Mediterranean

Healthy Diet, Healthy Aging.

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Middle-aged women following a healthy Mediterranean-type diet — with an emphasis on fruits, vegetables, whole grains and fish, moderate amounts of alcohol, and little red meat — have much greater odds of healthy aging later on, a new study reports.

“In this study, women with healthier dietary patterns at midlife were 40% more likely to survive to age 70 or over free of major chronic diseases and with no impairment in physical function, cognition or mental health,” said lead study author, Cécilia Samieri, PhD, Institut pour la Santé Publique et le Developpement, Université Bordeaux, France.

This new study adds to growing research on the health benefits of the Mediterranean diet recently reported. Various studies have shown that this diet may contribute to reduced fasting glucose concentrations and lipid levels in those at risk for diabetes, may lower the risk for cardiovascular events and stroke, and improve cognition.

The new study was published in the November 5 issue of Annals of Internal Medicine.

The analysis included 10,670 participants in the Nurses’ Health Study, which began in 1976 when female nurses aged 30 to 55 years completed a mail-in survey. Since then, study participants have been closely followed on a regular basis.

In 1980, participants completed a food-frequency questionnaire (FFQ) that asked how often on average they consumed standard portions of various foods. This questionnaire was repeated in 1984 and 1986 and then every 4 years.

To assess dietary quality at midlife, researchers averaged information from the 1984 and 1986 FFQs. They calculated scores on 2 diet indexes:

  • Alternative Healthy Eating Index-2010 (AHEI-2010): This index considers greater intake of vegetables, fruits, whole grains, nuts, legumes, and polyunsaturated fatty acids (PUFAs); lower intake of sugar-sweetened beverages, red or processed meats, trans fats, and sodium; and moderate intake of alcoholic beverages. Total AHEI-2010 scores range from 0 (nonadherence) to 110 (perfect adherence).

  • Alternate Mediterranean diet (A-MeDi): Developed to assess adherence to the traditional Mediterranean diet, this index includes 9 components that are similar to those in the AHEI-2010. Total A-MeDi scores range from 0 (nonadherence) to 9 (perfect adherence).

In 1992, 1996, and 2000, participants completed the Medical Outcomes Short-Form 36 Health Survey, a questionnaire that evaluates 8 health concepts, including mental health and physical functioning. Scores from the Telephone Interview for Cognitive Status, an adaptation of the Mini-Mental State Examination, were used to evaluate cognitive health. From 1995 to 2001, a cognitive study was administered to participants aged 70 years or older.

Investigators separated “healthy” from “usual” aging on the basis of 4 health domains. Overall, 11.0% of the participants were considered healthy (and so were free of chronic diseases, such as cancers, myocardial infarction, and diabetes, and with no limitation in cognitive function, mental health, and physical function), and the remaining participants were considered usual agers.

Several health domains were typically impaired among the “usual” agers, said Dr. Samieri. “For example, 33% had both chronic diseases and limitations in cognitive, physical, or mental health; 64% had only limitations in cognitive, physical, or mental health; and 3.4% had only 1 or more chronic diseases.”

The analysis revealed that greater adherence at midlife to AHEI-2010 and A-MeDi was strongly associated with greater odds of healthy aging (P for trend < .001 for AHEI-2010; P for trend = .002 for A-Medi).

For example, compared with women in the worst quintile of diet scores, women in the highest quintile of the AHEI-2010 and A-MeDi scores had 34% (95% confidence interval [CI], 9% – 66%) and 46% (95% CI, 17% – 83%) greater odds of healthy aging, respectively.

Individual Components

When they analyzed individual dietary components, researchers found statistically significant associations of greater intake of fruits (odds ratio [OR] for upper versus lower quintiles, 1.46) and alcohol (OR, 1.28), and lower intakes of sweetened beverages (OR, 1.28) and PUFAs (OR, 1.38) with healthy aging (P for trend ≤ .04).

The authors noted that they could not exclude participants with impaired cognition, mental health, and physical function in midlife, and although probably few women had severe impairments at baseline, reverse causation in these participants may still be possible. Because they didn’t follow participants through to death or onset of a condition that would classify them as no longer healthy, researchers couldn’t prospectively estimate risks for transitioning from healthy to usual aging. As well, measurement errors may have occurred in the assessment of dietary patterns.

Other possible limitations were that the study was observational and, because it included mostly white women, its results may not be generalizable to other populations.

Middle age is probably the most relevant period of exposure for preventing chronic conditions of aging that develop over many years.

“It’s largely accepted that cumulative exposures to environmental risk factors over the lifespan are probably more important than late-life exposures to determine health in older ages,” said Dr. Samieri. “Several mechanisms of age-related chronic diseases, for example, atherosclerosis in cardiac diseases, brain lesions in dementia, start in midlife.”

Various researchers have reported on other newly documented health benefits of the Mediterranean diet, including the following:

Mediterranean Diets Beat Low-Fat for CVD Prevention.

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 A Mediterranean diet supplemented with either extra virgin olive oil or mixed nuts may cut the risk of cardiovascular events by as much as 30% in subjects at high risk of developing heart disease, as compared with people advised to eat a reduced-fat diet [1].

Those are the key findings from the randomized controlledPREDIMED primary-prevention trial presented here at theInternational Congress on Vegetarian Nutrition.

The Mediterranean diet already reigns supreme in secondary prevention of CV events. PREDIMED, which looked at diet effects on hard clinical end points, carves out an important role for this dietary eating pattern in primary prevention.

“These results support the benefits of the Mediterranean diet for CV risk reduction [and] are particularly relevant given the challenges of achieving and maintaining weight loss,” investigators write in a paper published in advance of the presentation in the New England Journal of Medicine. PREDIMED was led by Dr Ramón Estruch(Hospital Clinic, Barcelona, Spain) and Dr Miguel Angel Martínez-González (Clinical Universidad de Navaraa, Pamplona, Spain).

Commenting on the study for heartwire , Dr Marc Gillinov (Cleveland Clinic, OH), who was not involved in the study, pointed out that there are very few studies of any diets that are rigorously designed and that address hard clinical outcomes. “This randomized controlled trial is by far the best in class when it comes to dietary studies. We should take its results seriously: if you have risk factors for cardiovascular disease–and the majority of adult Americans do–your best bet is to follow a Mediterranean diet.”

PREDIMED: Oil and Nuts Over Fat Restriction

PREDIMED enrolled 7447 men and women ranging in age from 55 to 80 years, none of whom had established cardiovascular disease but who were at high CV risk. Subjects were randomized to one of two Mediterranean diet groups (one supplemented with olive oil, the other with nuts) or to a control diet wherein subjects were advised to try to reduce dietary fat.

Patients in the Mediterranean-diet groups were invited to regular dietary training sessions; by contrast, those in the control group were, for the first three years, sent leaflets explaining a low-fat diet. After a protocol amendment at the three-year mark, low-fat-diet patients were also invited to regular group sessions and offered personalized advice at the same level of intensity as the Mediterranean groups.

The study was stopped when an interim analysis at 4.8 years revealed a clear signal of benefit among subjects eating the Mediterranean diets. In the olive-oil and mixed-nut Mediterranean diet groups, the primary end point (MI, stroke, or CV death) was reduced by 30% and 28% respectively, as compared with the control group.

Study dropouts, meanwhile, were twice as common in the control diet group as in the Mediterranean diet group (11.3% vs 4.9%). “Favorable trends” were seen for both stroke and MI rates among subjects eating the Mediterranean diet, but numbers were too low to be relevant statistically. A total of 288 subjects experienced an event in the study: 96 events in the olive-oil group, 83 in the nut group, and 109 in the control group.

Of special note, subjects randomized to the Mediterranean diets were not told to reduce calories, a major barrier to success in many dietary interventions, particularly the long-supported “low-fat” approach.

Good Fat and Bad

In an email to heartwire , Estruch highlighted the importance of differentiating between different types of fat “Animal fat should be avoided,” he said, whereas “vegetal fats–extra virgin olive oil and nuts–should be recommended [within] a healthy food pattern such as the Mediterranean diet.”

Asked whether the findings would be applicable to other parts of the world where saturated fats are such a common component of everyday eating, Estruch stressed the importance of education.

“People should know that the Mediterranean diet is a diet healthier than others and should know the key components of this food pattern. The plan should be to increase the intake of the key foods (vegetables, fruit, nuts, fish, legumes, extra virgin olive oil, and red wine in moderation), also increase the intake of white meat, and decrease the intake of red and processed meat, soda drinks, whole dairy products, commercial bakery goods, and sweets and pastries.”

He continued: “To achieve a score of 14 in the 14-item adherence scale to traditional Mediterranean diet [laid out in a supplemental appendix in the paper] is more or less impossible, but to upgrade two to three points in this score is enough to reduce your cardiovascular risk by 30%.”

Gillinov, in turn, pointed out that there are no data of a similar quality supporting a low-fat diet, although these have long been promoted by physicians and professional medical groups. “The Mediterranean diet contains moderate quantities of fat, and it clearly wins in this trial of primary prevention,” he said.

Dr Steven Nissen , also of the Cleveland Clinic, was even more effusive, calling PREDIMED “a spectacular study that was extremely difficult to perform.”

“The findings are compelling and should alter the dietary advice we give patients. The currently popular ultralow-fat diets . . . are clearly not best for patients,” he told heartwire in an email. “The standard AHA-recommended diet should be modified to reflect these findings: fat is not the problem with the American diet, we just eat the wrong types of fats.”

Source: Medscape.com

 

Mediterranean Diet May Reverse Genetic Risk for Stroke.

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Following a Mediterranean diet (MedDiet) may not only reduce fasting glucose concentrations and lipid levels in patients who are genetically at increased risk for type 2 diabetes but may also lower their risk for stroke, a new study suggests.

Polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene are strongly associated with type 2 diabetes, as well as, in some studies, plasma lipids and cardiovascular disease. In this study, researchers looked at whether the MedDiet, which features olive oil, nuts, fish, whole grains, fruits, vegetables, and healthier fats, could moderate the genetic risk for cardiovascular outcomes associated with one of these polymorphisms, TCF7L2-rs7903146.

“Being on the Mediterranean diet reduced the number of strokes in people with 2 copies of the variant,” said study author José M. Ordovás, PhD, professor, Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, in a press release. “The food they ate appeared to eliminate any increased stroke susceptibility, putting put them on an even playing field with people with one or no copies of the variant.”

The study results “support the benefits of a MedDiet, especially for genetically susceptible individuals and emphasize the importance of studying entire dietary patterns rather than individual components,” the authors, led by Dolores Corella, PhD, Department of Preventive Medicine and Public Health School of Medicine, University of Valencia, Spain, conclude.

The study was published online August 13 in Diabetes Care.

Genetically Susceptible

This analysis included 8018 older men and women entered in the PREvención con DIetaMEDiterránea (PREDIMED), a multicenter clinical trial aimed at assessing the effects of the MedDiet on the primary prevention of cardiovascular disease. Patients in the study had type 2 diabetes or at least 3 cardiovascular risk factors, such as hypertension, dyslipidemia, obesity, or smoking.

Previous reports from the PREDIMED study have shown that this diet reduced carotid plaque, improved cognitive function, reduced cardiovascular events by about half, and also halved new-onset type 2 diabetes vs the low-fat arm of the study during the trial.

For this analysis, DNA was extracted from these patients and genetic variation in TCF7L2-rs7903146 was determined. About 14% of the participants were homozygous carriers, meaning they carried 2 copies of theTCF7L2 gene variant, a group referred to as TT.

Study patients were randomly assigned to the MedDiet supplemented with extra-virgin olive oil, to the MedDiet supplemented with mixed nuts, or to a control group that followed a low-fat diet. The groups were followed for a median of 4.8 years.

As expected, the TCF7L2-rs7903146 polymorphism presented a highly significant association with type 2 diabetes at baseline. Researchers also noted a highly significant association (P < .001) between this polymorphism and increased fasting glucose, although the statistical significance was lessened after adjustment for type 2 diabetes.

Their results showed significant gene-diet interactions. When adherence to the MedDiet prior to randomization in PREDIMED was low (below sample mean of 9 points), patients carrying the TT genotype had higher fasting glucose concentrations than those with other genetic variations (132.3 vs 127.3 mg/dL; P = .001). When adherence to the diet was high (≥9 points), there was no such increase.

This modulation by diet was also detected for total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels.

Stroke Risk

During the study period, 262 major cardiovascular events occurred, including 130 strokes.

When adherence to the MedDiet was low, TT patients presented a higher risk for stroke than those with other genetic variants (hazard ratio [HR] in the adjusted model that included diabetes, 2.44; 95% confidence interval [CI], 1.26 – 4.72). No higher risk was found when adherence to the MedDiet was high (HR, 0.99; 95% CI, 0.44 – 2.22).The mechanism of this effect is unknown, said the authors.

Importantly, the study showed that in the low-fat control diet, homozygous carriers were almost 3 times as likely to have a stroke as people with 1 or no copies of the gene variant (adjusted HR, 2.91; 95% CI, 1.36 – 6.19; P = .006).

Because modulation of stroke incidence by the MedDiet was similar in the group that received the diet supplemented with olive oil and the one supplemented with nuts, “our results suggest once again that it is the overall MedDiet pattern rather than specific foods that contribute to not increasing stroke risk in TT individuals,” said the authors.

“Our study is the first to identify a gene-diet interaction affecting stroke in a nutrition intervention trial carried out over a number of years in thousands of men and women,” commented Dr. Ordovás in the release. “The PREDIMED study design provides us with stronger results than we have ever had before. With the ability to analyze the relationship between diet, genetics, and life-threatening cardiac events, we can begin to think seriously about developing genetic tests to identify people who may reduce their risk for chronic disease, or even prevent it, by making meaningful changes to the way they eat.”

Although the study’s sample size was large, the interactive findings of stroke risk with the MedDiet rest on relatively few stroke cases, the authors point out.

Source: medscape.com

Mediterranean Diet Reduces Stroke Risk Even in Those with High Genetic Risk.

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High risks for type 2 diabetes and cardiovascular complications conferred by variants in the TCF7L2 gene can be partially offset by strict adherence to a Mediterranean-style diet, according to a Diabetes Care study.

PREDIMED investigators followed some 7000 participants at very high risk for cardiovascular disease. Their genetic risks were determined by ascertaining the variant of the TCF7L2 gene they carried, with “TT” variants known to confer higher risk than “CT” or “CC” variants.

The subjects were randomized to Mediterranean or low-fat diets and followed for roughly 5 years. TT carriers who did not generally observe Mediterranean-style diets at baseline showed higher risks for cardiovascular events, although not significantly so. Furthermore, TT carriers randomized to and adhering to a Mediterranean diet had stroke rates similar to CT and CC carriers.

The authors conclude that their findings support the benefits of a Mediterranean diet, “especially for genetically susceptible individuals.”

Source: Diabetes Care

Cold-tolerant wasp spiders spread to northern Europe.

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Temperature tolerance is key to the spread of wasp spiders into northern Europe, according to scientists.

Since the 1930s the distinctive spiders have expanded their range from the Mediterranean coast to Norway.

Researchers in Germany traced the population boom to breeding between the native European spiders and an isolated colony living near the Black Sea.

Molecular Ecology reports the genetic mixing resulted in generations rapidly adapting to living in colder climates.

Wasp spiders (Argiope bruennichi) are commonly named for their bright, striped abdomens and were recently recorded by the Woodland Trust in Usk, south Wales for the first time.

The first official records of this conspicuous species in the UK were made in the 1920s.

Henrik Krehenwinkel from the Max Planck Institute for Evolutionary Biology, Germany, analysed the DNA of spiders caught across their current range, and museum specimens to understand more about their evolutionary history.

Piecing together the genetic puzzle, he found that the spiders diverged after the last ice age: part of the population stayed on the Mediterranean while a colony headed east to Central Asia.

While these eastern populations adapted to live in climates as diverse as the tropical south of Japan and cold south-eastern Siberia, the spiders in the Mediterranean remained limited to warm areas.

But, according to the research, rising temperatures across the continent in the last century allowed the Mediterranean spiders to join up and breed with a previously isolated Black Sea population.

“This possibly restored genetic variation within a few generations and allowed for rapid adaptation,” said Mr Krehenwinkel.

He theorised that the novel combination of genes resulted in new physical characteristics that helped spiders to survive in different environments.

Out in the cold

To test the whether these more northerly spiders adapted a different temperature tolerance than Mediterranean populations, the PhD student analysed how they reacted when moved into one another’s habitats.

Southern spiders could not survive the freezing temperatures in the north, and their counterparts suffered from heat stress in the south.

Mr Krehenwinkel explained that the eastern population had adapted to cooler temperatures and this was passed on to European spiders in the population boom.

The result was the rapid adaptation of hardier offspring that could settle further north than their predecessors.

The spiders found in northern Europe have smaller bodies and are not seen in the coldest months of the year.

Scientists attribute both traits to seasonal changes which do not affect southern species. Spiders found in northern Europe “overwinter”, meaning their young are buried during the coldest months; emerging in spring.

The spiders then have limited warm months in which they can mature, which restricts how large they can grow before they reproduce in the autumn and the cycle begins again.

Mr Krehenwinkel described the hatchlings as “highly dispersive”, commenting that they can cover huge distances via a method known as “ballooning”: riding the breeze on a special parachute made of gossamer silk threads.

“By aerial dispersal, little spiders can cover distances of several hundred kilometres,” he told BBC Nature.

“Members of different genetic lineages can thus quickly track warming climate, which increases the likelihood of contact.”

Source:BBC

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet.

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BACKGROUND

Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events.

METHODS

In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.

 

RESULTS

A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.

 

CONCLUSIONS

Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events.

Source:NEJM

 

 

Novartis drug Exjade® recommended by CHMP for EU approval to treat patients with non-transfusion-dependent thalassemia syndromes .

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  • Exjade would be the first oral treatment approved specifically for patients with non-transfusion-dependent thalassemia (NTDT) syndromes 

 

  • Clinical data show Exjade significantly decreases iron burden in NTDT patients compared to placebo, with similar overall adverse event rate[1] 

 

  • NTDT patients accumulate excess iron, increasing their risk of complications, including liver fibrosis, cirrhosis, blood clots and bone and vascular disease[2]

 

 Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Exjade® (deferasirox) for the treatment of chronic iron overload requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients aged 10 years and older with non-transfusion-dependent thalassemia (NTDT) syndromes. Exjade would be the first oral treatment in the European Union (EU) specifically indicated for the treatment of iron overload in patients with these types of thalassemia.

 

Results from the first prospective placebo-controlled study of iron chelation in NTDT patients, THALASSA, showed a significant dose-dependent decrease in iron burden compared to placebo[1]. In this pivotal study, Exjade was well tolerated, with an overall adverse event rate similar to the placebo arm[1].

 

Thalassemia refers to a diverse group of genetic disorders that affect red blood cell production, causing anemia. Unlike patients with other types of thalassemia, those with NTDT syndromes can live without regular transfusions, a significant cause of iron overload. However, even without transfusions, NTDT patients still accumulate excess iron through intestinal absorption, leading to debilitating health complications like liver fibrosis and cirrhosis, blood clots, bone disease, pulmonary hypertension and vascular and endocrine diseases[2],[3].

 

“Patients with NTDT have suffered the effects of iron overload without accurate diagnosis, clear treatment guidelines or specifically approved oral therapies,” said Hervé Hoppenot, President, Novartis Oncology. “The CHMP recommendation is an important step toward improving the outcomes of patients with this type of thalassemia.”

 

According to published studies, at least three quarters of a million people worldwide have NTDT syndromes, although as understanding of the disease increases, it is probable the number will grow[4],[5],[6]. Because NTDT patients are not symptomatic at birth, when most thalassemias are diagnosed, they are often underdiagnosed and undertreated[7]. Many complications associated with iron overload begin to appear as early as age 10 and become increasingly common as patients reach their 20s or 30s[8]. Most NTDT patients are of South and Southeast Asian, Mediterranean or Middle Eastern origin, with immigration broadening the global prevalence[7],[9].

 

The European Commission generally follows the recommendations of the CHMP and usually delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway. Exjade has been approved to treat chronic iron overload in patients with NTDT in Canada and several other countries; further regulatory submissions are ongoing.

 

About Exjade

Exjade is an oral iron chelation therapy indicated for the treatment of chronic iron overload due to frequent blood transfusions (>=7 ml/kg/month of packed red blood cells) in patients with beta thalassemia aged 6 years and older). It is also indicated for the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups: patients with beta thalassemia major with iron overload due to frequent blood transfusions (>=7 ml/kg/month of packed red blood cells) aged 2 to 5 years; patients with beta thalassemia major with iron overload due to infrequent blood transfusions (<7 ml/kg/month of packed red blood cells) aged 2 years and older; and patients with other anemias aged 2 years and older[10].

 

It is approved in more than 100 countries including the US, Switzerland, Japan and countries comprising the EU. The approved indication may vary depending upon the individual country.

 

Exjade important safety information

Exjade is contraindicated in patients with an estimated creatinine clearance <60 mL/min, with hypersensitivity to the active substance or any of the excipients, or in combination with other iron chelator therapies. Exjade is not recommended in patients with severe hepatic impairment.

 

There have been postmarketing reports of acute renal failure, hepatic failure and cytopenias. Renal failure requiring temporary or permanent dialysis, renal tubulopathy and interstitial nephritis have been reported. Upper gastrointestinal ulceration and hemorrhage, sometimes fatal, have been reported. Caution should be used in elderly patients due to a higher frequency of adverse reactions. Exjade is not recommended in patients with a short life expectancy (e.g., high-risk myelodysplastic syndromes), especially when co-morbidities could increase the risk of adverse events.

 

Skin rashes, serious hypersensitivity reactions, decreased hearing and lens opacities have been reported. The most common adverse reactions are nausea, vomiting, diarrhea, abdominal pain, rash, non-progressive increases in serum creatinine, increased transaminases, abdominal distension, constipation, dyspepsia, proteinuria and headache.

Please visit www.exjade.com for more information.

References

[1] Taher A, Porter J, Viprakasit V, et al. Deferasirox significantly reduces iron overload in non-transfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood. 2012. Published online before print May 15, 2012.

 

[2] Musallam KM, Cappellini MD, Wood JC, et al. Iron overload in non-transfusion-dependent thalassemia: a clinical perspective. Blood Reviews. 2012:26S:S16-S19.

 

[3] Musallam KM, Cappellini MD, Wood JC, Motta I, Graziadei G, Tamin H, Taher AT. Elevated liver iron concentration is a marker of increased morbidity in patients with ß thalassemia intermedia. Haematologica. 2011 Nov;96(11):1605-12.

 

[4] Vichinsky E. Hemoglobin E syndromes. Hematology Am Soc Hematol Educ Program. 2007;79-83.

 

[5] Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Reviews. 2012:26S:S3-S6.

 

[6] Vichinsky EP. Changing patterns of thalassemia worldwide. Ann NY Acad Sci. 2005;1054:18-24.

 

[7] Thalassaemia International Federation. The Thalassaemia International Federation’s (TIF) New Focus: Addressing the Management of Non-Transfusion-Dependent Thalassaemias (NTDT). Position Paper 5.2. March 20, 2012. Accessed at: http://www.thalassaemia.org.cy/pdf/NTDT_Position_Paper_Final.pdf.

 

[8] Taher AT. Age-related complications in treatment-naïve patients with thalassemia intermedia. Brit J Haematol. 2010;150:486-489.

 

[9] Taher A, Cappellini MD, Musallam KM. Recent advances and treatment challenges in patients with non-transfusion-dependent thalassemia. Blood. 2012;26S:S1-2.

 

[10] EMC. Summary of product characteristics: EXJADE 125 mg, 250mg, 500mg dispersible tablets. Last updated January 13, 2012. Accessed at: http://www.medicines.org.uk/emc/medicine/18805.

 

Source: Novartis newsletter.