By N. Hamlar. Rollins College.

Funding mechanisms bilities for prevention generic 20 mg nexium otc gastritis diet lunch, early detection cheap nexium 20mg with amex gastritis thin stool, response monito- need to be put in place to enable such long-term studies ring and treatment order nexium 20 mg fast delivery gastritis bad eating habits. The extensive characteri- certain disease (termed a susceptibility/risk biomarker), sation of diseases and their evolution should be extended to diagnose the disease itself (diagnostic biomarker), to and enhanced. Support development of new clinical trial de- and whether these applications have succeeded. Such an signs and promote integration with concomit- investigation could inform both the regulatory process ant preclinical testing. Traditional clinical trials test for safety frst, usually in he- Programmes in methodology research, trial design and althy volunteers and efcacy later. However, this appro- social science should be supported in order to maximise ach fails to take advantage of continuing advances in the information that can be gathered from clinical trials. Clinical trial networks should be developed allow for this early identifcation of efcacy, e. If a drug fails, scientists can de- As the stratifcation of patient cohorts into subgroups in- termine whether it does not work because the target is creases, the focus should shift from ‘fnding patients for a inappropriate, or because genetic diferences prevent the clinical trial’ to ‘fnding the best trials for the patients’. The new thods in which tissue samples of patients can be used to di- models may shift the focus from patient groups to the rectly test interventions hold signifcant promise. Given the inherent characteristics of more improve the predictability and efectiveness of interven- personalised treatments, innovative designs have to cope tions, an especially pressing issue in the feld. These new mo- importantly, patients must become involved in all stages of dels should be covered by guidelines and refection pa- the clinical trial process, from design and implementation pers to enable their inclusion in the regulatory framework to the consideration of regulatory issues. The acceptance of data coming conditions will patients occupy their rightful position. So drug developer need to seek advice on how to best use Genetic analysis represents an important parameter for this trials via the protocol scientifc advice procedures of- grouping diseases. To support such research, pre-disease data for pre- the question they were designed to answer, whether they vention and better understanding of disease mechanisms have been used for marketing authorisation purposes, in the patient have to be provided. This will only be realised through This will enable new partnerships, among others bet- support for excellent basic research conducted across ween clinicians, patients, and health insurers and re- Europe, and by harnessing data and outcomes to enable gulatory agencies, to develop more rapidly and allow translational opportunities to be identifed. A frst step could be to between sectors and the provision of the best possible en- elaborate suitable template agreements. Recognition of vironment, resources and infrastructure should be promo- the importance of translational research for the integra- ted. Go- cifc intended use in the context of research and de- vernments, charities, not-for-proft and private funders velopment relating to pharmaceuticals. This process should join forces to foster a collaborative culture in can also be used to evaluate and validate biomarkers. Continuity tegic Research Agenda entitled ‘The right prevention of high quality research lines has to be ensured by ins- and treatment for the right patient at the right time’ talling sustainable funding schemes that allow basic re- was published in 2013 (http://www. Member States and other countries tries of health and research; institutions for public health and health insurance, healthcare providers, The Academy of Finland’s research programme Perso- societies, patient organisations, ethics committees, nalised Health(2014–2019,http://www. In addition, the programme will look into the me- devices from the preclinical phase into clinical trials. In dical, treatment-related, technological, judicial, ethical, order to facilitate research in this feld methods and social and societal issues and impacts relating to data tools for integrating data from research need to be im- generation, collection, storage and use. This designation is aimed at ofering new oppor- cancer, diabetes, dementia, and infectious diseases; tunities for conducting translational cancer research, (2) to identify risk factors; (3) to highlight efective thus helping to optimise and hasten the production forms of prevention; and (4) to identify options for of new knowledge and promote its dissemination and the early detection of diseases. The French Alliance for Re- 200,000 people aged between 20 and 69 from across search in Life Sciences (Aviesan) has set up two strate- Germany will be medically examined and questioned gic valorisation felds on biomarkers and companion on their living habits (e. In the cour- relevant players across the value chain to: (1) identify se of their observation over a period of 10–20 years, the teams involved in biomarker research and validati- some of the participants are certain to develop di- on (pathological or technological); (2) make an inven- seases, which can then be correlated with the data tory of biomarkers and order them according to their collected. It is a unique database of personal of the analysis) and to ofer support in all project mo- and family medical histories collected during three des; (3) work alongside pharmaceutical, diagnostics intensive studies. In the third phase genetic data is and device manufacturers to assess the development being collected, and will be combined with clinical re- stage and level of interaction needed between these cords and cancer, stroke and death registries. These institutes are collaborative structu- on issues concerning business models and reimburse- res that bring together basic research groups from ment based on real cases and an exact defnition of academia and clinical research groups from hospi- ‘clinical utility’. Strategy Board) has invested £50m over the past fve years through a stratifed medicine innovation In Canada, as discussed in Challenge 1, a Genome Ca- platform – see Challenge 1 above for details. Following a competitive on a small scale how routine testing of patients’ tu- call, 17 such projects – for a total budget of 165 MioC$ mours could be scaled up to provide a national ser- over four years – have been funded. More rapid introduction of inno- vel molecule, which inevitably leads to the optimisati- vations into health systems needs to be based on regula- on of processes, an increase in efciency and security tory and reimbursement pathways that take into account and a decrease in adverse events, both in quantity and evolving knowledge on safety, efcacy, efciency and the quality. Moreover, there is a reduction in the number of necessary conditions of the health system that allow the patients in clinical studies, due to the inclusion of their promise of the innovation to be realised. For these appro- genotype and phenotype, resulting in an optimisation aches – both for drug and non-pharmaceutical products of resources and, most importantly, a contraction in the – processes need to be able to evaluate the use of in vitro time needed. But the resulting high cost and the lack and companion diagnostics, innovative clinical trial de- of knowledge in clinical outcomes if such a therapeutic signs and the balance between the inherent higher uncer- proposition were to be extended to a larger number tainty due to smaller sample size of target groups and the of patients will require the pharmaceutical, technolo- contrary inherent lower uncertainty due to higher impact gical and biotechnological industries to come up with or efectiveness on target groups. Another, at least equal- process in order to successfully bring innovation to the ly important, challenge for European regulators is the market (Rosenkötter et al. The inclusion of economic dimensions into macy especially in the case of multi-morbidity. For this growing group of tizens as well as patients will be signifcantly confronted patients, ways must be identifed to evaluate benefts and with it in ‘digital health’ (by information and training), in risks of medication which are usually tested in younger and the ‘internet of things’ (by devices) and in social networks healthier populations and where the evidence base is weak. Mo- plicit examination of what is necessary in order to allow reover, approaches for individualisation of drug therapy in the promise of the innovation to be realised. For example, the light of several comorbidities and patients’ preferences well-defned patient pathways are needed for the appro- should be tested and validated. Participation of patients and their commendations empowerment must play a crucial role in improving adhe- rence; otherwise the best drugs will not be efective. A combination of beneft–risk evaluation with real-time data and the use of observational, epidemiological or in Research on regulatory and legal issues should be sup- silico studies to demonstrate efectiveness even on indi- ported in order to update and adapt current regulations. These evaluations le regulatory procedure across all regulators, taking into will also enable post-marketing surveillance to spot rare account ethical, legal and social aspects. This would lead adverse events and include spontaneous reporting and to reduced costs and fewer administrative hurdles and analysis of electronic health records. Those approaches often include a combina- without considering the global perspective. These new models are based on a con- der collaboration in research and development tinuous adaption of the use of new technologies to the using an ‘Open Innovation’ approach. European bi-directional fow of ideas and interchange between harmonisation in these areas would also facilitate interna- companies. Innovation in lic, private and user partnerships, seems to be particular- the area of rare diseases has recently benefted from such ly interesting for enabling the introduction of promising international coordination through the International Rare innovation, where the added value is of high plausibility. The rare di- tems accompanied by research that reduces the inherent sease feld ofers many ‘lessons learned’ and can help to uncertainties under real-world conditions. Peer reviewed ensure that similar international structures can be esta- collaborative research using open data is a model that blished. Encourage a systematic early dialogue between innovators, patients and decision-makers th- In this context translational projects closer to the pati- roughout all regulatory steps to provide guidan- ent/market should be driven by the end-users’ needs. Companies are This recommendation is closely allied to the revision of the hesitant to access the market due to the limited under- regulatory and legal framework to produce a clearer and standing of certifcation, validation and regulations: for harmonised approach with interconnected components.

Attributions based on some data and country- tional uncertainty is associated with cause attribution discount 40mg nexium free shipping gastritis diet 2 days, as level predictions or assumptions were assumed to have less described earlier order 20mg nexium with mastercard gastritis y colitis nerviosa sintomas. For example nexium 20mg free shipping gastritis diet home remedy, the relative uncertainty correlation than those based simply on regional patterns. In ranges for ischemic heart disease range from around the case of the latter, we set the correlation at 75 percent; in 12 percent for high-income countries to ( 24 percent, the former, we set it at 50 percent or 25 percent depending 34 percent) for Sub-Saharan Africa (table 5. The proportion of deaths coded to these two groups parameters without uncertainty, we argue that unlike social of causes is surprisingly large for some high-income coun- choices such as the discount rate, no clear normative basis is tries (Mathers and others 2005). Ideally, these values should be derived from cross-country correlation of uncertainty. The broad pat- empirical data among representative populations (Salomon terns of the uncertainty ranges for causes across regions and others 2003). Numerous challenges are associated with provide useful additional guidance to policy makers in population-based data collection for the purpose of health interpreting regional differences, particularly in judging state valuations, particularly given the broad scope of valua- which policy questions these estimates can help address tions required for a comprehensive assessment of disease and for which the uncertainty levels are too great to allow burden. Note: Cross-country correlations in uncertainty distributions for countries without vital registration data were varied from 0 percent (left-hand bar) to 25 percent (middle bar) and 50 percent (right-hand bar) for each region. The logit transformation is valuations to overall uncertainty in burden of disease esti- given by logit(x) ln[x (1 x)]. We specific sequelae requires an understanding of (a) the distri- chose a value of 0. Although the single index value that captures the overall level of health variability in country means may reflect a range of different associated with a given health state (Salomon and others factors, including the possibility of real valuation hetero- 2003). A constant value in logit space yields absolute comparisons, computing disability weights based on an ranges that widen at the midpoint of the interval and nar- average global valuation function is the most appropriate row as the disability weight approaches 0 or 1 (figure 5. The need to under- In relative terms, the uncertainty is greatest for the smallest stand variation in the distribution of health states among disability weights and narrows as more severe weights are people living with given sequelae highlights the critical link attained (figure 5. Given that the current set of dis- (for the 622 sequelae included in the calculations). For each ability weights reflects the accumulation of a wide array of of the sequelae we applied a given sampled value as a perturba- different empirical inputs rather than the result of the tion of all age, sex, and region estimates of logit-transformed comprehensive and standardized approach defined earlier as the ideal, we operationalize our analysis of uncertainty in terms of error around the disability weights by sequelae 1. Among the other top 10 causes, the Disability weight disability weight uncertainty could change the rankings of Source: Authors’ calculations. This method implies the sim- to zero, particularly for health states with high prevalence in plifying assumption that errors are uncorrelated between many populations, such as mild to moderate sense organ sequelae but perfectly correlated for all estimates within a impairment or mild to moderate anemia. These assess- considerable uncertainty in case fatality rates for most low- ments took into account not only typical levels of measure- and middle-income countries and in models used to infer ment error in the input data sets, but also expert judgment the burden of nonfatal disease from mortality. Thesummarytablesprovidedinchap- cent to 90 percent, with a median value of 41 percent. A full uncertainty analysis of such burden older age groups; estimates has not yet been carried out, but would involve • uncertainty associated with estimating joint effects of assessment of the following additional types of uncertainty: risk factors. In one taxonomy,risk assessment uncertainty can mortality and incidence associated with specific expo- be divided into parameter uncertainty and model uncertainty Sensitivity and Uncertainty Analyses for Burden of Disease and Risk Factor Estimates | 421 (National Research Council 1994). Parameter uncertainty is of available data, such risk factors were represented using often quantifiable using random variable methods, for exam- indirect or aggregate indicators, for instance, smoking impact ple, uncertainty due to sample size or measurement error. Furthermore, for some risks multiple data causal relationships or the form of the exposure-response sources allowed limiting the range of exposure estimates. For relationship (for instance, threshold versus continuous or example, in the absence of alcohol surveys, information linear versus nonlinear), the level of bias in measurement, on total alcohol production, trade, and unrecorded con- and so on. Defined broadly, model uncertainty also includes sumption provided upper bounds on the fraction of the pop- extrapolation of exposure or hazard from one population to ulation that would be in the highest consumption category. Model uncertainty dominates uncertainty in risk Finally, some of the risk factors examined in chapter 4 were assessment, a result of difficulty in carrying out direct stud- represented using continuous exposure variables such as high ies on exposure, hazard, and background disease burden. Others used categorical variables, for This has motivated innovative assumptions and extrapola- example, indoor smoke from household use of solid fuels, tions even in the case of the most widely studied risk factors childhood underweight, and physical inactivity, even though like smoking (Peto and others 1992). This choice Uncertainty around disease causation (Evans 1978; Hill reflected the availability of exposure data and hazard esti- 1965) was, in practice, secondary to uncertainty around haz- mates in categories. In such cases, the contribution to disease ard size, for example, relative risk, because when causality within the baseline category would not have been captured. Collective scientific level, approaching 100 percent asymptotically, that is, the knowledge from disciplines such as social and behavioral rate of increase declines with increasing relative risk or sciences, physiology and neuroscience, and epidemiology prevalence (figure 5. Therefore, if a risk factor or group would confirm the possibility of a causal relationship in the of risk factors individually or jointly account for large foregoing cases, but would shift the uncertainty to hazard size. As a result, for some risk factors, we could only quantify the contribution to a subset of disease outcomes because 1. Chapter 6 subject to uncertainty, which varies across risk factors and presents some empirical evidence in making the case for a geographical regions. For further discussion of sources and stronger form of age weighting for infants and younger chil- quantification of uncertainty for specific risk factors see dren, that is, age weights that depart further from unity than Ezzati and others (2004). The validity and reliability, and duration of life lived with the sequelae of diseases and hence the utility, of burden of disease studies for public injuries, and some quantification of the severity of disability policy depend much more strongly on the quality and avail- assessed according to a common framework. The major effect of discounting and age comprehensive set of causes of death and disability results in weighting is to enhance the importance of neuropsychiatric estimates that are much less likely to be biased than those conditions and sexually transmitted infections. While disease that emerge from an examination of specific health condi- rankings are relatively unaffected, the share of the burden tions in isolation. It also avoids the tendency to assume that due to disability, the age distribution of the burden, and the if no data are available or the data are highly uncertain, then distribution of the burden by broad cause group are sensitive there is no disease burden. We maintain that providing large volumes of chronic diseases of older ages and somewhat less weight unsynthesized, biased, and incomplete data relating to pop- being given to mental disorders and injuries, which affect ulation health does not generally allow policy makers to younger adults disproportionately. However, they do give some indications that ing data from multiple studies or making adjustments for new evidence is becoming available for child deaths, and biases in relation to population, age groups, or time periods. The assessment of trends between 1990 and 2001 is tainty associated with extrapolating from a set of studies in a much more difficult task, as discussed in chapter 2. The subpopulations to the regional population is related to comparability of best point in time estimates is difficult to potential systematic (selection) biases and is much more dif- assess given changes in both the availability of data and in ficult to quantify than the uncertainty associated with sto- the methods used to synthesize those data for many of the chastic variation due to sample size or measurement error. Murray, Mathers, and Salomon (2003) discuss this Estimates of deaths from specific causes undergo contin- issue in more detail and conclude that to assess change or ual revision as new data and syntheses become available, yet evaluate programs, extrapolating current levels of burden of drawing a time cutoff is a necessary (if somewhat arbitrary) disease from past measurements is inadequate, and that the condition for preparing any volume such as this which assessment must include measurements carried out at both reports comprehensive and consistent global and regional points in time or explicit measurement of the relevant estimatesof deathsandburdenof disease(seealsoannex6C). This has the advantage that the deaths by cause (Bryce and others 2005), based on recent effects of changing preferences can be readily explored comprehensive reviews of epidemiological data, these analy- through sensitivity analysis, as illustrated in this chapter. Another is the need for a more rational assess- sistency between incidence, prevalence and mortality esti- ment of priority data for the health care sector that places mates for specific causes. The level are differ substantially for tetanus (46% higher), lower burden of disease framework, based on the estimated distri- respiratory infections (56% higher), and are somewhat bution and duration of health states resulting from incident lower for measles, malaria, low birthweight and noncom- cases, would benefit greatly from wider availability of linked municable diseases. It is not possible at this stage, to con- data sets on health outcomes and further longitudinal 424 | Global Burden of Disease and Risk Factors | Colin D. Salomon, Majid Ezzati, and others research into health state transition probabilities following base using novel methods that communicate what we do on from specific disease or injury causes (Kelman and Bass know, as well, if not more convincingly, than what we do not 2002). We might This uncertainty must be taken into account when making well take solace in the comments of a prominent medical cross-national comparisons, and needs to be carefully com- statistician who once cautioned that “Making the best the municated and interpreted by epidemiologists and policy enemy of the good is a sure way to hinder any statistical makers alike. The scientific purist who will wait for medical functioning vital registration systems for causes of death statistics until they are nosologically exact is no wiser than will always be substantially more uncertain than those Horace’s rustic waiting for the river to flow away” derived from systems where all deaths are registered and (Greenwood 1948, p. Despite the progress of the past decade, the incremental We wish to acknowledge stimulating discussions with and gains in advancing knowledge and understanding of global advice from Christopher J. Finally, we thank two referees for extremely lations (Murray, Lopez, and Wibulpolprasert 2004).

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Together they form a fearsome array of potential threats to the health and livelihood of those who visit 40mg nexium otc gastritis beans, work proven nexium 20 mg xenadrine gastritis, or live in the tropics where they exert their greatest impact purchase 40mg nexium overnight delivery gastritis diet 7-up. One such challenge is keeping employees and contractors safe from life-threatening vector-borne diseases. Business leaders and managers are often instinctively aware of these threats but uncertain of the means and measures that must be taken to assess the risks and impact of vector-borne diseases on the workforce. An inte- grated vector control program that involves assessment, ongoing surveillance, targeted treatment and on-site training and education is necessary. Customized vector control programs help corporations mitigate the risks associated with the spread of disease to employees and contractors across business operations. By preventing disease, corporations are also preventing the threat of employee and contractor fatalities, operational downtime, lost productivity and reputational damage that can hinder corporate ability to attract workers to a project. This article reviews the basic mechanisms by which arthropod vectors transmit pathogens and some of the vector/pathogen combinations of importance to industries. Examples of Integrated Vector Control Activities Identifcation Clothing Treatment Source Reduction Spraying Larval Surveillance 2 Vector-Borne Infections – Primary Examples The World’s Deadliest Animal – the female Anopheles mosquito Vectors, in General Pathogens transmitted by arthropod (insect) vectors are some of the most dan- gerous and unpredictable on earth. They are also the most difcult to prevent or control because they are so resilient to intervention and so deeply embedded in the ecologies and landscapes of the regions they infest. Vectors make all the diference in this equation because they exponentially increase the range and Characteristics of transmissibility of pathogens over those that would depend on transmission by Vector-Borne Diseases direct human contact. Vectors help pathogens bridge the gap from a diverse array • High disease transmissibility of host animals (mice, rats, monkeys, birds, prairie dogs, pigs, etc. Some harbor reservoirs of pathogens over periods less conducive to transmission • Explosive, unpredictable spread of disease (winters, dry seasons). Vectors are facilitators of many dangerous disease-causing organisms, the prevention and treatment of which cannot be efective for long • Resilient to control and prevention because of without addressing the vector directly. Directly transmitted infections like colds and infuenza depend on • Larger range vs diseases that require direct one-to-one contact between people or contaminated surfaces. Transmission of contact vector-borne infections is facilitated by multitudes of mobile, intelligent carriers who disperse from the source of an infection then home in like guided missiles on new victims. Vectors generally don’t become “ill” from carrying their various viral, proto- zoan and nematode infections. They might accrue some damage to their tissues, but in some cases this “damage” actually makes them more likely to transmit and infect. A mosquito with problems in its feeding apparatus will need to take additional bites to complete a blood meal. Vectors remain infected for their entire lives, which are longer than most people think. Many die 3 Vector-Borne Infections – Primary Examples within their frst week of life, but some can persist almost indefnitely. They are limited by the damage that accumulates on their non-repairable wings and ap- pendages and do not age as much as they wear out. Predation, desiccation and entrapment in water probably kill more mosquitoes than any other cause. West Nile vectors on the East Coast of the United States that emerge in August of one- year can over winter and become active in May of the following year for a lifespan of at least nine months. This becomes troublesome when we realize that their pro- gramming is also diverse and adaptable. Because the programs of Vectors shouldn’t be individual mosquitoes difer slightly from each other and only thought of as mere dumb the best programs survive long enough to produce progeny, their vessels or fying hypodermic programs are always getting better and adapting to changing con- needles. Like the Red Queen’s race in Alice in Wonderland, just think of them as tiny, well- to keep up, vector control operators must similarly adapt their programmed robots. Vectors, Specifcally Mosquitoes and ticks account for the majority of transmissions of the most important vector-borne diseases, although some close relatives of mosquitoes also get involved, including sand fies and black fies. Each of these organisms has unique habitat requirements and feeding behaviors, which can vary greatly, even within a closely related group. For example, dozens of species of Anopheles mosquitoes can transmit malaria around the world. The specifc habits of vectors provide the keys to controlling them and preventing them from spreading infection. Only the female mosquito can transmit disease because only she, and not the male, has the knife-like mouthparts needed to extract blood from her victims. Their bodies are so small (3 mm) they are hard to detect until after they begin biting. Unlike mosquitoes, black fies feed by slashing through the skin, and they never feed indoors. They can attack in such large numbers that their salivary fuids alone can cause a person to become ill, causing a condition called “black fy fever. They are typically found in structures with thatched roofs that ofer hiding places during the daytime. They are called “kissing bugs” due to their predilection for feeding on the soft skin of people’s faces, including lips. After feeding on the victim’s blood this insect releases its infected feces near the bite wound. Hard ticks feed only a few times during their lifespan, which tends to limit their odds of acquiring an infection. Never- theless, the longevity and host selectivity of hard ticks allows them to be relatively efcient vectors. Diseases vectored: Tick-borne Encephalitis, Lyme Disease, Tick-borne Relapsing Fever 5 Vector-Borne Infections – Primary Examples Important Vector-borne Diseases 1. Malaria Malaria exists in every tropical and subtropical landscape across the globe, some- times making seasonal excursions into temperate areas as well. The protozoan parasites that cause it have more complex genomes, metabolisms and life cycles than almost any other vector-borne threat. This complexity makes them a dif- fcult target for interventions such as drugs and vaccines because the parasite’s shape-shifting ways allow it to evade chemical and immunological defenses. They pose a moving target as well, intentionally changing their outer coating during each phase of their life cycle, and creating a diverse antigenic and metabolic ward- robe through sexual recombination, an engine of diversity creation unavailable to simpler microbes such as viruses and bacteria. Malarious Regions of the World Malaria endemicity Very high High Moderate Low No malaria Malaria is present in more than 100 countries, and imposes an economically signifcant burden on the populations of at least 80. Four species of parasites afect humans, but two of them, Plasmodium falciparum and P. In local populations most deaths occur in children between 6 months and 2 years old. The immune evasive- ness of malaria parasites prevents complete immunity from developing, but older children and adults who have experienced multiple infections, enjoy some level of protection from the most severe manifestations of the illness. Expatriates, tourists and urban dwellers share the immu- Dengue carrier, Aedes aegypti nological experience of an infant and thus remain particu- mosquito that has just taken a bloodmeal larly vulnerable to the life threatening aspects of this dis- ease. Certain complications, such as cerebral malaria, strike quickly, clogging small blood vessels in the brain to produce coma. Stories of expatriates falling ill on a Friday, putting of treatment till Monday and dying over the weekend are not uncommon. Tus, malaria prevention requires serious atten- tion when visiting areas where it is transmitted.

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In fact order nexium 20mg amex viral gastritis symptoms, sudden elimination of caffeinated drinks can result in rebound bronchoconstriction 20 mg nexium amex gastritis symptoms forum. Theophylline order nexium 40 mg without a prescription gastritis and duodenitis, a popular bronchodilating prescription drug, is a metabolite of caffeine. Eight randomized, controlled trials, six of parallel design and two cross-over stud- ies, produced little evidence to recommend that people with asthma supple- ment or modify their dietary intake of fish oil to improve their asthma control. However, clinical stud- ies in patients with asthma have yielded contradictory results. Controlled clinical trials have demonstrated that supplementation with 100 μg of selenium and/or 400 mg of magnesium pro- vides symptomatic relief but may not modify objective parameters. A high magnesium intake is negatively associated with and a low zinc intake is positively associated with bronchial hyperre- activity. Ephedra is one option because its sympathomimetic action favors bronchodilatation. The ginkgolides have the capacity to antagonize bronchoconstriction, bronchial hyperresponsiveness, and the allergic response effects of platelet-activating factor. Tryptophan should be avoided; it is the precursor of serotonin, a bronchoconstrictor in patients with asthma. Chapter 12 / Asthma 239 ● A trial of betaine or glutamic hydrochloride should be considered for patients who have hypochlorhydria as determined by gastric acid testing. Huntley A, Ernst E: Herbal medicines for asthma: a systematic review, Thorax 55:925-9, 2000. Picado C, Deulofeu R, Lleonart R, et al: Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity, Allergy 56:43-9, 2001. Kivity S, Ben Aahron Y, Man A, Topilsky M: The effect of caffeine on exercise- induced bronchoconstriction, Chest 97:1083-5, 1990. Brighthope I: Nutritional medicine—its presence and power, J Aust College Nutr Env Med 17:5-18, 1998. Schwartz J: Role of polyunsaturated fatty acids in lung disease, Am J Clin Nutr 71(suppl 1):393S-396S, 2000. Villani F, Comazzi R, De Maria P, Galimberti M: Effect of dietary supplementation with polyunsaturated fatty acids on bronchial hyperreactivity in subjects with seasonal asthma, Respiration 65:265-9, 1998. It is an androgen-dependent metabolic disorder associated with increased levels of dihydrotestosterone within the prostate. Increased conversion of testosterone to dihydrotestosterone may result from an increase in 5-α-reductase caused by drugs or pesticides. However, although the exact etiology remains poorly defined, 5-hydroxytestosterone is thought to have a permissive rather than causative role in benign prosta- tic hypertrophy. Dihydrotestosterone emerges as the most important bioavailable testosterone in prostatic tissue, and levels of intrapro- static estrogens and their receptors are elevated in benign prostatic hyper- plasia. Phytosterols, in addition to having anti-inflammatory and immune-modulating effects, inhibit the action of testosterone. Genistein, an isoflavone, is an estrogen ana- logue that inhibits growth of benign prostate hypertrophy tissue in culture, 241 242 Part Two / Disease Management possibly by impairing conversion of testosterone by 5-α-reductase to the more active androgen, dihydrotestosterone. Sympathetic dominance increases prostatic smooth-muscle tone and prostatic symptoms. Walking at least 3 hours each week may reduce sympa- thetic nervous system activity. Fruits are negatively, but butter and margarine are positively, related to an increased risk of benign prostatic hyperplasia. Depending on the source, the concentration of isoflavones varies from 1 to 3 mg per gram of soy protein. Two randomized, placebo-controlled trials that lasted 6 months with dosages of β-sitosterol from 60 to 130 mg daily resulted in improved peak urinary flow rate and an improvement in subjective symptoms. Although a nutritional supplement that included saw palmetto, androstenedione, and dehydroepiandrosterone did not prevent the conversion of ingested androstenedione to estradiol and dihydrotestosterone,19 a randomized, mul- ticenter, double-blind, clinical trial of patients with early benign prostatic hyperplasia showed that a fixed combination of extracts of saw palmetto fruit and nettle root (Urtica dioica) was as effective as the synthetic 5-α-reduc- tase inhibitor finasteride and was better tolerated. Nettle and pumpkin seed have both been approved by the German Commission E for use in the treatment of benign prostatic hypertrophy. Sciarra F, Toscano V: Role of estrogens in human benign prostatic hyperplasia, Arch Androl 44:213-20, 2000. Lagiou P, Wuu J, Trichopoulou A, et al: Diet and benign prostatic hyperplasia: a study in Greece, Urology 54:284-90, 1999. Mills S, Bone K: Principles and practice of phytotherapy, Edinburgh, 2000, Churchill Livingstone. Linde K, ter Riet G, Hondras M, et al: Systematic reviews of complementary therapies—an annotated bibliography. Diefendorf D, Healey J, Kalyn W, editors: The healing power of vitamins, minerals and herbs, Surry Hills, Australia, 2000, Readers Digest. Pinn G: Herbal medicine in renal and genitourinary disease, Aust Fam Physician 30:974-7, 2001. Fibrocystic breast disease typically presents as any combination of breast nodularity, swelling, and pain. Breast cancer is the third major cause of death and the second lead- ing cause of death from cancer in adult women. Women with fibrocystic breast disease may have lumpy or nodular breasts that change with the phase of the menstrual cycle; thickened breast tissue; solitary or multiple cysts; and/or rubbery, smooth, mobile, painless fibroadenomas. Breast cancer presents as a hard, nontender mass that later may become fixed and distort the breast, nipple, or overlying skin. Axillary lym- phadenopathy indicates early spread, and evidence of distal metastases (e. Breast cancer is detected in the early stages by mammography and in later stages by breast palpation. Inherited breast cancer is most likely to occur at an earlier age, be bilat- eral, and be encountered among close relatives. Breast disease seems to be linked to the cyclic hor- monal responses of breast tissue. To date, no satisfactory mechanism explaining the pathogenesis of benign breast disease has been provided. In the interim, intervention seeks to avoid exposure to variables that may trig- ger breast tissue proliferation. Mechanisms determining breast carcinogene- sis also remain unclear; however, certain nutrients that have a particularly important impact on breast tissue have been identified. Because some types of breast cancer are stimulated by estrogen, uncertainty has dogged their influence on female health. However, clinical studies have not, to date, attributed an unacceptable risk to consumption of dietary 245 246 Part Two / Disease Management ❑ How can I reduce my risk of female cancers?