con los equivalentes terapéuticos ha sido Juan Jesús Cruz, presidente de la Sociedad Española de Oncología Médica, que ha afirmado que, "al menos en el terreno oncológico no se puede hablar de equivalencias, pues cada paciente tiene un perfil propio y además, hacerlo, acabaría con la libertad de prescripción y afectaría a los pacientes".

Fuente

Clear evidence that long-term obesity can lead to heart disease

Researchers have tracked thousands of people in the three decades since the mid-1980s to see what effect getting obese might have on their heart risks. They say this is one of the few studies that can give proof of the consequences of long-term obesity.

Follow-up of the 3,275 adults - who were not obese at the start of the research in 1985-1986 - found that those who became obese were more likely to have coronary artery calcification (hardening of the arteries supplying the heart), a problem that can lead to a heart attack.

Of the people who became obese, the earlier they did - and the longer they stayed overweight - the more likely they were to be at risk of coronary artery disease. This risk was decided by computed tomography (CT), a form of X-ray scan that was used to pick up artery calcification.

The research participants were aged between 18 and 30 years at the beginning of the study, which has just been published in the Journal of the American Medical Association. They were almost equal in numbers of men and women, and in proportion of white and black people.

Study examined both "overall" and "abdominal" obesity

Two measures of obesity were made at specific points during the long-term study. Overall obesity was worked out by measuring body-mass index (BMI), and abdominal obesity was measured by waist circumference. These checks were done at 2, 5, 7, 10, 15, 20, and 25 years after baseline.

Being obese was defined as:
- Having overall obesity with a BMI of at least 30
- Having abdominal obesity with a waist circumference of more than 40.2 inches (102cm) in men, 34.6 inches (88cm) in women.

During follow-up, 40% and 41% of the subjects developed overall and abdominal obesity, respectively. The average duration of each type of obesity was 13 years and 12 years, respectively. The CT scans to check for hardening of the coronary artery were done at 15 years (in 2000-2001), 20 years (2005-2006), and 25 years (2010-2011).

There was an almost double chance of finding hardened coronary arteries in the people who were obese for 20 years or more, compared with the people who had never become obese.

The researchers - Jared Reis of the National Heart, Lung, and Blood Institute, Bethesda, MD, and colleagues - give percentage values for these results: "Approximately 38.2% and 39.3% of participants with more than 20 years of overall and abdominal obesity, respectively, had coronary artery calcification, compared with 24.9% and 24.7% of those who never developed overall or abdominal obesity."

Not only was the presence of artery hardening more likely in the obese people, but the longer people were too big, the greater the extent to which calcification got worse (disease "progression").

The authors conclude:

"These findings suggest that the longer duration of exposure to excess adiposity as a result of the obesity epidemic, and an earlier age at onset, will have important implications on the future burden of coronary atherosclerosis and potentially on the rates of clinical cardiovascular disease in the United States."

The study has been given the name CARDIA - Coronary Artery Risk Development in Young Adults. It is a large, multi-center, community-based study published in a world-renowned medical journal.

The design of the study, which set out to track future changes over time, means that the association between obesity and heart disease risk is a reliable one. This is because it was a "prospective" study as opposed to a "retrospective" one in which links are drawn from past data.

Source

Cauliflower Prevent Various Cancers

Cauliflower contains glucosinolates and thiocyanates — both sulfur-containing phytonutrients that cleanse the body of damaging free radicals. It also contains a substance called sulforaphane (SFN), a compound known to inhibit the occurrence of some cancers in rats caused by carcinogens, primarily colon cancer.

In the Rutger’s research, it was found once again that diet does matter in cancer prevention:

“Our research has substantiated the connection between diet and cancer prevention, and it is now clear that the expression of cancer-related genes can be influenced by chemopreventive compounds in the things we eat,” said Kong, a professor of pharmaceutics in the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey.

Even the American Cancer Society admits that more than two thirds of cancers can be prevented with lifestyle modification, and this includes diet. In this particular study, mice fed a diet high in sulforaphane, the substance naturally occurring in cauliflower and broccoli, enjoyed fewer cancerous tumors, polyps, and smaller tumors in the their colons. After three weeks, the mice fed sulforaphane had a 25% decline in tumors and those given double the dose had a 47% decrease in cancerous tumors.

The results are obvious, “Our results showed that SFN produced its cancer preventive effects in the mice by inducing apoptosis (programmed cell death) and inhibiting proliferation of the tumors; however, it was not clear what mechanism SFN employs to accomplish this,” Kong said.

Just how vegetables like cauliflower (and other cruciferous vegetables) help to kill cancer cells is still unknown, but Kong’s team found that SFN suppressed certain enzymes or kinases that are highly expressed both in the mice and in patients with colon cancer. The researchers concluded that this enzymatic suppression activity is the likely basis for the chemopreventive effects of SFN.

Along with cauliflower’s high levels of SFN, it is also a powerful antioxidant with high levels of vitamin C and vitamin A, also known as cancer inhibitors. Researchers also believe that if you consume cauliflower and turmeric spice together, you can prevent or eradicate prostate cancer totally. The scientists, once again from Rutger’s, tested turmeric and it’s active compound known as curcumin along with phenethyl isothiocyanate (PEITC), a naturally occurring substance in certain vegetables such as watercress, cabbage, winter cress, broccoli, Brussels sprouts, kale, cauliflower, kohlrabi and turnips. They found cancer-preventative qualities in the duo.

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Hambúrguer chef Jamie Oliver has just won a battle against McDonald's

Hambúrguer chef Jamie Oliver has just won a battle against one of the largest fast food chains in the world. After Oliver showed how McDonald’s hamburgers are made, the franchise announced it will change its recipe.

According to Oliver, the fatty parts of beef are “washed” in ammonium hydroxide and used in the filling of the burger. Before this process, according to the presenter, the food is deemed unfit for human consumption.

According to the chef and presenter, Jamie Oliver, who has undertaken a war against the fast food industry: “Basically, we’re taking a product that would be sold in the cheapest way for dogs, and after this process, is being given to human beings.”

Besides the low quality of the meat, the ammonium hydroxide is harmful to health. Oliver calls it “the pink slime process.”

“Why would any sensible human being put meat filled with ammonia in the mouths of their children?” asked the chef, who wages a war against the fast food industry.

In one of his initiatives, Oliver demonstrates to children how nuggets are made. After selecting the best parts of the chicken, the remains (fat, skin and internal organs) are processed for these fried foods.

The company, Arcos Dorados, the franchise manager in Latin America, said such a procedure is not practiced in the region. The same applies to the product in Ireland and the UK, where they use meat from local suppliers.

In the United States, Burger King and Taco Bell had already abandoned the use of ammonia in their products. The food industry uses ammonium hydroxide as an anti-microbial agent in meats, which has allowed McDonald’s to use otherwise “inedible meat.”

Even more disturbing is that because ammonium hydroxide is considered part of the “component in a production procedure” by the USDA, consumers may not know when the chemical is in their food.

On the official website of McDonald’s, the company claims that their meat is cheap because, while serving many people every day, they are able to buy from their suppliers at a lower price, and offer the best quality products.

In addition, the franchise denied that the decision to change the recipe is related to Jamie Oliver’s campaign.

On the site, McDonald’s has admitted that they have abandoned the beef filler from its burger patties.

Source

4 Foods that Help You Detox Safely and Gently

When you think of removing all the toxins from your body, you may shudder at the process – especially when considering that some experts estimate that we are exposed to 2,100,000 toxins each and every day. While there are numerous approaches to detoxing these poisons out of the body, many of them involve unpleasant side effects. Fortunately, there are gentler approaches to detoxing too.

Every day we come in contact with numerous toxins and pollutants. These toxins come from chemicals in our carpet, plastics, body care products and the air we breathe. But they also come from our water and our food choices. Cumulatively, the pollutants in our environment can have untold negative effects on our health and well-being. This is why keeping your exposure to a minimum may not be enough.

If you aren’t one for dramatic flushes or fasts, the following foods and herbs can offer a gentle detox.

1. Cilantro is a great herb that’s easy to find and simple to incorporate into your daily regimen. You can cook with it, juice it, or eat it raw. You can even find cilantro juice already made at your local health food store. Cilantro is a great detoxifier of mercury and other heavy metals. Cilantro’s antibacterial and antifungal properties make the herb work to reduce inflammation and infections while cleansing.
2. Wheatgrass is another versatile detoxifier. You can grow it yourself or find it in an increasing number of grocery stores. It’s potent so start slow with just a tiny amount of juice in your daily routine.
3. Pectin is found naturally in fruits like apples, citrus, grapes, and bananas. It helps remove heavy metals and other toxins. You can easily get the benefits of this natural detoxing agent by adding pectin-rich foods to your diet. Also, you can add pectin products to your smoothie or water. Be wary of pectin products that contain MSG.
4. Other greens like parsley, alfalfa, and chlorella are also great at chelating heavy metals and detoxing the body. You can juice any one of these or add them to salads.

To make your detox as gentle as possible stay hydrated, eliminate all processed and harmful foods, and listen to your body. You can avoid detox side-effects (a healing crisis), common in some more extreme fasts and detoxes, by simply paying attention to your body’s cues and taking heed.

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Drinking Water Can Boost Cognitive Performance

There is evidence that mild dehydration has a negative effect on the brain's performance. Caroline Edmonds and colleagues from the University of East London and the University of Westminster here report that drinking water can improve performance on tasks that require a rapid response, particularly when thirsty.

They tested 34 adults, who had not eaten or drunk anything overnight, for memory, attention, learning, and reaction time. Subjects were tested on two mornings: once after they had consumed a cereal bar and water, and once after eaten a cereal bar only.

Reaction times were up to 14% shorter after drinking water, especially for those who felt thirsty. Unexpectedly, performance on a complex-rule-learning task became slightly worse after drinking. Future research will have to determine why drinking water can be beneficial for some cognitive tasks, but not for others, say the authors.

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Children With Type 1 Diabetes Helped To Produce Their Own Insulin With Diet Additions

Adding foods rich in specific amino and fatty acids to the diets of youth with Type 1 diabetes kept them producing some of their own insulin for up to two years after diagnosis, said researchers at the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill."

The youth still required supplemental insulin, but they may have reduced risk of diabetes complications by continuing to produce some of their own insulin, said Elizabeth Mayer-Davis, professor of nutrition at Gillings and medicine at UNC's School of Medicine, who led the study of more than 1,300 youth. "This also opens the door for a new approach that could really benefit the lives of these children."

The study, "Nutritional Factors and Preservation of C-Peptide in Youth with Recently Diagnosed Type 1 Diabetes," was published in the July 2013 issue of the journal Diabetes Care.

The participating youngsters, ranging from toddlers up to age 20, are part of a multi-center "SEARCH for Diabetes in Youth," the largest U.S. study of childhood diabetes. Mayer-Davis is national co-chair of SEARCH, funded by the national Centers for Disease Control and Prevention and the National Institutes of Health.

Type 1 diabetes is almost always diagnosed between infancy and young adulthood, according to the American Diabetes Association. The body's pancreas is unable to produce adequate amounts of the hormone insulin, required to metabolize food properly and create energy for the body's cells.

Leucine, one of the branched-chain amino acids researchers looked at, is known to stimulate secretion. It is found in dairy products, meats, soy products, eggs, nuts and products made with whole wheat. Long-chain omega-3 fatty acids are found in fatty fish such as salmon.

The researchers analyzed how much (if any) insulin the subjects were producing up to two years after their diagnosis and compared this with nutritional intake.

Mayer-Davis noted the study reflects subjects eating actual foods rich in these nutrients, not taking supplements.

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Walnut-Enriched Diet Leads To Fewer, Smaller Prostate Cancers

New research from the School of Medicine at The University of Texas Health Science Center San Antonio indicates that eating a modest amount of walnuts can protect against prostate cancer.

The study is described in the journal Cancer Investigation. Researchers at the UT Health Science Center injected immune-deficient mice with human prostate cancer cells. Within three to four weeks, tumors typically start to grow in a large number of these mice. The study asked whether a walnut-enriched diet versus a non-walnut diet would be associated with reduced cancer formation. A previous study found this to be true for breast cancer.

Results

Three of 16 mice (18 percent) eating the walnut-enriched diet developed prostate tumors, compared with 14 of 32 mice (44 percent) on the non-walnut control diet. Also of note, the final average tumor size in the walnut-fed animals was roughly one-fourth the average size of the prostate tumors that developed in the mice eating the control diet.

"We found the results to be stunning because there were so few tumors in animals consuming the walnuts and these tumors grew much more slowly than in the other animals," said study senior author Russel Reiter, Ph.D., professor of cellular and structural biology at the Health Science Center. "We were absolutely surprised by how highly effective the walnut diet was in terms of inhibition of human prostate cancer."

Percentage of diet

The mice consumed a diet typically used in animal studies, except with the addition of a small amount of walnuts pulverized into a fine powder to prevent the rodents from only eating the walnuts. "The walnut portion was not a large percentage of the diet," Dr. Reiter said. "It was the equivalent to a human eating about 2 ounces, or two handfuls, a day, which is not a lot of walnuts."

Study co-author W. Elaine Hardman, Ph.D., of the Joan C. Edwards School of Medicine at Marshall University, published a study in 2011 that showed fewer and smaller tumors among walnut-fed mice injected with human breast cancer cells. Dr. Hardman formerly was a faculty member at the Health Science Center.

"The data to date suggest that using walnuts on a regular basis in the diet may be beneficial to defer, prevent or delay some types of cancer, including breast and prostate," Dr. Reiter said.

Source

Europa exige a España reducir su gasto farmacéutico en hospitales

Expertos reunidos por el Instituto Choiseul para la elaboración de su último informe, defienden el papel de las farmacias comunitarias en el Sistema Nacional de Salud (SNS)

El informe "La Farmacia ante los cambios estructurales" es un trabajo que supera escasamente las 200 páginas, destinado principalmente a defender el modelo de proximidad actual de la farmacia comunitaria e identificar las amenazas que se ciernen sobre él. Entre estos peligros, que ya están provocando que 3.000 oficinas sigan abiertas prácticamente sin generar ingresos, la crisis es el fenómeno más visible pero no el único, ya que es la posible pérdida de la titularidad de los establecimientos, tradicionalmente en reserva para los farmacéuticos, la que debe suscitar mayor inquietud.

El texto, que fue presentado por el presidente del Instituto Chosiseul, Eduardo Olier, transita por los puntos más calientes de la farmacia actual. Para tratar cada apartado, se ha contado con plumas de gran prestigio como la presidenta de los colegios oficiales de farmacéuticos, Carmen Peña, que analiza el estado nacional de la profesión, o John Chave, que disecciona los efectos de la liberalización de la titularidad de las farmacias en aquellos países de Europa donde ya ha tenido lugar. Olier reiteró además, en varias ocasiones, que las 23 medidas legislativas aplicadas contra el gasto farmacéutico, unidas a la larga crisis, han reducido este hasta un 30%. Para el presidente del Think Tank Choiseul, esta realidad va en contra de la propia sostenibilidad del sistema sanitario porque afecta a la farmacia, elemento financiaciador del propio sistema, al absorber parte de la demanda ciudadana en prevención y atención primaria, además de soportar impagos, especialmente de algunas CC.AA., con el efecto liberador (o aplazador) que eso supone para parte de los desembolsos que se deben realizar desde el erario público

En la presentación, realizada este martes en un hotel de Madrid, participó Juan Iranzo, presidente del Colegio de Economistas de Madrid. Iranzo, que es autor del capítulo destinado a explicar el contexto económico del sector farmacéutico en estos días, recalcó que el objetivo principal del informe es ayudar a mantener el actual modelo de Farmacia como garantía en el acceso a los medicamentos para el conjunto de la población. Para este profesor, el modelo actual viene a cubrir el déficit de políticas públicas de salud y aún prestaría mayores servicios, si se estableciera una buena coordinación con los hospitales, siendo muy útil su participación en la dosificación y seguimiento de los tratamientos. Sin embargo lamentó que 3.000 farmacias de las 21.300 que existen en España estén en situación de quiebra económica. Con un 15% de margen neto, elevados costes laborales, amortizaciones, gastos financieros y retrasos en los pagos, una farmacia media que puede facturar actualmente 850.000 euros, apenas supera los 40.000 de ingresos finales. En el plano internacional, Iranzo recordó que la única exigencia expresa de la troica europea es reducir el gasto farmacéutico en hospitales porque es allí donde se está produciendo, paralelamente a las bajadas que se están produciendo en la farmacia comunitaria.

Como es sabido, la troika, o troica, está formada por el Banco Central Europeo (BCE), el Fondo Monetario Internacional (FMI) y la Comisión Europea(CE).

Fuente

Harvard Scientists Urge You to Stop Drinking Milk

Vegans may have had it right all along; while raw, organic milk offers numerous health benefits, a Harvard

researcher and pediatrician argues that conventional milk and dairy products alike are a detriment to your health – thanks to added health-compromising sweeteners.

As David Ludwig mentioned in his research, which was published in the Journal of the American Medical Association Pediatrics, there have been countless pieces of research concluding the ill effects of sugar-sweetened beverages. The over-consumption of sugar has been tied to obesity, diabetes, inflammatory-related pain, and much more. And because of sugar’s negative effects on our health, even the United States Department of Agriculture, the American Academy of Pediatrics, and other organizations are recommending against consuming calories from sugary drinks.

The one calorie-containing beverage they still heavily promote, however, is reduced-fat milk, where the organization recommends drinking 3 cups daily. This is where Ludwig questions the scientific rationale for such recommendations.

“This recommendation to drink three cups a day of milk – it’s perhaps the most prevailing advice given to the American public about diet in the last half century. As a result, Americans are consuming billions of gallons of milk a year, presumably under the assumption that their bones would crumble without them,” says David Ludwig.

As far as Ludwig is concerned, if the USDA is recommending to drink reduced-fat milk, it is also inadvertently encouraging the consumption of added sugars – a piece of advice that goes against all the research saying not to consume sugar and sugar-sweetened beverages. The idea of consuming low-fat milk or chocolate milk cancels out the whole reasoning for the recommendation in the first place since the fats are simply being replaced with dangerous sugars.

“The worst possible situation is reduced-fat chocolate milk: you take out the fat, it’s less tasty. So to get kids to drink 3 cups a day, you get this sugar-sweetened beverage,” Ludwig says. ”…we can get plenty of calcium from a whole range of foods. On a gram for gram basis, cooked kale has more calcium than milk. Sardines, nuts seeds beans, green leafy vegetables are all sources of calcium.”

The Case Against Low-Fat Dairy, and Other Dangers of Milk

Harvard researcher David Ludwig certainly has a point in analyzing and ultimately criticizing the USDA’s recommendations, but there is much more to the full-fat vs reduced-fat argument for milk and dairy products.

There are plenty of reasons to avoid certain fats such as trans-fats and refined polyunsaturated fats in vegetable oils (like corn, soy, sunflower, and canola), but the evidence for moderate consumption of saturated fat, which is found in milk, coconut oil, and grass-fed land animals, is coming to the surface. While saturated fat was villainized for decades, a 2010 analysis published in the American Journal of Clinical Nutrition concluded that “there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of [coronary heart disease or cardiovascular disease].”

Further, there are numerous benefits to drinking full-fat dairy products. In it’s most pure state (raw, organic, and coming from grass-fed cows), full-fat dairy has been found in research to potentially promote heart health, control diabetes, aid in vitamin absorption, lower bowel cancer risk, and even aid in weight loss. But while pure dairy could promote your health, conventional dairy may prove damaging.

Before you consume more conventional dairy, please educate yourself as to what’s in your dairy. You’d be surprised that there could be 20+ painkillers, antibiotics, and much more lurking in your milk.

Source

Autoridades chilenas detectan 43.000 kg de carne de pollo posiblemente contaminadas con dioxinas

En el marco del programa oficial de control de residuos que desarrolla permanentemente el Servicio Agrícola y Ganadero (SAG) de Chile se ha hallado una partida de 43 t de carne de aves, provenientes del sector La Arboleda de la empresa Agrosuper, en la Región de O´Higgins, el cual se encuentra en proceso de confirmación.

Las autoridades han implementado medidas como la suspensión tanto de la certificación como la comercialización de productos provenientes de la zona de origen de las aves.

Conforme a los protocolos establecidos para este tipo de casos, las muestras en cuestión están bajo análisis en laboratorios de referencia nacional e internacional, de manera de verificar bajo los más estrictos parámetros los resultados preliminarmente encontrados.

Fuente

Chinese study finds fasting and calorie-restricted diets may increase lifespan

Science is a step closer to understanding how humans can live longer, with a study revealing a calorie-restricted diet and periods of fasting might increase lifespan.

The Chinese study reduced the calorie intake of mice by 30 per cent and found changes in specific bacteria in the gut, including Lactobacillus, that are correlated with long lifespans.

Shanghai Jiao Tong University professor of microbiology Liping Zhao said the study's results could be applied to extending human life.

"We found that this calorie restriction can promote the growth of beneficial bacteria and this might contribute to the extended lifespan and healthier status," Professor Zhao said.

"We cannot directly translate everything from mice studies to humans, however, the principle is applicable to humans.

"Each person is different in genetics, in physical activity, age and agenda and everything, so the nutritional requirement for every person is different."

Source

Los fármacos más usados en osteoporosis podrían no ser eficaces en prevenir fracturas de cadera

Un grupo de investigadores en farmacoepidemiología del Servicio Navarro de Salud (SNS) ha publicado dos artículos en la revista médica British Medical Journal (open access), en los que cuestionan la eficacia de los bifosfonatos en la prevención de fracturas de cadera y fracturas atípicas de fémur (subtrocánter y diáfisis) y proponen reevaluar su uso.

Los fármacos a los que hace referencia el estudio son los más utilizados hasta ahora en todo el mundo para la prevención de la osteoporosis y fracturas óseas, según ha informado en una nota el Gobierno de Navarra, que ha precisado que los nombres genéricos más conocidos son alendronato, risedronato e ibandronato y las marcas prescritas con mayor frecuencia, Fosamax, Fosavance, Actonel, Acrel, Miosen, Bonviva, Bondenza o Bondronat.

El SNS analizaba este aspecto desde 2009, cuando la Agencia Española del Medicamento publicó una alerta sobre los riesgos potenciales de utilizar esos medicamentos a largo plazo y se redujo en gran medida el número de pacientes tratados con ellos.

El objetivo era evaluar si el uso de estos medicamentos reduce la incidencia de fracturas de cadera y de fémur atípicas (subtrocánter y diáfisis) en mujeres mayores de 65 años en condiciones de uso habitual.

Para ello, se seleccionaron más de 2.000 casos de mujeres con fractura de cadera y se compararon con más de 10.000 mujeres sin fractura de cadera. Se estudió el uso de bisfosfonatos en ambos grupos, así como la presencia de otros factores que pueden influir en la enfermedad.

La conclusión del estudio es que no se observó que estos medicamentos sean eficaces en la prevención de fracturas de cadera. A partir del tercer año desde el inicio del tratamiento, el riesgo de fractura de cadera podría ser mayor entre las mujeres que toman estos medicamentos respecto a las que nunca los tomaron. En lo que se refiere a las fracturas de cadera atípicas (subtrocánter y diáfisis), el riesgo era cuatro veces superior en las mujeres que tomaron estos medicamentos.

Los autores del estudio y de los artículos publicados son Juan Erviti López; Javier Gorricho Mendívil y Antonio López Andrés (Servicio Navarro de Salud); el bioestadístico Álvaro Alonso (Universidad de Minnesota - EEUU); y Francisco de Abajo, Miguel Gil, Julia Timoner y Consuelo Huerta (de la Agencia Española del Medicamento, en el artículo de fracturas de subtrocánter y diáfisis).

Los estudios contaron con financiación del Ministerio de Sanidad y se realizaron con las historias clínicas contenidas en la base de datos de la Agencia Española del Medicamento (BIFAP), que en estos momentos cuenta con información clínicas de unos 5 millones de pacientes de España.

Fuente

Los huevos no elevan el colesterol en la adolescencia

La ingesta de huevo no conlleva riesgos de enfermedades cardiovasculares. Expertos sugieren una revisión de las recomendaciones alimentarias.

Un estudio de la Universidad de Granada concluye que comer más huevos no se relaciona con un mayor colesterol plasmático en adolescentes ni con un peor perfil cardiovascular, independientemente de su nivel de actividad física. El trabajo ha analizado la asociación entre la ingesta de huevo en adolescentes y los principales factores de riesgo de desarrollar enfermedades cardiovasculares. Pese a que se ha tendido a restringir la ingesta de huevos por asociarlos con un aumento en el colesterol, las investigaciones más recientes afirman que el incremento del colesterol plasmático parece estar más influido por la ingesta de grasas saturadas y grasas trans que por el colesterol de la dieta.

Uno al día

Los resultados del trabajo, perteneciente al estudio europeo Helena y con nueve países implicados, se publican en Nutrición Hospitalaria y "concuerdan con estudios recientes en adultos sanos que sugieren que una ingesta de hasta siete huevos por semana no está asociada con un mayor riesgo de enfermedades cardiovasculares", explica Alberto Soriano Maldonado, autor del trabajo.

Los autores sugieren una revisión de las recomendaciones para la alimentación de los adolescentes, si bien sostienen que sería conveniente replicar la investigación en una población en la que la ingesta de huevo fuese superior.

Fuente

China bars Glaxo exec from leaving country

China has barred a GlaxoSmithKline executive from leaving the country as it turns up the heat on the drugmaker over allegations of corruption.

Steve Nechelput, finance director for GlaxoSmithKline China, has been prevented from traveling outside China since the end of June, the company said Wednesday.

The U.K. drugmaker has been accused by China of using a network of more than 700 travel agencies and other firms to channel bribes to health officials since 2007.

Four senior Chinese executives of GSK have been detained, according to state news agency Xinhua, although the company says Nechelput was not among them.

"At no time has [Nechelput] been questioned or arrested, and he is not one of the individuals in detention," a GSK spokesperson said.

Nechelput, who holds a British passport, remained in his post. Mark Reilly, the top GSK executive in China, is currently in the U.K.

Meanwhile, Chinese state media has put the government's allegations against GlaxoSmithKline on public display.

The company was the subject of an editorial published Wednesday in the Communist Party's mouthpiece publication, and state central television aired the apparent confession of one of the four GSK executives.

The media campaign is the latest in a series of actions in recent days that suggest China is embarking on a concerted effort to crack down on corruption.

The commentary in the People's Daily was written under a pseudonym -- but one that sounds like "voice of China" when spoken.

"GlaxoSmithKline's bribery case shows how complicated and difficult the fight against commercial corruption can be," the commentary said. "Seriously attacking multinational companies' commercial bribery is of great significance to maintaining market economy order and keeping a fair competition environment."

GSK (GSK) is accused of funneling hundreds of millions of dollars in kickbacks to doctors, hospital and government officials in China. The activities appear to have been designed to encourage the use of GSK products, and to keep prices at artificially high levels.

Related story: China drugs scandal set to grow 

The CCTV report featured GSK executive Liang Hong explaining how the bribery scheme worked, including the use of fake conferences and travel agencies to create receipts for services that were never performed. The surplus funds were then used to pay bribes.

The circumstances of the interview are difficult to discern and it wasn't clear whether the confession was coerced.

How much damage the scandal will do to GSK's reputation or bottom line remains unclear. But the episode underscores the challenges of doing business in China, an enormous, rapidly developing market in which bribes and corruption are often deeply ingrained.

Related story: Rolls-Royce in China corruption probe

GlaxoSmithKline -- which makes Paxil, Avandia and Wellbutrin -- declined to comment on the CCTV report and reiterated a statement from earlier this week that it was "deeply concerned and disappointed" by the allegations.

"GSK shares the desire of the Chinese authorities to root out corruption," a spokesperson said Monday. "These allegations are shameful and we regret this has occurred."

China's investigation could expose the company to legal action in the U.K., and possibly the United States, under laws relating to the bribery of foreign public officials.

GlaxoSmithKline said it had informed the U.K.'s Serious Fraud Office about the allegations but had not yet been asked to provide any further information. The agency, which investigates and prosecutes corruption cases, said it could neither confirm nor deny an interest in the claims against GSK at this stage.

Asked about Nechelput's travel restrictions, the U.K. Foreign Office said it was seeking more information from the Chinese authorities and was in contact with GSK.

Source

Swedish Study Suggests Bipolar Disorder Associated With Premature Mortality

Bipolar disorder was associated with premature mortality in a large study of Swedish adults by Casey Crump, M.D., Ph.D., of Stanford University, California, and colleagues.

The study used outpatient and inpatient data from more than 6.5 million Swedish adults, including 6,618 with bipolar disorder, to examine the physical health effects associated with bipolar disorder. Bipolar disorder is a chronic mental illness and a leading cause of disability worldwide.

According to the results, women and men with bipolar disorder died nine and 8.5 years earlier on average, respectively, than the rest of the population. All-cause mortality was increased two-fold among women and men with bipolar disorder compared to the rest of the population. Patients with bipolar disorder also had increased mortality from cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries and suicide for both women and men, and cancer for women only.

"Timely medical diagnosis appeared to improve chronic disease mortality among bipolar disorder patients to approach that of the general population. More effective provision of primary, preventive medical care is needed to reduce early mortality among persons with bipolar disorder," the study concludes.

Source

Quote of the day

"Today, nearly 40 percent of a senior's healthcare spending is on pharmaceutical medications"

Dennis Hastert

American politician

Lynn Evans: Drop boxes part of prescription drug abuse battle

The Centers for Disease Control calls it an epidemic. The Mississippi Department of Public Safety calls it Mississippi’s No. 1 drug threat. Prescription drug abuse is killing men and women from all walks of life. The CDC reports that the deaths of women from prescription drugs has risen most dramatically: about 400 percent since 1999. Marshall Fisher of the Mississippi Bureau of Narcotics estimates that 90 percent of the 206 drug overdose deaths in this state in 2012 were due to the abuse of prescription narcotics.

Prescription narcotics, especially opioids such as Oxycontin and hydrocodone, are almost always prescribed for chronic pain — but medical science now shows that opioids are not a reliable treatment for noncancerous chronic pain. In other words, they mask but do not stop the pain.

The CDC reports that the sale of opiate pain relievers has increased by 300 percent since 1999. In 2008, there were more U.S. deaths from opiate pain relievers that from cocaine and heroin combined.

The misuse of prescription painkillers cuts across all social strata and is becoming as big a public health problem for people in the prime of life as heart disease and cancer. The CDC estimates that for every death due to prescription painkillers, there are 32 visits to the emergency room, 130 people who are addicted users, and 825 people who are so-called nonmedical users — people taking prescription painkillers without a medical reason. The total cost is staggering: about $28 billion for the estimated 40 million Americans with addiction.

Opiates, as well as the other commonly abused drugs such as benzodiazepines (Valium, Xanax, Ativan) and ADHD-treating drugs like Adderall and Ritalin, can be incredibly addictive. Although only some 12 percent to 20 percent of people who ever use these drugs become addicted, once addicted their brain chemistry has changed enough to overrule all reason and social pressure telling them to stop. Addiction is a disease that can both rule and ruin the addict’s life because it affects the production of dopamine, the brain’s “happy juice.” For that reason, the best way to stop prescription pain medication abuse is not to take it for non-cancer pain in the first place.

Source

Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study

An issue published by BMJ the risk of fertility treatment over childhood and adolescents. 

In conclusion, there was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination. Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously.

Retirada de productos con yohimbina, el afrodisíaco natural

La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) ha retirado productos con yohimbina, a través de una denuncia procedente del Cuerpo Nacional de Policía de la venta de los productos relacionados en la siguiente tabla como complementos alimenticios a base de plantas medicinales de origen natural, cuya comercialización no ha sido notificada como tal a la Agencia Española de Seguridad Alimentaria y Nutrición, de acuerdo con lo previsto en la normativa vigente.

Según los análisis llevados a cabo por el Laboratorio Oficial de Control de la Agencia Española de Medicamentos y Productos Sanitarios, los mencionados productos contienen el principio farmacológicamente activo yohimbina. Estos productos declaran la presencia de la planta “yohimbe” en su etiquetado.

La inclusión de este principio farmacológicamente activo les conferiría la condición legal de medicamento según lo establecido en el artículo 8 de la Ley 29/2006, de 26 de julio, de garantías y uso racional de los medicamentos y productos sanitarios.

La yohimbina es un antagonista α2 adrenérgico (simpaticolítico). A dosis débiles es hipertensor y a dosis más elevadas hipotensor, vasodilatador de los territorios vasculares periféricos. La vasodilatación inducida en los cuerpos cavernosos es la causante de su capacidad para mejorar la función sexual. También provoca un aumento del tono y motilidad intestinal así como un aumento de la lipólisis en el adipocito. Debido a su actividad farmacológica a estos niveles ha sido utilizada en algunos productos pretendidamente comercializados como complementos alimenticios.

En España no hay ningún medicamento autorizado que contenga esta sustancia en su composición. Sin embargo, en Francia está autorizado un medicamento que tiene como indicación el tratamiento de la disfunción eréctil y de la hipotensión ortostática. La ficha técnica del producto en Francia recoge una serie de acontecimientos adversos relacionados con su uso, que incluyen: trastornos del sistema nervioso central (SNC) como nerviosismo, irritabilidad, insomnio, temblor, vértigo, migraña; problemas digestivos como náuseas, vómitos y/o diarreas; problemas cardiovasculares tales como taquicardia, priapismo. También presenta interacciones medicamentosas con clonidina e inhibición de la actividad de los medicamentos antihipertensivos.

Según la información disponible se desprende que estos productos se comercializan a través de internet así como en establecimientos fuera del canal farmacéutico. ¿Hay que estar dentro del canal farmacéutico para comercializar productos naturales?

Considerando lo anteriormente mencionado, así como que los citados productos no han sido objeto de evaluación y autorización previa a la comercialización por parte de la Agencia Española de Medicamentos y Productos Sanitarios, de acuerdo con lo dispuesto en el Real Decreto 1275/2011, de 16 de septiembre, por el que se crea la Agencia estatal "Agencia Española de Medicamentos y Productos Sanitarios" y se aprueba su Estatuto y el artículo 9.1 de la Ley 29/2006, de 26 de julio, siendo su presencia en el mercado ilegal, esta Dirección de la Agencia Española de Medicamentos y Productos Sanitarios, conforme a lo establecido en el artículo 99 de la citada Ley y en relación con el mencionado Real Decreto, ha resuelto ordenar que se proceda a la retirada del mercado de todos los ejemplares de los citados productos.

Fuente

Quote of the day

"La salud de todo el cuerpo se fragua en la oficina del estómago"

Miguel de Cervantes

Poeta y dramaturgo español

Do clinical trials work? It depends on what you mean by “work”

One of the issues I discussed at our SBM workshop was something I’ve written before, namely the “methodolatry” that sometimes infests evidence-based medicine (EBM), “Methodolatry” has been defined as the profane worship of the randomized clinical trial (RCT) as the only valid method of clinical investigation, and it’s a symptom of the way that EBM relegates basic science knowledge, even well-established principles of science that show that something like, say, homeopathy or reiki is impossible under the current understanding of physics, chemistry and biology. However, never let it be said that RCTs aren’t actually important in SBM. Our problem with how EBM worships them derives from how it even bothers to do trials in the first place of modalities that can best be described by Harriet Hall’s brilliant appellation, Tooth Fairy Science. However, these days RCTs are widely perceived to have a serious problem. They have become so expensive to do and there have been so many failures of drugs that looked promising to show efficacy in clinical trials that some have even questioned whether there is something fundamentally wrong with how we do clinical trials now. Some even ask, as the title of an article by Clifton Leaf that appeared in the New York Times over the weekend, Do Clinical Trials Work?

It begins with the story of Avastin in brain tumors. I’m sure that Eric Merola will likely jump all over this, given how he tried to use the example of Avastin being approved for glioma on fast track approval that used phase II trials as the basis for doing so as an argument for why antineoplastons should be approved by the FDA. Or maybe he won’t. Here’s why. The story explains that there were two single-arm trials of adding Avastin to glioma therapy in which the tumors “shrank and the disease seemed to stall for several months when patients were given the drug.” Then Clifton points out the results of the randomized clinical trial presented at the American Society of Clinical Oncology (ASCO) meeting a month and a half ago:

But to the surprise of many, Dr. Gilbert’s study found no difference in survival between those who were given Avastin and those who were given a placebo.

Disappointing though its outcome was, the study represented a victory for science over guesswork, of hard data over hunches. As far as clinical trials went, Dr. Gilbert’s study was the gold standard. The earlier studies had each been “single-arm,” in the lingo of clinical trials, meaning there had been no comparison group. In Dr. Gilbert’s study, more than 600 brain cancer patients were randomly assigned to two evenly balanced groups: an intervention arm (those who got Avastin along with a standard treatment) and a control arm (those who got the latter and a placebo). What’s more, the study was “double-blind” — neither the patients nor the doctors knew who was in which group until after the results had been assessed.

The centerpiece of the country’s drug-testing system — the randomized, controlled trial — had worked.

This study could certainly be taken as evidence supporting a position that we shouldn’t approve drugs based on single-arm phase II clinical trials, even under fast track. It is indeed a very good example of how promising phase II clinical trial results are not always validated when the bigger and more rigorous phase III RCTs are performed. In one way, it is a good thing. Negative results, be they experimental or clinical trial, are just as important in science as positive results, if not more so. In another way, however, it’s a bad thing because, as the NYT article points out, “doctors had no more clarity after the trial about how to treat brain cancer patients than they had before.” A seemingly promising addition to the armamentarium against a deadly cancer that has too few effective treatments was shown not to work in an RCT that was designed to be, more or less, definitive. However, the key thing to remember about such an RCT is that it is looking at populations of patients. Overall, there was no difference in overall survival between the control and Avastin group, but that doesn’t necessarily mean that Avastin is useless against glioma.

Indeed, as someone who’s been studying angiogenesis and how to target it therapeutically in cancer since the heady days of the late 1990s, when findings by Judah Folkman and other pioneers in this field led to headlines in the lay press like “The Cure for Cancer” and it really did look as though the discovery that inhibiting angiogenesis produced dramatic results and outright cures in preclinical rodent models of cancer. Over the years, the study of angiogenesis has been gradually de-emphasized in my research, correlating inversely with the rise of other interests, but I do have a small project in targeting tumor-induced angiogenesis still ongoing and hope to publish on it before the end of the year. In any case, reality shut down those heady days, as it became clear that Avastin and other antiangiogenics were not as nontoxic in humans as they were in mice, nor were they nearly as effective. Still, it is clear that Avastin has contributed to significant increases in median survival in a number of tumor types, such as colorectal cancer. However, overall it’s hard not to conclude that antiangiogenic therapy has been, by and large, a disappointment, if only because the hype and hope were so sky-high 15 years ago. Rare indeed would have been the treatment that could have lived up to such expectations when tested in RCTs.

One thing that has been apparent for quite some time is that there appears to be a subset of patients who have remarkable responses to Avastin. Many oncologists get this feeling anecdotally, even if they don’t have evidence, and evidence has popped up in clinical trials. Assuming this is true, while it might not now make sense to treat all or most glioma patients with Avastin, it might very well make sense to treat that subset who have such dramatic responses if we could identify them beforehand. There’s the rub, though. We can’t, and Leaf points this out:

Some patients did do better on the drug, and indeed, doctors and patients insist that some who take Avastin significantly beat the average. But the trial was unable to discover these “responders” along the way, much less examine what might have accounted for the difference. (Dr. Gilbert is working to figure that out now.)

Indeed, even after some 400 completed clinical trials in various cancers, it’s not clear why Avastin works (or doesn’t work) in any single patient. “Despite looking at hundreds of potential predictive biomarkers, we do not currently have a way to predict who is most likely to respond to Avastin and who is not,” says a spokesperson for Genentech, a division of the Swiss pharmaceutical giant Roche, which makes the drug.

That we could be this uncertain about any medicine with $6 billion in annual global sales — and after 16 years of human trials involving tens of thousands of patients — is remarkable in itself. And yet this is the norm, not the exception. We are just as confused about a host of other long-tested therapies: neuroprotective drugs for stroke, erythropoiesis-stimulating agents for anemia, the antiviral drug Tamiflu — and, as recent headlines have shown, rosiglitazone (Avandia) for diabetes, a controversy that has now embroiled a related class of molecules. Which brings us to perhaps a more fundamental question, one that few people really want to ask: do clinical trials even work? Or are the diseases of individuals so particular that testing experimental medicines in broad groups is doomed to create more frustration than knowledge?

While it’s an excellent point that we don’t have predictive biomarkers (say, something in the blood we could measure) that tell us which patients are most likely to respond to Avastin (or most other drugs), Leaf seems to be indulging in a false dichotomy. Just because we don’t have predictive biomarkers for various drugs does not imply that clinical trials don’t work. Very clearly, they do. The problem is that they have limitations, and one of those limitations is that, without predictive biomarkers, we have no choice but to test the drug in a controlled population and see if there is a difference between control and the treated population that can be observed on a population level. The smaller the difference, the harder it is to detect and the more patients are needed to detect it. That’s why we need and want predictive biomarkers in the first place.

Worse, even the biomarkers we have are nowhere near 100% predictive. Let’s take a look at the prototypical targeted therapy, arguably the oldest targeted drug of all, Tamoxifen, which blocks estrogen activity. It is only used in tumors that make the estrogen receptor and are therefore presumed to be estrogen-responsive (i.e., estrogen stimulates them to grow). I remember a talk by the director of the Cancer Institute of New Jersey at the time I worked there, William Hait, who pointed out that Tamoxifen is effective in ER(+) cancers about 50% of the time. Around 70% of breast cancer is ER(+), and that means that if you treat all patients with breast cancer with Tamoxifen, you will see responses only 35% of the time, whereas if you treat only ER(+) cancers you will see responses 50% of the time. Another example is Herceptin, which targets amplified HER2 in breast cancer. Even though it is a targeted drug, it is effective against approximately 30% of HER2(+) cancers. Now, approximately 30% of breast cancers are HER2(+), which means that if you treat all comers with Herceptin, it will only be effective 0.3 x 0.3 = 0.09 (9%) of the time, but if you treat only HER2(+) cancers it should be effective 30% of the time. There are other examples he gave us. Taxol, for instance, is effective in 75% of breast cancer with p53 mutations. Since approximately 50% of breast cancers carry p53 mutations, if you treat all comers with Taxol you will get responses around 37.5% of the time, whereas if you treat only cancers with p53 mutations you should expect a 75% response rate. Of course, a 37.5% response rate is good enough that pretty much everyone with breast cancer who needs chemotherapy will get a Taxane, but you get the idea.

Now here’s where the devil is. These biomarkers that I’ve described are crude, and not even that predictive. But what, if anything, is better? That’s the problem, and that’s where most articles like this break down. They do an excellent job of identifying the problems with clinical trials, and there’s no doubt that Clifton Leaf does just that. None of these problems discussed in his NYT article are unfamiliar to most clinicians and clinical investigators, particularly in cancer. However, one notes that he has a book out entitled The Truth In Small Doses: Why We’re Losing the War on Cancer — and How to Win it. Personally, I hate that meme of “we’re losing the war on cancer,” because it’s not a war, and whether or not we’re “losing” depends on what your vision of “victory” is and how fast we can win the war. As I’ve pointed out many times, particularly around the 40th anniversary of Richard Nixon’s declaration of “war on cancer,” what do you expect in 40 years, given that the amount of resources we pour into this “war” are minuscule compared to what we spend on other things, such as—oh, you know—actual war? How much progress can we realistically expect in 40 years given that investment, the incredible complexity of cancer, and cancer’s ability to out-evolve almost anything we have as yet been able to throw at it. Clifton Leaf is a cancer survivor; so I can totally understand his frustration. However, that doesn’t stop his use of that tired old meme from irritating me. I’ll stop whining about that particular pet peeve of mine right now, but as everyone knows I do so love a good whine. Sorry.

My pet peeve aside, what can we do better? Most of us in oncology believe that the answer will likely come down to personalized medicine based on the genomic profile of each cancer, but how to get from the enormous amount of data from genomic studies of various cancer to actual validated treatments is not at all clear at this stage (other knowing that Stanislaw Burzynski’s doing it wrong). Right now, personalized medicine has a lot of promise but has even more hype with little or nothing as yet in the way of concrete results that clearly benefit patients. Many have been the ideas to overcome these problems and validate genomic-based personalized medicine. Leaf actually mentions an interesting one: The I-SPY2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2). (Whew, what a name!) It’s a very interesting prototype of how clinical trials might be done in the future, and if it works I can see a lot more trials like this:

The I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) is a clinical trial for women with newly diagnosed locally advanced breast cancer to test whether adding investigational drugs to standard chemotherapy is better than standard chemotherapy alone before having surgery. The treatment phase of this trial will be testing multiple investigational drugs that are thought to target the biology of each participant’s tumor. The trial will use the information from each participant who completes the study treatment to help decide treatment for future women who join the trial. This will help the study researchers learn more quickly which investigational drugs will be most beneficial for women with certain tumor characteristics. The I-SPY 2 TRIAL will test the idea of tailoring treatment by using molecular tests to help identify which patients should be treated with investigational drugs. Results of this trial may help make investigational drugs available to more women in the future.

The beauty of this trial is that it uses Bayesian analysis of responses to have the trial, in effect, evolve in response to what is found at earlier stages. My main quibble with the study is that it requires that all subjects undergo pretreatment breast MRI before surgery, which has a tendency to upstage women through the Will Rogers effect and thus result in more mastectomies. I understand that the trial investigators probably wanted advanced imaging to follow tumor response and that MRI can also show blood flow and therefore measure tumor angiogenesis, but I always worry when I see a design like this one, that it might promote unnecessary mastectomies. On the other hand, the inclusion criteria require a tumor that is 2.5 cm in diameter or greater so perhaps this will be less of a problem. That quibble aside, as Leaf describes, it is an intriguing design and it does evolve based on previous results:

In fact, a breast cancer trial called I-SPY 2, already under way, may be a good model to follow. The aim of the trial, sponsored by the Biomarkers Consortium, a partnership that includes the Foundation for the National Institutes of Health, the F.D.A., and others, is to figure out whether neoadjuvant therapy for breast cancer — administering drugs before a tumor is surgically removed — reduces recurrence of the disease, and if so, which drugs work best.

As with the Herceptin model, patients are being matched with experimental medicines that are designed to target a particular molecular subtype of breast cancer. But unlike in other trials, I-SPY 2 investigators, including Dr. Berry, are testing up to a dozen drugs from multiple companies, phasing out those that don’t appear to be working and subbing in others, without stopping the study.

Here’s the design (more details can be found here and here, and some of the investigational drugs tried can be found here):

The difficult part of the study, of course, is designing the algorithms by which drugs are swapped out as they appear not to be working. If these decisions are made willy-nilly, then this trial would be no better than what Burzynski does (i.e., making simplistic guesses). However, there is a sophisticated analysis and algorithm by which treatment decisions are made. It does have to be remembered, though, that, although I-SPY2 does represent personalized medicine, it is not yet full genomic medicine. Most of the biomarker tests used are biomarkers that already exist, and the additional biomarkers measured will not affect patient treatment. This part of the trial is for discovery of biomarkers, not validation.

The bottom line

I’ll be watching the progress of I-SPY2 closely, because it’s a new kind of clinical trial. Whether it will succeed in improving the success of the followup clinical trials of agents identified through I-SPY remains to be seen, as it also remains to be seen whether it will speed up the pace of discovery. I’m probably less hopeful than Clifton Leaf, but that doesn’t mean I’m not hopeful.

So do clinical trials work? It depends on what you mean by “clinical trials” and “work.” I would argue that they do, in fact, still work in that they are still the best method we have to determine whether science-based therapies with preclinical promise actually translate into useful therapies. They’re simply evolving with science, as they must under the “selective pressure” of advances in technology and understanding of biology.

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