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Zachary A. Weber, PharmD, BCPS, BCACP, CDE

• Clinical Associate Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, Indianapolis, Indiana

https://www.pharmacy.purdue.edu/directory/zaweber

Vehicle safety: enact legislation and enforcement of personal transport safety measures treatment using drugs is called order prasugrel 10 mg online, including Regulatory injuries seatbelts in vehicles and helmets for motorcycle users symptoms viral infection order prasugrel with a mastercard. Pesticides: enact strict control and move to selective bans on highly hazardous pesticides medicine escitalopram prasugrel 10mg fast delivery. Water and sanitation: enact national standards for safe drinking water 3 medications that cannot be crushed purchase prasugrel 10mg on-line, sanitation symptoms 4 months pregnant order cheap prasugrel line, and hygenic Regulatory behavior within and outside households and institutions treatment 20 purchase cheapest prasugrel and prasugrel. Hazardous waste: enact legislation and enforcement of standards for hazardous waste disposal. Lead exposure: take actions to reduce human exposure to lead, including bans on leaded fuels and Regulatory on lead in paint, cookware, water pipes, cosmetics, drugs, and food supplements. Agricultural antibiotic use: reduce and eventually phase out subtherapeutic antibiotic use in Regulatory agriculture. Emergency response: create and exercise multisectoral responses and supply stockpiles to Regulatory respond to pandemics and other emergencies. Safe sex: remove duties and taxes on condoms, then introduce subsidies in brothels and for key Fiscal at-risk populations. Exercise: take initial steps to develop infrastructure enabling safe walking and cycling. The famous 1952 London smog (smoke Bans on coal use, and successful enforcement of these and fog) episode, which killed 12,000 people, was bans have been followed by a reduction in premature mostly the result of indoor burning of coal for heat deaths from these conditions. These reductions suggest Pacific region, where it constitutes around 20 percent that Dublin experienced about 243 fewer cardiovas of all household fuel use (Duan and others 2010). Around two-thirds of the suicide ous) pesticide that farmers had been using in place deaths during this period were due to self-poisoning of Class I pesticides (figure B2. Consensus is lacking on the chief contributors to the changing An ecological analysis of time trends in suicide and rates of suicide in Sri Lanka, but these are likely to suicide risk factors in Sri Lanka from 1975 to 2005 include periods of civil war and economic reces found that these bans coincided with marked sion, changes in the rates of mental illness and its declines in the suicide rates of both men and women treatment, and the easy availability of hazardous (figure B2. Time trends in the data on agrochemicals (Abeyasinghe 2002; Gunnell and suicide method showed that the large reduction in others 2007). Further support In the 1980s and 1990s, a series of legislative activi for this interpretation came from in-hospital ties led to the stepwise banning of the most toxic of mortality data, which showed a halving in death the pesticides being used for self-poisoning. Suicide rates, by method All class I pesticides banned (1995) All class I pesticides baned (1995) 90 Endosulfan banned (1998) 40 Parathion and methyl 80 parathion banned (1984) Parathion banned (1984) 35 Endosulfan 70 banned (1998) 30 60 25 50 Outbreak of civil war 20 40 1981 census: revised Ceasefire 15 30 population estimates in civil war 10 20 10 2001 census: revised 5 population estimates 0 0 Year Year Male age-standardized rate Self-poisoning and other methods Burning Female age-standardized rate Hanging Shooting Drowing Sharp cutting instruments Source: Gunnell and others 2007. The presence of such externali countries with high-performing health systems, spend ties justifies the use of aggressive fiscal and regulatory ing on long-term care for individuals with chronic phys measures to correct the economic inefficiencies that ical or mental disability is significant and likely to result from the failure of households or firms to take continue increasing (de la Maisonneuve and Oliveira negative externalities into account in their decision Martins 2013). Yet that would eventually include greater incentives for another concerning result of the Dutch study is that healthy eating and physical activity. Greater incen about one-third of total health expenditure in recent tives for healthy eating and physical activity are likely years was on long-term care, and the distribution of this to be much more disruptive and potentially expensive share of expenditure was skewed toward a relatively to fully incorporate into a whole-of-government pol small number of individuals with severe disability (Bakx, icy but could lead to greater and more sustained gains ODonnell, and van Doorslaer 2016). Ministers of health observed to accompany economic growth and popula could seek to develop productive relationships across tion aging, including vision and hearing loss, dementias, these key sectors early in the process. Thus, the general conclusion is that such as home health services, institutional care (for although rapid declines in child and adult mortality example, in skilled nursing facilities), and palliative care, have facilitated population growth and aging, these but it will need more than the health sector can provide changes have not been matched by improvements in to care adequately for the whole person. In part, this phenomenon can policies can be developed to provide these individuals be attributed to unchanged or increased levels of non with assistance in obtaining affordable food, housing, communicable disease and injury risk factors that could and transportation, all of which are instrumental to pre potentially be addressed using intersectoral measures, as venting further health loss. At the same time, an equally under the category of transfer payments and may be important question is the role of health and nonhealth delivered directly as grants (nonwage income) or through Intersectoral Policy Priorities for Health 31 more targeted efforts such as subsidized housing or by country and would depend on the proportion of nutrition programs. In low-income social development and others to care for the whole indi countries, such a comprehensive program would vidual. In some settings, intersectoral collaboration has probably be unaffordable at current levels of govern led to large-scale anti-poverty, social welfare, and ment spending. There are examples of implement fiscal policies that address long-term care: successful social support programs that effectively inte grate health interventions, including support for older 1. One of these is Mexicos Prospera program, which countries because of population aging and high rates has been in operation since the late 1990s and covers the of nonfatal health loss. Unfortunately, there is a limited evidence and willing to assume a large part of the fiscal base on which to design and implement social sup responsibility. Further, the feasibility and sustainability of broad-based social support pro this last point suggests that countries could begin grams in low-income and lower-middle-income to develop a more inclusive notion of national health countries, in particular, are unknown. These costs could vary widely evidence and the rapid shifts in disease burden in Box 2. An even more larger because a significant part of health-related inclusive figure of the costs of ill health would economic activities, in particular those related to add income transfers of voluntary and legally long-term illness and injuries, goes unreported or mandated sick leave and disability insurance. Because long-term care for the combined value of (a) unpaid household the elderly or the chronically ill is not reimbursed members activities aimed at preventing ill health and by social or public health insurance schemes, fam caring for and maintaining health both within and ilies must step in and find ways to provide care, outside the household and (b) the volunteer work for sometimes for long periods of time. Mexicos abuse and musculoskeletal disorders accounted for omission in reporting expenditure on long-term care 40 percent (Kassebaum and others 2016), and an only reflects this institutional void. This burden has not only included in the satellite health accounts, but a signifi increased pressure in an already overwhelmed and cant amount of nursing home services paid for out of underfunded public health care system but also cre pocket by families possibly still goes unregistered. Not surprisingly, about half of total health care that goes beyond the traditional clinical and spending is from private sources, most of it paid out acute care settings, a broader perspective is needed to of pocket. Moreover, figures on the value of cash tease apart the economic and organizational impli benefits for temporary disability (resulting from ill cations. Adding pen other types of long-term care facilities needs to be sions for permanent disability would include this accounted for, even if this means considering a mix value. None of these figures are currently being of medical and other services (such as psychological accounted for as health-related spending neither in and nutrition services). More comprehensive estimates of the produc timetables, investing to adapt their homes to bet tion value of the health sector would increase aware ter suit their needs, hiring nonfamily caregivers, ness and inform policy formulation to better prepare or sometimes even quitting their own jobs or for the long-term care transition. A common theme in these suc might place a higher priority on controlling indoor cesses is that the government, including the health sector, sources of air pollution, improving maternal and child recognized the legitimacy of intersectoral action for nutrition through food fortification, and scaling up health, as the following examples show: water and sanitation measures. All countries could work col Cities and Healthy Villages (Sheikh and others 2012). The highlights three cross-cutting themes relevant to committee played a key role in the passage of Vietnams implementation: national mandatory helmet law (box 2. The risk to these different groups shows large cluded that motorcycle helmets reduce the risk of regional variations. For example, in Sub-Saharan head injury by around 69 percent and death by Africa pedestrians and cyclists are at highest risk, around 42 percent (Liu and others 2008). Several whereas in Southeast Asia motorcyclists are at countries in Southeast Asia have seen significant greatest risk. Note: Figure shows extent of motorcycle helmet wearing in three provinces of Vietnam before and after the introduction of mandatory helmet-wearing legislation. For example, after Vietnams man datory motorcycle helmet law went into effect in An extended cost-effectiveness analysis of the 2007 December 2007, an observational time-series study helmet policy suggests that it prevented about 2,200 using data from a random selection of the road net deaths and 29,000 head injuries in the year following work in three provinces (Yen Bai, Da Nang, and Binh its introduction (Olson and others 2016). The analy Duong) found significant increases in helmet wear sis found that the wealthy owned the greatest number ing among both motorcycle riders and their passen of motorcycles, so they accrued a larger share of the gers (Passmore, Nguyen, and others 2010), as shown absolute health and financial benefits from the law. Surveillance data from 20 rural and However, the policy probably prevented a larger urban hospitals found that the risk of road traffic number of cases of poverty among the poor and head injuries and deaths decreased by 16 percent middle class as well. They have been conducted for a wide anticipated effects of interventions on government and range of policies or plans, including biomass power private revenues and expenditures outside the health plant projects, patents on medicines, coal mining, sector, annex 2C provides ministries of health with some and industrial estate development (Phoolcharoen, sense of where opportunity and opposition may arise on Sukkumnoed, and Kessomboon 2003). Intersectoral Policy Priorities for Health 35 Estimating the costs and consequences of intersectoral added sugar in a product group would also require intervention can be challenging for a variety of reasons, information on the nutrient content in those foods. In some cases, cost if sugar-sweetened beverages are taxed, the decrease effectiveness analysis has been used to evaluate intersec in sugar intake from reduced consumption of sugar toral interventions. However, this perspective is quite sweetened beverages might be offset by increased con limited because many of the important economic costs sumption of fruit juice or confectionary products. At the and benefits of these interventions lie outside the health same time, not all substitution effects are negative: sector. Fortunately, interest in benefit-cost analysis has recently implemented soda taxes in Mexico were associ grown within health economics of late, and this approach ated with increased consumption of bottled water is ideal for evaluating intersectoral policies (see chapter 9 (Colchero and others 2016, Colchero and others 2017). For example, tobacco summarize benefit-cost studies, including program costs, taxes appear to decrease binge drinking, presumably of interventions focusing on injury prevention and envi because tobacco and alcohol use disorders co-occur in ronmental hazards, which are among the health topics many individuals (Young-Wolff and others 2014). Although the Hence, when designing taxes, policy makers need to con costs reviewed in volume 7 are neither totally representa sider substitution effects and balance these against tive nor exhaustive, they can provide a rough sense of the implementation feasibility. Tobacco taxes provide behavioral change and the positive revenue implications an important example in this regard. Tobacco, alcohol, carbon emissions, simplified and based on the quantity of cigarettes, not and unhealthy food products may all be considered as their price (the latter of which is easier for the tobacco candidates for taxation. The excises, as opposed to ad valorem (value-based) fundamental question to answer first is what to tax. This way, tax beverages, or to opt for a hybrid approach (for example, hikes raise prices by the same large amount on all a tax based on the amount of added sugar in a particular brands at once, pushing smokers to quit completely class of products, such as sugar-sweetened beverages) The first two steps would generate revenue and create fiscal space for subsidies, includingthe following annexes to this chapter are available at those that preferentially affect vulnerable populations. Intersectoral Policy Priorities for Health 41 Chapter 3 Universal Health Coverage and Essential Packages of Care David A. Notably, they also seek to provide protection ment emerged in response to a growing awareness of against the financial risks that individuals face when the worldwide problems of low access to health ser accessing health services. Watkins, University of Washington, Seattle, Washington, United States; davidaw@uw. However, as construed here, it would not be athe set of prioritized health services publicly perfect package for a particular country. This chapter also packages are intersectoral in nature, as discussed in aggregated a number of specific health services into chapter 2 of this volume, Watkins and others [2018]. The grouping sector perspective on costs and draws on estimates of of interventions into platforms is intended to illus incremental value for money in settings where the trate how they could be integrated with each other number and scale of current health services are limited. Annex 3D, which genetic disorders (annex 3A) and musculoskeletal disor accompanies annex 3C, examines issues related to spe ders (annex 3B). It includes a ages tailored to various platforms, defined as logis wide variety of delivery mechanisms. Thus, a platform is platforms include the following: the level of a health system at which interventions can be appropriately, effectively, and efficiently delivered. Health centers:the health center level captures two this platform model is a pragmatic typology types of facility. The first is a higher-capacity health rather than a comprehensive description of the myriad facility staffed by a physician or clinical officer and health facilities currently serving clients in low and often a midwife to provide basic medical care, minor middle-income countries. Contextual factors, includ surgery, family planning and pregnancy services, ing local culture, disease burden, resources, and geog and safe childbirth for uncomplicated deliveries. With changes in technology capacity facility (for example, health clinics, phar and delivery know-how, it is likely and desirable that macies, dental offices, and so on) staffed primarily by existing modalities of health care delivery will evolve a nurse or mid-level health care provider, providing and adapt over time. A platforms definition will also services in less-resourced and often more remote evolve as a countrys health system becomes more settings. First-level hospitals: A first-level hospital is a facil ity with the capacity to perform surgery and pro-the five platforms of a health system as defined in vide inpatient care. This platform also includes this chapter are as follows: outpatient specialist care and routine pathology Population-based health interventions: this platform services that cannot be feasibly delivered at lower captures all nonpersonal or population-based levels, such as newborn screening. In these cases, the geometric mean of incremen between modeled estimates and real-world impact. Variations in observed ventions not covered in chapter 7, other databases of clinical practice suggest that differential benefits from cost-effectiveness studies were searched for relevant health care are likely within and between populations. These drivers economic evaluations (Akachi and Kruk 2017; Kruk and include epidemiological context (such as high versus others 2017). In the assessments presented in annex 3F, moderate-transmission areas for malaria), price varia the authors have attempted to account for potential real tions in key technologies (such as vaccines for which world reductions in value-for-money caused by low certain countries may be eligible for subsidies), and the quality of care, particularly for complex and longitudinal quality and generalizability of the cost-effectiveness services in low-income countries. Universal Health Coverage and Essential Packages of Care 47 Priority given to the worse off. An indicator for the worse off was of all interventions that meet the following criteria, bal developed that attempted to identify individuals who, by anced against each other: virtue of having a particular disease or injury, would have a much lower level of lifetime health. This range of cost-effectiveness values draws severe or result in extremely premature mortality or from the growing literature on health care opportu both. This criterion is met by weight, for example, to selected noncommunicable dis an intervention being directed against a cause of dis eases (such as schizophrenia, congenital disorders, or ease or injury that has a low health-adjusted average childhood cancers) and injuries than might be given age of death. Empirical tize the needs of the poor but is relatively resource advances in these areas could facilitate their incorpora constrained may include more interventions that score tion into multi-criteria decision analysis as described by high on priority given to the worse off and fall below a Youngkong (2012) and others. Thus, policy makers may in boldface in annex 3C and also noted alongside the be somewhat less likely to include interventions that appraisals in annex 3F. In terms of the scope of health conditions than interventions for other conditions. Before the commission issued its lack of established methods and tools that span disease 2013 report, Global Health 2035: A World Converging groups.

Prevalence dynamics are dened by four parameters: the start time of the epidemic symptoms 9f diabetes buy prasugrel online now, t0; the fraction of the population in the at-risk category at the start of the epidemic symptoms 8 months pregnant cheap prasugrel 10 mg with visa, f0; the rate of infection symptoms urinary tract infection buy prasugrel 10 mg with amex, r (governs the rate at which people in the susceptible population become infected) treatment magazine buy prasugrel 10 mg cheap, and the behavioral response symptoms juvenile diabetes order prasugrel cheap, (this parameter aects the distribution of new entrants to the not at-risk and at-risk categories) medicine hollywood undead buy prasugrel 10mg line. We set a uniform prior for the rate of infection: r U[0, 15], a uniform prior for the fraction of the population in the at-risk category at the start of the epidemic f0 U[0, 1], a uniform prior for the start time of the epidemic t0 U[1970, 1990], and a uniform prior for the behavioral response: U[200, 400]. Here priors for r, f0 and t0 are similar to those used in (46), excepting the prior for, which was set as a normal distribution with mean 0. The algorithm targeted areas of parameter space corresponding to preva lences between 0. The gure 10 shows a scatter plot and marginal density distribution for two of four parameters: the rate of infection, and the fraction of the population in the at-risk category at the start of the epidemic. It can be seen that the relationship between parameters and infection prevalence is more complex than in the previous two case. We have found high uncertainty about prevalence dynamics before the time of mapped data, i. This restriction would be straightforward to implement in our algorithm by introducing an addi tional map in 1980 with values of prevalence qi,m U[0, 0. Malaria is a seri ous vector-born disease caused by the parasitic protozoan Plasmodium and transmitted among humans via the bites of female Anopheles mosquitoes (47). Although malaria infection prevalences have decreased by half in the past decade due to global eorts, there are still an estimated half a mil lion of deaths a year (48). Mathematical modelling of malaria transmission can help to identify localised areas where control eectiveness is failing and provide a rational for planning intervention programmes (49). The OpenMalaria platform combines an individual based stochastic simulation model of malaria in humans with a deterministic model of malaria in mosquitoes. This case study was dierent from the onchocerciasis case as we have a large number of pixels, but a small number of maps for each individual pixel. We set population size to 10,000 and run the model for 100 years to get to an epidemic equilibrium. These years were chosen arbitrary, as we were interested to use K = 2 time points to match for each simulated epidemic curve. Furthermore, we simulated projections of prevalence up to year 2015 to be able to compare the predicted and mapped prevalences. In order to simulate malaria transmission from 2000 to 2015, we had to ac count for the implementation of interventions during these years. Figure 13 shows a comparison of mapped and simulated prevalences at three levels of malaria endemicity. On average, the simulated epidemic curves tend to be lower than mapped prevalences in 2005 as well, which is in contrast to the onchocerciasis case, where simulated baseline prevalences were similar to the mapped prevalences. Our proposed framework allows the distribution of preva lences from high-resolution maps to be projected forward into the future under the transmission dynamics of complex disease transmission models. The diversity of diseases studied and the range of mathematical models used, allowed us to explore the performance of our framework under dierent con ditions. The proposed algorithm, utilizing the combination of all the samples from multiple proposals, was suitable for the task of parameter estimation based on geospatial maps, as it allowed us to explore complex dependencies between parameters and modelled preva lences with relatively small numbers of transmission model simulations. An alternative strategy where parameters are sampled for each individual pixel independently would require much higher numbers of simulations, as the number of pixels in a map can be large. The algorithm we propose has an additional step of calculating the average weight of parameter vectors based on individual weights of active pixels. The latter algorithm targets simulations towards the pixels that have already been well served by earlier iterations of the algorithm, and not towards the required posterior prevalences for all of the pixels, for example simulated prevalences between 0. This suggests that having a higher number of maps will not require more transmission model simulations, but in fact can decrease this number in comparison to a smaller number of maps. Having a smaller number of maps for each pixel can make it harder to match the sampled prevalences to the distribution of observed prevalences which translates into extra iterations. This may be because there is a spatial correlation between neighbouring pixels, so simulated prevalences close to some observed prevalences at particular pixels will be similar to those in neighbour pixels. In most case studies, we used a uniform distribution with parameter ranges informed by the available literature on biological processes governing infec tion transmission or previous analysis of mathematical models. Our frame work allows incorporating specic knowledge of the parameter space, for example excluding particular areas/combinations of parameters that have been deemed biologically unfeasible, or introducing dependencies between parameters and can be informed by additional data. We found a good agree ment between the mapped and simulated baseline prevalences. However, the uncertainty was propagated with time and simulations produce a wide range of future projected prevalences. A probabilistic approach, called Bayesian melding, combines via logarithmic pooling two priors: one implicit and one explicit, on each input and output (54). Therefore pixels should be divided into regions with dierent histories of control. The proposal distribution adapts to the target by locally tting a mixture component to areas which correspond to pixels with low eective sample sizes. However, our results for all case studies indicate that having sampled 1000 parameter sets was enough to gauge important regions of parameter space for further analysis, at least in 2 to 4 dimensions. The stability of the algorithm requires that the parameter space has been suciently explored in the initial iteration. We avoid this by ensuring that the initial iteration comprises suciently many samples so that at least some of them fall in regions with high weight. A further class of adaptive importance samplers has been proposed, in which the adaptation is driven by independent parallel or interacting Markov chain Monte Carlo chains (56). Parallelisation might be a promising route, for example, by sampling N /dt parameter vectors and running the model and projections on d parallel units, then combining them into a single iteration and using aggregated parameter vectors to sample next N /dt parameter vectors. We have introduced a novel method to sample parameters of disease transmission models given high-resolution prevalence maps. Our strategy of using a mixture of Gaussian distributions based on a trans mission models similarity to mapped prevalence distributions leads to an ecient exploration of the state space. In future work, applications of the methodology that account for routine surveillance data would allow greater 30 R. The views, opinions, assump tions or any other information set out in this article should not be attributed to the Bill and Melinda Gates Foundation or any person connected with the Bill and Melinda Gates Foundation. Geostatistical Methods for Disease Mapping and Visualisation Using Data from Spatio-temporally Refer enced Prevalence Surveys. T (1990)the relationship between the frequency distribution of Ascaris lumbricoides and the prevalence and intensity of infection in human communities. Modelling the impact of larviciding on the population dynamics and biting rates of Simulium damnosum (s. Community directed vector control to supplement mass drug distribution for onchocerciasis elim ination in the Madi mid-North focus of Northern Uganda. Modeling the Impact of Increased Ivermectin Treatment Frequency and Complemen tary Vector Control. How this transformation is impacting human health, whose health is at greatest risk, and the magnitude of the associated disease burden are relatively new subjects within the eld of environmental health. We discuss what is known about the human health implications of changes in the structure and function of natural systems and propose that these changes are affecting human health in a variety of important ways. We identify several gaps and limitations in the research that has been done to date and propose a more systematic and comprehensive approach to applied research in this eld. Such efforts could lead to a more robust understanding of the human health impacts of accelerating environmental change and inform decision making in the land-use planning, environmental conservation, and public health policy realms. However, over the last an uncertain future, not only for the biosphere, ing of the human health impacts of alter century, the eld of environmental health but for humanity itself. There is widespread ations in the structure and functioning of has focused increasingly on quantifying ex debate about the ability of an altered global Earths natural systems. Health is gaps and limitations that can be addressed by ment: from an initial focus on workplace one dimension of human well-being that has future research efforts, (iii)addressthescaleof exposures, to a population-level focus on ra received particular attentioninthisdiscussion. Growing evidence that changes in tion,improvedhealth,andenvironmental we intend here (5). As these reviewers have these natural systems can affect human health sustainability is unlikely to be sustained if most noted, the literature exploring connections in a variety of important ways and the increas of the ecosystem services on which humanity between human health and ecological alter ing pace and extent of these changes has relies continue to be degraded (3). In it, we review same time, the Director-General of the World across a variety of disciplines that leave many current understanding of this eld, identify Health Organization underscored that of the most important relationships incom some of its gaps and limitations, and suggest Natures goods and services are the ultimate pletely characterized. With the human systems to human health, the empirical evi Author contributions: S. E-mail: smyers@ tem, biogeochemical cycles, and the function infectious diseases (3). Here, we for agriculture and, in the case of bushmeat, vector-borne disease (59, 60). Recent modeling provide an overview of the types of relation rich sources of nutrients, but these activities work suggests the dilution effect may account ships that have been well studied and estab also create the potential for zoonotic infections for reduced malaria transmission in diverse lished as a prelude to exploring the gaps, to move from animal to human populations. Some more than 60% of the worlds rivers, alter explain the fact that roughly 75% of emerging recent research suggests that immunological ations to our planets land use and land cover infectious diseases are zoonoses (37). Early is the loss of coastal barrier systems in indicated that hosts with a high intrinsic rate efforts to reduce malaria in the Tennessee cluding coastal mangroves, coral reefs, veg of increase are both more ecologically re Valley (6) and countries in sub-Saharan Africa etated dunes, and coastal wetlands. Other including Nigeria (7) by draining swamps that systems can lessen storm surge and attenu work has emphasized the idiosyncratic nature were habitat for mosquito vectors, for exam ate wave energy, thereby reducing morbidity of particular disease/ecology relationships ple, proved very successful. Clarifying the impacts of disruption of critical building blocks for public health. Forest eases and ecosystems remains an important very large increases in the prevalence of cover may reduce ooding and land slide area for future research. They also lands and forest watersheds can lter pol ulation sizes of species can have other im increase exposure to other vector-borne lutants and pathogens from surface water portant human health impacts unrelated to diseases associated with signicant mor supplies (44, 45); and, to some extent, forests infectious disease. Deforestation increases exposure to One of the most dynamic areas of research health consequences (65). In parts of Africa, forest movement, physiological state, species rich tively new area of research indicates that cutting also alters the composition and density ness, and relative abundance of species within aquatic and terrestrial wildlife populations are of aquatic snail species in a manner that favors an ecological community can alter risks of an important dietary source of both micro transmission of schistosomiasis (32). For example, if house Some land-use changes affect disease ex cently, disease ecologists have shown that the holds in a population in Madagascar were posure less directly. There is growing vector Anopheles albimanus,leadingtoin the Brazilian Amazon, risk of human expo awareness that dwindling populations of creased malaria exposure among coastal sure is positively correlated with reduced marine and terrestrial wildlife may represent populations (33). All of these outcomes represent sig concurrently and the capacity for local ad res, creating a disproportionate burden on nicant public health threats, with impacts aptation may be the most important de women and girls who are often responsible thatarelikelytobeexacerbatedbytheirin terminant of the ultimate health impacts. Finally, and perhaps most important, the can have direct impacts on health through literature on ecological change and human reduced water quality and access to sanita Limitations health needs to be more specic about whose tion,aswellasbycreatinganadditionalwork We highlight four important limitations in the health is in question. First, much of the existing alteration may provide health benets for energy carrying or pumping water from its research on the human health impacts of one segment of a population while incurring source. The direct impacts of these types alterations in natural systems focuses narrowly health costs for another. The degradation of a particular eco nomic development in general is improving identity, depression, and emotional stress have system can result in multiple simultaneous health for most of the worlds people while all been documented in people experiencing impacts on health. A ercise, have been associated with increased health improvements for local communities. In the duced postoperative recovery times and expanding agriculture or building dams to case of climate change, for example, fossil lower analgesic requirements in hospital improve access to food and water). Assessing fuel consumption may be associated with ized patients with access to a natural view the net health effects of such changes would large public health benets as individuals through their room window point to a have more utility for conservation and public become less dependent on biomass burning deeply seeded relationship between the health policy and practice than the study of as a source of heat and cooking fuel, whereas natural world and the psycho-physiological only one dimension of health at a time. A related challenge is the need to evaluate disruption will accrue primarily to future There is a growing literature exploring the the health consequences of the complex in generations. Human health impacts world, land-use change, resource scarcities, pacts from alterations in natural systems is to of anthropogenic climatic disruption include and climate change effects are likely to in consider a renement of Smith and Ezzatis changes in exposure to heat stress, air pollu teract to alter exposure to infectious diseases, environmental risk transition (86). Smith tion, respiratory allergens, infectious disease, access to food and water, protection from and Ezzati make a compelling case that, in and natural hazards, as well as increased water natural hazards, and even population dis aggregate, household level environmental scarcity, food insecurity, and population dis placement with its additional associated health risks. Although these interactions can be exposures, and unsafe drinking water) are infectious diseases (particularly vector-borne represented schematically. Outbreaks of water-borne and food different research methodologies than those cess. Over the course of economic de borne disease are linked to extreme pre which have been applied to date.

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This work might fruitfully be ex mates of real world impacts of ecosystem al tended to other systems and populations to terations on human health symptoms 97 jeep 40 oxygen sensor failure discount prasugrel 10 mg with visa, and some work Fill the Gaps treatment works purchase prasugrel canada. Many of the relationships assess how wildlife management medicine online purchase prasugrel 10 mg without prescription, including has been achieved in this area (107 medicine woman cast order 10mg prasugrel otc, 108) medicine cabinets cheap prasugrel 10mg mastercard. Fi that have been explored in the studies out marine conservation (104) symptoms xanax purchase prasugrel with a visa, impacts the nu nally, we will reach more clarity by being very lined above remain incompletely character tritional status of local populations depen specic about whose health is being studied ized. Much of the need to understand how these changes might production of roughly one third of global existing research appears to have been driven 18758 Only after obtaining re pacts of incremental changes in those com vasive, and accelerating. For example, the use of re as a is generating a suite of health impacts that apply their ndings to policy. We propose land-clearing approach in Southeast Asia is remain, in many instances, poorly charac increased emphasis on policy-driven research. However, ample evidence exists and is also responsible for signicant partic of recent changes in Brazils forest code on that nearly every dimension of human ulate air pollution exposures for downwind malaria rates in Amazonian states (109, 110) Estimating the emissions associated the disease burden associated with these which would require eld experiments and aggregate ecosystem alterations is large with these res and modeling their chemical modeling to unravel, would almost in evolution as they are transported through and growing. In particular, we thank the in the form of promotions, funding, and quantication of specic health impacts as following individuals for valuable feedback on earlier a function of changes in environmental con versions of this manuscript: Stacy Jupiter, Carter success in publishing are consistent with Ingram, Arlyne Johnson, Mike Mascia, David Wilkie, this emphasis. We also thank Damien Joly for assis stract discussion about the importance of tance in preparing. The Changing Face of 21 Yasuoka J, Levins R (2007) Impact of deforestation and their natural hybrid. Irrigation in Kenya: Opportunities for Anticipating Change in Eastern agricultural development on anopheline ecology and malaria 33 Rejmankova E, et al. Philos Trans R Soc Lond B Biol Sci Health Depends on Biodiversity (Oxford Univ Press, New York). Disease Attribution to Selected Major Risk Factors, eds Ezzati M, and North American species. Ecology:the Effects of Ecosystems on Disease and of Disease on 78 Wayne P, Foster S, Connolly J, Bazzaz F, Epstein P (2002) 100 Alexandratos N (1999) World food and agriculture: Outlook for Ecosystems (Princeton Univ Press, Princeton). Production of allergenic pollen by ragweed (Ambrosia artemisiifolia the medium and longer term. Climate Change intake on blood pressure and serum lipids: Results of the OmniHeart on disease risk. Science 323(5911): Aguirre A, Ostfeld R, Daszak P (Oxford Univ Press, New York), pp diversity causing increased hantavirus prevalence. Differences Onchocerciasis (or river blindness) is a parasitic disease in the vectors in different regions of Africa, and differences in cause by the larial worm, Onchocerca volvulus. Man is the the parasite between its savannah and forest forms led to only known animal reservoir. The vector is a small black y different presentations of the disease in different areas. The black y breeds in well It is probable that the disease in the Americas was brought oxygenated water and is therefore mostly associated with across from Africa by infected people during the slave trade rivers where there is fast-owing water, broken up by catar and found different Simulium ies, but ones still able to acts or vegetation. Around 500,000 people were at risk near the breeding sites and the clinical signs of the disease in the Americas in 13 different foci, although the disease has are related to the amount of exposure and the length of time recently been eliminated from some of these foci, and there is the population is exposed. In areas of high prevalence rst an ambitious target of eliminating the transmission of the signs are in the skin, with chronic itching leading to infection disease in the Americas by 2012. Blindness begins slowly with Host factors may also play a major role in the severe skin increasingly impaired vision often leading to total loss of form of the disease called Sowda, which is found mostly in vision in young adults, in their early thirties, when they northern Sudan and in Yemen. Other effects include epilepsy and growth retar attributable to troublesome itching. The unprecedented donation of MectizanO (ivermectin) In Africa more than 100 million people are at risk of by Merck & Co Inc. Water and Sanitation-Related Diseases and the Environment: Challenges, Interventions, and Preventive Measures, First Edition. Some nd their way to the eye and probably other size of a mosquito, requires well-oxygenated water to lay its tissues of the body. If they are not ingested by the vector, they eggs, and where the larvae can develop. Here initially they undergo a big There are minor variations between the species but they increase in size into a sausage-shaped larva. Another interesting species is infective larvae (L3 stage) migrate actively into the wound S. The larvae of this species are found on going through a further larval stage (L4). After about a the underside of leaves oating down the River Congo and week they develop into juvenile worms (L5). In the Americas the most and moves toward the nodules where mating takes place and common complexes are S. The importance of the different species relates to their the communities that live near the river basin but also the bite capacity for transmission of the disease, and also the ease of of the ies causes intense irritation and a huge nuisance to the control. Communities are therefore compelled to aban tool in the control of onchocerciasis, it has been important to don their villages and ee from the river basin for fear of understand the detailed biology of each species, to establish acquiring the disease, notwithstanding the nuisance from the the best method of control. Generally, the Simulium poorer away from the fertile valleys and water is more try to feed as close to the breeding sites as possible. Communities living on the rivers edge are more at prevalence of blindness in young adults leads to further risk than those a little further away. These young nities very close to the breeding site to a certain extent adults are inicted at the time when they should be their most protect the population living a little further away. This is productive and when they have young families to care for and one reason why blindness is relatively rare in towns, even if educate. Its preferred insecurity in Africa (particularly in Central Africa and the biting times are in the early morning and late afternoon. Sudan) has led to large population movements, often out of these are also times when populations who depend on the infected areas. However, when peace returns, populations rivers for water, washing, and food are most likely to be at may return to their traditional homelands and once again the river for these various activities. Those working in elds become exposed to the disease, although the chronic skin nearby or shing in the river itself also tend to be less active changes and blindness may take some time to develop. The biting nuisance even where ies have been well controlled for a period has had a very positive effect on development, but the return of the ies after the control 11. In the area of Inga on Onchocerciasis has had a signicant impact on the popula the Congo River during peak breeding times, the biting rate tions in the savannah areas of West Africa. Movements of One use of nodules has been in establishing a community the Simulium have been mentioned above. It is possible that diagnosis for decisions on mass treatment and this is used in infected ies can be carried by winds into areas where the rapid mapping strategies described later. The fast runoff of water around a hydro turbine tions are reversible, but as the infection continues permanent produces highly oxygenated water, ideal to establish new changes occur. This must be considered during bacteria (symbionts of arthropods and larial nematodes) all construction and maintenance of new dams. Those that are found in subcutaneous tissues are easilythe rst changes are due to itching and the lesions produced palpable as a mobile mass in the subcutaneous tissues with by energetic scratching. Theskinisitchy,thickened,the more classic changes are changes in pigmentation of and hyperpigmented. This gradually spreads and may cover the skin, classically described on the lower limbs although large areas, particularly the lower limbs, but is often sometimes seen elsewhere on the body. This is reversible initially, but severe chronic infections lead to permanent changes. The cornea gradually loses its transparency and becomes white and hard (sclerosing keratitis). This begins at the 3 oclock and 9 oclock positions and then gradually lls in from the bottom, creating a semilunar keratitis until the whole cornea is affected with so-called sclerosing keratitis, as shown in. This chronic inammation can also lead to blindness due to secondary glaucoma or secondary cataract. The pupil often becomes small and deformed and sticks to the lens (posterior synechiae) and therefore nonre active. The most serious aspects of posterior segment disease, however, are chronic chorioretinitis and optic nerve atrophy. Optic nerve poverty, increased expenditure on health in spite of a reduced atrophy also provokes loss of vision (24, 25). Although bleeding and ulceration of skin, secondary infections, bone pain, head ache, and fatigue have also been suggested, these are rela 11. Evidence suggests that onchocerciasis is a risk factor for epilepsy (26, 27) and may be responsible for a type 11. With a heavy microlarial load there may be generalized lymphadenopathy and somethe most effective way to control the vector is to attack the dilatation of lymph vessels, leading to tissue swelling and larval forms. They are easier to control because of their mild elephantiasis, particularly in areas of Sowda. The y has a wind-assisted ight range of about 400 km, making the adult y more difficult to 11. Environ also leads to stigmatization of affected persons and their mental management involves clearing the vegetation and families. Unsightly acute and chronic skin lesions and thick applying agents like Paris Green and Creosote to the breeding ened and irritated skin limit the chances of young adolescent sites of the vector. West Africa the objective was to continue larviciding for a Unfortunately Suramin, which does kill adults (a macrolar sufficiently long period during which time the human reser icide), is also toxic and unsafe to give as a mass treatment. One drug is currently undergoing trials, Moxidectin, but it is For vector control to be effective larviciding needs to be unlikely to be cleared for mass usage before 2014 or 2015 carried out preferably weekly. Doxycycline also has take more than 7 days to about 12 days to change to the macrolaricidal effects by killing Wolbachia, obligatory next stage. Ground and aerial larviciding are both used for endosymbiotic bacteria in some species of laria including control. If Wolbachia are killed, the female cannot feasible, such as in small foci, and where the type of reproduce and will eventually die. Aerial larviciding on the other hand Doxycycline are that it has to be given for a prolonged has been used more extensively to cover large tracts of river period, at least a daily dose for 4 weeks, and it cannot be basins, which would otherwise be either impossible or very given to children under 12, which is a very signicant difficult to cover by ground larviciding. The formulation of insecticides used for large-scale treat Ivermectin is an effective microlaricide (killing micro ment of rivers must meet a range of requirements. It also has an effect on reproduction preventing the be highly effective against the vectors, safe to the rest of the release of microlaria by the adult female for approximately environment, including human and other life forms, with 4 months. When microlariae are released the repopulation guaranteed supply for a long period and the cost should be of the skin is very slow and after 12 months it reaches around low. This effect was not thought to be particularly impor Various insecticides are available. Temephos (AgrEvo tant but recent research shows that some of the early studies France) is a cheap and efficient organophosphorus with were not done in a closed system and some of the live adult insignicant impact on the nontarget fauna. Its use, however, worms found were possible worms from new infections needs careful attention given that insecticide resistance rather than adult worms resistant to ivermectin. Other environ is contraindicated in children under 5 (less than 90 cm height mentally friendly larvicides that have been used are the or 20 kg weight), pregnancy and during the rst week after organophosphates, carbamates, pyrethroids, and the biolog delivery and also patients with chronic disease, or central ical Bacillus thuringiensis serotype H14-B. Flubendazole is a macro cides to use for the maximum impact on the vector, while still laricide but the complications of administering the drug having the minimal impact on the environment. Because they are often multiple, and many are Ivermectin has proved to be such a safe and effective drug also impalpable in the deep tissues, it is impossible to that most onchocerciasis control programmes are now eliminate all adult worms by nodulectomy. In Africa the foci of the disease are not so small and transmission of the parasite for long enough periods to well dened. Initially planned annually, which is sufficient to control the main symptoms to last 20 years, the period for larviciding was reduced to of disease but will require 16 or more years to achieve 14 years upon new evidence, which suggested a shorter elimination depending on the initial prevalence and the reproductive life span (12 years) for the worm. First, health importance in West Africa and to place participating there was a sense of common purpose by all concerned. All concerned devoted their attention in Niger, Senegal, Sierra Leone, and Togo (35, 36). At the close of the program in contribution through the free drug donation by Merck was 2 remarkable.

The quality of notifed and unregistered Sciences collaborated on the development and over medicines cannot be assured symptoms stomach flu cheap prasugrel online master card, since they have not passed sight of the inspectors training medicine 7 day box purchase 10 mg prasugrel mastercard. The main focus of the intervention was on product ance program established in 2002 symptoms nausea headache fatigue buy discount prasugrel line. Since then symptoms of kidney stones purchase prasugrel 10mg without prescription, improved examination and testing at ports of entry and surveil efciencies have resulted in a doubling of the number of lance and testing of products circulating in the market treatment wetlands order prasugrel 10 mg amex. The program also prequalifed three Fund medicine man dispensary generic 10 mg prasugrel mastercard, and with support from the World Bank, launched new quality-control laboratories to bring the total to its prequalifcation of medicines program to assess and eleven. Since then, the program has agencies, the program has become a valuable resource for added medicines and commodities related to reproductive any purchaser, including countries themselves. It also includes the list of ofers training workshops on how to meet prequalifca prequalifed medicines and their manufacturers. Publications by medicine information services and when assessing ofers and awarding supply contracts. They include mation on suppliers performance and develop and apply criteria for personnel, facilities, equipment, materials, man operational defnitions and criteria to assess the reliability ufacturing operations, labeling, packaging, quality control, of suppliers and avoid subjectivity. A manufacturer may have accept samples of the product, packaging, and labeling is impor able standards for solid dosage forms but not for sterile tant. Ofen, a detect defective products, bear in mind that the samples supplier must approve or at least expedite requests for per are provided by the supplier, which will make every efort formance reports from national pharmaceutical control to ensure that the samples meet the standards. The sam agencies, and failure to obtain such reports for the buyer ples may not, however, be representative of what is actually makes past performance suspect. Keeping a record of condition of received goods, compliance Countries that participate in the scheme agree to certify with contract terms, and timeliness of delivery is essential. For the turing take place in diferent countries before the product procurement ofce, it is an inexpensive means to help ensure reaches the fnal destination. Local manu pharmaceutical product submitted, especially when it facturers that do not have their own quality-control labo is submitted through the manufacturer or importing ratories may contract quality-control testing services from agent other manufacturers, private testing facilities, or national reference laboratories. For this reason, certifcates should be ratory testing of samples from individual batches. To facilitate registration of generic medicines, the Contract specifications evaluation and approval process should not be complicated. Moreover, in some countries, manufactur material is used to assign qualitative and quantita ers may produce exclusively for export; the exporting coun tive properties, its identity must be assured and its 19 / Quality assurance for pharmaceuticals 19. Its uses range rial is generally assessed by infrared spectral com from tracking shipping containers to individual dosage parisons and quantitative assessments performed by units. The airline industry makes extensive use of this ultraviolet-visible spectral measures, either directly technology to track and direct baggage, and the retail or in conjunction with chromatographic procedures. Because of their widespread use identity and quality of solid materials can be assessed and simplicity, bar-code detecting devices are relatively by melting point/mixed melting point measurements, inexpensive. Holograms: Hologram technology provides visual authenti To reduce thef and resale, some programs may require cation that can be very difcult to counterfeit or remove labeling and logos to indicate that the product is solely for (although instances of fake holograms have been found distribution within a particular health care program (for on counterfeit antimalarial products in Southeast Asia). However, the technology is not easily automated and Contract specifcations are discussed in detail in Chapter optimally requires an authentic label or accurate image 39. As The quality of products received should be verifed as soon the technologies mature, several will likely be used to assure as possible by physically inspecting each shipment and diferent aspects of the supply chain. The continuing adop testing selected products in the laboratory as required by tion of these authentication technologies will make product regulation. In addition, more advanced product-tracking counterfeiting more difcult and expensive, but unfortu technologies have been introduced to help ensure the integ nately will not likely eliminate it. Inspection of shipments Product identification technology Regardless of other quality assurance procedures in use, eachthe traditional approach to assuring product integ pharmaceutical shipment should be physically inspected. This means verifying adherence to contract specifcations Unfortunately, this labeling is easily duplicated. To make and order completeness as well as inspecting samples of fraud more difcult, several approaches are available that all items to spot any major problems. Overt technologies are visible receiving staf can be an economical means of ensuring to the eye, and covert technologies require devices for detec pharmaceutical quality and reducing losses from supplier tion. The Minilab uses a thin-layer chromatography method that does not require stan Tiered pharmaceutical quality assessments dard laboratory resources, so it can be used in the feld, such as at ports of entry, while providing a good level As mentioned earlier in the chapter, the safety and efcacy of quality assurance. Tat level of efcacy is called the therapeu technologies are required to support litigation con tic window (see Box 19-4). Specialized instruments: Methods such as high whether products are grossly substandard and to performance liquid chromatography coupled with Box 19-4 Therapeutic window Fortunately, the overwhelming majority of pharmaceuti cal products have a large therapeutic window, which is 50 a great advantage for manufacturers and consumers. A 45 Maximum tolerated dose wide therapeutic window allows the production of fewer dosage levels, which reduces production, supply, and 40 inventory costs and allows consumers to more easily take a dose of a medicine that is efcacious and well toler 35 ated. Products with a narrow therapeutic window require strict monitoring of the patients therapeutic response; 30 for example, patients taking the anticoagulant warfarin Therapeutic sodium must have their individual coagulation times 25 window strictly monitored to determine the ideal dose. A further 20 indicator of the critical dosing requirement for this prod uct is the large number of tablets available containing 1, 15 2, 2. Tese dosing levels contrast markedly with those of acetaminophen (paracetamol), 10 which has a wide therapeutic window. In the United Minimum therapeutic effect States, acetaminophen is ofen marketed as a 325-mg 5 dosage unit, whereas in Europe the dosage unit gener ally is 500 mg. The dosing instructions for both products 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 instruct the user to take one or two units up to four times per day. Generally, these or potency, uniformity, impurities, disintegration, and dis technologies are expensive and require highly trained solution. Biological testing is more specialized and can be per formed only in established facilities with staf trained In summary, wide-therapeutic-index products may be to use microbiological and pharmacological methods. Narrow medicines and eye preparations and microbiological assays therapeutic-index products and those that fail the rapid of antibiotics and vitamins. Pharmacological tests include screening technologies should be assessed by validated the pyrogen test; toxicity tests; hormone assays, such as for technologies that are fast and efcient. Products that fail the insulin and pituitary derivatives; and tests to determine the validated technologies may require further assessments by bioavailability of selected pharmaceuticals. Testing by ity construction, testing equipment, furniture, sup exception means that analyses are done only when a supplier plies, equipment maintenance, salaries, training, and or a particular product is suspect. In some countries, a college of pharmacy or an inde Suppliers whose failure rates are unacceptable are dropped pendent laboratory may have some of the required test from future tenders. Also, many international quality-control pliers is done much less frequently, ofen only for at-risk laboratories provide pharmaceutical analyses at a relatively products. If analyses are performed by foreign Programs that require routine testing of samples for all laboratories, foreign exchange and billing problems may products prior to distribution to health facilities ofen pro be reduced by requiring the suppliers to pay the labora duce signifcant delays in product availability at the health tory directly, with the arrangement clearly described in facility level. In addition, chain-of-custody and reported to have problems should be carefully assessed; legal standing of the testing laboratory in the importing many problems with quality are detectable on visual inspec country may be at issue. For example, verifed observations of tablets that crumble before their expiry date, oral suspensions that harden, or injectable solu 19. Maintaining medicine quality requires careful attention to The tests that should be performed depend on the phar storage conditions and transport, as well as to dispensing maceutical and the reason for testing. The prescriber and the dispenser should counsel the patient on the proper use of medications, explaining what Product problem reporting system the medicine is, why the patient needs it, how to take it, and where and how to store it until treatment is completed, in Establishing a national product problem reporting system addition to possible contraindications and adverse reactions is important so that health workers can report suspected (see Chapter 30). Product problem reporting should be part of an overall Pharmaceutical product presentations: treatment pharmacovigilance system, which also includes monitoring kits, co-packaging, and fixed-dose combinations and reporting adverse drug events and medication errors. Chapter 35 covers those areas of pharmacovigilance in Medicines can be packaged according to therapeutic detail. For example, els can use to report suspected lapses in pharmaceutical or a tuberculosis treatment kit could include enough anti packaging quality. Standard procedures for product prob microbial products for a particular number of patients. Product problem reports and results should be employed at all levels, including the district hospitals, and recorded to provide information for future procurement. In addition, they report problems or questions Product recalls concerning individual medicines to the main ofce. In other countries, locally trained dispensers are responsible for Pharmaceutical products found to be defective should be much of the day-to-day work and must be trained to detect recalled quickly. The central distributors In addition to pharmacists and pharmaceutical assis inventory control system should include information on all tants, other staf members involved in quality assurance batches that have been received. Because tracking individual need training and supervision as a part of quality assurance batches to the health facility is ofen either impractical or eforts. The procurement ofce should pursue with pharmaceutical labeling and packaging materials other remedies specifed in the contract, such as withhold to determine whether contract conditions regarding ing payment or obtaining reimbursement for or replace pharmaceutical dosage, packaging, and labeling have ment of the defective products. Center for Pharmaceutical Management: Technical Frameworks, Approaches, and Results. Prepared and Simulation Studies on Ergometrine, Methylergometrine and for the Strategies for Enhancing Access to Medicines Program. Pharmaceuticals: Counterfeits, Substandard Manufacturing Practice Guide for Active Pharmaceutical Ingredients Drugs and Drug Diversion. Ensuring the Quality of Medicines in Resource-Limited Epidemiological Investigation into the Criminal Fake Artesunate Countries: An Operational Guide. Agency for International Ritonavir Capsules at Ambient Temperatures in Sub-Saharan Africa: Development). Survey of the Quality of Selected Antimalarial 19 / Quality assurance for pharmaceuticals 19. Quality Assurance of Pharmaceuticals: A Compendium publications/druginformation/DrugInfo2010Vol24-1. General Guidelines for the Establishment, Development Programme, United Nations Population Fund, World Maintenance and Distribution of Chemical Reference Substances. In general terms, quantifcation is method is the most complex and time-consuming, and the process used to determine how much of a product is it can produce major discrepancies between projections required for the purpose of procurement. Nevertheless, this method is ofen cifcally, quantifcation involves estimating not only the useful for new and expanding programs and may be quantities needed of a specifc item, but also the fnancial the most convincing approach for justifying a budget means required for purchasing the item. The lead time has a major efect on quanti health systems ties required for safety stocks. In virtually all supply systems, adjustment is necessary for losses caused by The quantifcation method must be chosen in light of the wastage and thef. Quantifcation estimates can be cross-checked by com The consumption method, which uses data on medicine bining diferent methods. No matter which method is consumption, gives in many instances the most accu used, a gap may exist between the initial estimates of rate prediction of future needs. The quantif pharmaceutical supply systems rely primarily on the cation process itself may help justify an increase in the consumption method. To be reliable, the consump budget, but ofen the quantifcation estimates must be tion data must come from a stable supply system with a adjusted and reconciled to match available funds. The relatively uninterrupted supply and a full supply pipe choice between manual and computerized quantifca line. Consumption data may or may not refect rational tion may be dictated by circumstances, but the process prescribing and use of medicines or actual demand for is much easier with computer assistance. This nel and time requirements depend on the quality and method requires reliable data on morbidity and patient accessibility of source data and on the type and scope of attendances (visits to health facilities) and uses standard quantifcation. The goal is to maintain the most cost-efective balance between service levels and Quantifcation is the frst step in the procurement pro inventory costs. In general terms, quantifcation is the process used to determine how much of a product is Major options for quantification required for the purpose of procurement.

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