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Saturday, June 14, 2008

Gardeners: Be Cautious Of These Fungal Spores

A previously healthy man died after inhaling fungal spores from dead plant material while gardening in May 2007, and is discussed in a Case Report released on June 13, 2008 in The Lancet.

The man, 47 years old, was considered in good health, though he was a professional welder and smoked approximately ten cigarettes per day. He was admitted after one week presenting a sputum-producing cough, chest pain, and worsening shortness of breath. Running a fever of 100.4°F (38°C,) he had a low lymphocyte and neutrophil count. He also had coarse crackles in his lungs, and his chest radiography showed irregular nodules.

Assumed to have community-acquired pneumonia, he was treated with intravenous co-amoxiclav and clarithromycin, but when his symptoms worsened, a third antibiotic, flucloxacillin, was administered. In the next day, he became so short of breath that even with supplementary oxygen he needed to be transferred to the intensive care unit (ICU.) In the ICU, it became clear from blood gas measurements that despite intubation and ventilation, adequate gas exchange was not being provided in his tissues. Additionally, he showed signs of serious sepsis.

At this point, an HIV test was negative. However, two sputum samples cultured the fungus Asperillus fumigatus. According to the authors, "On closer questioning, the patient's partner revealed that his symptoms had started less than 24h after he had dispersed rotting tree and plant mulch in the garden, where clouds of dust had engulfed him." Treatment with intravenous liposomal amphotericin B was started.

The man was subsequently transferred to another unit for extracorporeal membrane oxygenation (ECMO,) which is similar to being supported by a heart-lung machine. Upon his arrival, despite the ECMO treatment, his blood pressure remained too low and he developed kidney failure. Although a continuous dialysis was initiated, as his condition worsened, escalation of treatment was considered inappropriate. After 72 hours, ECMO was terminated and he died soon after. The diagnosis of aspergillosis was confirmed through a laboratory analysis of blood samples.

Spores of aspergillus are often found on decaying plant matter, and inhalation of these spores can cause several different types of aspergillosis. These can range from acute and invasive, like in the aforementioned patient, to chronic and necrotizing.

The authors conclude with a statement regarding how this patient was an unusual example of aspergillosis, and that his case may have been influenced by immunosuppression. "Unlike most patients with acute, invasive, aspergillosis, our patient did not seem to be immunosuppressed; however, smoking and welding could have damaged his lungs, increasing his vulnerability. Since he died so quickly, we cannot exclude the possibility that he had an undetected immunodeficiency. Acute aspergillosis after contact with decayed plant matter is rare, but may be considered an occupational hazard for gardeners," they say.

Additionally, they add, immediate antifungal treatment is essential in these cases: "Although liposomal amphotericin B has been used in such cases, and was the recommended treatment of choice within our hospital trust at the time of this case, more recent guidelines suggest voriconazole may currently be the optimum empirical therapy."

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Nicotine Addiction: Prevalence And Treatment

A Seminar released on June 13, 2008 in The Lancet discusses nicotine addiction, and the potential for reducing its disease burden and death toll by improving public knowledge and using treatments individual to patients. This includes the potential creation of an antinicotine vaccine.

Nicotine is a stimulant classically found in tobacco, and its chronic addiction is primary cause of habitual smoking. According to the seminar, there are approximately 1.2 billion smokers and approximately half of them will die from diseases directly caused by smoking. Currently, about five million smokers die each year, and if present trends continue this could increase to ten million each year by 2025.

More of these smokers are men than women, necessitating separate studies by gender. For instance, of the world's male population, 92% of them live in countries where more than 25% of all males smoke. In contrast, in the world's female population, 10% live in countries where female smoking frequency is above 24%. In the United Kingdom and the United States, between 25-35% of all males smoke. In the female population, however, there is some discrepancy, as in the USA 14-24% of women smoke but more than 24% smoke in the UK.

The distribution of smokers varies by country, ranging from as little to 5% of the population to over 55%. Some countries where male smoking prevalence is above 55% include Russia and Kenya. The female smoking frequencies are above 24% in Brazil, Germany, Spain, and the UK.

Terminating an addiction to smoking is often recognized as a significant challenge. In the USA, over 70% of the smoking population want to quit every year and 45% attempt it. However, less than 5% of the general population is successful in this endeavor.

Even simple advice from a health care professional can help improve these rates. Following guidelines set forward recently in the US, the Seminar first examines the role of counseling in quitting smoking, addressing topics including problem solving, coping, and motivational skills.

According to the Seminar, this rate of termination can be enhanced by treatment for nicotine addiction itself. "Pharmacotherapies for nicotine dependence can enhance quit rates by about
two-three fold," state the authors. They discuss and evaluate a number of nicotine-replacement therapies (NRTs) such as patches or nicotine gum, non-nicotine products based on efficacy, side effects, and precautions for each. Additionally, they examine improved rates of success with combinations of the nicotine patch and other products such as nicotine gum.

The authors of the Seminar examine not just the characteristics of termination, but also the limited benefits of cigarette reduction, which is also achieved with higher frequency with the use of NRTs. They say, however, that these effects are counteracted by changes in the habits of the smokers: "Smokers engage in substantial compensatory smoking - deeper inhalation per cigarette - so that a reduction of cigarette consumption of 50% or more results only in a 30% decrease in biomarkers for toxicant exposure." Cigarette reduction's primary benefit, therefore, may be that it acts as an intermediate step towards quitting.

There are some new treatments in development. One example is a nicotine vaccine which prompts the body's immune system to develop antibodies against the substance, and for which preliminary trials are in progress. Another is the drug rimonabant, which selectively blocks a specific cannabinoid receptor, for which large, randomized trials are being performed. Finally, pharmacogenetics, a field in which treatment is matched to the patient based on his genetic profile, is examined.

The authors conclude with comments about nicotine addiction: "Nicotine or tobacco addiction should be treated as a chronic disorder. Treatment can need persistent efforts to try to assist tobacco users in their attempts at quitting. Relapse should be seen as a probable event... Treatment can improve these outcomes... The most crucial component of care is the actual delivery of such treatments."

Dr. Kenneth Warner of School of Public Health, Ann Arbor, MI, USA, and Dr. Judith Longstaff Mackay, Bloomberg Initiative to Reduce Tobacco Use, Hong Kong, China, contributed an accompanying Comment in which they state the importance of The Framework Convention on Tobacco Control (FCTC,) which has presently been ratified by 154 countries. They indicate that the medical community should make a higher priority of treatment of tobacco dependence, especially in every day practice, and that they should lobby governments, who may have conflicts of interest due to tobacco lobbies, to put this legislation into effect. "Here is something simple, achievable, and unequivocally good that would relieve the suffering of literally millions of human beings," they say.

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For Smokers, Lung Cancer Risk Not Greater For Women

A paper published in The Lancet Oncology has concluded that women smokers are not at a greater risk of developing lung cancer than male smokers. However, among those who have never smoked, women appear to be more likely to develop the disease than men.

In the United States, the medical and health community mostly agrees that cigarette smoking is responsible for about 90% of lung cancers. One point of contention among researchers and scientists, however, deals with how cigarette smoking affects men and women differently. Existing research has not been able to provide conclusive evidence that smoking makes women more or less susceptible to lung cancer than men.

Further investigating this issue, Neal Freedman (National Cancer Institute, Rockville, MD, USA) and colleagues studied a data set of almost 500,000 American men and women that contained information on smoking habits, diet, physical exercise, and incidence of lung cancer. Regarding smoking, the 279,214 men and 184,623 women (all 50 to 71 years old) were asked if they currently smoked, if they had ever smoked, and how many cigarettes per day they had smoked.

Key results from the study include:

* Lung cancer incidence rates were 1.47% for men and 1.21% for women.
* Compared to men who never smoked, women who had never smoked were still 1.3 times more likely to develop lung cancer.
* The correlation between smoking and cancer risk was strong in both men and women.
* Smoking two packs of cigarettes per day makes you 50 times more likely to develop lung cancer than never smoking at all.
* Compared to male smokers, women smokers were only slightly less likely (0.9 times) to develop lung cancer.

Lung cancer comes in several different forms. Rates of small cell, squamous, and undifferentiated tumors were about the same for both men and women who had never smoked. Adenocarcinomas, however, were more common in women than in men. Male smokers were twice as likely as female smokers to develop squamous tumors and about as likely as female smokers to develop the other tumors.

"Our findings suggest that women are not more susceptible than men to the carcinogenic effects of cigarette smoking in the lung. Vigorous efforts should continue to be directed at eliminating smoking in both sexes," conclude the authors.

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Tuesday, June 10, 2008

AIDS Epidemic Far From Over Says UN

A new report by United Nations Secretary-General Ban Ki-moon to be released today, Tuesday 10th June, at UN headquarters in New York, says that the global fight against HIV/AIDS is making significant progress, but officials said in a press conference yesterday that the global epidemic is far from over.

Although considerable progress has been made, it is too early to celebrate, was the overall tone of the meeting between UN officials and the press at UN headquarters in New York yesterday, where the Secretary-General is today presenting the report (document A/62/780) at the opening session of the General Assembly's high-level meeting on HIV/AIDS.

"The report highlights real results," Michel Kazatchkine, Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria, told journalists.

There has been a 15-fold increase since 2001 in the number of people receiving life saving antiretroviral (ARV) treatment, from under 200,000 to 3 million, including 2 million in Africa, says the report. In 2001, more than half of the people in receipt of ARV treatment were in Brazil, the only developing country that was offering free ARV therapy to its people.

The report also says that the global rate of new infections has come down, and pregnant women living with HIV are now increasingly able to obtain drug therapy that stops the virus passing from mother to child, said Kazatchkine. At the end of 2007, around one third of pregnant women in low and middle income countries who are living with HIV accessed ARV therapy, and 200,000 children living with HIV in developing nations were also being treated, a huge leap of 80,000 from the year before.

But the UN officials tempered their optimism with a reminder of what still remains to be accomplished.

6,000 people die every day from HIV/AIDS, and another 7,000 become infected, "that's a crisis by any standard", said Peter Piot, Executive Director of the Joint United Nations Program on HIV/AIDS (UNAIDS).

"The AIDS epidemic is far from over," said Piot, in spite of the fact that resources to fight HIV/AIDS had exceeded the targets set in the Declaration of Commitment on HIV/AIDS, adopted by the General Assembly in 2001. The target was 7 billion dollars by 2005, and last year the global mobilization of HIV/AIDS resources came to 10 billion dollars.

"Despite the progress," said Kazatchkine, "only 30 per cent, or close to one third, of the people we believe to be in need of antiretroviral treatment access ARV therapy currently".

One of the problems, says the report, is that the rate at which access to essential treatment is expanding is not keeping up with the rate of expansion of the epidemic. For instance, although one million more people started ARV treatment in 2007, the rate of new infections in that year was 2.5 million people.

The report estimates there are 33.2 million people worldwide living with HIV, as of December 2007. Although the global rate of new infections has fallen, a number of countries are seeing rising rates of new infections, including China, Indonesia, Russia and Ukraine, and some European Union and North American countries.

AIDS remains the leading cause of death in Africa, and the overall rate of infection among women is rising more rapidly than among men.

Other reasons why ARV therapy does not reach the people who need it are weak healthcare systems, critical shortages in skills, and not knowing for sure what funds will be available in the long term, said Kazatchkine.

Kazatchkine said the Global Fund enabled over 50 per cent of the people on ARV therapy to get their treatment, and it also funded over two thirds of the international fight against malaria and tuberculosis.

The Global Fund to Fight AIDS, Tuberculosis and Malaria was officially set up by the heads of state at the 2001 G8 summit, along lines suggested by two Harvard academics urging a step up in the world's commitment to fighting these devastating diseases.

Last year there was a funding gap of around 7 billion dollars, said Kazatchkine. 17 billion was needed in order for all the people who needed ARV therapy to get it, but only 10 billion was forthcoming. He told reporters that while some countries like the United Kingdom had pledged money to the Global Fund through to 2014, this was not the norm, and more long term funds were needed, such as through official development assistance (ODA), and other private and public funding channels.

Kazatchkine went on to explain that "there will always be a gap", but he hoped this will get narrower. He said we have to be careful, he did not want 2008 to be the year when nations turn and say, "You're doing alright with the AIDS epidemic. Now we have to focus on something else".

"We need a very sustained effort and we still need increased resources," urged Kazatchkine.

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Vitamin D May Help Prevent Heart Attacks

An article published in the June 9 issue of Archives of Internal Medicine reports that men who have low levels of vitamin D are at a higher risk of heart attack (myocardial infarction).

It has been shown that deaths related to cardiovascular disease are more frequent in higher latitudes and during the winter months - when and where the sun rarely shines - and are less frequent at higher altitudes. Edward Giovannucci, M.D., Sc.D. (Harvard School of Public Health and Brigham and Women's Hospital, Boston) and colleagues note that, "This pattern is consistent with an adverse effect of hypovitaminosis D [vitamin D deficiency], which is more prevalent at higher latitudes, during the winter and at lower altitudes." Although there are most likely several reasons for these observations, researchers do know that vitamin D impacts the body in ways that affect the risk of heart attack and heart disease.

Giovannucci and colleagues reviewed the medical records and blood samples of 454 men between the ages of 40 to 75 who had non-fatal heart attack or fatal heart disease. Initial data collection occurred between January 1993 and December 1995, and patients were followed until January 2004. The researchers compared this first sample with records and blood samples of 900 living men who had no history of cardiovascular disease. Self-administered questionnaires were used to collect data on the diets and lifestyles of the men.

The main finding was that men who had a vitamin D level of 15 nanograms per milliliter of blood or less (vitamin D deficiency) had a higher risk of heart attack compared to those with 30 nanograms per milliliter of blood (vitamin D sufficiency).

"After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega 3 intake, low- and high-density lipoprotein cholesterol levels and triglyceride levels, this relationship remained significant," write the researchers. Even men with intermediate vitamin D levels were found to have a greater risk of heart attack than those with sufficient levels.

The authors conclude their study by noting: "Vitamin D deficiency has been related to an increasing number of conditions and to total mortality. These results further support an important role for vitamin D in myocardial infarction risk. Thus, the present findings add further support that the current dietary requirements of vitamin D need to be increased to have an effect on circulating 25(OH)D [vitamin D] levels substantially large enough for potential health benefits."

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Thursday, June 5, 2008

Restless Leg Syndrome Relief Found In Rotigotine Skin Patch

Patients with restless leg syndrome (RLS) - the irresistible urge to move one's body to limit uncomfortable or odd sensations - may get some relief during day and night by using skin patches that contain the drug rotigotine. The findings come from a randomized, placebo-controlled, double-blind study published in the July edition of The Lancet Neurology.

Researchers studying RLS have analyzed the genetic basis of the disease and determined that it should be treated as a general neurological disorder. Currently, many patients with this condition are prescribed dopaminergic drugs that stimulate the body's dopamine system - a first line of treatment. Rotigotine is a type of dopaminergic drug, and it has been used to treat Parkinson's disease. To investigate the effects of transdermal rotigotine patches as treatment of RLS, Dr. Claudia Trenkwalder (Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany) and colleagues conducted a randomized controlled trial.

The researchers analyzed a sample of 458 patients with moderate-to-sever RLS. Their average baseline score on the International Restless Leg Syndrome study group severity rating scale (IRLS) was 28.1, and they had a score of 4 or more on a test to measure severity of symptoms called the clinical global impressions (CGI) item 1 assessment. Random assignment resulted in 115 patients receiving transdermal rotigotine 1 mg, 112 patients receiving a 2 mg dose, 114 receiving a 3 mg dose, and 117 receiving placebo. Rotigotine was delivered via skin patches that were applied one time a day over a 6 month period. The main outcome measures were the changes from baseline to the end of the treatment period in the IRLS score and in the CGI item 1 score.

The mean changes in the IRLS group were as follows:

* -13.7 in the 1 mg group,
* -16.2 in the 2 mg group,
* -16.8 in the 3 mg group, and
* -8.6 in the placebo group.

The mean changes in the CGI item 1 score were:

* -2.09 in the 1 mg group,
* -2.41 in the 2 mg group,
* -2.55 in the 3 mg group, and
* -1.34 in the placebo group.

Three quarters of patients indicated that their rotigotine patches were "good" or "very good" in a follow-up survey, though 43% of patients (145 of 341) had (mostly mild or moderate) skin reactions to rotigotine. Only 2% of participants who received placebo reported skin reactions. Rotigotine was associated with serious adverse events in 10 patients: one patient had an elevation of liver enzymes, one had a worsening of tinnitus, one had a non-response to anticoagulation, one had electrocardiogram changes, and six had reactions at the application site. Skin reactions at the patch site were not severe enough to warrant hospital treatment, and shortly after removing the patch, the issues were resolved. There were no signs of an increase in the severity of symptoms in RLS during dopaminergic treatment, and the patients demonstrated a low the rate of typical dopaminergic side-effects.

"The results of this 6-month trial indicate that transdermal delivery of low doses of rotigotine for 24 h per day are more effective than placebo in relieving the symptoms of RLS in patients who are moderately to severely affected. This trial, together with a pilot study and dose-finding trial, suggest that, despite differences in treatment duration and other design features, there exists a clear therapeutic window in terms of dose of rotigotine to treat restless legs syndrome between 1 mg over 24 h to 3 mg over 24 h," conclude the authors.

A comment accompanying the research article is written by Dr. Kapil Sethi (Medical College of Georgia, Augusta, GA, USA). Dr. Sethi notes that, "The introduction of a patch with a constant delivery of a dopamine agonist is a welcome addition to the armamentarium. Unfortunately, the rotigotine patch has been temporarily withdrawn from the US market because of problems with manufacturing and the unreliable delivery of the drug.

"RLS causes significant discomfort and adversely affects the quality of life of patients. Whether it has more ominous consequences is unclear. A recent study showed that RLS is associated with a greater risk of cardiovascular disease, particularly in patients with greater frequency or severity of RLS symptoms. Whether treatment of RLS will reduce this risk is unknown, and further studies should help answer this question."

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