Barbara Caldwell, MS, MT(ASCP)SHCM

• Administrative Director, Clinical Laboratory Services
• Montgomery General Hospital
• Olney, Maryland

The sicker the patient antiviral y retroviral starlix 120mg buy mastercard, the more drugs are given hiv infection rate from needle stick discount starlix generic, and there is a corresponding increase in the likelihood of adverse drug reactions hiv infection vectors purchase starlix 120mg without prescription. When <6 different drugs are given to hospitalized patients hiv infection signs and symptoms order starlix from india, the probability of an adverse reaction is 5% hiv infection effects generic 120mg starlix fast delivery, but if >15 drugs are given, the probability is >40%. Retrospective analyses of ambulatory patients have revealed adverse drug effects in 20%. A small group of widely used drugs accounts for a disproportionate number of reactions. Because of the reactive nature of these metabolites, covalent binding often occurs close to the site of production, typically the liver. The most common cause of drug-induced hepatotoxicity is acetaminophen overdosage (Chap. Normally, reactive metabolites are detoxified by combining with hepatic glutathione. When glutathione becomes depleted, the metabolites bind instead to hepatic protein, with resultant hepatocyte damage. The hepatic necrosis produced by the ingestion of acetaminophen can be prevented or attenuated by the administration of substances such as N-acetylcysteine that reduce the binding of electrophilic metabolites to hepatic proteins. The morbidity and mortality from these adverse effects often present diagnostic problems because they can involve every organ and system of the body and may be mistaken for signs of underlying disease. As well, some surveys have suggested that drug therapy for a range of chronic conditions such as psychiatric disease or hypertension does not achieve its desired goal in up to half of treated patients; thus, the most common "adverse" drug effect may be failure of efficacy. One type results from exaggeration of an intended pharmacologic action of the drug, such as increased bleeding with anticoagulants or bone marrow suppression with antineoplastics. The second type of adverse reaction ensues from toxic effects unrelated to the intended pharmacologic actions. The latter effects are often unanticipated (especially with new drugs) and frequently severe and may result from recognized as well as previously undescribed mechanisms. Drugs can also cause rare and serious adverse effects, such as hematologic abnormalities, arrhythmias, severe skin reactions, or hepatic or renal dysfunction. Prior to regulatory approval and marketing, new drugs are tested in relatively few patients who tend to be less sick and to have fewer concomitant diseases than those patients who subsequently receive the drug therapeutically. Such toxicity has even occurred with therapeutic dosages, so patients at risk through these mechanisms should be warned. Most pharmacologic agents are small molecules with low molecular weights (<2000) and thus are poor immunogens. Generation of an immune response to a drug therefore usually requires in vivo activation and covalent linkage to protein, carbohydrate, or nucleic acid. Drug stimulation of antibody production may mediate tissue injury by several mechanisms. The antibody may attack the drug when the drug is covalently attached to a cell and thereby destroy the cell. Antibody-drug-antigen complexes may be passively adsorbed by a bystander cell, which is then destroyed by activation of complement; this occurs in quinine- and quinidine-induced thrombocytopenia. Heparin-induced thrombocytopenia arises when antibodies against complexes of platelet factor 4 peptide and heparin generate immune complexes that activate platelets; thus, the thrombocytopenia is accompanied by "paradoxical" thrombosis and is treated with thrombin inhibitors. Drugs or their reactive metabolites may alter a host tissue, rendering it antigenic and eliciting autoantibodies. For example, hydralazine and procainamide (or their reactive metabolites) can chemically alter nuclear material, stimulating the formation of antinuclear antibodies and occasionally causing lupus erythematosus. Complement activation occurs, chemotactic factors are generated locally, and an inflammatory response develops at the site of complex entrapment. Arthralgias, urticaria, lymphadenopathy, glomerulonephritis, or cerebritis may result. Foreign proteins (vaccines, streptokinase, therapeutic antibodies) and antibiotics are common causes. Contact with a drug antigen initiates a series of biochemical events in the mast cell and results in the release of mediators that can produce the characteristic urticaria, wheezing, flushing, rhinorrhea, and (occasionally) hypotension. Topically administered substances may interact with sulfhydryl or amino groups in the skin and react with sensitized lymphocytes to produce the rash characteristic of contact dermatitis. Other types of rashes may also result from the interaction of serum factors, drugs, and sensitized lymphocytes. Recognition of the role of a drug or drugs in an illness depends on appreciation of the possible adverse reactions to drugs in any disease, on identification of the temporal relationship between drug administration and development of the illness, and on familiarity with the common manifestations of the drugs. A suspected adverse drug reaction developing after introduction of a new drug naturally implicates that drug; however, it is also important to remember that a drug interaction may be responsible. Thus, for example, a patient on a chronic stable warfarin dose may develop a bleeding complication after introduction of amiodarone; this does not reflect a direct reaction to amiodarone but rather its effect to inhibit warfarin metabolism. Many associations between particular drugs and specific reactions have been described, but there is always a "first time" for a novel association, and any drug should be suspected of causing an adverse effect if the clinical setting is appropriate. For example, side effects such as cardiac arrhythmias in patients receiving digitalis, hypoglycemia in patients given insulin, or bleeding in patients receiving anticoagulants are more readily related to a specific drug than are symptoms such as fever or rash, which may be caused by many drugs or by other factors. However, exhaustive compilations often provide little sense of perspective in terms of frequency and seriousness, which can vary considerably among patients. Loss of efficacy of oral contraceptives or cyclosporine with concurrent use of St. Every physician should determine what drugs a patient has been taking, for the previous month or two ideally, before prescribing any medications. Medications stopped for inefficacy or adverse effects should be documented to avoid pointless and potentially dangerous reexposure. A frequently overlooked source of additional drug exposure is topical therapy; for example, a patient complaining of bronchospasm may not mention that an ophthalmic beta blocker is being used unless specifically asked. Since these patients have shown a predisposition to drug-induced illnesses, such a history should dictate added caution in prescribing new drugs. Laboratory studies may include demonstration of serum antibody in some persons with drug allergies involving cellular blood elements, as in agranulocytosis, hemolytic anemia, and thrombocytopenia. For example, both quinine and quinidine can produce platelet agglutination in vitro in the presence of complement and the serum from a patient who has developed thrombocytopenia following use of this drug. Once an adverse reaction is suspected, discontinuation of the suspected drug followed by disappearance of the reaction is presumptive evidence of a drug-induced illness. Confirming evidence may be sought by cautiously reintroducing the drug and seeing if the reaction reappears. However, that should be done only if confirmation would be useful in the future management of the patient and if the attempt would not entail undue risk. With concentration-dependent adverse reactions, lowering the dosage may cause the reaction to disappear, and raising it may cause the reaction to reappear. When the reaction is thought to be allergic, however, readministration of the drug may be hazardous, since anaphylaxis may develop. If the patient is receiving many drugs when an adverse reaction is suspected, the drugs likeliest to be responsible can usually be identified; this should include both potential culprit agents as well as drugs that alter their elimination. All drugs may be discontinued at once or, if this is not practical, discontinued one at a time, starting with the ones most suspect, and the patient observed for signs of improvement. The time needed for a concentration-dependent adverse effect to disappear depends on the time required for the concentration to fall below the range associated with the adverse effect; that, in turn, depends on the initial blood level and on the rate of elimination or metabolism of the drug. Adverse effects of drugs with long half-lives or those not directly related to serum concentration may take a considerable time to disappear. Molecular pharmacology, pharmacokinetics, genetics, clinical trials, and the educated prescriber all contribute to this process. No drug response should ever be termed idiosyncratic; all responses have a mechanism whose understanding will help guide further therapy with that drug or successors. This rapidly expanding understanding of variability in drug actions makes the process of prescribing drugs increasingly daunting for the practitioner. However, fundamental principles should guide this process: · the benefits of drug therapy, however defined, should always outweigh the risk. It has become clear that both sex chromosomes and sex hormones contribute to these differences. Indeed, it is recommended that the term sex difference be used for biologic processes that differ between males and females and the term gender difference be used for features related to social influences. Breast cancer is the second leading cause of cancer death in women, but it causes about 60% fewer deaths than does lung cancer. Men are substantially more likely to die from suicide and accidents than are women. In the industrialized world, women spend one-third of their lives in the postmenopausal period. Estrogen levels fall abruptly at menopause, inducing a variety of physiologic and metabolic responses. In the United States, women live on average about 5 years longer than men, with a life expectancy at birth in 2011 of 81. Elderly women outnumber elderly men, so that age-related conditions such as hypertension have a female preponderance. However, the difference in life expectancy between men and women has decreased an average of 0. If this convergence in mortality figures continues, it is projected that mortality rates will be similar by 2054. Public awareness campaigns have resulted in a marked increase in the percentage of U. Although awareness of heart disease has improved substantially among black and Hispanic women over this time period, these groups were 66% less likely than white women to recognize that heart disease is the leading cause of death in women. Nevertheless, women younger than 65 years still consider breast cancer to be their leading health risk, despite the fact that death rates from breast cancer have been falling since the 1990s. Similarly, a minority of women are aware that lung cancer is the leading cause of cancer death in women. These misconceptions are unfortunate as they perpetuate inadequate attention to modifiable risk factors such as dyslipidemia, hypertension, and cigarette smoking. There is emerging evidence for sex-specific differences in gene expression, not only for genes on the X and Y chromosomes but also for some autosomal genes. Estrogens have pleiotropic genomic and nongenomic effects on the central nervous system, including neurotrophic actions in key areas involved in cognition and memory. Source: Data from Centers for Disease Control and Prevention: National Vital Statistics Reports, Vol. Note that the scale of the y axis is increased in the graph on the right compared with that on the left. These increases were paralleled by an increasing prevalence of abdominal obesity and other components of metabolic syndrome in women. Sex steroids have major effects on the cardiovascular system and lipid metabolism. In 1997, cancer was cited as the leading cause of death in women, not heart disease. The rate of awareness that heart disease is the leading cause of death in women was significantly higher in 2012 (56% vs 30%, p <. Estrogen has direct vasodilatory effects on the vascular endothelium, enhances insulin sensitivity, and has antioxidant and anti-inflammatory properties. Women more often have atypical symptoms such as nausea, vomiting, indigestion, and upper back pain. Although awareness that heart disease is the leading cause of death in women has nearly doubled over the last 15 years, women remain less aware that its symptoms are often atypical, and they are less likely to contact 9-1-1 when they experience such symptoms. The improvement in survival is due largely to a reduction in comorbidities, suggesting a greater attention to modifiable risk factors in women. Nevertheless, physicians are less likely to suspect heart disease in women with chest pain and less likely to perform diagnostic and therapeutic cardiac procedures in women. Women undergoing percutaneous transluminal coronary angioplasty have lower rates of initial angiographic and clinical success than men, but they also have a lower rate of restenosis and a better long-term outcome. Women may benefit less and have more frequent serious bleeding complications from thrombolytic therapy compared with men. Women younger than age 65 years had substantially greater mortality than men of similar age in 1994­1995. Mortality rates declined markedly for both sexes across all age groups in 2004­2006 compared with 1994­1995. However, there was a more striking decrease in mortality in women younger than age 75 years compared with men of similar age. Higher bioavailable testosterone levels are associated with increased risk in women, whereas lower bioavailable testosterone levels are associated with increased risk in men. These women have impaired endothelial function and reduced coronary vasodilatory responses, which may predispose to cardiovascular complications. Both normotensive and hypertensive women have higher blood pressure levels during the follicular phase than during the luteal phase. Among secondary causes of hypertension, there is a female preponderance of renal artery fibromuscular dysplasia. The benefits of treatment for hypertension have been dramatic in both women and men. A meta-analysis of the effects of hypertension treatment, the Individual Data Analysis of Antihypertensive Intervention Trial, found a reduction of risk for stroke and for major cardiovascular events in women. The effectiveness of various antihypertensive drugs appears to be comparable in women and men; however, women may experience more side effects. For example, women are more likely to develop cough with angiotensin-converting enzyme inhibitors. Sex differences in both immune responses and adverse reactions to vaccines have been reported. Adaptive immune responses are more robust in women than in men; this may be explained by the stimulatory actions of estrogens and the inhibitory actions of androgens on the cellular mediators of immunity. Consistent with an important role for sex hormones, there is variation in immune responses during the menstrual cycle, and the activity of certain autoimmune disorders is altered by castration or pregnancy.

In western Europe hiv infection flu starlix 120mg order, 39 medical schools (24% of those responding) devote no time to the teaching of clinical pharmacology hiv infection rates toronto buy 120 mg starlix with mastercard, and in a further 20 schools there is less than 12 hours in the whole medical course devoted to the subject hiv infection early warning signs order generic starlix pills. In eastern Europe hiv infection by oral purchase online starlix, there is no teaching of clinical pharmacology in seven of the medical schools (17% of those responding) hiv-1 infection cycle cheap 120mg starlix with mastercard, while a further five schools teach less than 12 hours of clinical pharmacology. There is considerable variation within a country in the hours devoted to clinical pharmacology teaching. In some universities, the subject is developed while in other universities the discipline is not represented at all. On average, each medical school has about 2 staff members 20 trained in the subject. There is also a lack of posts in the subject, with on average only one post in the subject in each medical school. In France 15 medical schools (out of 28 responding), in the Federal Republic of Germany 19 (out of 25), and in Italy 9 (out of 15) have no posts of clinical pharmacology. Attention should be focused on the importance of clinical pharma- cology as a teaching discipline so that the rational use of drugs can be improved in the Region. This would be achieved by establishing units of clinical pharmacology in those universities where the subject has no current presence and by strengthening those units that are functioning, albeit under considerable strain. The current plans to reduce clinical pharmacology teaching in the Federal Republic of Germany, Italy and Spain thus seem particularly retrogressive. Following the initial clinical trials of a drug and the grant of a product licence, the drug will be promoted for use in primary health care. The physicians involved at that stage will have had little experience in any of the initial trials and will be exposed to promotional information from the pharmaceutical company concerned. Second, their prescriptions may also be for clinical conditions which do not correspond to those which have been subject to controlled evaluation. The information available to them is not always pertinent or relevant to their decisions. These unfavourable conditions of drug use become apparent in connection with major drug problems and occasional surveys of drug use. With rare exceptions, clinical pharmacology has developed in the academic hospital setting. In addition to advantages regarding the efficacy and safety of drug therapy, important benefits may be anticipated with regard to public drug expenditure. Clinical pharmacology is a medical discipline which, on a scientific basis, combines pharmacological, clinical and epidemiological know- ledge with the aim of ensuring the rational use of drugs. One is the uneven development of clinical pharmacology within the European Region (4) and indeed throughout the world. Rational drug use Drugs are not always used for the purpose for which they have been developed, investigated and approved. They may be used for entirely unproven indications or in cases for which there is no rationale. Doses may be excessive or too low, and multiple prescribing may lead to interactions. Safety -efficacy balance the safety- efficacy balance of certain drugs and therapeutic strategies is inadequately established in primary health care, if not completely unknown. Compliance with the drug regimen There is a serious problem about patient compliance with therapy, even when there is a clear need for the drug. On the other hand, inappropriate use of therapeutic drug monitoring without proper assessment of its utility may mislead the clinician and cause unnecessary cost. If conducted properly, they could provide valuable epidemiological data on morbidity and the quality of care in different settings, thus forming a basis for educational opportunities and for the promotion of better oriented research projects. Cost -benefit ratio Concern is often expressed about expenditure on drugs in general or in special situations. It is difficult to decide whether a particular therapy is cost -effective: the cheapest drug is not always the best in this respect. Moreover, adequate use of modern, allegedly expensive drugs may be highly cost -effective if the need for inpatient care is reduced. On the other hand, inadequate use of inexpensive drugs may lead to extra inpatient care due to adverse effects. The commercial influence often distorts the information, particularly about such issues as the extent to which a drug should be used, or whether the drug produced by the informant or by a competitor should be selected. It is important to know whether they would consult a clinical pharmacologist and, if so, under what circumstances, and with what type of problem. As an example, would they find the clinical pharmacologist useful as a resource person for drug research matters It is particularly important in this situation to realize that clinical pharmacology is much more than the individual clinical pharmacologist or his or her staff. In fact, it is the entire body of knowledge available about drugs and their proven or suspected effects in humans. The problems outlined so far may be classified into four broad categories: (a) teaching and training, (b) service aspects, (c) research and (d) finance. Teaching and training Teaching in clinical pharmacology should start early in the undergraduate medical curriculum, so that the graduate has a firm theoretical base on which to build future therapeutic advances. A final -year course in practical therapeutics will enable the newly qualified doctor successfully to transfer his or her theoretical knowledge to the everyday clinical setting in hospital. Primary health care physicians also learn from their experiences and they should 27 play a more active role in the therapeutic process by, for example, being members of formulary and therapeutics committees. Sophisticated studies are needed to assess the safety -efficacy balance of drugs, i. A positive interaction would be of help in the development of an effective and reliable scheme for adverse reaction monitoring. Studies of drug use require methods which have been well developed by certain clinical pharmacology and other centres. Therapeutic drug monitoring is available for some drugs in virtually all hospitals. There is a good argument that rational drug prescribing in hospitals, while perhaps not reducing drug costs, has markedly reduced the rise in costs that might have been expected. Conclusions and Recommendations Both in the short and the long term, the coming together of clinical pharmacology and primary health care should be planned and carried out with four main objectives in mind, namely education, service, research and financial organization. Initially, the aim should be to make the clinical pharmacologists already established in academic and hospital centres available to provide expertise and support to general practitioners throughout the European Region. Ultimately, the goal must be to have sufficient numbers of individuals trained in clinical pharmacology actually working in primary health care. Countries that have not instituted clinical pharmacology as a permanent discipline in their universities (4) should be urged to do so. In all countries, increased resources may be required, but there is an excellent chance in the long run of financial savings and improved cost -benefit ratios in drug therapy. The teaching and organisation of clinical pharmacology in European medical schools. People interested in the subject or in taking part in clinical pharmacological activities usually have training in both pharmacology and a clinical field: usually internal medicine. In spite of the absence of formal structures, a number of people are working in clinical pharmacology, usually in academic departments of pharmacology or internal medicine. Most are involved in the undergraduate teaching programme for pharmacology and therapeutics as well as in teaching postgraduates. In five of these departments, doctors with training in both pharmacology and internal medicine hold senior positions. Although clinical pharmacology has little presence in the hospital service, units of clinical pharmacology are active in the pharmaceutical industry. Long -term Plans There are no plans for the formalization or further development of clinical pharmacology in Belgium in the near future. National Association the Belgian Society for Experimental and Clinical Physiology and Pharmacology provides a regular forum for most of the people active in clinical pharmacology. Bogaert Department of Pharmacology University of Ghent Medical School De Pintelaan 185 9000 Ghent. The main activities take place in the capital, Sofia, where the Medical Academy has a department of clinical pharmacology, founded in 1981 and headed by a professor of clinical pharmacology. In addition, a clinical pharmacology unit is established at the research institute of the state pharmaceutical enterprise Pharmachim. In general, people interested in clinical pharmacology have a background in pharmacology rather than internal medicine. People with interest or duties in clinical pharmacology are present in the medical schools in Pleven, Plovdiv, Stara Zagora and Varna. Clinical pharmacology is taught in some of the medical schools - usually in the fifth year of study. The subject is also taught at 35 the postgraduate level to doctors and pharmacists, particularly by the department in Sofia. Research is pursued in a variety of areas and most clinical pharmacologists have responsibility in health care for solving pharmacokinetic problems or therapeutic drug monitoring. Long -term Plans It is hoped to have divisions or departments of clinical pharmacology in all medical schools in the foreseeable future. National Association the Bulgarian Pharmacological Society has a Clinical Pharmacology Section to which most interested people belong. Czechoslovakia differs from most European countries in that this development has mostly taken place at non -academic institutions. Clinical pharmacology was recognized as an independent specialty in 1976 and this status was confirmed in official documents in 1982. Clinical pharmacology has developed in regional and district hospitals with an emphasis on health care, while the emphasis in state research institutes is naturally on research. There are four departments of clinical pharmacology in Czechoslovakia but only one of these (in Plzen) is at a university. The initial specialty training focuses on internal medicine or paediatrics, although other disciplines may be included later. Then follow three years of practice in a clinical pharmaco- logy department, one year of which is spent learning techniques in experimental pharmacology. The teaching of clinical pharmacology in undergraduate medical schools does not reflect its importance in the country. There is no formal course in clinical pharmacology, although some lectures in the subject are given in most medical schools. Postgraduate training in clinical pharmacology is centred on the Czeck and Slovak institutes for postgraduate education in medicine and pharmacy. Here lectures are given and courses arranged for doctors working in clinical pharmacology. Research in clinical pharmacology addresses all phases of the clinical development of drugs and is directed by the State Research Plan. In the hospital service, regional units of clinical pharmacology provide services such as therapeutic consultation, adverse drug reaction monitoring and drug information. The plan is to have independent clinical pharmacology departments in all the regional hospitals and state research institutes. National Association the Czech and Slovak republics each have a society of pharmacology; each society has a clinical section. University chairs in clinical pharmacology were established some 8 -10 years ago, although that in Aarhus was vacant from 1978 to 1985. Units or divisions of clinical pharmacology have been organized around the university chairs and within the departments of pharmacology in Odense and Aarhus and the University Hospital in Copenhagen. In the past, other academic personnel have been temporarily associated with these units as research fellows or clinical research assistants. More recently, however, positions for senior research associates have been established in Odense and Aarhus. These clinical pharmacology units 39 have a formal responsibility for teaching undergraduates and research; they also provide services to the University Hospital and are active in postgraduate training. Clinical pharmacology has so far not been recognized as a separate specialty in Denmark. Several people who meet these criteria hold positions in pharmacology or clinical specialties. Long -term Plans Committees of the national health service (in 1974) and the Danish Society of Clinical Pharmacology (in 1982) proposed that a clinical pharmacology position be established at the general hospital in each county (14 -15 in total). In the immediate future, however, clinical pharmacology is likely to develop mainly at the university centres. National Association the Danish Society of Clinical Pharmacology was established in 1978 and has about 100 members. The development of the specialty in general health care, however, has been very slow. The department in Helsinki was founded in 1969 and the unit of clinical pharmacology in Turku was started in 1983. The department is responsible for the operation of the Finnish poisons information centre. In addition, individuals are working in clinical pharmacology in other medical schools. A clinical pharmacologist, for example, holds the chair of toxicology and pharmacokinetics in Kuopio. Medical students learn about clinical pharmacology during the clinical part of the course. In addition to lectures (30 - 44 hours), 41 demonstrations, seminars and therapy meetings are held. Teaching in clinical pharmacology is also offered to postgraduates from a variety of professions.

Spirometry is of value before lung resection in determining candidacy for coronary artery bypass; however hiv infection in south africa order 120mg starlix mastercard, it does not provide a spirometric threshold for extrathoracic surgery below which the risks of surgery are unacceptable anti viral hand wash starlix 120 mg purchase on-line. Pulmonary artery catheterization hiv infection neuropathy buy 120mg starlix otc, administration of total parenteral nutrition (as opposed to no supplementation) hiv infection essay order starlix 120mg with mastercard, or total enteral nutrition has no benefit in reducing postoperative pulmonary complications hiv infection rates uk 2013 starlix 120mg purchase on-line. Evidence supports intensive perioperative glycemic control to achieve nearnormal glucose levels (90­110 mg/dL) rather than moderate glycemic control (120­200 mg/dL), using insulin infusion. Patients whose diabetes is diet controlled may proceed to surgery with close postoperative monitoring. In 2010, according to the Centers for Disease Control and Prevention, 2,468,435 individuals died in the United States (Table 10-1). The epidemiology of mortality is similar in most developed countries; cardiovascular diseases and cancer are the predominant causes of death, a marked change since 1900, when heart disease caused ~8% of all deaths and cancer accounted for <4% of all deaths. It is estimated that in developed countries ~70% of all deaths are preceded by a disease or condition, making it reasonable to plan for dying in the foreseeable future. Cancer has served as the paradigm for terminal care, but it is not the only type of illness with a recognizable and predictable terminal phase. Many patients with illness-related suffering also can benefit from palliative care regardless of prognosis. Ideally, palliative care should be considered part of comprehensive care for all patients. Palliative care can be improved by coordination between caregivers, doctors, and patients for advance care planning, as well as dedicated teams of physicians, nurses, and other providers. The rapid increases in life expectancy in developed countries over the last century have been accompanied by new difficulties facing individuals, families, and society as a whole in addressing the needs of an aging population. These challenges include both more complicated conditions and technologies to address them at the end of life. The development of technologies that can prolong life without restoring full health has led many Americans to seek out alternative end-of-life care settings and approaches that relieve suffering for those with terminal diseases. Over the last few decades in the United States, a significant change in the site of death has occurred that coincides with patient and family preferences. By 2000, the trend was reversing, with ~31% of Americans dying as hospital inpatients. In the last decade, it has been associated with the increased use of hospice care; in 2008, approximately 39% of all decedents in the United States received such care. About 79% of patients receiving hospice care die out of the hospital, and around 42% of those receiving hospice care die in a private residence. Consequently, providing optimal palliative and end-of-life care requires ensuring that appropriate services are available in a variety of settings, including noninstitutional settings. Terminally ill patients have a wide variety of advanced diseases, often with multiple symptoms that demand relief, and require noninvasive therapeutic regimens to be delivered in flexible care settings. Fundamental to ensuring quality palliative and end-of-life care is a focus on four broad domains: (1) physical symptoms; (2) psychological symptoms; (3) social needs that include interpersonal relationships, caregiving, and economic concerns; and (4) existential or spiritual needs. A comprehensive assessment screens for and evaluates needs in each of these four domains. Goals for care are established in discussions with the patient and/or family, based on the assessment in each of the domains. Because failing to address any one of the domains is likely to preclude a good death, a well-coordinated, effectively communicating interdisciplinary team takes on special importance in end-of-life care. The assessment of physical and mental symptoms should follow a modified version of the traditional medical history and physical examination that emphasizes symptoms. Further research on and validation of these assessment tools, especially taking into account patient perspectives, could improve their effectiveness. These instruments are long and may be useful for initial clinical or for research assessments. Shorter instruments are useful for patients whose performance status does not permit comprehensive assessments. Suitable shorter instruments include the Condensed Memorial Symptom Assessment Scale, the Edmonton Symptom Assessment System, the M. Using such instruments ensures that the assessment is comprehensive and does not focus only on pain and a few other physical symptoms. Invasive tests are best avoided in end-of-life care, and even minimally invasive tests should be evaluated carefully for their benefit-to-burden ratio for the patient. Aspects of the physical examination that are uncomfortable and unlikely to yield useful information can be omitted. Regarding social needs, health care providers should assess the status of important relationships, financial burdens, caregiving needs, and access to medical care. Relevant questions will include the following: How often is there someone to feel close to Helpful assessment questions can include the following: How much are you able to find meaning since your illness began In addition, it can be helpful to ask how the patient perceives his or her care: How much do you feel your doctors and nurses respect you If concern is detected in any of these areas, deeper evaluative questions are warranted. Communication Especially when an illness is life-threatening, there are many emotionally charged and potentially conflict-creating moments, collectively called "bad news" situations, in which empathic and effective communication skills are essential. Although these conversations can be difficult and lead to tension, research indicates that end-of-life discussions can lead to earlier hospice referrals rather than overly aggressive treatment, benefiting quality of life for patients and improving the bereavement process for families. Just as surgeons plan and prepare for major operations and investigators rehearse a presentation of research results, physicians and health care providers caring for patients with significant or advanced illness can develop a practiced approach to sharing important information and planning interventions. In addition, families identify as important both how well the physician was prepared to deliver bad news and the setting in which it was delivered. Ensure the appropriate setting for a Ensure that patient, family, and appropriate social supports are present. Begin the discussion by establishing Start with open-ended questions to encourage participation. Ease tension by having the patient When you first had symptom X, what did you think it might be Discover what information needs the Possible phrases to use: patient and/or family have and what If this condition turns out to be something serious, do you want to know Provide the bad news or other inforDo not just dump the information on the patient and family. Identify the cause of the emotions- Strong feelings in reaction to bad news are normal. Empathize with the patient and/or Remind them such feelings are normal, even if frightening. Delineate for the patient and the fam- It is the unknown and uncertain that can increase anxiety. Recommend a schedule ily the next steps, including additional with goals and landmarks. If the patient and/or family are not ready to discuss the next steps, schedule a follow-up visit. Aim of the Interaction Mentally prepare for the interaction with the patient and/or family. Additional research that further considers the response of patients to systematic methods of delivering bad news could build the evidence base for even more effective communication procedures. Continuous goal Assessment Major barriers to ensuring quality palliative and end-of-life care include difficulty providing an accurate prognosis and emotional resistance of patients and their families to accepting the implications of a poor prognosis. With this approach, palliative care no longer conveys the message of failure, having no more treatments, or "giving up hope. Alternatively, some practices may find it useful to implement a standard point in the clinical course to address goals of care and advance care planning. Goals for care are numerous, ranging from cure of a specific disease, to prolonging life, to relief of a symptom, to delaying the course of an incurable disease, to adapting to progressive disability without disrupting the family, to finding peace of mind or personal meaning, to dying in a manner that leaves loved ones with positive memories. Discernment of goals for care can be approached through a seven-step protocol: (1) ensure that medical and other information is as complete as reasonably possible and is understood by all relevant parties (see above); (2) explore what the patient and/or family are hoping for while identifying relevant and realistic goals; (3) share all the options with the patient and family; (4) respond with empathy as they adjust to changing expectations; (5) make a plan, emphasizing what can be done toward achieving the realistic goals; (6) follow through with the plan; and (7) review and revise the plan periodically, considering at every encounter whether the goals of care should be reviewed with the patient and/or family. Each of these steps need not be followed in rote order, but together they provide a helpful framework for interactions with patients and their families about goals for care. It can be especially challenging if a patient or family member has difficulty letting go of an unrealistic goal. One strategy is to help them refocus on more realistic goals and also suggest that while hoping for the best, it is still prudent to plan for other outcomes as well. Advance Care Planning · practIces Advance care planning is a process of planning for future medical care in case the patient becomes incapable of making medical decisions. A 2010 study of adults 60 or older who died between 2000 and 2006 found that 42% required decision making about treatment in the final days of life but 70% lacked decision-making capacity. Among those lacking decision-making capacity, around one-third did not have advance planning directives. Ideally, such planning would occur before a health care crisis or the terminal phase of an illness. Polls suggest 80% of Americans endorse advance care planning and completing living wills. Most patients expect physicians to initiate advance care planning and will wait for physicians to broach the subject. Yet patients with unrealistic expectations are significantly more likely to prefer aggressive treatments. Fewer than one-third of health care providers have completed advance care planning for themselves. Hence, a good first step is for health care providers to complete their own advance care planning. This makes providers aware of the critical choices in the process and the issues that are especially charged and allows them to tell their patients truthfully that they personally have done advance planning. Lessons from behavioral economics suggest that setting this kind of social norming helps people view completing an advance directive as acceptable and even expected. Steps in effective advance care planning center on (1) introducing the topic, (2) structuring a discussion, (3) reviewing plans that have been discussed by the patient and family, (4) documenting the plans, (5) updating them periodically, and (6) implementing the advance care directives (Table 10-3). Two of the main barriers to advance care planning are problems in raising the topic and difficulty in structuring a succinct discussion. Raising the topic can be done efficiently as a routine matter, noting that it is recommended for all patients, analogous to purchasing insurance or estate planning. Many of the most difficult cases have involved unexpected, acute episodes of brain damage in young individuals. Identify the health care proxy and recommend his or her involvement in the process of advance care planning. Select a worksheet, preferably one that has been evaluated and demonstrated to produce reliable and valid expressions of patient preferences, and orient the patient and proxy to it. Discuss with the patient and proxy one scenario as an example to demonstrate how to think about the issues. It is often helpful to begin with a scenario in which the patient is likely to have settled preferences for care, such as being in a persistent vegetative state. After having the patient and proxy sign the document, place it in the medical chart and be sure that copies are provided to relevant family members and care sites. The first includes living wills or instructional directives; these are advisory documents that describe the types of decisions that should direct care. Some are more specific, delineating different scenarios and interventions for the patient to choose from. A second type is a less specific directive that provides general statements of not wanting life-sustaining interventions or forms that describe the values that should guide specific discussions about terminal care. These can be problematic because, when critical decisions about specific treatments are needed, they require assessments by people other than the patient of whether a treatment fulfills a particular wish. The third type of advance directive allows the designation of a health care proxy (sometimes also referred to as a durable attorney for health care), who is an individual selected by the patient to make decisions. The procedures for completing advance care planning documents vary according to state law. A potentially misleading distinction relates to statutory as opposed to advisory documents. Both are legal, the first under state law and the latter under common or constitutional law. Supreme Court has ruled that patients have a constitutional right to decide about refusing and terminating medical interventions, including life-sustaining interventions, and that mentally incompetent patients can exercise this right by providing "clear and convincing evidence" of their preferences. In fact, I feel that this is such an important topic that I have done this myself. Indicate that you as a physician have completed advance care Have you thought about the type of care you would want if you ever planning. Indicate that you try to perform advance care planning with all There is no change in health that we have not discussed. Provide the patient relevant literature, including the advance care Know resources for state-specific forms (available at directive that you prefer to use. Recommend the patient identify a proxy decision-maker who should attend the next meeting. Document the Formally complete the advance care directive and have a witness sign it. Update the directive Periodically, and with major changes in health status, review the directive with the patient and make any modifications. Apply the directive the directive goes into effect only when the patient becomes unable to make medical decisions for himself or herself. Most commentators believe that a state is required to honor any clear advance care directive whether or not it is written on an "official" form. If a patient is not using a statutory form, it may be advisable to attach a statutory form to the advance care directive being used. Wallace ruled that a brain dead woman who was 23 weeks pregnant should be removed from life support. As of 2013, advance directives are legal in all states and the District of Columbia either through state specific legislation, state judicial rulings, or United States Supreme Court rulings. Massachusetts and Michigan do not have living will laws, although both have health care proxy laws. In 27 states, the laws state that the living will is not valid if a woman is pregnant. However, like all other states except Alaska, these states have enacted durable power of attorney for health care laws that permit patients to designate a proxy decision-maker with authority to terminate life-sustaining treatments. Only in Alaska does the law prohibit proxies from terminating life-sustaining treatments.

Gram stain hiv infection process in the body buy starlix 120mg line, eye cultura hiv infection rate namibia purchase starlix without prescription, or scrap· ings from the epithelial cells of the eyelid may help identify a common infectious etiology stages of hiv infection to aids order 120mg starlix visa. J·Iilt3:1:iit J) Neonatal chlamydia of the aye hiv symptoms sinus infection discount starlix 120mg with visa, called traclloma antiviral ointment 120mg starlix buy amex, is responsible tor 3% o1 worldwide blindness. Nonspecific central and autonomic nervous system regulatory dysfunction seen when exposure to drugs used by mother in pregnancy ceases after delivery of infant 2. Neurologic: irritability, jittery/tremulous, shrill cry, hypertonia, myoclonic jerks, seizures c. Abstinence scoring scales like Finnegan, lipsitz, Neonatal Withdrawal Index: infants scored serially to assess for treatment and response b. Meconium toxicology screen: reflects prior drug use (days to months before); rarely sent D. Pharmacologic therapy: once symptoms are controlled, opiates are weaned by 10% of dose daily 3. Treatment of mother Neonatal abstinence syn· drome gana rally presents as a jittery, irritable baby with diarrhea. Facial features: tenting of upper lip or inverted V-shape often referred to as "fish-shaped" or "carp mouth"; bitemporal flattening b. Others: respiratory distress, poor suck or swallow, hypotonia, arthrogryposis (multiple joint contractures), and developmental delay D. Many congenital infections share common phenotype because fetal pathophysiology is similar (Table 14-12) 5. Symptomatic infants may present with similar physical exam and laboratory findings, regardless of pathogen (see Table H-12) b. Vaccines are available for some pathogens and have resulted in near-elimination of congenital infection in developed world, as in congenital rubella F. Fetal infection can lead to stillbirth, pretenn birth, and congenital infection d. Symptomatic infants can present with hepatosplenomegaly, adenopathy, rash, jaundice, rhinitis, metaphyseallucencies (periostitis) on radiography f. Late findings include notched teeth (Hutchinson teeth), sensorineural hearing loss, snuflles, saddle nose, saber shins, and neurodevelopmental delay g. Human infection can occur by direct contact with cat stool or ingestion of encysted muscle in raw or undercooked meat c. Prevention: pregnant mothers should avoid litter boxes and raw or under~ cooked meat and use good hand hygiene 4. Documenting patterns of feeding, elimination, sleep, adjustment to school, family stressors +. Guidance for care of routine childhood illnesses including identifying when medical attention is required 5. Routine use of screening tools to identify early medical, developmental, or behavioral problems B. Exclusive breastfeeding is recommended until age 6 months; if breastfeeding is not chosen, then recommend iron-fortified infant formula b. Bowel movement frequency is variable; stools should be soft, not firm or watery c. Introduce solid foods when infant has good head and trunk control and is able to feed from spoon, usually -age 6 months i. Discuss developmental milestones and screen for atypical development with referral to early intervention as needed b. Do not administer any medication or substance to infant age <6 months without supervision of physician ii. Car safety: current recommendations include using approved rear-facing car seat in middle back seat of car until child is age 24 months or until maximum height and weight for car seat is reached 4. Elimination: children are generally ready to begin potty training by age 2 years 3. All children age <I3 years should ride in back seat (a) <40 pounds: front-facing car seat in back seat (b) >40 pounds: booster seat in back seat (c) Belt positioning: booster seat should be continued until4 feet 9 inches taU and ages 8-I2 years b. Household safety: locks and gates to prevent access to dangerous areas such as stairs, cabinets, sharp objects, electronic appliances, outlets, swimming pools 6. Purified protein derivative test for at-risk children: urban, immigrant from endemic area, or other known tuberculosis exposure b. Encourage use of proper protective gear for sports and recreational activities and educate about concussion symptoms and treatment b. Personal risk behaviors: Counsel adolescents about safe sex, smoking, alcohol and drug avoidance, and safe driving practices 5. Most children develop motor, language, and adaptive (cognitive and social) skills in predictable sequence, for example, roll ~sit ~ pull up ~ stand ~ walk 2. Development proceeds in head-to-toe (cephalocaudal) and proximal-distal sequences a. For example, a 28·week prema· ture infant who crawls at 12 months chronologie ege is developing typically. Babinski: stroking lateral foot in heel-to-toe direction elicits extension of great toe and fanning of toes 7. Plantar/palmar grasp: touching center of palm or sole elicits fiexion of fingers/ toes 8. Psychosocial: parental sttessfunpairment, food and shelter insecurity, neglect, abuse ii. Medical: illnesses/infections, trauma, seizures, visual or hearing impairments, genetic factors iii. Language and/or speech delays most common, either in isolation or with delays in other areas of development 2. Impairment in at least 2 of these areas of function: communication, self-care, home living, social and interpersonal skills, use of community resources, functional academic skills, work and leisure, health and safety b. Most correlated with environmental factors: maternal education, poverty, neglect, and malnutrition f. Some examples include trisomy 21 and fragile X, Angelman, Prader-Willi, and Rett syndromes 3. Early identification and referral to early intervention aervices can aignificantly improve outcomes for children with developmental delays. Definition: behavioral style with which a person experiences and responds to environment 2. Separate from behavioral adjustment, physical and neurologic status, and cognitive skills ~f~ [tlltd:I! By ages 5-6 years, children can often learn to suppress expresaion of aome challenging traits such as shyness. Certain individual traits can lead to stressful relationships with caregivers in certain situations. Goodness or poorness of fit between values and expectations of parents, teachers, or other caregivers and child 3. Physical problems: increased incidence of some conditions and problems in feeding, sleep, elimination iv. Development may be influenced by temperament and ability to adapt to environmental stimuli like social skills or language C. Way for parents/caregivers to teach children responsibility, self·reliance, and social skills 2. Used in context of supportive environment and loving relationship between caregiver and child c. Parenting styles: continuum from highly controlling to highly permissive, often influenced by cultural or religious beliefs 1. Children can become rebellious/aggressive or submissive and dependent on parents as adolescents or adults 2. Children more likely to be more socially competent, responsible, and independent as adolescents and adults C. Provide distraction with different activity or object if child does not relinquish object or stop behavior 3. Beginning at age ~24 months, children learn rules and understand consequences of behavior a. Caregiver should be removed from but aware of child and should not interact with child verbally until time-out is over b. Use sticker chart or other tokens for young child or obtaining privileges to reinforce desired behaviors 4. Significant impairment in functioning in at least 2 settings due to impulsivity, inattention, and/or hyperactivity 2. Combined type: most common; children have difficulty with attention/ focus and some hyperactive/impulsive behaviors b. Inattentive type: 2nd most common; children do not have significant hyperactive or impulsive behaviors c. Chromosomal abnormalities: Klinefelter, Turner syndrome, fragile X, neurofibromatosis type I, Williams, 22qll deletion b. Q) Q) Con1ider getting e hearing test because it is common for children with a hearing deficit to be mialabeled as having an attention problem. Smaller right prefrontal cortex, caudate nucleus, and globus pallidus than age-matched controls ii. May suggest lack of connectivity of key brain regions that modulate attention, stimulus processing, and impulsivity B. Often able to cope early on in academic career, but history of some struggles with attention and focus b. Increased academic demands along with need for organization and independence become overwhelming c. Complete medical evaluation to evaluate growth and look for neurologic and genetic differences a. Allow use of technology including tape recorder, laptop, and calculator to assist in meeting learning goals 4. Symptoms do not occur exclusively during the course of a pervasive developmental disorder, sthizophrenia, or other psychotic disorder and are not better accounted for by another mental disorder. Side effects: decreased appetite, headache, stomachache, sleep difficulty, moodiness, tics, social withdrawal, elevated blood pressure, activation of mania or psychosis (very rare) iii. Can be used if coexisting conditions exist, including tics and anxiety, which may worsen with stimulants iv. Side effects: sedation (most common and may decrease over time), dry mouth, decreased compliance due to need for frequent dosing, decrease in blood pressure iv. Qualitative impairments in communication as manifested by at least 1 of the following: (al Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime (b) In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others (c) Stereotyped and repetitive use of language or idiosyncratic language (d Lack of varied. Lack of coordination of nonverbal communication, including gaze, facial expression, gesture, and sound ii. Atypical play (a) Spinning wheels (b) Peering: examining toys/objects from odd angles (c) Uning objects up (d) Collecting objects but not using them 2. Hypotonia, motor delays (gross and/or fine motor), postural instability, motor incoordination. Diagnosis: based on observed behaviors, and educational, developmental, and psychological evaluations 2. Radiologic imaging: not routinely recommended unless neurologic abnor~ malities present. Behavioral, communication, and socialization interventions should be incorporated into educational program b. Irritability including aggression, tantrums, self~injurious behaviors: may improve with atypical antipsychotics and anticonvulsants b. Separation anxiety from caregivers is e nonnsl developmental milestone in infancy seen at ages 10-18 months. Persistent/excessive fear of being alone or separated from parent/caregiver/ attachment figure b. Persistent, recurrent, or intrusive thoughts or behaviors that cause significan t distress b. Separation anxiety doaJ not interfa ra with daily life and occurs in younger children. Definition: mental health disorders with features of disobedience, anger, explosiveness, and defiance of authority ftgures causing significant impairment in social and school functioning B. Persistent anger, argumentativeness, and resistant behaviors directed especially toward authority figures b. Persistent, serious, and potentially destructive behaviors that violate societal or legal rules b. Characterized by physical aggression resulting in destruction to persons, animals, or property D. Depressive disorder is equally common in young boys and girls, but, by ado· lescence, it is more common in girls. Suicide is the 3rd lnding cause of death of ell 1~18·year-olds, after accidents and homicide. Irritability, rage, and explosive behaviors may be phenotype of "mania" in children D. Depressive disorders: best response with combination of medication and supportive therapy a. Atypical antipsychotics: aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone X. Conductive: mechanical problem of conduction of air from middle/outer ear to inner ear 2. Look at patency of external auditory meatus and for obstruction in external auditory canal ~~ c a ~. Otoacoustic emissions: measures acoustic transduction from external auditory meatus to cochlear outer hair cells c. Auditory brainstem response: measures auditory stimulus transduction to brainstem. Early intervention referral for appropriate speech therapy All infants should receive e newborn hearing screen by age 1 month end then be informally screened in the office regularly.

Initially hiv infection rate spain 120 mg starlix buy visa, the situation in poor countries was characterized primarily in terms of high fertility and high infant antiviral detox order starlix 120mg online, child highest infection rates of hiv/aids generic starlix 120mg overnight delivery, and maternal mortality rates hiv infection rates in southern africa purchase starlix 120mg online, with most deaths and illnesses attributable to infectious or tropical diseases among remote hiv infection rates by age buy starlix with a visa, largely rural populations. With growing adult (and especially elderly) populations and changing lifestyles linked to global forces of urbanization, a new set of health challenges characterized by chronic diseases, environmental overcrowding, and road traffic injuries has emerged rapidly 1 Institute of Medicine. The majority of tobacco-related deaths globally now occur settings such as Cuba and Kerala State in India. That some countries Hence, low- and middle-income countries in the twenty-first century continue to lag far behind can be understood through a comparison face a full spectrum of health challenges-infectious, chronic, and of regional differences in progress in terms of life expectancy over injury-related-at much higher incidences and prevalences than are this period. While most regions have made impressive documented in high-income countries and with many fewer resources to address these challenges. Analysis of the association between wealth and 1975 health across countries reveals that, for any given 75 level of wealth, there is a substantial variation in life expectancy at birth that has persisted despite overall global progress in life expectancy during the past 30 years. Nations such as Cuba and Costa Rica have life expectancies and childhood mortality rates 55 similar to or even better than those in high-income Namibia countries; in contrast, countries in sub-Saharan South Africa Africa and the former Soviet bloc have experienced significant reverses in these health markers in the 45 past 20 years. Despite decades of "essential packages" and "basic" health campaigns, the effective implementation of what is already known to work appears (deceptively) to be difficult. Recent analyses have begun to focus on "the how" (as opposed to "the what") of health care delivery, exploring why health progress is slow and sluggish despite the abundant availability of proven interventions for health conditions in low- and middle-income countries. Three general categories of reasons are being identified: (1) shortfalls in performance of health systems; (2) stratifying social conditions; and (3) skews in science. However, the delivery of different interventions is often facilitated by a common set of resources or functions: money or financing, trained health workers, and facilities with reliable supplies fit for multiple purposes. Unfortunately, health systems in most lowand middle-income countries are largely dysfunctional at present. In the large majority of low- and middle-income countries, the level of public financing for health is woefully insufficient: whereas highincome countries spend, on average, 7% of the gross domestic product on health, middle-income countries spend <4% and low-income countries <3%. External financing for health through various donor channels has grown significantly over time. The predominant form of health care financing-charging patients at the point of service-is the least efficient and the most inequitable, tipping millions of households into poverty annually. Health workers, who represent another critical resource, are often inadequately trained and supported in their work. Recent estimates indicate a shortage of >4 million health workers, constituting a crisis that is greatly exacerbated by the migration of health workers from low- and middle-income countries to high-income countries. Sub-Saharan Africa carries 24% of the global disease burden but has only 3% of the health workforce. The International Organization for Migration estimated in 2006 that there were more Ethiopian physicians practicing in Chicago than in Ethiopia itself. As average levels of health vary across regions and countries, so too do they vary within countries. Indeed, disparities within countries are often greater than those between high-income and lowincome countries. For example, if low- and middle-income countries could reduce their overall childhood mortality rate to that of the richest one-fifth of their populations, global childhood mortality could be decreased by 40%. Disparities in health are mostly a result of social and economic factors such as daily living conditions, access to resources, and ability to participate in life-affecting decisions. In most countries, the health care sector actually tends to exacerbate health inequalities (the "inverse-care law"); because of neglect and discrimination, poor and marginalized communities are much less likely to benefit from public health services than those that are better off. Reforming health systems toward people-centered primary care provides an opportunity to reverse these negative trends. Mortality of children under 5 years old, by place of residence, in five countries. Moreover, facilities fail to provide safe care: new evidence suggests much higher rates of adverse events among hospitalized patients in low- and middle-income countries than in high-income countries. Weak government planning, regulatory, monitoring, and evaluation capacities are associated with rampant, unregulated commercialization of health services and chaotic fragmentation of these services as donors "push" their respective priority programs. With such fragile foundations, it is not surprising that lowcost, affordable, validated interventions are not reaching those who need them. Most worrisome are the pervasive forces of social inequality that serve to marginalize populations with disproportionately large health needs. Why should a poor slum dweller with no income be expected to come up with the money for a bus fare needed to travel to a clinic to learn the results of a sputum test for tuberculosis How can a mother living in a remote rural village and caring for an infant with febrile convulsions find the means to get her child to appropriate care Shaky or nonexistent social security systems, dangerous work environments, isolated communities with little or no infrastructure, and systematic discrimination against minorities are among the myriad forces with which efforts for more equitable health care delivery must contend. The past decade has seen growing efforts to right this imbalance with research and development investment for new drugs, vaccines, and diagnostics that effectively cater to the specific health needs of populations in low- and middleincome countries. For example, the Medicines for Malaria Venture has revitalized a previously "dry" pipeline for new malaria drugs. As discussed above, the primary constraint on better health in low- and middle-income countries is related less to the availability of health technologies and more to their effective delivery. Underlying these systems and social challenges to greater equity in health is a major bias regarding what constitutes legitimate "science" to improve health equity. The complexity of systems and social context is such that this issue of delivery requires an enormous investment in terms not only of money but also of scientific rigor, with the development of new research methods and measures and the attainment of greater legitimacy in the mainstream scientific establishment. These common challenges to low- and middle-income countries partly explain the resurgence of interest in the primary health care approach. In some countries (mostly middle-income), significant progress has been made in expanding coverage by health systems based on primary care and even in improving indicators of population health. More countries are embarking on the creation of primary care services despite the challenges that exist, particularly in low-income countries. Even when these challenges are acknowledged, there are many reasons for optimism that low- and middle-income countries can accelerate progress in building primary care. This interest has been driven by many of the same issues that led to the Declaration of Alma Ata: rapidly increasing disparities in health between and within countries, spiraling costs of health care at a time when many people lack quality care, dissatisfaction of communities with the care they are able to access, and failure to address changes in health threats, especially noncommunicable disease epidemics. These challenges require a comprehensive approach and strong health systems with effective primary care. Weak health systems have proved a major obstacle to delivering new technologies, such as antiretroviral therapy, to all who need them. Changing disease patterns have led to a demand for health systems that can treat people as individuals whether or not they present to a health facility with the public health "priority". We discuss experiences in low- and middle-income countries in relation to primary care in greater detail below. First, we consider the features of primary health care and primary care as currently understood. This resolution did not suggest that nothing had changed in the intervening 30 years since the declaration, nor did it dispute that its prescription needed reframing in light of changing public health needs. As discussed below, this report highlights four broad areas in which reform is required. One of these areas-the need to organize health care so that it places the needs of people first-essentially relates to the necessity for strong primary care in health systems and what this requirement entails. All four areas require action to move health systems in a direction that will reduce disparities and increase the satisfaction of those they serve. Universal Coverage Reforms to Improve Health Equity Despite progress in many countries, most people in the world can receive health care services only if they can pay at the point of service. More than 100 million people are driven into poverty each year by health care costs, with countless others deterred from accessing services at all. Moving toward prepayment financing systems for universal coverage, which ensure access to a comprehensive package of services according to need without precipitating economic ruin, is therefore emerging as a major priority in low- and middle-income countries. Increasing coverage of health services can be considered in terms of three axes: the proportion of the population covered, the range of services underwritten, and the percentage of costs paid. Moving toward universal coverage requires ensuring the availability of health care services to all, eliminating barriers to access, and organizing pooled financing mechanisms, such as taxation or insurance, to remove user fees at the point of service. It also requires measures beyond financing, including expansion of health services in poorly served areas, improvement in the quality of services provided to marginalized communities, and increased coverage of other social services that significantly affect health. Service Delivery Reforms to Make Health Systems People-Centered Health systems have often been organized around the needs of those who provide health care services, such as clinicians and policymakers. The result is a centralization of services or the provision of vertical programs that target single diseases. The principles of primary health Total health expenditure care, including the development of primary care, reorient care around the needs of the people to whom services cater. This "people-centered" approach aims to provide health care that is both more effective and appropriate. The increase in noncommunicable diseases in low- and middleincome countries offers a further stimulus for urgent reform of service delivery to improve chronic disease care. As discussed above, large numbers of people currently fail to receive relatively low-cost interventions that have reduced the incidence of these diseases in high-income countries. Delivery of these interventions requires health systems that can address multiple problems and manage people over a long period within their own communities, yet many low- and middle-income countries are only now starting to adapt and build primary care services that can address noncommunicable diseases and communicable diseases requiring chronic care. People-centered care requires a safe, comprehensive, and integrated response to the needs of those presenting to health systems, with treatment at the first point of contact or referral to appropriate services. This enhanced understanding is made possible by improvements in the continuity of care so that responsibility transcends the limited time people spend in health care facilities. Primary care plays a vital role in navigating people through the health system; when people are referred elsewhere for services, primary care providers must monitor the resulting consultations and perform follow-up. All too often, people do not receive the benefit of complex interventions undertaken in hospitals because they lose contact with the health care system once discharged. Comprehensiveness and continuity of care are best achieved by ensuring that people have an ongoing personal relationship with a care team. Public Policy Reforms to Promote and Protect the Health of Communities Public policies in sectors other than health care are essential to reduce disparities in health and to make progress toward global public health targets. While tobacco control provides a striking example of what is possible if different sectors work together toward health goals, the lack of implementation of many evidence-based tobacco control measures in most countries just as clearly illustrates the difficulties encountered in such intersectoral work and the unrealized potential of public policies to improve health. At the local level, primary care services can help enact health-promoting public policies in other sectors. Leadership Reforms to Make Health Authorities More Responsive the Declaration of Alma Ata emphasized the importance of participation by people in their own health care. Contemporary health challenges require new models of leadership that acknowledge the role of government in reducing disparities in health but that also recognize the many types of organizations that provide health care services. This difficult task requires a massive reinvestment in leadership and governance capacity, especially if action by different sectors is to be effectively implemented. Moreover, disadvantaged groups and other actors are increasingly expecting that 13e-5 Chapter 13e Primary Care in Low- and Middle-Income Countries Reduce cost sharing Include other services Height: what proportion of the costs is covered Extend to uninsured Public expenditure on health Depth: which benefits are covered The complex landscape for leadership at the national level is mirrored in many ways at the international or global level. The transnational character of health and the increasing interdependence of countries with respect to outbreak diseases, climate change, security, migration, and agriculture place a premium on more effective global health governance. This section describes the experiences of a selection of low- and middle-income countries in improving primary care services that have enhanced the health of Health Program has already contributed to impressive gains in population health, particularly in terms of childhood mortality and health their populations. In fact, this program has already had an especially marked health care on a national level. Rather, most focused on expanding impact on childhood mortality reduction in less developed areas primary care services to specific communities (often rural villages). Chile has also built on its existing primary care services in the past making use of community volunteers to compensate for the absence of facility-based care. The Chinese expansion of primary effort has been made in concert with measures aimed at reducing care services included a massive investment in infrastructure for pub- social inequalities and fostering development, including social welfare lic health. They received a basic level of training improved maternal and child health and have reduced health inequithat enabled them to provide immunizations, maternal care, and basic ties. In addition to directly enhancing primary care services, Brazil medical interventions, including the use of antibiotics. Through the and Chile have instituted measures to increase both the accountability work of the barefoot doctors, China brought low-cost universal basic of health providers and the participation of communities in decisionhealth care coverage to its entire population, most of which had previ- making. In Brazil, national and regional health assemblies with high levels of public participation are integral parts of the health policy­ ously had no access to these services. Other countries that have made recent progress with primary health health care at low cost appeared to have been achieved. Despite lower levels of economic development and health spending, all of these juris- care include Bangladesh, one of the poorest countries in the world. Analysis of these has seen a dramatic increase in life expectancy, and childhood mortalexperiences revealed a common emphasis on primary care services, ity rates are now lower than those in neighboring nations such as India with expansion of care to the entire population free of charge or at and Pakistan. The expansion of access to primary health care services low cost, combined with community participation in decision-making has played a major role in these achievements. During the three decades since tion on improving the lives and livelihoods of poor women and their the Rockefeller meeting, some of these countries have built on this families through innovative and integrated microcredit, education, progress, while others have experienced setbacks. The above examples, along with others from the past 30 years in in developing primary care services show that the same combination of features is necessary for success. For example, Brazil-a large countries such as Thailand, Malaysia, Portugal, and Oman, illustrate country with a dispersed population-has made major strides in how the implementation of a primary health care approach, with a increasing the availability of health care in the past quarter century. In greater emphasis on primary care, has led to better access to health this millennium, the Brazilian Family Health Program has expanded care services-a trend that has not been seen in many other low- and progressively across the country, with almost all areas now covered. This trend, in turn, has contributed to this program provides communities with free access to primary care improvements in population health and reductions in health inequiteams made up of primary care physicians, community health work- ties. However, as these nations have progressed, other countries have ers, nurses, dentists, obstetricians, and pediatricians. In responsible for the provision of primary care to all people in a specified sub-Saharan Africa, undermining of primary care services has congeographic area-not only those who access health clinics. Countries such as Botswana and Zimbabwe of people within the area covered by the primary care team. Problems implemented primary health care strategies in the 1980s, increasing with access to health care persist in Brazil, especially in isolated areas access to care and making impressive gains in child health.

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