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Researchers are actively studying supplements and natural therapies that can reduce or reverse these problems 160 mg fenofibrate fast delivery 10 best cholesterol lowering foods. This allows the brain to compensate for injury and disease and to respond to new situations and changes in the environment order fenofibrate 160 mg with mastercard cholesterol test how to prepare. This could be stopping or even reversing the course of the disease generic 160mg fenofibrate with amex cholesterol binding drug definition, the holy grail of Parkinson’s research (there is more information about this in the next chapter) buy fenofibrate 160mg visa cholesterol levels liver disease. Our brains change subtly all the time – influenced by our daily actions, activities, and thoughts. Stress causes 49 Parkinson’s Disease: Medications the body to release chemicals that can harm the brain, which is why stress often leads to fatigue, inactivity and even isolation. Therefore, learning to manage stress and participating in creative and emotionally- and spiritually- rich activities can help protect the brain from harm. Exercise can strengthen brain networks and improve the health of brain cells that have been weakened by Parkinson’s. These strategies engage the parasympathetic nervous system, the “rest and digest” response that slows many high-energy body functions, as opposed to the “fight or flight” response of the sympathetic nervous system, which increase heart rate, blood pressure, and other reflexes in response to a perceived threat. The strength of placebo effect depends on the expectations you have for a treatment, your prior experience with a similar treatment, and how much you value a treatment. If you fear or don’t want a treatment, it can give you a “nocebo” effect – a negative effect that you experience because of fear or rejection of the treatment. Researchers perform blinded placebo-controlled studies to insure that treatment results are due to the biological effects of the treatment rather than the psychological effects of being involved in a study. A study is blinded when neither the doctor nor the patients know who is getting the drug or treatment being studied or a dummy treatment such as a sugar pill (placebo). If a new treatment is better than the dummy treatment in the study, then health care providers can choose that treatment to help their patients. In Chapter 6, the importance of double-blind, placebo-controlled studies and their role in modern science will be briefly described. Unfortunately, this level of evidence showing both safety and efficacy does not exist for many integrative therapies. On the other hand, because they are often based on natural products, exercise, or therapies, integrative treatments tend not to be so strictly regulated. Many products are promoted as able to treat symptoms and even cure disease, without the evidence to support these claims. Anecdotal reports and passionate personal stories are used in place of carefully conducted scientific research. The fact that most physicians trained in Western medicine do not have formal training in complementary therapies also makes them cautious, and perhaps uncomfortable, with the use of such products and techniques. This is understandable; however, a treatment can be helpful even if it has not been studied. Some treatments just do not lend themselves to placebo-controlled studies or are too difficult or too expensive to study. For example, supplements can be studied in a controlled manner, similar to prescription medication, but such a trial can be expensive. Massage, another example, is difficult to study, as it is difficult to find an effective placebo treatment. How to Evaluate and Incorporate Integrative Therapies • Discuss therapies with your medical provider. See helpful talking points in the section “How to Talk to Your Neurologist about Integrative Therapies” on page 52. If you determine that a treatment is high risk, you should not try it unless you find scientific evidence supporting its benefit. For example: ► There is no clear scientific explanation for the effects of Reiki therapy, yet there are measurable physiologic changes to suggest that Reiki can enhance the relaxation response important for health and healing. For example: 51 Parkinson’s Disease: Medications ► You choose not to go to the gym because you receive massage therapy. If the cost of a therapy could otherwise be used for an activity with proven benefit, such as exercise, healthy diet, or mindfulness classes, then it might not be money well spent. For example, in 1998 the California Department of Health reported that 32% of Chinese patent supplements contained undeclared chemicals such as lead, mercury, and arsenic. Active therapies require work and focus; examples include mindfulness meditation and maintaining a healthy diet. Passive therapies do not require such focus and include massage therapy and vitamins. Some people do not bring it up because they don’t want their providers to know, or because they don’t think it’s important. This might be because they lack knowledge of these therapies or are skeptical of – and therefore hesitant to discuss or promote – them. Trying these therapies also gives me a sense of hope and control, which is important to me. There is cost associated with this treatment, so I will discuss my pain control goals with the therapist before starting and agree on a specific number of treatments before re-evaluating benefit. I will also be sure not to change any medicines without discussing with you [neurologist] first. Natural products include plant-derived chemicals and products, vitamins and minerals, and probiotics. They are widely marketed and available and are often sold as nutritional supplements. Mind and body practices include a range of procedures and techniques administered by someone who is trained in that method. The focus is on the interaction between mind, body, social, mental, and spiritual factors, and include yoga, chiropractic manipulation, meditation, massage, and acupuncture. The information provided should not be taken as recommendations for these substances, but should be used as discussion points when consulting with your licensed health care professional. Natural Therapies Natural therapies – plant-derived chemicals and products, vitamins, and supplements – are used by people who believe they will promote cell health and healing, control symptoms, and improve emotional wellbeing. Vitamins and Minerals Vitamins and minerals are not produced by the body, but they are needed in small amounts for cell growth and development. Vitamins are complex organic chemicals, meaning they can be broken down by chemical reaction; minerals are inorganic compounds, which cannot be broken down by chemical reaction. Both vitamins and minerals are found in foods and also can be taken as supplement pills. Research across many different disease states has indicated that people benefit more when they get their vitamins and minerals primarily from foods, rather than pills. This is based in part on the concept of food synergy: vitamins in their natural form are better absorbed and work together for benefits compared with the artificial ratios and chemical derivatives found in many vitamin supplements. Furthermore, there is no data to suggest that taking vitamin supplements when you are not actually deficient in those vitamins will improve health or symptoms. In other words, if you have regular levels of vitamin D, for example, you are not likely to receive benefits from taking extra vitamin D pills. It improves bone strength and protects against osteoporosis (low bone density) and fractures from falls.

Here it is easy to see that buy cheap fenofibrate 160mg online cholesterol score of 5.1, unlike the Laspeyres buy fenofibrate 160 mg low price what should my cholesterol ratio be uk, the Fisher uses expenditure shares from both periods trusted fenofibrate 160mg cholesterol ratio explanation. So order 160 mg fenofibrate with amex is cholesterol medication necessary, as market shares change over time, the Fisher places a higher weight on goods that are gaining market share whereas the Laspeyres does not. Just like the Laspeyres, however, this index ignores the entry of new goods and the exit of older goods. In a dynamic industry such as pharmaceuticals, the omission of new and exiting drugs can have important empirical implications. For drugs, the evidence is that pricing for new drugs can be very different from that of older, more established drugs, indicating that an index that includes new drugs will likely show different price growth than one that does not (Berndt 2002). One way to better incorporate any price change for new drugs is to construct indexes over shorter spans of time and to cumulate, or chain, the resulting price indexes. One could construct two Fisher price indexes, one for price change from F F 2003 to 2004 (I 2003,2004 ) and another for price change from 2004 to 2005 (I 2004,2005). While the only new drugs included in (4) are those introduced in 2003, the chained F index includes drugs introduced in 2004 in the I 2004,2005 index. Chained indexes thus provide a way of folding in new goods more quickly and so the index more closely tracks prices for the goods actually sold in the market. However, as discussed earlier, it is widely understood that the applicability of this theory in the health care setting is tenuous at best. Fortunately, there are other criteria that one can use to compare the relative merits of these formulas. In his “axiomatic approach,” Diewert (1992) considers about 20 properties that one would like to see in a price index. For example, one property is a time-reversal test which requires that if the prices and quantities in the two periods being compared are interchanged the resulting price index is the reciprocal of the original price index. Diewert showed that the Fisher index formula met this and other criteria better than other available formulas. Empirical results An important contribution of the empirical literature was to demonstrate that the choice of formula and chaining method matters. The Fisher formula takes into account any changes in the relative importance of drugs over time, whereas the Laspeyres formula does not. For example, in their study of drugs sold by four companies making up about 25% of the market, Berndt, 10 Griliches and Rosett (1993) found that price growth in chained indexes was slower than that in fixed-based indexes. But, in their study of antidepressant drugs, Berndt, Cockburn and Griliches (1996) found the opposite—chained Laspeyres tended to show faster price growth than the unchained counterparts. Which way it goes depends on how fast prices for new goods grow relative to established goods, and how the composition of drugs in the market is changing over time. This says that folding in new goods into the index more quickly yields indexes that grow slower and suggests that, in our sample, prices of new drugs grow slower than those of older drugs. First, the chained price indexes show faster (not slower) price growth than the unchained ones. This reflects the fact that prices for new molecules grow faster than those of older molecules that include generics: as molecules lose patent protection, the diffusion of the less expensive generics pushes down the price of the molecule. Hence, folding in new molecules faster—as the chained indexes do—yields an index that includes molecules with faster price growth and so the chained index grows faster. The unchained Laspeyres—the dotted line in chart 2—grows until mid- 2004 and then exhibits a declining trend through the last quarter in our data. This contour is driven entirely by the influx of generics into the market over this period. The pattern we see in the price index is mirrored in the number of generic prescriptions as a share of total: the rise in prices in the earlier period is associated with a decline in the generic share and the subsequent decline in the price index coincides with sustained increases in 11 the generic share. The patterns in the Fisher and Laspeyres indexes are similar because both indexes include the same molecules (both exclude entry and exit). But, the Fisher shows slightly faster price growth because molecules with the fastest price growth also gain market share over time and thus have a bigger weight in the Fisher index than in the Laspeyres. Summing up, chained and unchained indexes can show very different rates of price growth. Implications for decompositions of spending growth Spending on prescription drugs grew 30. Because different price indexes yield different growth rates for measured price change, they also yield different growth rates for the implied growth of quantities, or “utilization. In each case, we deflate the growth in spending using the price index to obtain the implied growth in utilization: growth in spending / growth in prices = growth in quantities. The use of different price indexes does not materially change the qualitative conclusion that all of the indexes attribute most of the growth in spending to growth in utilization, not price: Of the 9. After five years, the level of one index would be 7 times the level of the other if these rates were sustained. We close by noting that this type of decomposition is similar in many respects to 4 the decompositions that health economists use to parse out the drivers of cost growth but there are differences. In those decompositions, they first decompose overall spending growth into spending on new drugs versus growth in spending on established drugs (drugs that were sold in both periods). They separate spending on new drugs because that spending growth is qualitatively different. For example, increases in spending that are due to spending on new, better, drugs have a different implication for patients than increases in spending that arise from higher prices for older drugs. They then construct a price index for the established drugs (drugs sold in 2003:1 that were also sold in 2005:4). They use this price index, just as we have, to estimate the growth in spending on established drugs and separate it into price and utilization components. Although the price index literature argues that the Fisher formula is superior to the Laspeyres, empirically, the choice of formula does not make much of a difference in our sample: the Fisher and Laspeyres price indexes are very similar and, so, the implied growth rates for quantity are also very similar. Measuring Quality Change Ideally, one would want a price index that would take into account changes in the quality of goods. For example, while the average price of computers has stayed fairly constant over the last two decades, the performance (speed of processor, data storage capabilities, etc. Price indexes that take these enhancements into account should, and do, show rapid declines, reflecting rapid improvements in quality. These indexes are typically constructed by relying on market prices as a gauge of the market’s valuation of quality differences across goods to measure the value of quality indirectly—as is done in price indexes—or more directly—as in a hedonic regression. At the end of the day, many believe that the complicated features of medical care markets do not allow the interpretation of prices as a gauge of patients’ valuations of drugs and hence question the ability of methods like price indexes and hedonics to adequately capture the quality of goods. As we show here, the rates of quality change implied by standard methods are quite low. Assuming that the quality of goods is improving over time, price growth measured using these techniques should perhaps be viewed as an upper bound on true price change, where the “true price change” would account for increases in quality over time. Indeed, this is the view taken in studies that aim to assess the biases in official statistics.

The country’s more prominent role was also Colombian authorities purchase fenofibrate 160mg visa cholesterol levels garlic,8 in 2009 fenofibrate 160mg on-line mayo clinic on cholesterol lowering foods, 48% of cocaine sei- visible in reports of cocaine consignments seized in zures in Colombia were made in territorial waters cheap fenofibrate 160 mg amex cholesterol test youtube. Europe involving Ecuador in the trafficking route 160mg fenofibrate overnight delivery cholesterol levels slightly elevated, Colombia also continued to seize large quantities of which rose from 6 seizure cases in 2005 (amounting to substances that may be used in the extraction and a total of 25 kg of cocaine) to 67 in 2009 (amounting to processing of naturally occurring alkaloids. It appears that Ecuador, which shares borders with both In the Bolivarian Republic of Venezuela, seizures peaked Colombia and Peru, may have acquired increased impor- at 59 mt in 2005, and have fallen to approximately one tance as a hub for cocaine trafficking. National Drug Law Enforcement Agencies, Latin America and the Caribbean, Lima, Peru, 4-7 October 2010. A variety of number of seizures involving the Bolivarian Republic of other trafficking methods are also used in Peru, includ- Venezuela in the trafficking route fell from 151 (amount- ing land routes, rivers, couriers, postal services and ing to a total of 9. Expressed as a proportion of In recent years, seizures of cocaine have also increased the total cocaine seizures made in Europe (where infor- significantly in Brazil, going from 8 mt in 2004 to 24 mt mation on provenance was included), these cases fell in 2009, of which 1. In 2009, Brazil was the most prominent increased from 36% to 41% in terms of quantity. The in both the Plurinational State of Bolivia and Peru, com- number of seizure cases which involved Brazil as a transit country rose from 25 in 2005 (amounting to 339 kg of pared to previous years. The Plurinational State of Bolivia (apart from the Plurinational State of Bolivia, Colombia assessed that, in 2009, more than 95% of cocaine traf- and Peru) were the Bolivarian Republic of Venezuela, ficking on its territory occurred by land; moreover, Ecuador, Brazil and Argentina (ranked in order of the according to Bolivian authorities,17 cross-border traf- total weight of seized consignments departing from a ficking occurred from Bolivia into Argentina, Brazil and given country). In contrast, Europe, the World Customs Organization also noted according to Peruvian authorities,18 international traf- the high quantity of cocaine arriving from Ecuador and ficking organizations operating in Peru preferred mari- the growing significance of Brazil and Suriname. Drug Law Enforcement Agencies, Latin America and the Caribbean, 18 Country report by Peru to the Twentieth Meeting of Heads of Lima, Peru, 4-7 October 2010. National Drug Law Enforcement Agencies, Latin America and the 20 Based on seizures recorded in the Customs Enforcement Network Caribbean, Lima, Peru, 4-7 October 2010. Trafficking of cocaine from Mexico continued to be a key transit country for cocaine Argentina to Chile was reported by both countries in trafficked into the United States. Cocaine seizures in 2009; Argentina also assessed that, in 2009, some of the Mexico fell sharply in 2008 (19 mt, down from 48 mt cocaine trafficked on its territory was intended for in 2007), in line with the trend in the United States, and Europe, apart from Argentina itself. The rose markedly in 2007, and have since then declined vast bulk - almost three quarters - was seized on the slightly, amounting to 8. However, which followed a generally decreasing trend between the these seizures tended to be small in comparison with 22 last quarter of 2005 and the second quarter of 2008. It appears that Central America and the Caribbean such as the Domin- several factors have contributed to a shift in the traffick- ican Republic, Costa Rica and Panama. In 2009, sei- ing routes from Mexico to the United States, including zures in Panama were the third largest in Latin America high levels of inter-cartel violence in Mexico and efforts and the Caribbean (53 mt). Although the seizures appeared to stabilize at slightly more than half the 2005 involving the Dominican Republic in Europe were not level – 109 mt. Together with other indicators, this sug- large in comparison with other transit countries, some gests that the availability of cocaine in the United States large seizures were made in the Dominican Republic has stabilized at a reduced level. According to Costa Rican authorities,21 in National Drug Law Enforcement Agencies, Latin America and the Caribbean, Lima, Peru, 4-7 October 2010. This was largely Several countries in the Americas, notably in Central due to a decline in purity, which fell from an average of America and the Caribbean, as well as Brazil, the United 70% in the last quarter of 2006 to 45% in the last quar- States and the Bolivarian Republic of Venezuela, report ter of 2008 and 46% in the last quarter of 2009. They accounted for approximately amounted to 194 kg in Panama, 163 kg in the United one half of the total for the United States in 2009. In States and 80 kg in the Bolivarian Republic of Vene- terms of seizure cases, the majority continued to be zuela; in 2008, the largest quantity was seized in Brazil smaller domestic cases. The price at the Europe wholesale level is about one quarter of the price at the Europe is the world’s second largest consumer market retail level, while the price in producing countries only for cocaine and continues to account for the majority of amounts to 1% of the final (retail) price. Seizures At the global level, the total reported quantity of crack- peaked at 121 mt in 2006, then declined for three years cocaine seizures is negligible in comparison with seizures in a row, falling to less than half this level – 57 mt – in of cocaine base and cocaine salts. The decreasing trend was observed in the West to the fact that some countries do not report seizures of European countries that account for the biggest seizures crack-cocaine, but also because individual seizures of in Europe, though several other countries have regis- crack-cocaine, possibly made at street levels, tend to be tered increases. In Ireland, seizures peaked in 2007, and have also used is that corresponding to the year 2008, and is only included declined significantly since then. One pos- sible explanation could be that heightened law enforce- 25 ment efforts impacted on the availability of cocaine in the European cocaine market, and traffickers responded to this by selling the drug at reduced purities rather than 0 raising the bulk price. The purity-adjusted price – expressed in euros - declined between 2006 and Spain Portugal 2008, and appeared to stabilize in 2009. France United Kingdom** Italy Belgium When adjusted for inflation, the purity-adjusted retail Rest of Europe Netherlands* price in 2009, expressed in euros, was equal to (within 1%) that in 2005, prior to the increase in 2006. While The Iberian peninsula is an important point of entry for these data need to be interpreted with caution, it is plau- cocaine reaching continental Europe. Spain consistently sible that alternative cocaine trafficking methods and reports the highest cocaine seizures in Europe, though routes adopted by traffickers to counter more effective seizures fell from 50 mt in 2006 to 25 mt in 2009. In law enforcement efforts have corrected a short-term neighbouring Portugal, the decrease has been more pro- drop of cocaine availability in the European market. In relative terms, seizure trends across Europe in recent Africa years appear to fall broadly along a continuum ranging Cocaine seizures remained limited in Africa, amounting from strong declines close to the trafficking hubs that to less than 1 mt in 2009, down from 2. Although this quantity is very small Europe to strong increases in countries, notably further in comparison with the quantities likely to be trafficked east, that historically have not been associated with traf- in and via Africa, seizure data from other regions also ficking of cocaine in large amounts. When comparing point to a decreasing trend for Africa, notably West average seizures over 2005-2006 with 2008-2009, Africa, for cocaine trafficking from South America to marked declines (in both relative and absolute terms) Europe. Nevertheless, cocaine trafficking in West Africa were registered in Portugal, Spain, Belgium and the 26 persisted, and Africa, especially West Africa, remained Netherlands; more moderate declines were registered vulnerable to a resurgence. Benin, Burkina Faso, Ethio- in the United Kingdom and France, while seizures were pia, the Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, essentially stable in Italy and Germany. In 2009, China 300 reported seizures of 163 kg, including 112 kg in Hong 200 Kong, China. According to Chinese authorities, cocaine 100 was mainly smuggled from South America across the Pacific ocean to cities on China’s south-east coast. The increase was partly due to a large quantity of cocaine that was jettisoned in December The Asia-Pacific region continued to account for less 2009 close to the Eastern Samar province from a vessel than 1% of global cocaine seizures. Two other signs that cocaine trafficking might be making inroads significant cases resulted in the seizure of a total of 15. The size of the United of the decline may be explained by improved upstream States’ market – the single largest cocaine market for interception efforts as a result of improved sharing of decades – has been shrinking in recent years, mainly due intelligence with counterparts in South America. Cocaine trafficking and use have started to limited (a few studies conducted in North America, affect countries in the Oceania region (already showing South America, Europe and Australia) and any calcu- high annual cocaine use prevalence rates by interna- lated results must be treated with caution (and results tional standards), countries in western and southern are subject to change, whenever more reliable informa- Africa affected by the transit flow, and in some parts of tion becomes available). The best reading of existing Asia (some countries in the Near and Middle East as data and estimates suggests that some 440 mt of pure well as some emerging pockets in a few countries in the cocaine were consumed in 2009. Cocaine use in East Europe, in con- Of the 440 mt available for consumption, around 63% trast, is still limited. The volume of cocaine consumed were consumed in the Americas, 29% in Europe, 5% in in Europe has doubled over the last decade, even though Africa, 3% in Asia and less than 1% in Oceania. The data for the last few years show signs of stabilization at largest subregional markets were found in North Amer- the higher levels. These three subregions account for increased their efforts, traffickers continue to innovate, 63% of global cocaine consumption. The single largest seeking novel ways of getting their product to the con- cocaine market – despite strong declines in recent years sumer.