A larger randomized controlled trial with greater power and greater control over laboratory assessments should be a high priority erectile dysfunction ed natural treatment order levitra oral jelly 20 mg with mastercard. If future investigations conrm these nd ings erectile dysfunction desensitization buy 20mg levitra oral jelly visa, methyl B12 may be a useful treatment option for children with Limitations autism and impaired methylation capacity erectile dysfunction doctors los angeles discount 20 mg levitra oral jelly with visa. The most Acknowledgments signicant are the relatively small sample size and the fact that many children were not able to adequately adhere to the laboratory We gratefully acknowledge the families and children who par instructions to fast prior to laboratory draws; therefore erectile dysfunction pills for sale purchase levitra oral jelly 20 mg with visa, only a ticipated in this study to help advance scientic research in autism impotence means buy levitra oral jelly 20 mg with visa. This Disclosures limited laboratory assessment limits the power of our analyses to In the past year erectile dysfunction ed drugs generic 20 mg levitra oral jelly mastercard, Dr diabetes and erectile dysfunction causes cheap levitra oral jelly 20mg visa. Robert Hendren has received research grants detect differences in laboratory values between groups erectile dysfunction treatment with viagra cheap generic levitra oral jelly uk. Although it from Autism Speaks, BioMarin Pharmaceutical, Curemark, Forest is possible that this could signicantly affect the overall laboratory Pharmaceuticals, Inc. He is on Advisory Boards for BioMarin, Forest, Janssen, associations observed in the three metabolites. This may be because of a lack of sen funding agency and the manufacturer of methyl B12 (which was sitivity of these outcome measures, improvements in other symp purchased and not donated) had no role in the design of the study; tom areas that are not captured by these surveys, or improvements the collection, management, analysis, and interpretation of the data; that were noted only by the clinician assessment and not by the or the preparation, review, and approval of the manuscript. Autism method for the simultaneous determination of oxidized and reduced Res Treat 2013:609705, 2013. Davis David Sklan July 10, 2001 Blacksburg, Virginia Key Words: Folic acid, homocysteine, lactation, growth, exercise, anti-folate drugs Copyright 2001, Amy L. Therefore, mares and foals maintained on quality grass/legume pastures and offered a pasture supplement did not require additional folate supplementation to maintain folate status during lactation and growth. First, I would like to thank the members of my PhD committee for taking time out from their busy schedules to help me. It is with great respect and admiration that I first acknowledge and express my appreciation to my advisor and committee chair, Dr. He was instrumental in my professional development as an independent thinker and scientist. He is a truly brilliant and unique individual and deserves a great deal credit for turning the graduate equine nutrition program at Virginia Tech into a nationally recognized program. Not only did he continually try to keep me on track via long distance e-mails, but he was also a great source of humor, sarcasm, and support. Larry Lawrence for giving me many extension and teaching opportunities, and for always being making time to answer questions, have a friendly chat, or prepare me for my job interview. Barbara Davis for being excellent teachers in and outside of the classroom, and for appreciating the need for equine scientist to collaborate with faculty studying other species. Houston and his graduate students for inviting me to participate in weekly journal club meetings that kept me abreast on cutting edge research on oxidative stress and exercise and aging. Mark Wahlberg for providing much needed advice and guidance during the course of my job interview and for taking a personal interest in my career and my personal development. He was absolutely instrumental in my success in obtaining a job at the University of Maryland. I am greatly indebted to our laboratory technician, Louisa Gay, for teaching me the basics of lab methodology and for either assisting me with sample analysis. She was also a good friend and provided much needed fun conversation during my long hours in the lab. My heartfelt thanks are expressed to Bobbie Moriarty for her kindness, generosity, friendship, and for her support of my yearling auction efforts. My gratitude is extended to Alvin Harmon, Bill Helsel, and Scotty Gerbich for their help in maintaining the dry lot for the folate depletion study, fixing things in the grad apartment, providing general comedic entertainment, and for making feed runs enjoyable on the weekends. Many thanks are extended to my good friend Burt Staniar who entered the equine nutrition program with me five short years ago. He is a genuine, kind, honest, and amazingly bright individual whose friendship is truly irreplaceable. His very competitive nature inspired me to push myself harder and to set even higher goals (in order to keep up with him). Some of my fondest memories include our discussions/debates/arguments about anything and everything, intense, but successful study sessions, taking blood from mares and foals in the middle of the night, trying to save Charlotte and Wilbur (the twins), and his never ending lectures about my need to improve my diet and exercise. I am also very grateful to Carey Williams for her friendship, loyalty, support, humor, and for always being there when I needed her. It has certainly been a wonderful and rewarding experience assisting her in her iv graduate degree pursuits and I am honored that she allowed me share in the joy of her successes. She has been an asset to our program and she will be an even bigger asset to the field of equine science. Many thanks are extended to Theresa McDonald for allowing the Virginia Tech Equitation horses to participate in the folic acid supplementation study, and for fitting in two standard exercise tests despite their busy schedule. Also, much appreciation is given to Jennifer Durbin for always being available to answer my questions about the horses and the management practices at the barn and for always. Thanks are also expressed to the many undergraduates who volunteered their time to assist with data collection in the folate studies in Middleburg and Blacksburg. They were always bright, cheerful, and comedic even after they stayed up late cheering on Michael Vick and the rest of the Tech football team the night before. My deepest appreciation is extended to my dear friend, Rob Burk, for being the greatest source of support, encouragement, and laughter during the completion of my degree and the writing of this dissertation. He was completely understanding and supportive when I needed to work long hours and was always there to cook me a great meal or pull me off the computer to go running. His friendship during the last year made one of the most trying times of my PhD almost completely enjoyable. In hindsight, it was that first horseback riding lesson nearly 20 years ago that changed my life forever and started me on an unforgettable journey. Each step of the way, my parents supported my efforts and were active participants in every part of my personal and professional life. Body weight, rectal temperature, and hematological indexes in geldings administered Pyrimethamine and Sulfadiazine during Period 1. Body weight, rectal temperature, and hematological indexes in geldings coadministered Pyrimethamine and Sulfadiazine and either Peptidoglycan or folic acid during Period 2. Latin square design for six treatments administered to six horses over a 6 wk experimental period. Folate deficiency in humans is caused by factors that include low dietary intake, increased requirements, and conditions or drugs that alter folate metabolism. In addition, genetic mutations in key enzymes in folate and homocysteine metabolism in humans increase the dietary intake of folate and thus increase the risk of certain folate related disorders. However, the daily supplementation of folic acid in humans has been shown to improve folate status and lower the incidence of folate related disorders. The implications of low folate status and disease states and the success associated with folic acid supplementation should prompt the reevaluation of folate nutriture in numerous other species. With the exception of laboratory animal species, few studies have been conducted that investigate the role of folate status and supplementation in other animal species. This is partly due to the potentially large contribution and utilization of microbially derived folate in the foregut of ruminants and the hindgut of non-ruminants or monogastrics and partly due to the high forage diets containing adequate amounts of folate. However, species including dogs, cats, guinea pigs, swine, and poultry require supplemental folate to meet dietary folate requirements. Horses are unique monogastrics in that they appear to be capable of utilizing folate derived from microbial synthesis in their hindgut and cecum (Carroll et al. Exercise training in horses has also been shown to lower folate status (Allen, 1978; Allen and Powell, 1983). These earlier reports led to the recommendation for and routine supplementation of folic acid in equine concentrates and vitamin supplements. These 1 recommendations were made despite the lack of knowledge regarding the bioavailability and efficacy of synthetic folic acid supplementation in the horse. Given the importance of folate in health and disease in the human and the lack of understanding regarding the role of folate in the equine, the need for studies on folate status and supplementation in the horse has arisen. Assess the effects of long-term oral folic acid supplementation in moderately exercising horses 3. Assess the effects of long-term administration of pyrimethamine and sulfadiazine on folate status in mature geldings 4. There are three main changes to that structural backbone that account for the numerous folate derivatives that can occur naturally. Second, the folate derivative may have additional glutamate residues attached at in peptide linkage resulting in a polyglutamate structure instead of its original monoglutamate structure. Folate polyglutamates are more commonly found in nature, metabolically active tissue, and in tissue storage sites, whereas the monoglutamate form is more prevalent in blood and milk (Herbert and Das, 1994). Third, the N-5 and/or N-10 positions on the folate structure can serve as sites for attachment of one-carbon units including methane and formate, which plays a major role in one carbon metabolism. Folic acid, on the other hand, has an oxidized pterin ring making it the most stable folate derivative, and has thus been used in the fortification of foods and feedstuffs and inclusion in vitamin supplements. The relative ease of oxidation and destruction of folate requires attempts to keep samples away from light, heat, and oxygen during collection, processing, and analysis. To prevent loss of folate during sample storage, reducing agents such as ascorbate, 2-mercaptoethanol, and dithiothrietol should be added to all samples and samples should be kept at freezing temperatures with ultralow temperatures being most favorable (Gregory, 1989). Folate derivatives are widely distributed in various concentrations in plant and animal tissues. The folate content in some food and feedstuffs has been published (Brody, 1991; Bailey, 1995; McDowell, 2000). In addition to meeting folate requirements by consumption of food, humans and animals are capable of absorbing and utilizing folate synthesized by gut microbes (Miller and Luckey, 1963; Klipstein and Samloff, 1966; Rong et al. The site of microbial folate production and amount of folate produced vary depending on the species. It has also been shown that humans are capable of absorbing bacterially synthesized radiolabeled folate in the upper small intestine (Camilo et al. In animals that contain large fermentation vats like the rumen or cecum, microbial synthesis of folate is most likely produced in greater amounts and provides a greater contribution to the meeting folate requirements. The mechanisms and site of absorption of microbially derived folate is not fully understood. The horse is a unique monogastric species in that it has a cecum that contains microbes that can synthesize folate (Carroll et al. The highest values of folate occurred in the cecum and large colon indicating microbial synthesis of folate was greatest in those sections. Several factors can influence bioavailability of folate including the form of folate in the diet, composition of the diet, and nutritional status, age, and health of the individual. Therefore, it appears that the determining factor in bioavailability is how the folate source is supplied to the body. Absorption and transport Dietary folate entering the intestinal lumen are primarily in the reduced polyglutamated form and must first have the glutamate residues hydrolyzed to yield mono and diglutamate folate prior to absorption. The hydrolysis of the glutamate tail is catalyzed by an exocarboxypeptidase enzyme called folate glutamylhydrolase, which is commonly known as folate conjugase. Folate conjugase is located at the lumenal surface and has an optimal pH between 6. Active folate conjugases have also been found in bile, pancreatic juice, kidney, liver, placenta, bone marrow, leukocytes, and plasma, although the importance and function of the enzyme in these tissues is uncertain (Combs, 1992a). Once hydrolyzed to the monoglutamate form, folate is ready to be absorbed by cells. The major site of folate absorption in the human occurs in the proximal jejunum with very little being absorbed in the distal jejunum and ileum (Hepner et al. In addition, folate has been shown to be absorbed in colonic epithelium in the human (Dudeja et al. There are two main types and one minor type of transport processes involved in the + intracellular internalization of folate. The first type of transport process is by a Na -coupled saturable carrier-mediated process binding to a transporter at the membrane surface to mediate internalization through membranes (Sirotnak and Tolner, 1999). Carrier-mediated processes are present in the intestinal and colonic epithelium exhibiting an optimal pH of 5. A saturable transport system for folate in the basolateral membrane of the rat small intestinal enterocyte was found to have similar attributes except that its not affected by either sodium or potassium (Said and Redha, 1987). The second type of transport method is via a receptor-mediated processes that utilizes high affinity binding of folate at the membrane surface to a receptor-like protein, which mediates unidirectional flux following internalization of the receptor-folate complex (Sirotnak and Tolner, 1999). The membrane associated binding proteins are 38 to 44 kD, which bind to physiological folate with high affinity in the nanomolar range (Antony, 1996). The third type of transport process is via simple diffusion, which has been documented at pharmacological doses of folate and during transplancental folate transport occurring in concert with folate receptors (Antony, 1996). The nonsaturable process proceeds linearly related to 7 lumenal folate concentrations and accounts for 20 to 30 % of folate absorption at high folate intakes (Combs, 1992a). When pharmacological doses of the monoglutamate form of folate are consumed, it is also absorbed by a nonsaturable mechanism involving passive diffusion. The overall efficiency of folate absorption in the human appears to be about 50 % (10 to 90 %) and can be affected by malabsorption syndromes (Gregory, 2001). After uptake of folate into the enterocyte, reduction of oxidized folate monoglutamate derivatives takes place. Administration of non-physiological concentrations will saturate the system allowing a greater proportion of absorbed folate to pass through the enterocyte without reduction or methylation (Mason and Rosenberg, 1994). In addition to the release of folate into the circulation, a larger percentage of the folate monoglutamates are also incorporated into bile and excreted into the small intestine (Steinberg et al. As much as 50 % of the folate ultimately reaching peripheral tissues may be accounted for by this recirculation processes (Steinberg, 1984). Interruption of the enterohepatic cycle results in a drastic decline in serum folate levels indicating the importance of the enterohepatic cycle in folate homeostasis (Steinberg et al. After absorption, reduced folate monoglutamates are transported in the portal circulation to the liver where they can be polyglutamated and retained or released in blood or bile. It has been 8 suggested that protein binding may facilitate folate transported by tissues such as liver (Combs, 1992a). Plasma also contains low levels of high affinity folate binder, which appears to be the same protein as the cellular high affinity folate binding protein, which can be released from cells after hydrolysis of its glycosylphosphatidylinositol anchor. The binding affinity of swine binding proteins was found to be much greater than that of other animals including sheep, goat, cattle, horse, rabbit, dog, rat, guinea pig, and chicken (Mantzos et al. Cellular uptake and distribution Cellular uptake of folate monoglutamates occurs either by a folate receptor via a carrier mediated process requiring energy and sodium, or by a reduced folate carrier anion-exchange system (Combs, 1992a). The folate receptor is a glycoprotein, has bound fatty acids and is attached to the membrane via a glycosylphosphatidylinositol anchor (Weitman et al. The regulation and distribution of folate receptors has been reviewed (Weitman et al. These transport systems are not saturated by folate under physiological conditions, and folate influx into tissues would be expected after any elevation in plasma folate after supplementation. Once transported inside the cell, monoglutamates must be converted to polyglutamates by glutamate synthetase after demethylation for the retention and storage inside the cell (Steinberg, 1984). Folate that are polyglutamated are better substrates for folate-dependent enzymes and folate-related cell functions are related to polyglutamate reserves (Steinberg, 1984). Within the cell, there is nearly equal compartmentalization of folate polyglutamates between the cytosol and the mitochondria (Shane, 1995). The mitochondrial and cytosolic folate pools are distinct from each other and also have a distinct one-carbon metabolism. Within the body, nearly half of the folate derivatives are concentrated in the liver, with the remaining folate accumulating in greater amounts in rapidly dividing tissue. The type of folate derivatives, length of glutamyl residues and concentration varies within different tissues (Cossins, 1984; Whitehead, 1994). Folate deficiency lowers the folate concentrations in tissues with longer polyglutamates predominating (Varela-Moreiras and Selhub, 1992). However, folate concentrations in the brain are unresponsive to changes in dietary folate intake (Shane, 1995). The rate of folate catabolism appears to be related to the rate of intracellular folate and is therefore greatest during conditions of high cell turnover. The turnover of folate in the human is less than 1 % of their total body folate per day (Von den Porten et al. The primary excretory site of folate catabolism products is through the urine (Scott, 1984). Folate is freely filtered at the glomerulus, but is reabsorbed in the proximal renal tubule by folate receptors along the brush border membrane resulting in low losses of folate in the urine (Combs, 1992a; Antony, 1996). The total urinary excretion of folate and metabolites is small and is estimated to be less than 1 % of total body stores per day (Combs, 1992a). Fecal folate excretion 10 is variable and is not a measure of folate availability due to the confounding contribution from the enterohepatic cycle, lysed intestinal cells, and microbially synthesized folate in the gut (Scott and Weir, 1986). Metabolic Functions the primary function of folate derivatives is to exchange one-carbon units from various sources in what is commonly called one-carbon metabolism. The one-carbon units exist in various levels of oxidation including those that are reduced as in methane to those that are more oxidized including carbon dioxide.
Syndromes
Vegetables
Red blood cell transfusions to fight anemia
You can also steam up the bathroom shower and bring your child in there before bed.
Emphysema
Placenta previa
Surgery
Permits generally convey non-exclusive use rights erectile dysfunction at age 20 cheap 20 mg levitra oral jelly free shipping, while licenses provide exclusive rights for a 71 limited purpose and leases provide exclusive ownership rights for a broader purpose erectile dysfunction performance anxiety purchase levitra oral jelly 20 mg visa. The Act specifically requires that gold obtained under a Small-Scale Mining Lease (which 78 includes artisanally-mined gold) be sold to a licensed Mineral Buying Center erectile dysfunction treatment in urdu levitra oral jelly 20mg on-line. Although most of the Act is directed at large-scale erectile dysfunction levitra order genuine levitra oral jelly online, commercial mining activities what age does erectile dysfunction happen cheap levitra oral jelly online, it does include a short chapter (Chapter 2) on Small-Scale Mining psychological erectile dysfunction young discount 20mg levitra oral jelly visa, following the example of its predecessor erectile dysfunction treatment without medicine order levitra oral jelly 20 mg without prescription, the 1999 Decree erectile dysfunction jelly discount levitra oral jelly generic. The Act defines artisanal mining as a subset of small-scale mining; as such, artisanal mining is included in the requirements governing small-scale mining. Both artisanal and small-scale miners can apply for a small-scale mining lease (with artisanal miners first required to form a cooperative), but there is no lease available under the Act specifically for artisanal mining activities. The specific requirements for a small-scale mining lease are discussed further below. The regulations include a brief section on Artisanal and Small Scale Mining Operation, which allows miners to register as artisanal and small-scale mining cooperatives and obtain extension services from the Ministry, including assistance in securing financial support from the Solid Minerals Development Fund. As noted above, artisanal mining cooperatives are also eligible to apply for mineral titles in the form of a small-scale mining lease. Small-Scale Mining Leases Under the 2007 Act, the Mining Cadastre Office grants small-scale mining leases for operations 79 between three acres and five square kilometers. As noted above, the small-scale mining lease covers both artisanal and small-scale mining activity. Each small-scale lease application must be accompanied by a showing of technical competence (at minimum, a certificate in mining or a related field) and financial capability (evidence of sufficient working capital through a bank 80 statement or reference letter). In addition, applicants must provide a land survey and a pre 81 feasibility study. A small-scale mining leaseholder cannot engage in extensive and continued use of toxic chemicals, cannot dig more than seven meters, and cannot continually use 82 explosives. In practice, the Mining Cadastre Office encourages small-scale (and artisanal) miners to form cooperatives in order to decrease transaction costs and formalize mining 83 practices. All 84 leaseholders must apply in order to export minerals for commercial purposes. The holder of the small-scale mining lease (and any other mineral title holders) must also pay compensation to the occupier or owner of the land for any disturbance to the surface of the 86 land. In addition, a small-scale mining leaseholder may apply to transfer the ownership of the 87 mineral title, subject to the fee below. Fees for small-scale mining leases are as follows (all in 88 Naira): Application Processing Fee: 10,000 Annual Service Fee: 10,000 Renewal Processing: 30,000 Tailing Deposit Application: 10,000 Application to Abandon Work: 20,000 Application for Transfer: 50,000 Permit to Export Minerals: 10,000 89 Mine operators are also required to ensure that all tailings are properly treated before disposal, although in practice, many tailings are sold for further processing. In addition, all mineral processors must ensure that toxic materials are stored and used in a safe and secure manner. Mine health and safety is monitored through periodic inspections (conducted by the Mines 90 Inspectorate) that analyze whether each mine is in compliance with technical requirements. During extraction, a small-scale leaseholder must keep detailed records and must pay royalties 91 92 based on production. In addition, every leaseholder must contribute to an Environmental Protection and Rehabilitation 94 Fund, in proportion to potential adverse impacts from that particular operation. All small-scale miners must also submit a Community Development agreement, outlining the rights and 95 arrangement between the miner and the community representatives. The 2008 Policy calls for a comprehensive approach to mineral resources development that supports artisanal and small-scale miners. Related objectives include the promotion of small-scale mining activities and the formalization of informal mining activities, as well as the development of a legal and regulatory framework reflecting international best practices. The Policy also identifies seven specific objectives for government action, including access to funding, needs-driven research, training opportunities, information sharing, promoting small-scale mining activities, facilitating co-existence of large and small mining operations, and establishing the Solid Minerals Development Fund. Federal Environmental Laws, Policies, and Regulations In 1999, Nigeria replaced the Federal Environmental Protection Agency with the Federal 96 Ministry of the Environment. Environmental Impact Assessment Under the Environmental Impact Assessment Decree No. Mining-specific requirements include a surface infrastructure plan (including water pollution management), and surface water, groundwater, and air pollution 103 analysis. The regulations seek to minimize pollution from the mining and processing of coal, ores, and industrial minerals and 106 contain emissions limits for specific pollutants, among other things. International Law the Ministry of the Environment must also enforce compliance with the provisions of 108 international agreements, protocols, conventions and treaties on the environment. Minamata Convention the Minamata Convention, named after a Japanese port city that experienced decades of mercury poisoning after chronic industrial discharges into the Minamata Bay, was finalized in January 2013 and opened for signature in October 2013. The National Action Plan must include eleven elements designated in Annex C of Minamata, as set forth in Box 1 below. However, restrictions on the supply and trade of mercury under the agreement may make it more expensive 115 and difficult to secure. Basel Convention 121 the Basel Convention controls the transboundary movement of hazardous wastes. Impetus for the Convention developed after the 1988 toxic waste incident in Koko, Nigeria that spurred the development of Nigerian environmental law. Under the Convention, the generation of mercury waste should be reduced to a minimum, taking into account social, technological and economic 123 aspects. According to the standard, resource companies must disclose payments, and governments must disclose their revenues. Upon a finding that a company has given false information or submitted false receipts, the company: (1) is required to pay the actual amount of revenue due; (2) may be fined; 132 and (3) may have its permit revoked at the discretion of the President. Managers, directors, and government officials are subject to personal liability unless they can prove that the relevant 133 act occurred without their consent and that they performed due diligence. The brief cited health concerns, environmental degradation, and water pollution as primary incentives to spur legislative 137 action. State Environmental Laws and Policies Nigerian states possess the authority to enact environmental laws that are not preempted by 138 conflicting laws passed by the National Assembly. However, Nigeria has a constitutional provision that enumerates an exclusive legislative list that vests legislative power solely in the 139 National Assembly, including with respect to mines and minerals. These state agencies act under the principle of cooperative federalism, where states have concurrent authority over most environmental matters, subject to a floor established by regulations promulgated by the 141 Ministry of Mines and the Ministry of the Environment. They are also responsible for deciding all disputes between 145 a mineral title holder and the local community. State Environmental Laws Even though states do not have authority over mining activities, as mentioned above, they can regulate environmental pollution. The role of the agency is to protect and improve the environment by helping communities understand their environmental responsibilities. The Pollution Department is charged with regulating activities that cause harmful pollution by monitoring the quality of air, land, and sewages. The Emir of Anka has also sought to help mining communities deal with issues of land access and consent, as discussed further in Part 5 below. These local governments constitute the third tier of government below the federal and 152 state levels. That is, [p]utting an efficient legal framework into place without enhancing the financial capacity of miners or raising 156 their awareness of their legal obligations does not help to eradicate illegal mining activities. First, there must be sufficient incentives for all parties involved in artisanal mining operations for a formalization approach to succeed. For example, the benefits to miners of registering and acquiring title must outweigh the cost of registering and seeking a license, paying taxes or royalties, and complying with environmental and other requirements. Regulators, mining companies, and the public should also have an interest in the formalization of miners, and this interest should outweigh any costs that formalization might impose on them (although it is not clear what form these costs would justifiably even take). Some incentives that formalization can bring to other parties include the capturing of taxes or royalties that are currently being lost by the federal government; the availability of skilled workers for employment by mining companies (while Nigeria has relatively few large companies right now, this number is likely to increase); reduced environmental and public health harms to the public; fewer conflicts with mining companies, miners, and communities over land access and other issues; and, if revenues are managed properly, stronger economic development for communities, states, and the national economy. Second, formal title in the form of a mining license is a critical element of safer mining practices. Currently, relatively few miners hold title to the land on which they are working. Often, title has already been acquired by another party or parties, or miners do not know how to (or have not been able to) obtain a small-scale mining lease. While the absence of title does not prevent artisanal miners from carrying out their mining activities, it can lead to conflicts with landowners and discourage miners from investing in improved technologies or practices. It also means that miners cannot use their land as collateral to secure formal credit, an important means of obtaining new technology and scaling up mining operations even if the mechanisms for accessing formal credit are not yet in place in Nigeria. Third, the focus on lead contamination should not detract from the issue of mercury use in gold processing, as both lead and mercury exposure pose serious risks to public health and the environment. Fifth, the Nigerian government is taking a number of positive steps with respect to some of these areas (note that this paper does not address the remediation and treatment efforts related to lead poisoning). In addition, it is taking steps to enforce some of its existing legal authorities, such as the use it or lose it provision governing mineral titles, to free up lands for artisanal miners. While these and other initiatives are helping to pave the way for greater formalization of artisanal miners, the recommendations focus on remaining gaps in the legal, regulatory, and policy framework. In light of these considerations, the recommendations presented below can be grouped under four principal themes. These themes can help inform the process of designing and implementing changes to the legal and policy framework as well as the institutional and financial backdrop. Although the Mining Act and Regulations include a number of incentives to attract larger investors, there has been no large-scale gold rush in Nigeria by larger mining companies at this level so far. In the meantime, artisanal miners are extracting and processing gold using dangerous methods, without sufficient 29 access to land, equipment, and financing, while their revenues are going untaxed. The Minerals and Mining Act and Mining Regulations only briefly address the needs of artisanal miners, primarily by requiring miners to form cooperatives in order to access extension services. The legal and policy recommendations presented below are intended to enable and encourage formalization of artisanal miners by focusing primarily on licensing and the related issues of access to land and organization into mining cooperatives or other associations. Priority 1: Address the Cooperative Barrier the Challenge: Under the Minerals and Mining Act and Regulations, artisanal miners are strongly encouraged, and in some cases required, to form a cooperative in order to proceed with their activities. Miners must be part of a registered cooperative in order to receive extension 158 services from the Ministry, and while both individuals and cooperatives are allowed to apply for a small-scale mining lease, the Ministry holds the view that the only way for artisanal miners to obtain such a lease is through a registered cooperative. The requirements for forming a cooperative are specific to each state, but commonly include the preparation of bylaws and payment of a registration fee, among other things. These dual registration requirements impose financial and time-consuming burdens that are difficult for many miners to meet. For example, in Zamfara, the State Ministry of Rural Development and Cooperatives is supposed to register artisanal miners, but in reality, it is the State Ministry of Environment and Solid Minerals that is helping the miners to form cooperatives. As such, groups of miners who might wish to form a cooperative do not necessarily know whom to contact for help with the process. The most commonly articulated justification for the cooperative requirement is that artisanal miners are numerous, unorganized, and highly mobile, thus making it impossible to regulate them as individuals. However, field visits suggest that many artisanal miners have already organized themselves by processing task and/or other means of labor division, with large mining sites functioning in what appears to be a fairly regularized manner. In some cases, this might even be a more effective approach, as mining cooperatives are sometimes composed of arbitrarily-formed groups that might not have chosen to work together. Moreover, with a minimum requirement of 10 persons, it is not clear how large mining processing groups should break themselves down into cooperatives. In Bagega, where hundreds of miners work together, a single large cooperative apparently exists, but field interviews indicated at least some of the miners had no idea they belonged to one. Given the collective nature of artisanal mining activities, it makes sense for miners to work together in groups and for the legal framework to recognize such groups. Indeed, there are a number of benefits to combining resources and efforts, and where cooperatives or other organized groups can enhance this approach, they should be promoted. For example, members of the mining cooperative in Bagega explained that they were motivated to form one when they saw how another cooperative helped one of its members who had fallen ill. Cooperatives and other recognized mining associations should constitute a path towards formalization, not a barrier that serves to prevent it. This might best be achieved by encouraging rather than requiring miners to form cooperatives, as well as by providing assistance to miners to form such groups. Ideally, miners would have a choice as to whether or not to join a cooperative, and the legal framework would allow individual miners to seek an artisanal mining license (discussed in more detail under Priority 3) under appropriate circumstances. Overview of Recommendations Incentives and assistance are needed to help miners form cooperatives or other (potential) legally recognized groups. Greater focus should also be placed on streamlining and decentralizing the cooperative requirements as much as possible. Gold produced outside of a cooperative would not be eligible for purchase by the government. Address the Cooperative Barrier: Short-Term Recommendations a) Determine who should be registering artisanal miners in each state, either alone or working together with other entities. Priority 2: Strengthen Access to Land the Challenge: Many miners do not hold title (in the form of a Small-Scale Mining Lease) to the lands where they are working to extract gold-containing ore. This may be because they do not know how to obtain a mining lease, they lack the resources to obtain a lease, or because title to the land in question is already held by somebody else. A lack of formal title can discourage artisanal miners from making longer-term investments to improve their mining activities, without 160 the assurance that they can recover their investment. It also means that miners cannot use the land on which they are working to secure credit for obtaining new tools and developing improved technologies. Nor do they have the security of knowing they can continue to mine in a given location for a specific length of time. In Ghana, the lack of available land has been tied to the reluctance of artisanal miners to register, even under a strengthened legal framework, and the 161 resulting expansion of the informal artisanal gold mining economy. Many mineral deposits lie on lands that have been formally registered to titleholders (predominantly small and medium-scale operators, as Nigeria has few 162 large-scale gold mining operators at present). This creates a significant problem of access for artisanal miners, and can lead to conflicts with the license holders. Moreover, although applicants for mineral titles on private land are required to obtain consent from the owner or occupier of the land, such consent is not always lawfully obtained. In some cases, mining companies are alleged to have collaborated with traditional rulers to take title to lands. This set of recommendations addresses access-to-land challenges where title to mineral lands is already held, or is in the process of being obtained, by another party. The recommendations focus on finding creative ways to give artisanal and 33 small-scale miners access to titled lands, as well as how to improve accountability in the licensing process for mining companies and landowners. There is a sizable body of research on how to improve the often-tense relations between artisanal 163 miners and larger companies, with continued development of best practices and approaches. With few large-scale gold mining operators to date, Nigeria still has a chance to develop a model for engagement that could set a standard for addressing this problem going forward. Experiences from a number of countries reflect the potential benefits that can result when companies engage artisanal miners in a non-confrontational manner. At the same time, issues of mistrust remain and an effective model of how large-scale companies can work with artisanal miners proactively (rather than simply co-existing) has yet to be developed. In the meantime, examples of efforts to bridge the divide between these two groups include: In Mongolia, the establishment and institutionalization of multi-stakeholder councils consisting of mining companies, artisanal miners, and local governments and communities has facilitated dialogue on issues such as mitigation of negative environmental impacts, reducing conflict between stakeholders, and sharing responsible 164 mining practices. This initiative led to the creation of Tembo mine in Geita, now owned by the Canadian company Tembo 167 Gold Corp, which is pursuing a strategy for a community development partnership. Overview of Recommendations the first set of recommendations focuses on bringing mining companies and artisanal miners together to reach an agreement or arrangement regarding access to titled land. Typically, the area ceded consists of a plot of land with marginal deposits of little use to larger operators but that can be effectively mined using artisanal techniques; however, artisanal miners should not necessarily be restricted to low-grade deposit areas under this approach. The strategy of ceding a portion of land should be encouraged particularly for larger titleholders, whose 170 concession areas may take up more space than needed for actual mining operations. This approach is preferable because the miners would receive full rights to the land and to the activities they conduct on it, and could choose to apply for a small-scale mining lease. Incentives in the form of tax benefits could be used to encourage title holders to cede land to artisanal miners; other advantages include fewer conflicts over access to mineral deposits on concession areas. Because artisanal miners would be responsible for paying royalties on gold produced on ceded lands, there is also an incentive for the government to facilitate this type of arrangement. In Zamfara, the Ministry of Environment and Solid Minerals is said to be helping miners negotiate with landowners for mineral titles. If the title holder is not willing to sever a portion of its land for the miners, the holder can still negotiate an agreement with artisanal miners to give them access to marginal land on its concession. Often, such an agreement gives miners access to marginal lands that are of little use to the mining companies, while helping companies avoid conflicts with artisanal miners. As described above, this approach has been used successfully in Mongolia and Ghana. Reportedly in Nigeria, the company Savannah Gold has executed a Memorandum of Agreement with local miners in Kebbi State. The federal government can use such agreements to collect royalties (via the mineral title holder) from artisanal miners, which it is not currently capturing.
Recently best herbal erectile dysfunction pills purchase 20mg levitra oral jelly fast delivery, a large Chinese randomised-controlled trial of circumcision combined with a triple oral therapy (ciprofloxacin erectile dysfunction treatment aids quality 20 mg levitra oral jelly, ibuprofen erectile dysfunction diabetes causes levitra oral jelly 20mg online, tamsulosin) vs erectile dysfunction treatment garlic buy levitra oral jelly 20 mg online. However impotence pills for men purchase levitra oral jelly discount, despite a large cohort erectile dysfunction medications and drugs order levitra oral jelly line, the study results are questionable because of the weak theoretical background erectile dysfunction zyprexa buy levitra oral jelly 20mg without a prescription, and a potential large placebo effect lacking a sham control impotence under hindu marriage act discount levitra oral jelly 20 mg visa. Before having an impact on recommendations, the results of this study have to be independently confirmed and the treatment effect must persist. Testicular Pain Syndrome Microsurgical denervation of the spermatic can be offered to patients with testicular pain. In a long term follow up study, patients who had a positive result on blocking the spermatic cord were found to have a good result following denervation [496]. An early scar excision before three to six months after pain onset was associated with better pain relief. Adhesiolysis is still in discussion in the pain management after laparotomy/laparascopy for different surgical indications in the pelvis and entire abdomen. A recent study has shown, that adhesiolysis is associated with an increased risk of operative complications, and additional operations and increased health care costs as compared to laparoscopy alone [498]. One trial comparing two forms of laser reported good results, but did not compare with sham treatment [500]. The majority of publications on treatment of urethral pain syndrome have come from psychologists [189]. In patients with adenomyosis, the only curative surgery is hysterectomy but patients can benefit from hormonal therapy and analgesics (see 5. Pudendal Neuralgia and surgery Decompression of an entrapped or injured nerve is a routine approach and probably should apply to the pudendal nerve as it applies to all other nerves. There are several approaches and the approach of choice probably depends upon the nature of the pathology. The most traditional approach is transgluteal; however, a transperineal approach may be an alternative, particularly if the nerve damage is thought to be related to previous pelvic surgery [196, 263, 505-509]. This study suggests that, if the patient has had the pain for less than six years, 66% of patients will see some improvement with surgery (compared to 40% if the pain has been present for more than six years). On talking to patients that have undergone surgery, providing the diagnosis was clear-cut; most patients are grateful to have undergone surgery but many still have symptoms that need management. These techniques are only used as part of a broader management plan and require regular follow-up. These are expensive interventional techniques for patients refractory to other therapies. There has been growing evidence in small case series or pilot studies, but more detailed research is required [511]. Its role in overactive bladder and faecal incontinence is more robust but is limited for pain. Over 90% of patients treated with neuromodulation stated that they would undergo implantation again [512]. Long-term results were verified in a retrospective study of patients from 1994 to 2008 [513]. The most frequent reason for explantation was poor outcome (54% of the failed patients). In a study of women who underwent permanent device implantation from 2002 to 2004 [465], mean pre /post operative pelvic pain and urgency/frequency scores were 21. Pudendal Neuralgia Pudendal neuralgia represents a peripheral nerve injury and as such should respond to neuromodulation by implanted pulse generators. However, it is important that the stimulation is perceived in the same site as the perceived pain. There is limited experience with sacral root stimulation and as a result stimulation for pudendal neuralgia should only be undertaken in specialised centres and in centres that can provide multi-disciplinary care [514-517]. Chronic Anal Pain Syndrome In a large cohort of 170 patients with functional anorectal pain from the St. Sacral neuromodulation has been reported to be somewhat beneficial in two uncontrolled studies, showing improvement in about half the patients [518, 519]. Martellucci et al have evaluated sacral neuromodulation in 27 patients, including 18 patients with previous pelvic surgery. Sixteen patients (59%) responded to testing and had a definitive implantation with long-term follow-up of 37 months with sustained response, while no patients after stapler surgery responded to neuromodulation [519]. Textbooks have been written on the subject and practitioners using them should be trained in appropriate patient selection, indications, risks and benefits. Many such interventions also require understanding and expertise in using imaging techniques to perform the blocks accurately. Diagnostic blocks can be difficult to interpret due to the complex mechanisms underlying the painful condition or syndrome. There is a weak evidence base for these interventions for chronic non-malignant pain [521]. First, an injection of local anaesthetic and steroid at the sight of nerve injury may produce a therapeutic action. The possible reasons for this are related to the fact that steroids may reduce any inflammation and swelling at the site of nerve irritation, but also because steroids may block sodium channels and reduce irritable firing from the nerve [522]. It has already been indicated that when the pudendal nerve is injured there are several sites where this may occur. Differential block of the pudendal nerve helps to provide information in relation to the site where the nerve may be trapped [261-271]. As well as injecting around the pudendal nerve, specific blocks of other nerves arising from the pelvis may be performed. Strong Offer oral pentosane polysulphate plus subcutaneous heparin in low responders to Weak pentosane polysulphate alone. Administer intravesical lidocaine plus sodium bicarbonate prior to more invasive methods. Weak Administer intravesical pentosane polysulphate before more invasive treatment alone or Strong combined with oral pentosane polysulphate. Do open instead of laparoscopic inguinal hernia repair, to reduce the risk of scrotal pain. Strong In patients with testicular pain improving after spermatic block, offer microsurgical Weak denervation of the spermatic cord. All other gynaecological conditions (including dysmenorrhea, obstetric injury, pelvic organ prolapse 3 and gynaecological malignancy) can be treated effectively using pharmacotherapy. Recommendations Strength rating Involve a gynaecologist to provide therapeutic options such as hormonal therapy or Strong surgery in well-defined disease states. Provide a multi-disciplinary approach to pain management in persistent disease states. Strong Offer botulinum toxin type A and electrogalvanic stimulation in chronic anal pain Strong syndrome. Offer pelvic floor muscle therapy as part of the treatment plan to improve quality of life Weak and sexual function. Weak Offer biofeedback as therapy adjuvant to muscle exercises, in patients with anal pain due Strong to an overactive pelvic floor. The decision to instigate long-term opioid therapy should be made by an appropriately Strong trained specialist in consultation with the patient and their family doctor. Where there is a history or suspicion of drug abuse, involve a psychiatrist or psychologist Strong with an interest in pain management and drug addiction. First evaluation should take place after about six weeks to see if the treatment has been successful or not. Ask the patient if they have taken the medication according to the prescription, if there were any side effects and if there were any changes in pain and function. Another important thing to do is to read the reports of other caregivers like the physiotherapist and the psychologist. Has the therapy been followed until the end, what was the opinion of the therapist about the changes that were observed In cases where the sessions had been ended by the patient, ask the patient why they made that decision. Check if the patient has understood the idea behind the therapy that was prematurely stopped. Unfortunately, the terminology used to describe the nature and specialisation level of centres providing specialised care for visceral pain patients is not standardised and country-based. It is advised that patients are referred to a centre that is working with a multi-disciplinary team and nationally recognised as specialised in pelvic pain. Such a centre will re-evaluate what has been done and when available, provide specialised care. They will need to manage their pain, meaning that they will have to find a way to deal with the impact of their pain on daily activities in all domains of life. The patient may also benefit from shared care, which means that a caregiver is available for supporting the self-management strategies. Together with this caregiver the patient can optimise and use the management strategies. If the patient feels the same pain again, it helps to start at an early stage with the self-management strategies that he/she has learned during the former treatment. By doing so they will have the best chance of preventing the development of pelvic pain syndromes again. Clinical phenotyping of patients with chronic prostatitis/chronic pelvic pain syndrome and correlation with symptom severity. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Chronic pelvic pain in women of reproductive and post-reproductive age: a population-based study. Non-urological syndromes and severity of urological pain symptoms: Baseline evaluation of the national institutes of health multidisciplinary approach to pelvic pain study. Increased risks of healthcare-seeking behaviors of anxiety, depression and insomnia among patients with bladder pain syndrome/interstitial cystitis: a nationwide population based study. Patient beliefs about pain diagnosis in chronic pelvic pain: relation to pain experience, mood and disability. Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome. Endometriosis is associated with central sensitization: a psychophysical controlled study. The community prevalence of chronic pelvic pain in women and associated illness behaviour. Attitudes of women with chronic pelvic pain to the gynaecological consultation: a qualitative study. Catastrophizing: A predictor of persistent pain among women with endometriosis at 1 year. Depressive disorders and panic attacks in women with bladder pain syndrome/ interstitial cystitis: a population-based sample. Association between chronic prostatitis/chronic pelvic pain syndrome and anxiety disorder: a population-based study. Sexual functioning in women reporting a history of child sexual abuse: review of the empirical literature and clinical implications. Trauma and medically unexplained symptoms towards an integration of cognitive and neuro-biological accounts. Childhood sexual trauma in women with interstitial cystitis/bladder pain syndrome: a case control study. Sexual abuse and lifetime diagnosis of somatic disorders: a systematic review and meta-analysis. Sexual abuse history: prevalence, health effects, mediators, and psychological treatment. The association of abuse and symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome: results from the Boston Area Community Health survey. Understanding inflammatory pain: ion channels contributing to acute and chronic nociception. Prevalence and impact of bacteriuria and/or urinary tract infection in interstitial cystitis/painful bladder syndrome. Sexual functioning, catastrophizing, depression, and pain, as predictors of quality of life in women with interstitial cystitis/painful bladder syndrome. Catastrophizing and pain-contingent rest predict patient adjustment in men with chronic prostatitis/chronic pelvic pain syndrome. An Exploratory Study into Objective and Reported Characteristics of Neuropathic Pain in Women with Chronic Pelvic Pain. A new classification is needed for pelvic pain syndromes-are existing terminologies of spurious diagnostic authority bad for patients Urogenital pain-time to accept a new approach to phenotyping and, as a consequence, management. Bladder Pain Syndrome Committee of the International Consultation on Incontinence. Identification of diagnostic subtypes of chronic pelvic pain and how subtypes differ in health status and trauma history. Depression and Posttraumatic Stress Disorder Among Women with Vulvodynia: Evidence from the Population-Based Woman to Woman Health Study. Associations Between Penetration Cognitions, Genital Pain, and Sexual Well being in Women with Provoked Vestibulodynia. Psychological factors and chronic pelvic pain in women: a comparative study with women with chronic migraine headaches. Qualitative research as the basis for a biopsychosocial approach to women with chronic pelvic pain. Long-term results and complications of augmentation ileocystoplasty for idiopathic urge incontinence in women. Neurological factors in chronic pelvic pain: trigger points and the abdominal pelvic pain syndrome. Overlap of different urological symptom complexes in a racially and ethnically diverse, community-based population of men and women. Low agreement between previous physician diagnosed prostatitis and national institutes of health chronic prostatitis symptom index pain measures. Epidemiology of prostatitis in Finnish men: a population-based cross-sectional study. Interstitial cystitis in the Netherlands: prevalence, diagnostic criteria and therapeutic preferences. Chronic pelvic pain of bladder origin: epidemiology, pathogenesis and quality of life. Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland. Incidence of physician-diagnosed interstitial cystitis in Olmsted County: a community-based study. Prevalence and correlates for interstitial cystitis symptoms in women participating in a health screening project. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. Prevalence and correlates of painful bladder syndrome symptoms in Fuzhou Chinese women. Discrimination between the ulcerous and the nonulcerous forms of interstitial cystitis by noninvasive findings. Interstitial cystitis: clinical manifestations and diagnostic criteria in over 200 cases. Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. Adverse impact of sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome. Prevalence, incidence estimation, risk factors and characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter case-control observational study. Prevalence of premature ejaculation in Turkish men with chronic pelvic pain syndrome. Fears, sexual disturbances and personality features in men with prostatitis: a population-based cross-sectional study in Finland. Acute bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: andrological implications. Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial. Sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome: improvement after trigger point release and paradoxical relaxation training. Prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome. The prevalence of chronic pelvic pain in women in the United Kingdom: a systematic review. Chronic pelvic pain in women in New Zealand: comparative well-being, comorbidity, and impact on work and other activities. Prevalence and correlates of three types of pelvic pain in a nationally representative sample of Australian women. The prevalence of sexual dysfunction and associated risk factors in women with chronic pelvic pain: a cross-sectional study. Sexual behavior and findings on laparoscopy or laparotomy in women with severe chronic pelvic pain. Pelvic floor muscle dysfunctions are prevalent in female chronic pelvic pain: A cross-sectional population-based study. Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levator ani syndrome.
The Efficacy of Stroke Care There is level 1a evidence that overall erectile dysfunction radiation treatment buy generic levitra oral jelly 20 mg on line, specialized stroke care is associated with reductions in the odds of mortality erectile dysfunction protocol guide order levitra oral jelly visa, the combined outcome of death or dependency erectile dysfunction suction pump cheap 20mg levitra oral jelly with visa, the need for institutionalization and the length of hospital stay impotence pills for men cheap levitra oral jelly online american express. The Elements of Stroke Rehabilitation Care Pathways in Stroke Rehabilitation There is conflicting evidence as to whether stroke care pathways improve rehabilitation outcomes age related erectile dysfunction causes safe levitra oral jelly 20 mg. Timing to Stroke Rehabilitation There is level 1a evidence that earlier admission to rehabilitation results in improved overall functional outcomes erectile dysfunction lubricant order cheap levitra oral jelly on-line. There is level 1a evidence that the amount of therapy needed to result in a significant improvement in motor outcomes is 17 hours of physiotherapy and occupational therapy over a 10 week period of time erectile dysfunction vasectomy levitra oral jelly 20mg low price. Intensity of Language Therapy There is conflicting evidence that greater evidence of aphasia therapy results in improved language outcomes erectile dysfunction medication patents cheap 20 mg levitra oral jelly amex. Durability of Rehabilitation Gains There is level 1a evidence that relatively greater functional improvements are made by patients rehabilitated on specialized stroke units when compared to general medical units and the effects are maintained over both the short-term and long-term. There is level 1a evidence that functional outcomes achieved through stroke rehabilitation are maintained and actually improve for up to one year. There is level 1b evidence that by five years post-stroke functional outcomes plateau and may decline. By ten years, overall functional outcome scores significantly decline although it is unclear to what extent the natural aging process and comorbidity may contribute to these declines. Outpatient Stroke Rehabilitation Early Supported Discharge There is level 1a evidence that stroke patients with mild to moderate disability, discharged early from an acute hospital unit, can be rehabilitated in the community by an interdisciplinary stroke rehabilitation team and attain similar or superior functional outcomes when compared to patients receiving in-patient rehabilitation. There is level 1a evidence that the cost associated with early-supported discharge is lower when compared to usual care; however, savings are generally not dramatic or consistent across the studies. There is conflicting level 1b evidence that treatment of patients using an accelerated protocol in an emergency department observation unit results in shorter lengths of stay and reduced costs, but does not result in an improved risk for stroke when compared to inpatient admission for transient ischemic attack. There is level 1a evidence that personalized secondary preventative care management programs may not improve risk factor management. There is level 1b and level 2 evidence that a pharmacist-led educational intervention, a stroke prevention group workshop or post-discharge management of risk factors conducted using a model of shared care may improve long-term benefits in terms of blood pressure reduction, reduced lipid levels, reduced body mass and increased physical activity. There is level 1b evidence that recording stroke-related events with an electronic support tool or pharmacist-led care management with direct prescription of medication (versus nurse-led management) may not improve stroke or cardiovascular risk management. Hypertension There is level 1a evidence that incidence of cardiovascular events, fatal or nonfatal stroke and mortality were reduced by commonly used antihypertensive agents. There is level 1b evidence that a reduction in blood pressure is associated with a decreased risk of stroke particularly among patients with a previous history of intracerebral haemorrhage. There is level 1a evidence that diuretics at high doses, diuretics at low doses. There is level 1a evidence that a composite of stroke, coronary heart disease, and heart failure can be significantly lowered by diuretics deliveredd at high and low doses. There is level 1a evidence that cardiovascular death can be significantly reduce by Thiazides at low doses, calcium antagonists, and centrally acting drugs, while all-cause mortality can only be significantly reduced by the use of low dose Indapamide and calcium antagonist, when compared to control therapy. There is level 1b evidence that chlorthalidone (diuretic) may be superior to both doxazosin ( adrenergic blocker) for stroke and cardiovascular risk management. Management of Diabetes and Associated Macrovascular Complications There is level 1a and level 1b evidence that pioglitazone may not be associated with a relative reduction in the risk of stroke; however, it may be effective at lowering the composite risk of stroke, myocardial infarction, and death. There is level 1b evidence that in patients with no history of previous stroke, pioglitazone was not effective at reducing the risk of stroke however, in patients with a history of stroke, the use of pioglitazone was associated with a reduction in the risk of a recurrent stroke. There is level 1a evidence that intense glucose lowering therapy is not significantly different than standard therapy for reducing the risk of stroke. Intensive glucose lowering therapy may only be an effective treatment for type 2 diabetes and for patients with a history of macrovascular events. There is level 1b evidence that empagliflozin was not significantly different than placebo therapy at reducing the relative risk of stroke; however, more research is needed to identify the mechanism of action of metformin and potential benefits on cardiovascular health. There is level 1a evidence that metformin has no additional benefits on cardiovascular health other than reducing blood glucose levels for the treatment of type 2 diabetes. There is level 1a evidence that treatment of hypertension in diabetic patients reduces the risk of stroke. Furthermore, tighter control of blood pressure is associated with greater reduction of risk for stroke Executive Summary (17th Edition) pg. Use of this amlodipine may be associated with increased risk for hospitalization due to heart failure. There is level 1a evidence that all hypertensive medications reduce the risk of stroke, especially among patients with diabetes. There is conflicting level 1b evidence regarding the effectiveness of pravastatin for the prevention of stroke and composite endpoints of coronary and cardiac complications. There is conflicting level 1b evidence regarding the efficacy of atorvastatin in the secondary prevention of stroke and cardiovascular complications. There is level 1b evidence that simvastatin may reduce the odds of stroke as well as the incidence of major coronary and atherosclerotic events when compared to placebo. There is level 1b evidence that a structured care intervention for hyperlipidemia using atorvastatin and strict implementation of guidelines may decrease mortality, coronary morbidity and incidence of stroke versus usual care. There is level 1a evidence that statin treatment in patients with diabetes may reduce the risk of stroke; however, in patients with diabetes and existing coronary heart disease, statin treatments only reduced the risk of subsequent coronary heart disease but not stroke. There is level 1a evidence that fibrate treatment may not reduce the risk of stroke or coronary events. There is conflicting level 1b evidence regarding the effect of gemfibrozil on lowering the risk of stroke in patients with diabetes. There is level 1a evidence that fenofibrate and simvastatin combination therapy or fenofibrate treatment alone may not be more efficacious in the prevention of stroke and cardiovascular events when compared to simvastatin monotherapy or placebo. Additional level 1b evidence suggests that unaccompanied fenofibrate administration may decrease the risk of nonfatal myocardial infarction. Hyperlipidemia There is level 1a evidence that statin therapy is effective at lowering the risk of further strokes however, it may not reduce the risk of intracerebral hemorrhage. There is level 1a evidence that intensive statin therapy may be more effective than less intense therapy in reducing risk for ischemic stroke events. There is level 1a evidence that statin therapy may not reduce stroke-related mortality, however the evidence is unclear regarding its effects on all-cause mortality. There is level 1b evidence that withdrawal of statin treatment at the time of acute stroke is associated with increased risk for death and dependency when compared to continuous statin use. There is level 1b evidence that pre-treatment with atorvastatin may not improve ischemic or haemorrhagic stroke outcome when compared to placebo. There is level 2 and level 3 evidence that pre-stroke treatment with statins may improve functional disability on the Barthel Index but may not improve stroke severity on the National Institutes of Health Stroke Scale when compared to no statin pre-treatment. Conflicting level 2 and level 3 evidence suggests no consistent data for functional independence on the Modified Rankin Scale or mortality up to 6 months. Macrolide Antibiotics the Prevention of Cardiovascular Events There is level 1a and level 1b evidence that azithromycin or roxithromycin (macrolide antibiotic) may not decrease the incidence of cardiovascular events Lifestyle Modification There is level 1a evidence that engaging in physical activity is associated with substantial benefits in terms of a reduced risk for stroke and cardiovascular disease. Conflicting level 1a evidence from a meta-analyses of 10 cohort studies suggests that this relationship may only be significant for men. There is level 1a evidence that moderate to high levels of leisure and occupational activity may be beneficial for a reduced rate of cardiovascular disease compared to low level exercise. There is level 1b evidence that a detailed, personalized activity program with regular verbal instruction and encouragement does not effectively increase level of physical activity when compared to the provision of basic information regarding physical activity and no training program. There is level 1a evidence that low-fat, low-cholesterol diets rich in fruits, vegetables and low-fat dairy products are effective in reducing blood pressure when compared to control diets low in fruits and vegetables, and with average fat content. There is level 1a evidence that Mediterranean type diets (rich in whole grains, fruits, vegetables, legumes, walnuts, almonds and alpha-linolenic acid) may improve blood pressure and reduce risk of cardiovascular events including stroke when compared to a prudent type diet. There is level 1a evidence that the use of vitamin C and vitamin E together may reduce atherosclerotic progression. There is conflicting level 1b evidence suggesting variable efficacy of daily antioxidant vitamins (vitamin E, vitamin C and carotene) when used alone on clinical cardiovascular endpoints including stroke, and mortality. Additional level 1b evidence suggests a beneficial effect of combinatorial therapy with ascorbic acid (vitamin C) and vitamin E on stroke risk. There is conflicting level 1a evidence regarding the effect of B-vitamins (folic acid, vitamin B6 and B12) on cardiovascular outcome or risk of stroke. There is level 1a evidence that supplementation with folic acid and vitamins B6 and B12 is associated with significant reductions in plasma homocysteine levels (tHcy) up to one year from baseline. There is level 1b evidence that folic acid alone may have no effect on a combined cardiovascular outcome when compared to standard care. There is level 1b evidence that high dose vitamin B therapy concurrent with antiplatelets may increase risk of stroke versus low dose therapy. There may be no effect on incidence of stroke or a cardiovascular composite endpoint among patients not supplementing vitamin therapy with antiplatelets. There is level 1b evidence that homocysteine-lowering therapy with B-vitamins may not improve the risk of recurrent stroke, stroke severity or functional outcome when compared to placebo. There is level 1b evidence that high dose homocysteine-lowering therapy may improve risk of stroke, myocardial infarction or death in patients 67 years old versus low dose treatment. There is level 1a evidence that smoking or exposure to environmental tobacco smoke may increase risk of stroke in a dose-dependent manner. There is level 1b evidence that an intensive smoking cessation program providing a period of counselling and support may be as effective as a minimal intervention providing a single 30-minute session of counselling only. There is level 1a evidence that light (1-2 drinks per day) alcohol consumption reduces the risk for ischemic stroke while heavy drinking (>5 drinks per day) and binge-drinking increase the risk of haemorrhagic stroke in a linear dose-dependent fashion. There is level 1b evidence that a multi-factorial behavioural intervention focussing on eating habits and smoking cessation may substantially improve smoking cessation, mortality, and serum cholesterol and glucose concentrations, and reduce the risk of cardiovascular events. There is level 1b evidence that a program of e-counselling that promotes self-directed lifestyle change in the area of diet, exercise and smoking cessation may be associated with reductions in systolic blood pressure and total cholesterol. There is level 1a evidence that treatment with clopidogrel may be as effective as ticlopidine in terms of prevention of secondary vascular events, including stroke. There is level 1a evidence that treatment with ticlopidine may be associated with a significantly greater risk for adverse events, including hepatic dysfunction, than clopidogrel. There is level 1a evidence suggesting that cilostazol is superior to aspirin monotherapy in reducing the risk of recurrent stroke and hemorrhagic events however, it is unclear whether its use results in an increased risk of gastrointestinal bleeds. There is level 1b evidence that major bleeding events are more common among patients using aspirin monotherapy compared to those using a combination therapy consisting of aspirin, clopidogrel, and dipyridamole. Anticoagulants There is level 1a evidence that treatment with oral anticoagulant therapy of moderate intensity is not superior to antiplatelet therapy in preventing death, recurrent ischemic stroke or myocardial infarction however, it may result in a greater risk for bleeding. Atrial Fibrilation There is level 1a evidence that the use of anti-coagulation therapy, particularly with adjusted dose warfarin, may substantially reduce the risk of primary and secondary stroke in individuals with atrial fibrillation. Risk for major bleeding events with dual therapy may be similar to that reported for oral anticoagulation with vitamin-K antagonists. Alternative Therapies There is level 1b evidence that Indobufen may be as effective as warfarin, but is associated with a reduced risk of bleeding events. There is level 1a evidence that treatment with the direct thrombin inhibitor ximelagatran/melagatran may not be inferior to treatment with warfarin. Ximelagatran treatment is associated with risk for liver injury and due to concerns with safety, it has been withdrawn from the market and its development terminated. There is level 1a evidence that a dabigatran may be more effective in preventing stroke than warfarin. The risk or mortality is comparable amongst the two doses and based on a composite of major ischemic, hemorrhagic, and fatal events, both doses demonstrate a similar net clinical benefit. Treatment with rivaroxaban may also be associated with less risk for intracranial bleeding when compared with dose-adjusted warfarin. There is level 1b evidence that treatment with apixaban may be associated with reduced risk for death from any cause and for major bleeding events when compared to treatment with dose-adjusted warfarin. Drug Management There is level 1a evidence that the use of patient decision aids may be associated with an increase in patient knowledge and a decrease in uncertainty regarding treatment. There is level 2 evidence that incorporating narrative information in the form of patient anecdotes may help increase patient knowledge and belief in the importance of laboratory testing. There is level 1b evidence that, among high risk patients with atrial fibrillation, use of patient aids may be associated with a temporary increase in the use of appropriate warfarin-based therapy. There is level 1a evidence that self-management programs are associated with a reduced risk of thromboembolic events and mortality. However, these programmes are more likely to be feasible for a small, select group of patients only. There is level 1a evidence that self-testing and self-management programmes may not be associated with increased risk of bleeding events. There is level 2 evidence suggesting that a coordinated, multidisciplinary approach may result in improved adherence to specific targeted guidelines. Carotid Endarterectomy There is level 1a evidence that carotid endarterectomy may be an effective procedure to reduce the risk of stroke in individuals with symptomatic carotid artery stenosis of 70-99%. There is level 1a evidence that carotid endarterectomy may be an effective procedure to reduce the risk of stroke in individuals with asymptomatic carotid artery stenosis of 60% however, the operative risks associated with the procedure outweigh the benefit if they exceed 3%. Current guidelines do not recommend regular revascularization in asymptomatic patients. There is level 1b evidence that nursing-led coordinated case management may be associated with short term improvements in knowledge of stroke warning signs and self-reported lifestyle and dietary changes. Mobility and the Lower Extremity Restorative and Compensatory Rehabilitation There is level 1a evidence that Motor Learning and Bobath may improve motor recovery but they are not superior to one another. Intensity of Training There is level 1a and limited level 2 evidence that early intensive therapy may improve gait and general motor function. There is conflicting level 1a evidence regarding the effect of augmented physical therapy on gait at follow-up. Balance Disorders There is level 1a evidence that whole body and local vibration training programs may not improve balance or gait. There is level 1a evidence that trunk-specific training may improve balance outcomes. There is conflicting level 2 evidence regarding the effect of virtual reality balance training on gait and balance outcomes. There is level 1a and level 2 evidence that feedback training may not improve balance or motor function of the lower limb. Falls Prevention Training There is level 1a evidence that exercise-based falls prevention programs may not reduce the rate of falls following stroke. Task-Specific Training There is level 1b and limited level 2 evidence that sit-to-stand training may not improve balance or strength of the impaired lower limb when compared to conventional therapy. There is level 1a and limited level 2 evidence that resistive/strength task-oriented training may improve gait, cadence and lower limb mobility; however, it may not be beneficial for improving balance. There is level 1a and level 2 evidence that partial body weight support treadmill training may not improve gait or balance outcomes compared to conventional or other gait training interventions. Virtual Reality Training There is level 1a and limited level 2 evidence that virtual reality combined with treadmill training may improve gait and balance post stroke. There is level 1a and level 2 evidence that virtual reality-based interventions compared to conventional therapy may improve balance; however evidence is conflicting for gait outcomes. Auditory and Visual Feedback There is level 1a and level 2 that auditory feedback may improve gait and muscle activity. There is limited and conflicting level 1a and level 2 evidence regarding the effect of visual feedback on balance and gait. Bilateral leg Training There is level 1b evidence that that bilateral leg training with a custom-made device may not improve lower limb motor function. Motor Imagery/ Mental Practice There is level 1b evidence that mirror therapy combined with repetitive transcranial magnetic stimulation may improve balance. There is level 1b evidence that mirror therapy compared to conventional therapy may not improve balance or gait outcomes. There is level 1a and limited level 2 evidence that mental practice/motor imagery may improve gait and balance outcomes. Hippotherapy There is level 1a and level 2 evidence that hippotherapy may not improve gait outcomes; however there may be an improvement on foot pressure. Rhythmic Auditory Stimulation There is level 1a and level 2 evidence that rhythmic auditory stimulation training may improve gait and balance outcomes; however there is limited evidence for its effect on ankle range of motion. Self-Management Programs There is level 1a evidence that self-management programs may not improve gait and balance. Caregiver Mediated Programs There is level 1b evidence that caregiver mediated programs may improve gait and balance outcomes. There is Level 1a evidence that progressive resistance training may improve strength and knee extension but may not gait. There is level 1b evidence that eccentric resistance training may result in greater muscle activation compared to concentric resistance training but may not improve gait speed. Cardiovascular Training There is level 1a evidence that cardiovascular fitness, aquatic therapy, and mobility training programs may improve gait. There is level 1b evidence that home-based cardiovascular exercise programs may also improve gait outcomes. There is level 1b and level 2 evidence that cycling training interventions may not improve gait. There is conflicting level 1a evidence regarding supervised exercise training programs compared to unsupervised programs on gait. There is level 1b and limited level 2 evidence that community or outpatient exercise programs may improve mobility, lower limb strength and flexibility. There is level 1b evidence that high-intensity circuit training may not improve balance when compared to low-intensity circuit training. There is limited level 2 evidence that walking exercises on stairs compared to flat surfaces may improve balance post-stroke. Canes and Walking Aids There is level 1b and level 2 evidence that quad canes or walkers are significantly better than a one point cane or no cane for improving gait and balance. There is limited level 2 evidence showing no significant difference between brace-assisted walking and partial body weight-supported treadmill training for the improvement of gait outcomes. Electromechanical Gait Training Devices There is level 1a and level 2 evidence that the Gait Trainer device may improve gait in the acute phase but not in the subacute or chronic phase of stroke recovery.
Order 20 mg levitra oral jelly overnight delivery. I USE A SURGICAL PUMP FOR ERECTIONS | AWKWARD PICK UPS.
