Females who are poor sleepers have increased risks for cardiovascular disease than males exhibiting similar sleeping patterns.

“Self-reported ratings of sleep quality and symptoms of poor sleep have been linked to increased risk of coronary heart disease (CHD), type 2 diabetes and hypertension with recent evidence suggesting stronger associations in women”, according to a recent report [1].

Poor sleep quality, defined as long periods to fall asleep (>30 minutes), was associated with greater psychosocial distress, higher fasting insulin, fibrinogen and higher levels of the inflammatory biomarkers C-reactive protein and interleukin-6 only for women. A survey by the National Sleep Foundation shows that 60% of female respondents suffer from poor sleep and 43% suffer from daytime sleepiness which adversely affects daily activities.

In another study [2], delayed sleep phase syndrome is associated with irregular menstrual cycles and increased premenstrual symptoms in women. Sleep quality is even likely to deteriorate during and after menopause.

“The hormonal and physical changes that occur during and after menopause can also affect a woman’s sleep. Sleep disturbances are more common, and sleep quality can decline. Insomnia related to menopause often occurs.”

Meanwhile, researchers at the University of Minnesota [3] found strong associations between disturbed sleep and mortalities in men older than 67.

“Waking early, staying up late, and severely disturbed sleep patterns may have a detrimental impact on health in older men.”

References:

1. Suarez EC. Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: Evidence for gender disparity. Brain Behav Immun. 2008 Mar 5. [Epub ahead of print] Links

2. American Academy of Sleep Medicine. Delayed Sleep Phase Syndrome Linked to Irregular Menstrual Cycles, Premenstrual Symptoms in Women. Press release 10 June 2008.

3. University of Minnesota News. Disturbed Rest, Activity Linked to Mortality in Older Men. 11 June 2008.

“For the first time in history, the industry will have negative growth in 2011″ according to Alexis de Rosnay, global co-head of healthcare at Lehman Brothers.

The reasons for the bad prognosis are expiration of patents coinciding with shrinking pipelines and increasing competition from generics. Furthermore, the counterstrategy of mergers and acquisition isn’t seems to be working as expected.

Meanwhile, drug regulations are getting tighter. Alternative medicine, dietary supplements, and homeopathic medications are conquering the market while biotechnology and stem cell research are not delivering the promised blockbuster therapies everybody is hoping for.

In 2007, Roche outperformed for the first time its Swiss archival Novartis in earnings. However, even Roche delivered lower than expected results in the first quarter of 2008 due to decreasing demand for Tamiflu.

Other drug companies are expecting tough times as the patent of their blockblusters are about to expire. GSK’s Lamictal goes off patent this year and Pfizer’s Lipitor in 2010. Other best-selling drugs whose patents are due to expire are Johnson & Johnson’s Risperdal, Astra Zeneca’s Seroquel and GSK’s Avandia, according to FT.

References:

1. Piazza N, Gregoire J. Images in clinical medicines. Starr-Edwards heart valves. N Engl J Med. 2008 May 22;358(21):e24.
2. Gödje OL et al. Thirty-year results of Starr-Edwards prostheses in the aortic and mitral position. Ann Thorac Surg. 1997 Mar;63(3):613-9.
3. Suezawa T et al. Forty-year survival with Smeloff-Cutter and Starr-Edwards prostheses. Ann Thorac Surg. 2008 Mar;85(3):e14-6.

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Stem cells in menstrual blood [1, 2]

Researchers at the University Pittsburgh’s McGowan Institute of Regenerative Medicine observed that menstrual blood stromal cells (MenSCs) exhibit a great capacity for self-renewal and multipotency.

“MenSCs could differentiate into adipogenic, chondrogenic, osteogenic, ectodermal, mesodermal, cardiogenic, and neural cell lineages… [They] expanded rapidly and maintained greater than 50 percent of their telomerase activity when compared to human embryonic stem cells and better than bone marrow-derived stem cells.”

Stem cells in breast milk [3]

On the other side of the globe, researchers at the University of Western Australia recovered the stem cell markers nestin from breast milk. These cells physically resemble stem cells and could potentially behave like stem cells.

If nestin and MenSCs indeed prove to be as plastic and pleuripotent as embryonic stem cells, then, we may have found stem cell sources which are unlimited, inexpensive, most of all, noncontroversial. Furthermore, these cells are easily collectable without resorting to invasive techniques.

Sources:

1. Eureka Alert, 23 April 2008
2. Patel et al. Cell Transplantation 2008; 17: 303-311
3. Science Alert, 10 February 2008

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Successful trials whose results have been published: [1,2]

This “randomized, controlled, investigator-blinded, parallel-group trial” investigated the effect of chocolate consumption (6.3 g of dark chocolate per day = 30 kcal) on the blood pressure of prehypertensive adults. “From baseline to 18 weeks, dark-chocolate intake reduced mean systolic BP by 2.9 mm Hg (p<0.001) and diastolic BP by 1.9 mm Hg (p<0.001) without changes in body weight, lipids, glucose, or 8-isoprostane. Hypertension prevalence decreased from 86% to 68%.”

In this double-blind randomized study, Swiss researchers at the Zurich University Hospital studied the effect of dark chocolate in 22 heart transplant patients. An intake of 40 g of dark chocolate (70% cocoa) “induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.”

The not so-successful: [3]

The Chocolate Happiness Undergoing More Pleasantness (CHUMP) study was designed as a double-blinded clinical trial “to compare the effects of dark chocolate, milk chocolate and normal chocolate consumption on happiness.” However, data analysis somehow went awry because “many participants switched groups mid-study because of their personal chocolate preferences. Although the CHUMP study was pleasurable, it demonstrated the difficulties associated with performing a truly blinded clinical trial.”

This one is ongoing:

The Phase I trial on the “Effects of Dark Chocolate on Insulin Sensitivity in People with High Blood Pressure” (ClinicalTrials.gov Identifier: NCT00099476) examines “whether dark chocolate affects the way patients with hypertension (high blood pressure) respond to insulin, a hormone secreted by the pancreas that regulates blood glucose (sugar) levels. In many people with hypertension, insulin is not as effective in helping the body use glucose. This is called insulin resistance. Insulin also increases blood flow into muscle by opening inactive blood vessels. Laboratory studies suggest that eating dark chocolate may improve blood pressure. This study will determine whether dark chocolate improves insulin resistance or changes how blood vessels react to insulin in hypertensive people.”

This one is still recruiting:

This trial, due to start in June, will investigate whether flavonoids found in chocolate and other foods can reduce the risk of cardiovascular diseases in menopausal women with type 2 diabetes. “The study is funded by … Diabetes UK, and is led by a team at the University of East Anglia (UEA) in Norwich, partnered by the Elsie Bertram Diabetes Centre, Norfolk, Norwich University Hospital (NNUH) and the Institute of Food Research (IFR).”

References:

1. Taubert D, Roesen R, Lehmann C, et al. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide. A randomized controlled trial. JAMA 2007; 298:49-60
2. Flammer A, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation 2007;116:2376-2382.
3. Chan, K. A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness (CHUMP) study. CMAJ 2007; 177 (12).

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I cringe every time the term “ghost writing” comes up in connection with the medical and scientific writing profession. Are we really “ghost writing” when we, medical writers, draft manuscripts for clients in the pharmaceutical industry? Is this unethical? Let’s see what the experts say.

Citing Rennie et al. (1994), Ross et al. defined ghost writing as “failure to designate an individual (as an author) who has made a substantial contribution to the research or writing of a manuscript.”

According to the World Association of Medical Editors (WAME), “ghost authorship exists when someone has made substantial contributions to writing a manuscript and this role is not mentioned in the manuscript itself.” However, it is not quite clear where the role of the medical writer should be mentioned in the manuscript.

The International Committee of Medical Journal Editors (ICMJE) is much clearer with its guidelines which provide that “authorship credit should be based on 1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published. Authors should meet conditions 1, 2, and 3.”

Based on the ICMJE criteria, most medical writers clearly do not qualify for authorship. So where does the role of the medical writer come in? ICMJE states that “all contributors who do not meet the criteria for authorship should be listed in an acknowledgments section.”

I, therefore, object to Ross et al.`s definition of “ghost writing” in their paper as non-compliant ICMJE`s guidelines.

The paper also referred to “an industry specializing in medical writing” as if this is something new. Though are no figures available, it is quite a common and accepted practice in the healthcare and pharmaceutical industry to employ the services of professional writers to write press releases, educational materials, clinical documents, submission dossier, and yes – scientific papers.

The American Medical Writers Association (AMWA has been in existence since 1940 and the European Medical Writers` Association (EMWA) since 1989. These organizations have established guidelines and code of conduct. Members of these organizations have drafted and proposed the “Good Publication Practice (GPP): Guidelines for Pharmaceutical Industries.”

Ross et al.`s article, although aimed to question the credibility of Merck, also placed medical writers in a bad light. Whereas the article gives the number of papers with financial disclosures, it does not give the number of papers which acknowledged the use of medical writing services as provided for in the ICMJE guidelines.

I do not condone data manipulation as well as blatant misleading publication strategies such as the examples cited by Ross et al. as having been practiced by Merck. I simply want to defend medical writing as a valid profession.

Medical writers play an important role in the drug development process. Clinicians and biomedical scientists are busy people. As chief investigators and head of laboratories, they do not have the time to sit down and write papers.

In the academia, writing is usually delegated to PhD students and postdocs. In the pharmaceutical industry, writing is mainly done by trained and accredited medical writers who may be in-company or on-contract. Based on data provided to us, we try to write the text to the best of our ability. In the process the health care industry is benefited by fast and timely publication of scientific information which could be crucial to public health.

According to a statement drafted by several AMWA members

“We believe that medical writers are valuable to the writing process and can facilitate and speed the publication of important scientific information. Professional writers ensure that the literature cited is current; the study and statistical methods are complete, appropriate, and adequately detailed; and the author’s interpretation of the study findings is clearly and concisely communicated.  Because of their contributions, manuscripts may be reviewed more easily by peer reviewers with fewer queries to be answered before final acceptance. 

Medical writers have an important role in conveying valuable information to physicians and others in both a clearly communicated and a timely manner.”

However, as medical writers, we also have the duty to maintain the ethical standards of our profession. We can do these by

• advising our clients on GPP especially in authorship and acknowledgement of medical writing services rendered.

• refusing to take part in or condone data manipulation and other scientific misconduct.

• advising our clients on complete transparency by conflicts of interest and financial involvement.

Only then can we stand and lift our heads proudly to declare that we are not “ghost writers”, but professional medical writers.

References:

Joseph S. Ross, Kevin P. Hill; David S. Egilman; Harlan M. Krumholz. Guest Authorship and Ghostwriting in Publications Related to Rofecoxib A Case Study of Industry Documents From Rofecoxib Litigation. JAMA 299:15, April 16, 2008.

D Rennie, A Flanagin. Authorship! Authorship! Guests, ghosts, grafters, and the two-sided coin. JAMA 271: 469 - 471. Feb 1994.

E Wager, EA Field, L Grossman. Good publication practice for pharmaceutical companies. Curr Med Res Opin. 2003;19(3):147-8

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You`d think that such a constitution must be based on religions such as Buddhism which holds all living creatures sacrosanct from the single-celled to the high complex.
Actually, what is being referred to is the Swiss Federal Constitution. Based on this, the Gene Technology Law took effect in 2004 which stipulates that any scientific research should respect “the dignity of creation.” (German: Würde der Kreatur).

Animal activists were the first to agree that such a law is needed to protect the rights of animals, be it from toxicology studies to genetic manipulation. And rightly so. However, recent propsed addition to the Animal Protection Act actually requires everybody - not only scientists - but also farmers and pet owners to uphold the dignity of animals. Dog owners, for example, might be required to have a license, a document that may be granted only if they are proven to be capable of caring for their pets. Hamsters should only be kept in pairs and  fish can only be killed under anesthetics.

But that`s not all.  There is a new angle to this legislation that baffle both scientists and laymen alike. The “dignity of plants” has also been recently brought into the forefront which can drastically affect current as well as future plant research.

The main problem is how to define “plant dignity”, a term which is not clear to either plant biologists and funding agencies. The Federal Ethics Commitee on Non-Human Biotechnology (ECNH) gives the following concrete example:

“Terminator technology” is a genetic modification of plants so that a sown seed germinates normally, but the developing plant then produces seeds that are unable to germinate. What impacts does this technology have on agriculture? Does this affect the Würde der Kreatur in plants? And what precisely constitutes the dignity of a plant?” [1]

According to Nature News [2], ECNH
“… has created a decision tree presenting the different issues that need to be taken into account for each case. But it has come up with few concrete examples of what type of experiment might be considered an unacceptable insult to plant dignity. The committee does not consider that genetic engineering of plants automatically falls into this category, but its majority view holds that it would if the genetic modification caused plants to ‘lose their independence’ — for example by interfering with their capacity to reproduce. The statement has confused plant geneticists, who point out the contrast with traditional plant-hybridization technologies, for example in roses, which require male sterility, and the commercial development of seedless fruits.”

As a resident of Switzerland, I cannot help but wonder at the extremes and contrasts I have observed in this country. Respecting “dignity” of animals nonwithstanding, authorities granted the permission to shoot down a border-crossing brown bear earlier for human safety reasons, causing strong outcry in neighboring Italy.

Switzerland is home to 2 of the most innovative and highly respected research institutions in the world – European Organization for Nuclear Research- (CERN) in Geneva and ETH (Swiss Federal Institute of Technology) in Zurich. It is also the proud headquarters of two of the biggest pharmaceutical companies in the world – Roche and Novartis, both based in Basel. Yet, it has one of the most restrictive legislation on biotechnology research in Europe. While many European countries, including Germany are slowly easing up restrictions on stem cell research, Switzerland is moving in the opposite direction.

How the new legislation will affect research in Switzerland, only time will tell. Currently, Switzerland is home to many of the world`s talented scientists.  Among many Europeans, most especially Germany, Switzerland is a highly desirable destination because it offers good research facilities, high pay, low taxes, and overall good quality of life. However, if such legislations make life difficult for these scientists, an exodus of of talent out of this country cannot be ruled.

Sources:

[1] Dignity of creation, ECNH

[2] Nature News 23 April 2008

With the acquisition, Roche also acquires Piramed`s two major P13-K projects on oncology and inflammatory medicine. This solidifies the collaboration between Piramed and Genentech (partly owned by Roche) on these research programs.

This is not the first time that big pharma takes over small but promising biotech firms. Pfizer bought Angiosyn in 2005. Merck acquired Sirna in 2006.  Sanofi Aventis joined forces with Regeneron last year.

According to analysts [2], such mergers and acquitions are not necessary favorable in the long run. Small companies are saved from financial troubles at the expense of the larger firms which tend to suffer from slow growth and postmerger integration problems – problems which can divert cash from R&D and further slow down the pipeline.

References:

1. Roche Media News, 15 April 2005

2. Danzon et al. Mergers and acquisitions in the pharmaceutical and biotech industries. NBER Working Paper No. 10536, May 2004

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Vitamin D and Alzheimer’s disease [1]
A small retrospective study (n= 32) found strong links between low serum levels of vitamin D and low performance in cognitive tests in patients with Alzheimer’s disease. Supplementation with vitamin D improved test outcomes. The results suggest that optimal vitamin D levels are important in cognitive function in older adults.

Vitamin D and myopia [2]
Vitamin D deficiency is linked to myopia in the Asia-Pacific region. Results show that 90% of conscription-aged Singaporean males are myopic. This is a dramatic increase compared to the incidence of 20 to 30% about 40 years ago. In Australia on the other hand, the incidence went from 15% to 20-25% within the same time period.
Ethnicity may play a role because of the “genetic susceptibility to environmental risk factors associated with intensive education and urbanisation” among East Asians. However, myopia seems equally prevalent across all ethnic groups (including Malay and Chinese) in Singapore.
Furthermore, the prevalence of myopia was found to be 10 times more among Chinese-Singaporean children than Chinese children based in Sydney. The difference lies in the number of hours of exposure to the sun. The Australian children stayed outdoors 4 times longer than their Singaporean counterparts. Researchers hypothesize that exposure to sunlight encourages the release of dopamine, which in turn inhibit excessive eye growth that leads to myopia. In many Asian countries, sun exposure is actually avoided due to a cultural preference for lighter skin.

Vitamin D and multiple sclerosis [3]
Multiple sclerosis is strongly linked to genetics. However, there are strong geographical patterns in the incidence of multiple sclerosis that cannot be fully explained by genetics alone. It has been observed, for example, that multiple sclerosis is less prevalent in the tropics and subtropics than in higher latitudes. Environmental factors are involved in the epidemiology of this disease and one of these is vitamin D.

Vitamin D3and osteoporosis [4]
Vitamin D plays a major role in the prevention and management of osteoporosis. Vitamin D deficiency has been linked to osteopenia, osteoporosis and osteomalacia. Cholecalciferol or vitamin D3 enhances the absorption of calcium and phosphorous in the intestine.

Vitamin D and pregnancy [5]
Vitamin D during pregnancy can lead to craniotabes or softening of the skulls in newborn infants. This deficiency may persist one month after delivery especially among breastfed babies. This probably the reason behind prescription of vitamin D supplement to breastfed infants in many countries.

Vitamin D synthesis in the skin is influenced by “season, latitude, skin pigmentation, sunscreen use, clothing and aging” [4] as well as lifestyle and cultural preferences [2]. To prevent deficiency, appropriate exposure to sun should be encouraged. A daily supplement of 800 to 1000 IU of vitamin D3 may also help.

Sources:

1. Przybelski RJ, Binkleya NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007; 460(2):202-205
2. Nowak R. Lifestyle causes myopia, not genes. New Scientist 2004.
3. Ascherio A, Munger K. Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention. Seminars in Neurology 2008; 28: 017-028.
4. Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs and Aging, 2007; 24(12): 1017-29.
5. Yorifuji J et al. Craniotabes in normal newborns; the earliest sign of subclinical vitamin D deficiency. Journal of Clinical Endocrinology & Metabolism February 12, 2008.

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The latest research on air pollution looks into the neurological effects with following results:

Air pollution and brain function [2]
Exposure to diesel fumes triggers a stress response in the human brain. Researchers were able to demonstrate this using dilute diesel exhaust fumes (300 µg/m3) as model for ambient particulate matter exposure and monitoring brain activities by quantitative encephalogram (QEEG). In this double-blind randomized crossover study, those exposed to diesel exhaust showed a significant increase in the median power frequency of the QEEG after 30 minutes of exposure. This functional response in the brain continued to rise with longer exposure.

Air pollution and children`s IQ [3]
Children exposed to traffic-related pollution perform poorly in intelligence and memory tests compared those who breathe cleaner air. This prospective birth cohort study looked into children`s exposure to black carbon, a particulate matter component generated by traffic vehicles. Heavy exposure to black carbon translated to drops in averages scores in intelligence, vocabulary, memory and learning scales and indices. “Higher levels of black carbon predicted decreased cognitive function across assessments of verbal and nonverbal intelligence and memory constructs.”

It is speculated that “ultrafine” or “nanoparticles” found in the environment translocate to the brain and cause increased oxidative stress and brain inflammation.

Sources:

1 Andersen et al. Ambient Air Pollution Triggers Wheezing Symptoms in Infants. Thorax.Published Online First: 11 February 2008

2. Cruts et al. Exposure to diesel exhaust induces changes in EEG in human volunteers. Particle and Fibre Toxicology. Particle and Fibre Toxicology 2008, 5:4.

3. Franco Suglia et al. Association of black carbon with cognition among children in a prospective birth cohort study. American Journal of Epidemiology 2008 167(3):280-286.