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Public Interest Law Initiative

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S. Grim. Carnegie Institution of Washington.

How research contributes to universal health coverage 57 Case-study 1 61 Insecticide-treated mosquito nets to reduce childhood mortality Case-study 2 63 Antiretroviral therapy to prevent sexual transmission of HIV Case-study 3 65 Zinc supplements to reduce pneumonia and diarrhoea in young children vii Case-study 4 67 Telemedicine to improve the quality of paediatric care Case-study 5 69 New diagnostics for tuberculosis Case-study 6 71 The “polypill” to reduce deaths from cardiovascular disease Case-study 7 73 Combination treatment with sodium stibogluconate (SSG) and paromomycin compared to SSG monotherapy for visceral leishmaniasis Case-study 8 75 Task shifting in the scale-up of interventions to improve child survival Case-study 9 77 Improving access to emergency obstetric care Case-study 10 79 Conditional cash transfers to improve the use of health services and health outcomes Case-study 11 81 Insurance in the provision of accessible and afordable health services Case-study 12 82 Afordable health care in ageing populations Conclusions: general lessons drawn from specifc examples 84 4 250mg zithromax mastercard antibiotic you can't drink alcohol. Building research systems for universal health coverage 95 Setting research priorities 96 Strengthening research capacity 98 A framework for strengthening capacity 99 Creating and retaining a skilled research workforce 103 Ensuring transparency and accountability in research funding 105 Building research institutions and networks 107 Defning and implementing norms and standards 110 Ethics and ethical review 110 Reporting and sharing research data order 500 mg zithromax visa antibiotics for steroid acne, tools and materials 110 Registering clinical trials 110 Using evidence to develop policy, practice and products 113 viiiviii Translating evidence into policy and practice 113 Monitoring and coordinating research, nationally and internationally 116 Financing research for universal health coverage 117 National and international governance of health research 118 Conclusions: building efective research systems 118 5. Research has the power to address a wide range of questions about how we can reach universal coverage, providing answers to improve human health, well-being and development. The creativity and skills of researchers should be used to strengthen investigations not only in academic centres but also in public health programmes, close to the supply of and demand for health services. To make the best use of limited resources, systems are needed to develop national research agendas, to raise funds, to strengthen research capacity, and to make appropriate and effective use of research findings. In 2005, all WHO Member States made the commitment to achieve universal health coverage. Te commitment was a collective expression of the belief that all people should have access to the health services they need without risk of fnancial ruin or impoverishment. Working towards universal health coverage is a powerful mechanism for achieving better health and well-being, and for pro- moting human development. Chapter 1 explains how the resolution adopted by all WHO Member States embraces the two facets of universal health coverage: the provision of, and access to, high-quality health services; and fnancial risk protection for people who need to use these services. Te term includes ways of taking action on social and environmental determinants both within and beyond the health sector. Financial risk protection is part of the package of measures that provides overall social protection. Scientifc research has been fundamental to the improvement of human health. Research is vital in developing the technology, systems and services needed to achieve universal health coverage. On the road to universal coverage, taking a methodical approach to formulating and answering questions is not a luxury but a necessity. When WHO Member States made the pledge to achieve universal coverage they took a signifcant step forward for public health. As described in Chapter 1, taking that step efectively launched an agenda for research. In this report, research is the set of formal methods that turns promising ideas into practical solutions for improving health services, and consequently for improving health. Te goal of the report is to identify the research questions that open the way to universal health coverage and to discuss how these questions can be answered. Many recent advances have been made in health service coverage and in fnan- cial risk protection as shown, for example, by progress towards the United Nations Millennium Development Goals (MDGs). Despite this progress, the gap between the present coverage of health services and universal health coverage remains large for many conditions of ill-health in many settings. For instance, nearly half of all HIV-infected people eligible for antiretroviral therapy were still not receiving it in 2011, and an estimated 150 million people sufer fnancial catastrophe each year because they have to pay cash out-of-pocket for the health care they need. Te focus of this report is on the research needed to provide wider access to essential services of this kind, and how to create the environment in which this research can be carried out. Chapter 1 identifes research questions of two kinds. Te causes of ill-health difer from one setting to another and so too must the necessary health services, includ- ing mechanisms for fnancial risk protection. Te frst group of questions therefore asks how to choose the health services needed in each setting, how to improve service coverage and fnancial protection, and consequently how to protect and improve health and well-being. Tese questions throw up a wide range of topics for research. Research is needed to fnd out how to improve the coverage of existing interventions and how to select and introduce new ones. Research must explore the development and use of both “sofware” (such as schemes for fnancial protection and simplifed approaches to treatment) and “hardware” (research and development for commodities and tech- nology). And research is needed to investigate ways of improving health from within and outside the health sector. Te most pressing research questions have been identifed for many specifc health topics, such as maternal and child health, communicable diseases, and health systems and services.

AP-1 complex composed of altered Fos-like proteins in brain by 83 discount zithromax 250mg mastercard antibiotic xanax. Synaptic tagging and long-term potentiation chronic cocaine and other chronic treatments cheap zithromax 100mg with amex bacteria webquest. Blockade of morphine- and am- stage of LTP in hippocampal CA1 neurons. Science 1993;260: phetamine-induced conditioned place preference in the rat by 1661–1664. Influence of novel versus synthesis-dependent late potentiation in the CA1 region of the home environments on sensitization to the psychomotor stimu- hippocampus [see comments]. Proc Natl Acad Sci USA 1995;92: lant effects of cocaine and amphetamine. Sensitization to the behavioral effects nergic D1 receptor blockade during tetanization on the expres- of cocaine: modification by Pavlovian conditioning. Pharmacol sion of long-term potentiation in the rat CA1 region in vitro. Dopaminergic antagonists of sensitization induced by psychomotor stimulants. NIDARes prevent long-term maintenance of posttetanic LTP in the CA1 Monogr 1990 á:208–241. Dopamine D1-defi- tor stimulant effects of amphetamine: modulation by associative cient mutant mice do not express the late phase of hippocampal learning. Models of information processing North Ami 1986;9:413–425. In vivo activity-dependent plasticity diction and stages of change models. Dopamine reverses the putative 'effector' immediate early gene, by cocaine in rat brain. Nature 1989;340: plasticity in an in vitro slice preparation of the rat nucleus accum- 474–476. Requirement of a critical period factor and activity-regulated gene, encodes a novel cytoskeleton- of transcription for induction of a late phase of LTP. Science associated protein that is enriched in neuronal dendrites. Homer: a protein cleus accumbens and prefrontal cortex neurons produced by that selectively binds metabotropic glutamate receptors [see com- previous experience with amphetamine. KOOB DEFINITIONS AND VALIDATION OF butes of a drug (e. This chapter reviews animal models currently used to Definitions of Drug Addiction examine the neurobiological basis of drug addiction and the Drug addiction is defined as a compulsion to take a drug role of reinforcement processes in its initiation, mainte- with loss of control in limiting intake (33). Emphasis is place on more re- a chronic disorder because the risk of relapse remains high cently developed models, and where possible, the models even after completion of treatment and prolonged absti- are evaluated in terms of reliability and predictability to nence. In 1968, the term drug dependence replaced that of the human condition. Potential pitfalls to consider when addiction in the nomenclature of the World Health Organi- interpreting data also are discussed. Defined as a cluster of cognitive, behavioral, and physiologic symptoms ANIMAL MODELS OF THE POSITIVE indicative of an individual continuing substance use despite REINFORCING EFFECTS OF DRUGS significant substance related problems, this term has become the accepted diagnostic term for compulsive use of a psy- Drugs of abuse function as positive reinforcing stimuli; this choactive substance. When defined as described, it is analo- action has provided the framework for currently used animal gous to the term addiction. It is also clear that humans and experi- be confused with physical or psychic dependence, condi- mental animals will readily self-administer these agents in tions in which the cessation or reduction of drug usage the absence of a withdrawal state. Earlier models of drug results in a withdrawal syndrome. Withdrawal and tolerance reinforcement used operant paradigms in nonhuman pri- often are associated with compulsive drug use; however, mates; however, many of these same paradigms now are they are not required for drug addiction. The use of these rodent models, together als suffering from chronic pain may develop tolerance to with the development of modern neurobiological tech- the analgesic effects of an opiate and experience withdrawal niques, has provided important information regarding the symptoms, they do not exhibit signs of compulsive drug- neurobiology of addiction (11,15,36,45,51). The concept of reinforcement has provided the corner- Operant Intravenous Drug stone for current theories and animal models of drug addic- Self-Administration tion. A reinforcer is defined operationally as 'any event that increases the probability of a response' and often is used Drugs of abuse are readily self-administered intravenously interchangeably with 'reward.

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Finally buy zithromax 500mg with amex antibiotics for boxer dogs, patients with central diabetes insipidus have a predilection for drinking cold water buy zithromax 250 mg antibiotics for sinus infection for adults. Plasm a osm olality above 295 m O sm /kg suggests central diabetes insipidus and below 270 m O sm /kg suggests com pulsive water drinking. The causes of diabetes insipidus can be divided into central and nephrogenic. M ost (about 50% ) of the central causes are idiopathic; the rest are caused by central nervous Central diabetes insipidus Nephrogenic diabetes insipidus system involvem ent with infection, tum ors, granulom a, or traum a. The nephrogenic causes can be congenital or acquired. Congenital Congenital Autosomal-dominant X-linked Autosomal-recessive Autosomal-recessive Acquired Acquired Post-traumatic Renal diseases (medullary cystic disease, Iatrogenic polycystic disease, analgesic nephropathy, Tumors (metastatic from breast, sickle cell nephropathy, obstructive uro- craniopharyngioma, pinealoma) pathy, chronic pyelonephritis, multiple myeloma, amyloidosis, sarcoidosis) Cysts Hypercalcemia Histiocytosis Hypokalemia Granuloma (tuberculosis, sarcoid) Drugs (lithium compounds, demeclocycline, Aneurysms methoxyflurane, amphotericin, foscarnet) Meningitis Encephalitis Guillain-Barré syndrome Idiopathic FIGURE 1-35 Congenital central diabetes insipidus (DI), autosom al-dom inant form. This condition has been described in m any fam ilies in Europe and N orth Am erica. It is an autoso- m al dom inant inherited disease associated SP VP NP NP NP CP with m arked loss of cells in the supraoptic nuclei. M olecular biology techniques have Exon 1 Exon 2 Exon 3 revealed m ultiple point m utations in the vasopressin-neurophysin II gene. This con- 83 dition usually presents early in life. This has been linked 17 to a defect in chrom osom e-4 and involves 57 abnorm alities in m itochondrial DN A. Central DI m ay be treated with horm one replacem ent or drugs. In acute settings when renal water losses are extensive, aqueous vasopressin (pitressin) is Condition Drug Dose useful. It has a short duration of action that allows for careful m on- itoring and avoiding com plications like water intoxication. This Complete central DI dDAVP 10–20 (g intranasally q 12–24 h drug should be used with caution in patients with underlying coro- Partial central DI Vasopressin tannate 2–5 U IM q 24–48 h nary artery disease and peripheral vascular disease, as it can cause Aqueous vasopressin 5–10 U SC q 4–6 h vascular spasm and prolonged vasoconstriction. For the patient Chlorpropamide 250–500 mg/d with established central DI, desm opressin acetate (dDAVP) is the Clofibrate 500 mg tid–qid agent of choice. It has a long half-life and does not have significant Carbamazepine 400–600 mg/d vasoconstrictive effects like those of aqueous vasopressin. It can be conveniently adm inistered intranasally every 12 to 24 hours. It is safe to use in pregnancy and resists degradation by circulating vasopressinase. In patients with partial DI, agents that potentiate release of antidiuretic horm one can be used. These include chlorpropam ide, clofibrate, and carbam azepine. They work effectively only if com bined with horm one therapy, decreased solute intake, or diuretic adm inistration. FIGURE 1-37 T T S A M Extracellular P * S L M –NH2 Congenital nephrogenic diabetes insipidus, P S H V A 1 S L L G P X-linked–recessive form. This is a rare dis- N S P S ease of m ale patients who do not concen- S F trate their urine after adm inistration of Q R E D R antidiuretic horm one. The pedigrees of R T G P A P A E P affected fam ilies have been linked to a L P L F W G L D D K D C R group of Ulster Scots who em igrated to R T W A A S G G P E A P A L W G E R H alifax, N ova Scotia in 1761 aboard the R A V T D L A L C C V Y * W E ship called “H opewell. Recent studies, howev- A L H V M T A L V V L I T L Y A * * L I L V F M S er, disproved this hypothesis. The A P R D P E R R S S F L C C R A H R I V S A gene defect has now been traced to 87 dif- R H V L R R W A N A T S S G ferent m utations in the gene for the vaso- G H W S K S E L R R R R G I H S A pressin receptor (AVP-R2) in 106 presum - C L V T R A V H A V P G * A A ably unrelated fam ilies. In the autosom al recessive form of N DI, m utations D N A T G A 8 P G have been found in the gene for the antiiuretic horm one (ADH )– R L N K sensitive water channel, AQ P-2. This form of N DI is exceedingly I S M F D N S D rare as com pared with the X-linked form of N DI. Thus far, a A S 13 C D total of 15 AQ P-2 m utations have been described in total of 13 P T G H T 6 T T W fam ilies. The acquired form of N DI occurs in various kidney I A Y V Q A L P E G H F diseases and in association with various drugs, such as lithium S V H L Q I W P W L L A T V G L L I G and am photericin B. Hypernatremia always Causes and mechanisms of acquired nephrogenic diabetes insidpidus.

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Methods The methods for this CER follow those suggested in the AHRQ Methods Guide for Effectiveness and Comparative Effectiveness Reviews (hereafter referred to as the Methods 23 Guide) cheap zithromax 250 mg overnight delivery antibiotic gel for acne. Input From Stakeholders During the topic refinement stage buy zithromax 250 mg online virus hunter island, we solicited input from Key Informants representing medical professional societies/clinicians in the areas of general internal medicine, geriatrics, cardiology, electrophysiology, and primary care; patients; scientific experts; Federal agencies; and payers to help define the KQs. The KQs were then posted for public comment for 4 weeks from September 27 to October 25, 2011, and the comments received were considered in the development of the research protocol. We next convened a Technical Expert Panel (TEP) comprising clinical, content, and methodological experts to provide input to the draft protocol in defining populations, interventions, comparisons, and outcomes, and in identifying particular 24 studies or databases to search. Before involvement in the CER process, the Key Informants and members of the TEP were required to disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts. Any potential conflicts of interest were balanced or mitigated. Neither Key Informants nor members of the TEP performed analysis of any kind, nor did any of them contribute to the writing of this report. ES-5 Literature Search Strategy ® ® To identify relevant published literature, we searched PubMed , Embase , and the Cochrane Database of Systematic Reviews (CDSR), limiting the search to studies published from January 1, 2000, to August 1, 2012. We believe that the evidence published from 2000 on represents the current standard of care for patients with AF and relevant comorbidities. In addition, a 2001 25-27 AHRQ report on the management of new-onset AF summarized the evidence prior to 2000. Where possible, we used existing validated search filters (such as the Clinical Queries Filters in PubMed). An experienced search librarian guided all searches. We supplemented the electronic searches with a manual search of citations from a set of key primary and systematic review articles, and also considered studies suggested by peer and public reviewers of the draft report. We used several approaches to identify relevant gray literature, including requests to drug and device manufacturers for scientific information packets and searches of study registries and conference abstracts for relevant articles from completed studies. Gray literature databases searched included ClinicalTrials. Inclusion and Exclusion Criteria Criteria used to screen articles for inclusion/exclusion at both the title-and-abstract and full- text screening stages are detailed in Table 1 of the full report. Across all KQs, we focused on English-language studies published since January 1, 2000, that represented comparative assessments of pharmacological and nonpharmacological rate- or rhythm-control therapies aimed at treating adult patients with AF. We excluded patients whose AF was postoperative or had a known reversible cause. For all KQs, RCTs were acceptable if they met a minimum sample size of 20 or more patients. Observational studies with a minimum sample size of 100 or more patients were also considered for KQ 2 and for studies providing data for CRT relevant to KQ 5. The following outcomes were considered: restoration of sinus rhythm (conversion); maintenance of sinus rhythm; recurrence of AF at 12 months; development of cardiomyopathy; mortality (all-cause and cardiovascular); myocardial infarction; cardiovascular hospitalizations; heart failure symptoms; control of AF symptoms (e. Study Selection Using the prespecified inclusion and exclusion criteria, titles and abstracts were reviewed independently by two investigators for potential relevance to the KQs. Articles included by either reviewer underwent full-text screening. At the full-text review stage, paired researchers independently reviewed the articles and indicated a decision to include or exclude the article for data abstraction. When the two reviewers arrived at different decisions about whether to include or exclude an article, they reconciled the difference through review and discussion, or through a third-party arbitrator if needed. Full-text articles meeting our eligibility criteria were included for data abstraction. Relevant review articles, meta-analyses, and methods articles were flagged for ES-6 manual searching of references and cross-referencing against the library of citations identified through electronic database searching. All screening decisions were made and tracked in a DistillerSR database (Evidence Partners Inc. Data Extraction The research team created data abstraction forms and evidence table templates for each KQ.

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