Tobacco use has predominantly negative effects on human health and concern about health effects of tobacco has a long history. Research has focused primarily on cigarette tobacco smoking. In 1950, Richard Doll published research in the British Medical Journal showing a close link between smoking and lung cancer. Four years later, in 1954, the British Doctors Study, a study of some 40,000 doctors over 20 years, confirmed the suggestion, based on which the government issued advice that smoking and lung cancer rates were related. Tobacco smoke contains more than fifty chemicals that cause cancer. Tobacco also contains nicotine, which is a highly addictive psychoactive drug. When tobacco is smoked, nicotine causes physical and psychological dependency. Cigarettes sold in underdeveloped countries tend to have higher tar content, and are less likely to be filtered, potentially increasing vulnerability to tobacco smoking related disease in these regions. Tobacco use is the single greatest cause of preventable death globally. As many as half of people who use tobacco die from the results of this use. The World Health Organization (WHO) estimates that each year tobacco causes about 6 million deaths (about 10% of all deaths) with 600,000 of these occurring in non smokers due to second hand smoke. In the 20th century tobacco is estimated to have caused 100 million deaths. Similarly, the United States Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide." Tobacco use leads most commonly to diseases affecting the heart, liver and lungs. Smoking is a major risk factor for heart attacks, strokes, chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), and cancer (particularly lung cancer, cancers of the larynx and mouth, and pancreatic cancer). It also causes peripheral vascular disease and hypertension. The effects depend on the number of years that a person smokes and on how much the person smokes. Starting smoking earlier in life and smoking cigarettes higher in tar increases the risk of these diseases. Also, environmental tobacco smoke, or secondhand smoke, has been shown to cause adverse health effects in people of all ages. Tobacco use is a significant factor in miscarriages among pregnant smokers, and it contributes to a number of other health problems of the fetus such as premature birth, low birth weight, and increases by 1.4 to 3 times the chance of sudden infant death syndrome (SIDS). Incidence of erectile dysfunction is approximately 85 percent higher in male smokers compared to non-smokers. Several countries have taken measures to control the consumption of tobacco with usage and sales restrictions as well as warning messages printed on packaging. Additionally, smoke-free laws that ban smoking in public places such as workplaces, theaters, and bars and restaurants reduce exposure to secondhand smoke and help some people who smoke to quit, without negative economic effects on restaurants or bars. Tobacco taxes that increase the price is also effective, especially in developing countries.