Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria

--Blackground
Artemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the addition of a single gametocytocidal dose of primaquine.

--Methods
In an open-label randomised trial in clinics in Rakhine state, Kachin state, and Shan state in Myanmar (Burma) between Dec 30, 2008, and March 20, 2009, we compared the effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate—mefloquine, artesunate—amodiaquine, dihydroartemisinin—piperaquine, artemether—lumefantrine) and loose artesunate—mefloquine in Burmese adults and children. Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection, who were older than 6 months, and who weighed more than 5 kg. Treatments were randomised in equal numbers within blocks of 50 and allocation was in sealed envelopes. All patients were also randomly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not. Patients were followed up for 63 days. Treatment groups were compared by analysis of variance and multiple logistic regression. The primary outcome was the 63 day recrudescence rate. This study is registered with clinicaltrials.gov, number NCT00902811.

--Findings
155 patients received artesunate—amodiaquine, 162 artemether—lumefantrine, 169 artesunate—mefloquine, 161 loose artesunate—mefloquine, and 161 dihydroartemisinin—piperaquine. By day 63 of follow-up, 14 patients (9·4%; 95% CI 5·7—15·3%) on artesunate—amodiaquine had recrudescent P falciparum infections, a rate significantly higher than for artemether—lumefantrine (two patients; 1·4%; 0·3—5·3; p=0·0013), fixed-dose artesunate—mefloquine (0 patients; 0—2·3; p<0·0001), p="0·0018)," p="0·0012)." p="0·01)," p="0·04)," p="0·08).">

--Interpretation
Artesunate—amodiaquine should not be used in Myanmar, because the other ACTs are substantially more effective. Artesunate—mefloquine provided the greatest post-treatment suppression of malaria. Adding a single dose of primaquine would substantially reduce transmission potential. Vivax malaria, not recurrent falciparum malaria, is the main complication after treatment of P falciparum infections in this region.

-Funding
Médecins sans Frontières (Holland) and the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme.

**Published in "The Lancet"

Unas 200.000 personas se ven afectadas por espondilitis anquilosante en España

La espondilitis anquilosante afecta a unas 200.000 personas en España principalmente a gente joven entre 17 y 35 años, siendo más frecuente en hombres (2 de cada 3 casos), según ha explicado el presidente de la Asociación Provincial de Espondilitis Anquilosante y otras Espondiloartropatías de Ciudad Real (AEACR), José Antonio Cabanillas, que ha organizado en Puertollano (Ciudad Real) las III Jornadas Nacionales de Convivencia de Enfermos de Espondilitis Anquilosante.

Durante la celebración de estas jornadas, los afectados pedirán la adopción de medidas que favorezcan la detección precoz de esta patología altamente discapacitante, que se manifiesta en brotes dolorosos y una limitación de la movilidad de las articulaciones afectadas, principalmente columna lumbar y cervical y caderas.

"Si no se diagnostica a tiempo puede llegar a soldar las articulaciones afectadas y, con el paso de los años, los enfermos van adquiriendo una silueta muy característica con el cuello y los hombros rígidos y echados hacia adelante y sin capacidad para mover la cintura", ha explicado Cabanillas.

El presidente de la asociación considera como prioritario "la incorporación de más reumatólogos y la mejor formación de los médicos de Atención Primaria en esta enfermedad". "Hay enfermos que pasan años sin saber exactamente qué es lo que tienen, especialmente en las zonas rurales, y cuando llegan a un gran hospital ya es demasiado tarde", ha subrayado.

Además, ha añadido que "uno de los peores aspectos de la enfermedad es el dolor, presente en todos los brotes, que nos obliga a estar de baja a veces durante mucho tiempo". En este sentido, ha lamentado que "esto no suele ser comprendido en las empresas y muchos afectados tienen dificultades para mantener su puesto de trabajo".

La doctora María del Carmen Castro Villegas, del servicio de Reumatología del Hospital Universitario Reina Sofía de Córdoba y una de las especialistas que participan en las jornadas, atribuye la dificultad del diagnóstico a "la inespecificidad de los síntomas --principalmente dolor de espalda-- que hace que tanto el paciente como el propio médico le resten importancia en las fases iniciales de la enfermedad". "La rapidez en la detección es fundamental puesto que los diez primeros años de evolución son determinantes en las secuelas que sufrirá el enfermo a largo plazo y máxime cuando disponemos de armas terapeúticas específicas para el control de la enfermedad como la terapia biológica que ha demostrado mayor efectividad en las fases iniciales de la enfermedad", ha asegurado.

Asimismo, desde las asociaciones de pacientes también se demanda mayor acceso a la rehabilitación, fisioterapia y el ejercicio físico, clave en la evolución de la enfermedad

Un estudio científico identifica mecanismos genéticos vinculados a la diabetes tipo 1

Investigadores del Centro de Ciencias Clínicas del Consejo de Investigación Médica de Londres en Reino Unido han identificado una red de genes y de regiones reguladoras que podrían contribuir al riesgo de desarrollar diabetes tipo 1. Los resultados del trabajo se publican en la revista 'Nature'.

Los estudios de asociación amplia del genoma han desvelado una variedad de genes vinculados con la diabetes tipo 1 pero en el trabajo actual los investigadores han utilizado un método que proporciona nueva información sobre las causas de esta enfermedad.

El análisis combina diversos métodos genéticos que implican estudios de expresión genética y datos genéticos de rata y humanos para desvelar regiones de ADN que controlan la expresión de un grupo de genes asociado a T1D, el factor 7 regulador de interferon (IRF7), que dirige la red inflamatoria. El mecanismo de respuesta viral innata y las células inmunes denominadas macrófagos también están implicadas en T1D.

El estudio es también de interés porque combina con éxito redes de genes y variaciones en la secuencia de ADN y subraya el hecho de que las regiones reguladoras que perturban las redes biológicas pueden tener un importante papel en el riesgo de enfermedad.

**Foto de Reuters

Lilly invests $150 Million with Venture firms seeking new drug candidates

Eli Lilly & Co. plans to invest as much as $150 million in three venture capital funds to aid development of new medicines, as the company faces generic competition next year to its top-selling antipsychotic drug.
The funds may be worth a total of $750 million, up to $250 million each, and Lilly will contribute as much as 20 percent of the money, Darren Carroll, vice president of the Lilly group that oversees venture investments, said yesterday in an interview. CMEA Capital, a San Francisco venture-capital firm, started raising money in August for one of the funds with Lilly, according to two people with knowledge of CMEA’s plans.
Lilly is seeking new treatments as drugs accounting for more than 45 percent of its 2009 sales are set to lose patent protection in the next three years, led by its top-seller, Zyprexa, in 2011. The Indianapolis-based drugmaker spoke with more than 80 venture-capital and private-equity firms over a year before choosing partners, Carroll said. He declined to name the two in addition to CMEA.
“A lot of pharma companies have their own venture funds,” said Les Funtleyder, an analyst with Miller Tabak & Co. in New York, citing London-based GlaxoSmithKline Plc and Swiss drugmaker Novartis AG. New York-based Pfizer Inc., the world’s largest drugmaker, also has a fund. “To Lilly’s credit, they’re trying new things. Lilly has more to do than some others in terms of developing its pipeline.”

-Alzheimer’s Study
The company halted trials of a late-stage experimental Alzheimer’s disease medicine last month, one of eight products in the third and final stage of testing generally required for U.S. regulatory approval. Effient, a blood-thinner introduced in the U.S. in August 2009, “got off to a slower start than we anticipated,” Chief Executive Officer John Lechleiter said in July.
In 2013, Lilly will lose patent protection on the antidepressant Cymbalta and the insulin Humalog. Zyprexa and the two medicines brought in almost $10 billion of the company’s $21.8 billion in 2009 sales.
Lilly rose 3 cents to $34.84 at 9:49 a.m. in New York Stock Exchange composite trading. The shares lost 2.5 percent this year before today.
The company’s goal is for each of the three venture-capital funds to work on up to 20 potential medicines, Carroll said. Of the possible 60 new drugs, he said Lilly would hope as many as 15 to 20 would reach a “clinical proof of concept,” meaning the point in development when the medicine proves to be safe and hits the right target. Lilly would have the right to buy some of those at fair market value ahead of competitors, Carroll said.

-Weighing Risk
“At that point -- what’s really critical here -- we will have discharged an enormous amount of risk,” he said. “We’ll have a good indication not only about safety, but also we’ll know something about the efficacy of the drug.”
The three venture-capital firms Lilly ended up choosing have, on average, been in the business for more than 20 years, have more than $1.5 billion under management and have worked with more than 40 companies, Carroll said.
“We really wanted to work with very highly experienced folks who had a track record that we could evaluate and who we trusted,” he said. “These are long-term relationships and require a great deal of trust.”

-Biotechnology Funding
Biotechnology was the biggest industry for venture funding in the first half of this year, with investors pouring $2.1 billion into 243 companies, according to the National Venture Capital Association, which tracks 17 categories. Industrial and energy was second at $1.94 billion.
Venture fundraising is showing signs of picking up again after dropping 56 percent in the second quarter from a year earlier. Institutional Venture Partners and Founders Fund, as well as smaller firms such as Floodgate Fund and Felicis Ventures, completed funds in the third quarter.
Lilly’s strategy is “another way in which companies can spread research and development dollars to more emerging opportunities without necessarily having to buy a company or make a direct investment,” Tony Butler, an analyst with Barclays Capital in New York, said yesterday in a telephone interview.
Still, it won’t fill the revenue gap the company faces in the next few years, he said. Any new drugs arising from the partnerships would come “way beyond 2015.”

**Published by "BLOOMBERG"

GSK signs biologics manufacturing deal with Lonza

GlaxoSmithKline has entered into a manufacturing pact with Lonza and sold an R&D facility in Croatia to Galapagos.
First up, GSK has signed a deal with Lonza which will see the latter manufacture clinical trial batches of five monoclonal antibodies currently in Phase I and II. The Swiss firm will also provide "access to flexible capacity to enable GSK to respond to future demand, dependent upon progression of molecules through late stage development and commercial launch", the companies said. Financial details of the agreement were not disclosed.
Ian Tomlinson, head of biopharm R&D at the drugs giant, said the pact is "a critical step in the ongoing and future success of GSK in biopharmaceuticals”. He noted that the firm's goal is to establish a portfolio of biopharmaceuticals that by 2015 "consistently exceeds 20% of our R&D pipeline" and "to make this a reality we need to ensure that we have the right resources in place, which include flexible and expert manufacturing capabilities".
As part of the deal, the two companies said they will work together to "assess options for the design, specification, location and construction of a bespoke biopharmaceutical manufacturing facility within the UK".
Staying with facilities, Galapagos has acquired GSK's state-of-the art research centre in Zagreb, thus providing additional capacity for the Belgian firm's growing R&D requirements.
The deal involves the transfer of 130 staff and in addition, Galapagos will provide R&D services to GSK under a three year fee-for-service contract to the value of 14 million euros. Further terms were not disclosed.
GSK announced in February that it was stopping R&D activity at Zagreb and research chief Moncef Slaoui said the deal "is a great outcome...as it meets the capacity requirements of both companies". At the same time, he added, it "assures continuity of employment and a preservation of expertise at this excellent scientific facility.”
Heslop to step down as CFO in March
GSK also announced that Julian Heslop is to retire as chief financial officer at the end of March 2011. He will be succeeded by Simon Dingemans, who joins from Goldman Sachs where he is currently managing director and partner.

Links http://www.gsk.com/

**Published in "Pharma Times"

EU agency poses new questions on Glaxo's Avandia

The European Medicines Agency said it was asking GlaxoSmithKline (GSK.L) additional questions about its diabetes drug Avandia before giving a final verdict later this month on whether it should stay on the market.
The EMA -- the European body that originally licensed Avandia in 2000 -- held an extraordinary expert meeting to review the drug's safety on Wednesday and said it would finalise its review on Sept. 20 to 23 at its next scheduled meeting.
Pressure has increased for the watchdog to pull the drug, which has been linked to heart risks, after British regulators said on Monday the risks from taking it were greater than the benefits. [ID:nLDE6850I3]
The EU agency said it had identified a number of unspecified questions it was putting to Glaxo that would help it decide whether marketing authorisation "should be maintained, changed, suspended or revoked."
Avandia used to be Glaxo's second-biggest drug, with sales of $3 billion in 2006 until health concerns emerged in 2007. Its sales plunged to $1.2 billion in 2009, or some 2.7 percent of group sales, as many doctors switched to Takeda's (4502.T) rival drug, Actos.
Glaxo said an extensive research programme showed Avandia was safe and effective when used according to label.
In the United States, health advisers recommended to regulators on July 14 that Avandia be allowed to stay on the market but with additional warnings. [ID:nN14274445]
The U.S. Food and Drug Administration is expected to make a final decision on Avandia shortly and the agency usually follows recommendations from its advisory committees.

The Six Super Foods Every Woman Needs

From the food pyramid to the Internet to your local bookstore, there is certainly no shortage of advice on nutrition and healthy eating. But with all the media hype surrounding many “health foods,” it can be hard for a woman to tell the nutrients from advertising ploys.
“We are sometimes led to believe that a specific food is healthier than it really is,” says nutritionist Elizabeth Somer, MS, RD, author of Age-proof Your Body. “Or that you need some exotic or expensive form of certain nutrients to gain benefits -- and most of the time that’s not true.”
Moreover -- as happened in the '90s when low fat cookies made everyone temporarily forget about calories -- Somer says some of today’s advertising sways us toward one healthy aspect of a food to keep us from noticing other, less healthy attributes. “A product may advertise itself as ‘no cholesterol’" she says, “but it still can be loaded with bad fats or tons of calories. You have to look at the total food to know for sure.”
NYU nutritionist Tara Miller, MS, RD, agrees. “You have to read the whole label, look at all the ingredients and the portion sizes, before you know for sure just how healthy a food is.”
Or you can let us do the work for you! To help you zero in on the healthiest foods that women can eat, we asked a panel of experts for their advice.
What follows is a description of the six super foods they say every woman needs. While these foods won’t cover all your nutrient bases, incorporating them into your diet as often as possible can help give you a wide range of protection.

**Published in "Web MD"