Carmen B. Smith, PharmD, BCPS

• Assistant Professor—Pharmacy Practice, Division of Acute Care Pharmacy, St. Louis College of Pharmacy, St. Louis, Missouri

https://www.stlcop.edu/directory/employee/carmen-smith

Castor oil medications routes purchase mesalamine 400 mg with visa, hot baths 7 medications that can cause incontinence order mesalamine 400mg overnight delivery, sexual intercourse medical treatment cheap mesalamine 400 mg online, and nipple stimulation all have been recommended for labor induction medications voltaren mesalamine 800 mg with mastercard. Maintenance therapy with tocolytics has not been shown conclusively to be of value medications prescribed for ptsd order mesalamine 800 mg on-line. Antenatal Corticosteroids A Cochrane meta-analysis demonstrates the benefit of administering antenatal corticosteroids for fetal lung maturation in order to prevent respiratory distress syndrome medications zanaflex purchase mesalamine 800mg visa, intraventricular hemorrhage, and death in infants delivered prematurely. The most commonly used agents are evening primrose oil, black haw, black and blue cohosh, and red raspberry leaves. Cervidil, a vaginal insert, contains 10 mg dinoprostone with a slower, more constant release of medication than the gel. Patients must be attached to a fetal heart rate monitor for the duration of Cervidil use and for 15 minutes after its removal. Misoprostol, a prostaglandin E1 analog, is an effective and inexpensive drug for cervical ripening and labor induction. The most commonly encountered side effects are uterine hyperstimulation and meconiumstained amniotic fluid. Use of misoprostol is contraindicated in women with a previous uterine scar because of its association with uterine rupture, a catastrophic medical event. Mifepristone is an antiprogesterone agent that is being studied as an induction agent. Oxytocin is the most commonly used agent for labor induction after cervical ripening. By the end of pregnancy, the number of oxytocin receptors has increased by 300-fold. Oxytocin has been shown to be effective in both low-dose (physiologic) and high-dose (pharmacologic) regimens. Pharmacologic Approaches to Labor Pain Management A joint position statement on pain in labor published in 2000 stated that labor is a medical indication for women to receive pain relief upon request. Between 39% and 56% of women receive parenteral narcotics to alleviate labor pain. In comparison with epidural analgesia, parenteral opioids have lower rates of oxytocin augmentation, result in shorter stages of labor, and require fewer instrumental deliveries. Approximately 60% of women choose an epidural for pain relief during labor and report better pain relief than with other analgesic modalities. Side effects of the regional anesthesia include hypotension, pruritus, and inability to void. One study showed difficulty breast-feeding in women who had received labor epidurals. A rare complication of epidural anesthesia is puncture of the subarachnoid space leading to a severe headache, which occurs in approximately 2% of women. Low back pain has not been shown to be associated with the use of epidural analgesia. Paracervical blocks using local anesthesia may decrease pain associated with the first phase of labor. During the second phase of labor, the pain is associated with perineal stretching. To the contrary, two systematic reviews have not substantiated an increased rate of cesarean delivery with epidural analgesia compared with parenteral opioids. However, one of the reviews did caution that data are not sufficient to rule out such an association. Women who receive continuous support from a doula, a laywoman trained in labor support, have fewer operative vaginal deliveries, cesarean deliveries, and requests for pain medication. Warm water baths provide temporary pain relief but have not been shown to decrease the use of pharmacologic pain treatments. Intradermal injections of sterile water in the sacral area have been shown to decrease back pain during labor for 45 to 90 minutes. One study of acupuncture versus no acupuncture showed that women required less analgesia but were no more satisfied with this mode of pain control. Postpartum hemorrhage is defined as loss of more than 500 mL of blood within 24 hours of delivery. Active management of the third stage of labor involves administration of a uterotonic medication (intramuscular oxytocin, ergotamine, or combination) before delivery of the placenta; early clamping and cutting of the umbilical cord; and controlled traction of the cord. However, use of ergotamines is associated with an increased risk of maternal elevated blood pressure, nausea, and vomiting. Healthcare providers should encourage breast-feeding women who require medications to continue breast-feeding whenever possible. Extensive research has demonstrated the wide variety of benefits (health, nutritional, immunologic, psychological, economic, developmental, and social) imparted by breast-feeding to infants, mothers, families, and society. Healthy People 2010 set a target of 75% of neonates being breast-fed at the time of birth and 50% of infants continued being breast-fed at 6 months of age. Low-molecular-weight (<200 kDa) drugs passively diffuse into breast milk, but larger molecules are not likely to transfer in large amounts. Colostrum is lower in fat content than mature milk, so a drug with high lipid solubility will achieve a higher concentration in mature milk. However, upon encountering the lower pH of breast milk, molecules become ionized and less likely to diffuse back into maternal circulation. Likewise, drugs with longer half-lives are more likely to maintain higher levels in breast milk, resulting in greater exposure to the infant. Infant-related factors also may influence the amount of drug ingested through breast-feeding. Exclusively breast-fed younger infants are more likely to ingest larger amounts of drugs than older infants who receive other foods. Drugs that denature in gastric acid (aminoglycosides, omeprazole, heparin, insulin) are less likely to be absorbed by infants. Finally, infants may vary in their ability to metabolize and excrete ingested medication. Strategies for reducing the amount of drug transferred to the infant may include selection of medicines that would be considered safe for use in the infant. Drugs with lower oral bioavailability and lower lipid solubility are good choices. Because of the scarcity of industry-based research on transfer of drugs into breast milk, information from drug manufacturers is generally a poor source of information for the provider. About 1% to 2% of women who breast-feed will experience mastitis, and the highest incidence of mastitis occurs within 1 to 2 weeks of beginning breast-feeding. Risk factors for developing mastitis include breast engorgement, plugged milk ducts, and cracked nipples. Nondrug therapies that may be helpful are application of warm or cold pack and wearing a bra. Symptoms such as anxiety, anger, and sadness generally resolve within 2 weeks postpartum. Postpartum psychosis is more severe but is rare, affecting one in 1,000 new mothers. Postpartum depression usually begins within the first 3 months after delivery and affects 8% to 15% of women. In cases where pharmacotherapy is warranted, selection of medication with low transfer to breast milk is desired. Treatment should continue for a minimum of 29 weeks, consistent with treatment guidelines for a single episode of depression. This can be problematic, as well as distressing, for mothers who desire to breast-feed their infants. Breast milk production can be increased up to 100% or more in women who are 1 month postpartum or less. In mothers who are 8 to 12 weeks postpartum, milk production may be increased up to 40%. Breast milk production may decrease after metoclopramide therapy is stopped, but production will continue if lactation has been established successfully. Risk classifications systems for drug use during pregnancy: Are they a reliable source of information Management of gestational diabetes: Pharmacologic treatment options and glycemic control. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Many women perceive a high inherent risk of birth defects with drug exposure during pregnancy. This perception, linked with a high rate of unplanned pregnancies, may create anxiety because of drug exposure prior to the discovery of pregnancy. Some medications are considered safe for use in pregnancy because of frequent use with no apparent increase in the rate of congenital problems. Women using these medications should be reassured that these choices are unlikely to increase the risk of birth defects. In some cases, ensuring the health of the mother and, in some instances, of the fetus will require selection or continuation of medications that have been associated with a higher risk of adverse effects to the fetus. In these instances, realistic information about the types and likelihood of adverse effects will aid the patient and her family in making decisions. Healthcare providers who care for pregnant women must work in collaboration to seek, evaluate, and present the most contemporary and accurate information to their patients. Use of technology to access evidence-based resources, databases related to drug use in pregnancy, and primary and secondary literature may assist healthcare practitioners in accessing relevant medication information to manage drug therapy needs during pregnancy and lactation. Ensuring the safe and effective use of medications during pregnancy: Planning and prevention through preconception care. Quick reference from the Working Group Report on Managing Asthma During Pregnancy: Recommendations for pharmacologic treatment. Department of Health and Human Services, National Institutes of Health National Heart, Lung, and Blood Institute, 2005. Increased risk for nonsyndromic cleft palate among infants exposed to lamotrigine during pregnancy [abstract]. Practice parameter: Management issues for women with epilepsy (summary statement). National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Tocolytic treatment for the management of preterm labor: A review of the evidence. Magnesium sulphate for preventing preterm birth in threatened preterm labour: Review. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Effect of labor epidural anesthesia on breast-feeding healthy full-term newborns delivered vaginally. Adverse effects or difficulties using the chosen method should be monitored carefully and managed in consideration of patient-specific factors. Accurate and timely counseling on the optimal use of the contraceptive method and strategies for minimizing sexually transmitted diseases must be provided to all patients when contraceptive pharmacotherapy is initiated and on an ongoing basis. Certain oral contraceptives in high doses can be used as emergency contraception to prevent pregnancy after unprotected intercourse. The cycle of menstruation begins with menarche, usually around age 12 years, and continues to occur in nonpregnant women until menopause, usually around age 50 years. The menstrual cycle comprises three phases: follicular (or preovulatory), ovulatory, and luteal (or postovulatory). The time after ovulation is referred to as the luteal phase, which lasts until the beginning of the next menstrual cycle. The median menstrual cycle length is 28 days, but it can range from 21 to 40 days. Generally, variation in length is greatest in the follicular phase, particularly in the years immediately after menarche and before menopause. Unintended pregnancy is a significant public health problem with economic, health, personal, and social consequences. Estradiol serves to stop the menstrual flow from the previous cycle, thickening the endometrial lining of the uterus to prepare it for embryonic implantation. Estrogen is responsible for increased production of thin, watery cervical mucus, which will enhance sperm transport during fertilization. If a follicle has insufficient aromatase, androgen will accumulate, and the follicle will not survive. After ovulation, the oocyte is released and travels to the fallopian tube, where it can be fertilized and transported to the uterus for embryonic implantation. Conception is most successful when intercourse takes place from 2 days before ovulation to the day of ovulation. If fertilization or implantation does not occur, the corpus luteum degenerates, and progesterone production declines. As progesterone levels decline, endometrial shedding (menstruation) occurs, and a new menstrual cycle begins. Luteal Phase After rupture of the follicle and release of the ovum, the remaining luteinized follicles become the corpus luteum, which synthesizes androgen, estrogen, and progesterone. The actual effectiveness of any contraceptive method is difficult to determine because many factors affect contraceptive failure.

Prevalence data are confounded by the lack of a standardized definition of anemia medicinenetcom medications buy mesalamine 400 mg on line. Because no screening guidelines for anemia in the elderly exist medicine ball chair order 400 mg mesalamine overnight delivery, the prevalence may be even higher than suspected medicine gabapentin 300mg capsules purchase 400mg mesalamine. Evidence suggests that anemia is not an innocent bystander; it can affect both length and quality of life medications used to treat anxiety discount 400 mg mesalamine amex. Retrospective observational studies in hemodialysis patients and heart failure patients suggest that anemia is an independent risk factor for mortality 4 medications at walmart cheap 400mg mesalamine with amex. Similarly stroke treatment 60 minutes order mesalamine 400mg with visa, among adults, anemia is associated with cognitive dysfunction in patients with renal failure, those with cancer, and among community-dwelling elders. The effect of treatment on patient outcomes must be the focus of research on each specific type of anemia. Global goals of treatment in anemic patients are to alleviate signs and symptoms, correct the underlying etiology, and prevent recurrence of anemia. They can be a manifestation of a host of systemic disorders, such as infection, chronic renal disease, or malignancy. Because anemias are often a sign of underlying pathology, rapid diagnosis of the cause is essential. An example of a microcytic anemia is iron deficiency, whereas a normocytic anemia may be associated with recent blood loss or chronic disease. Inclusion of the underlying cause of the anemia makes diagnostic terminology easier to understand. Microcytic anemias are pathogenically a result of a quantitative deficiency in Hb synthesis, usually due to iron deficiency or impaired iron utilization. Microcytosis and hypochromia are the morphologic abnormalities that provide evidence of impaired Hb synthesis. Macrocytic anemias can be divided into megaloblastic and nonmegaloblastic anemias. The type of macrocytic anemia can be distinguished microscopically by peripheral blood smear examination. The most common cause of megaloblastic anemia is vitamin B12 and/or folate deficiency. Nonmegaloblastic anemias do not have a common pathogenic mechanism and may be macrocytic or normocytic. This type of macrocytic anemia may be due to etiologies such as liver disease, hypothyroidism, hemolytic anemia, and alcoholism. Hemolytic anemias often are macrocytic, resulting in increased reticulocyte counts, and reticulocytes are larger on average than more mature red cells. Subsequent divisions yield basophilic erythroblasts, polychromatic erythroblasts, pyknotic erythroblasts, reticulocytes, and finally erythrocytes. During this process, the nucleus becomes smaller with each division, finally disappearing in the normal erythrocyte. The reticulocyte loses its nucleus and becomes an erythrocyte within several days. More than 90% of the protein content of the erythrocyte consists of the oxygen-carrying molecule Hb. Erythrocytes compose 40% to 50% of the total blood volume and have a normal survival time of 120 days. Each chain is linked to a heme group consisting of a porphyrin ring structure with an iron atom chelated at its center, which is capable of binding oxygen. The initial step in the synthesis of heme from the substrate succinyl CoA and glycine requires the presence of pyridoxine phosphate (vitamin B6) as a catalyst. The affinity of Hb for oxygen is influenced by three intracellular components and by temperature. This physiologic compensation also increases plasma volume, which can increase tissue perfusion. Another 3 to 7 mg of iron is bound to transferrin in plasma, and the remaining iron exists as storage iron in the form of ferritin or hemosiderin. Due to the toxicity of inorganic iron, the body has an intricate system for iron absorption, transport, storage, assimilation, and elimination. Hepcidin is a regulator of intestinal iron absorption, iron recycling and iron mobilization from hepatic stores. Hepcidin synthesis is increased by iron loading and decreased by anemia and hypoxia. Hepcidin is induced during infections and inflammation, which allows iron to sequester in macrophages, hepatocytes, and enterocytes. Epidemiologic studies show a correlation between milk intake and prevalence of iron deficiency. Finally, because gastric acid improves iron absorption, patients who have undergone a gastrectomy or have achlorhydria have decreased iron absorption. Transferrin enters cells by binding to transferrin receptors, which circulate and then attach to cells needing iron. Conversely, there are fewer transferrin receptors on the surface of cells that do not need iron, thus preventing iron-replete cells from receiving excess iron. Transferrin delivers extra iron to other body storage sites, such as the liver, marrow, and spleen, for later use. Ferritin consists of a Fe3+ hydroxyphosphate core surrounded by a protein shell called apoferritin. Hemosiderin can be described as compacted ferritin molecules with an even greater iron/protein shell ratio. The normal daily western diet contains approximately 12 to 15 mg of iron, mainly in the ferric (Fe3+) nonabsorbed form. After iron is ionized by stomach acid and then reduced to the Fe2+ state, it is absorbed primarily in the duodenum, and to a smaller extent in the jejunum, via intestinal mucosal cell uptake. As physiologic iron levels decrease, gastrointestinal absorption of iron increases. The daily recommended dietary allowance for iron is 8 mg in adult males and postmenopausal females, and 18 mg in menstruating females. Children require more iron because of growth-related increases in blood volume, and pregnant women have an increased iron demand brought about by fetal development. Iron overload does not occur, however, because only the amount of iron lost per day is absorbed. Heme iron, which is found in meat, fish, and poultry, is approximately three times more absorbable than the nonheme iron found in vegetables, fruits, dried beans, nuts, grain products, and dietary supplements. Heme and nonheme iron are absorbed by different receptors on the intestinal mucosa. Gastric acid and other dietary components such as ascorbic acid increase the absorption of nonheme iron. Dietary components that form insoluble complexes with iron (phytates, tannates, and phosphates) decrease absorption. Polyphenols bind the iron and decrease nonheme iron absorption when large amounts of tea or coffee are consumed with a meal. Amino acids from the globin chains return to an amino acid pool; heme oxygenase acts on the porphyrin heme structure to form biliverdin and to release its iron. Iron returns to the iron pool to be reused, although biliverdin is further catabolized to bilirubin. The bilirubin is released into the plasma, where it binds to albumin and is transported to the liver for glucuronide conjugation and excretion via bile. If the liver is unable to perform the conjugation, as occurs with intrinsic liver disease or oversaturation of conjugation enzymes by excessive cell hemolysis, the result is an elevated indirect (unconjugated) bilirubin. If the biliary excretion pathway for the already conjugated bilirubin is obstructed, an elevated direct bilirubin results. Comparison of direct and indirect bilirubin values helps to determine if the defect in bilirubin clearance occurs before or after bilirubin enters the liver. Occupation, social habits, travel history, and diet all can be important in identifying causes of anemia. Additionally, information about concurrent nonhematologic disease states and a drug ingestion history are essential when evaluating the cause of the anemia (see Chap. History of blood transfusions, liver disease, peptic ulcers, gastrointestinal tract malignancies, and exposure to toxic chemicals also should be obtained. Because anemias are a sign of disease, clinical presentation may relate to the underlying pathology. Presenting signs and symptoms of anemias depend on the rate of development and the age of the patient, as well as the cardiovascular status of the patient. If the myocardium is healthy and the anemia evolves slowly, the combined effects of the shift in the oxygen dissociation curve and increased cardiac output may allow acclimatization at very low Hb concentrations. The signs and symptoms in elderly patients with anemia may be attributed to their age or concomitant disease states. Premature infants with anemia may be asymptomatic or have tachycardia, poor weight gain, increased supplemental oxygen needs, or increased episodes of apnea or bradycardia. With severe intravascular blood volume loss, peripheral vasoconstriction and central vasodilation preserve blood flow to vital organs. Vascular compensation results in decreased systemic vascular resistance, increased cardiac output, and tachycardia. If onset is more chronic, presenting symptoms may include fatigue, weakness, headache, symptoms of heart failure, vertigo, 1644 faintness, sensitivity to cold, pallor, and loss of skin tone. Traditional signs of anemia, such as pallor, have limited sensitivity and specificity and may be misinterpreted. With chronic bleeding, there is time for equilibration with extravascular space, and total blood volume remains normal. These symptoms are not likely to appear until the Hb concentration falls to a level of 9 g/dL or below. Clinically, patients with vitamin B12 deficiency may be pale and mildly icteric, and they may develop gastric mucosal atrophy. Neurologic findings in vitamin B12 deficiency, which often precede hematologic findings, may be partly due to impairment of conversion of homocysteine to methionine, as methionine is necessary for production of choline and choline-containing phospholipids. Neurologic effects of vitamin B12 deficiency may occur even in the absence of anemia. Early neurologic findings include numbness and paresthesias, then peripheral neuropathy, ataxia, diminished vibratory sense, decreased proprioception, and imbalance, as demyelination of the dorsal columns and corticospinal tract develop. Psychiatric findings include irritability, personality changes, memory impairment, dementia, depression, and, infrequently, psychosis. Other reported symptoms include glossitis, muscle weakness, dysphagia, and anorexia. Symptoms associated with folate deficiency are similar to those seen in patients with vitamin B12 deficiency, with the absence of neurologic symptoms. Although the symptoms of anemia will improve with folate replacement and a partial hematologic response will occur, the neurologic manifestations of vitamin B12 deficiency will not be reversed with folic acid replacement therapy and consequently may progress or become irreversible if not treated. An alteration in this ratio may occur with abnormal cell size or shape and often indicates the pathology. The results of the preliminary evaluation determine the need for other studies, such as examination of a peripheral blood smear. Based on laboratory test results, anemia can be categorized into three functional defects: 1. There are many exceptions and additions to this algorithm, but it can serve as a guide to the typical presentation of common types and causes of anemia. Cells are considered macrocytic if they are larger than normal, microcytic if they are smaller than normal, and normocytic if their size falls within normal limits. Folic acid and vitamin B12 deficiency anemias yield macrocytic morphology, whereas iron deficiency and thalassemia are examples of microcytic anemias. A Hemoglobin Values given for Hb represent the amount of Hb per volume of whole blood. The Hb level can be used as a very rough estimate of the oxygen-carrying capacity of blood. The reticulocyte count in normocytic anemia can differentiate hypoproliferative marrow from a compensatory marrow response to an anemia. It is used to exclude other causes of anemia and to detect evidence of marrow replacement. Additionally, it provides information on variations in cell size (anisocytosis) and shape (poikilocytosis). Ferritin levels indicate the amount of iron stored in the liver, spleen, and bone marrow cells. Serum ferritin is an acute phase reactant, so chronic infection or inflammation can increase its concentration independent of iron status, masking depleted tissue stores. This limits the specificity and utility of the serum ferritin if the level is normal or high in a chronically ill patient. In these patients, iron, even if present in these tissue stores, may not be available for erythropoiesis. The sTfR concentration is inversely correlated with tissue iron stores, and elevated levels are predictive of iron deficiency. Unlike conventional laboratory tests, the sTfR is not an acute phase reactant, so its level remains normal in patients with chronic disease. Serum Iron the level of serum iron is the concentration of iron bound to transferrin. Serum iron levels show 20% to 30% diurnal variation (higher in the morning, lower in the afternoon) and 20% to 25% day-to-day variation. Folic Acid the results of folic acid measurements vary depending on the assay method used.

Nutrient requirements vary with age 9 treatment issues specific to prisons discount mesalamine 800mg fast delivery, gender symptoms for pregnancy mesalamine 800 mg generic, size medications you cannot crush purchase mesalamine 400mg amex, disease state symptoms 2016 flu cheap 800mg mesalamine free shipping, clinical condition medicine x xtreme pastillas purchase mesalamine 800 mg, nutrition status treatment 7 buy mesalamine 800 mg with visa, and physical activity level. An estimate of nutrient requirements must be made using guidelines interpreted in the context of these patient-specific factors. Estimated average requirements can be used for planning nutrient intakes for groups, as they are defined as the amount of the nutrient that meets the needs of 50% of persons in a given group. Adequate intakes are defined as the average intake of a designated group that appears to sustain a particular nutrition state, growth, or other functional indication of health. Finally the tolerable upper intake level is the maximum nutrient intake that is unlikely to pose adverse affects in almost all persons in a designated group. Hand-grip strength (forearm muscle dynamometry), respiratory muscle strength, and muscle response to electrical stimulation have been used. Measuring hand-grip strength is a relatively simple, noninvasive, and inexpensive (most hand-grip dynamometers cost less than $400) procedure that correlates with patient outcome. In the setting of malnutrition, increased fatigue and a slowed muscle relaxation rate have been noted; these indices return to normal after refeeding. Both these parameters have the advantage of being indicators of tissue function rather than composition. Their usefulness in clinical practice is currently hampered by a lack of appropriate reference standards and limited data confirming their sensitivity and specificity for nutrition assessment. These methods generally are complex, require expensive technology, and at present are limited to research centers. The recommendations for children are similar: carbohydrate, 45% to 65%; fat, 30% to 40%; and, protein, 10% to 30%. Infants, especially premature infants, need a higher proportion of fat (approximately 40% to 50% of total calories) in their diets to ensure normal neurologic development. Supporters of total calories state that the nonprotein calorie approach overestimates energy needs because 15% of daily energy expenditure is derived from protein breakdown. Even with adequate energy intake, protein metabolism is not necessarily prioritized for anabolism, especially during stress. Additionally, standard equations for estimating energy needs were derived using total energy-expenditure measurements. Regardless of the method chosen, the practitioner should consistently document which method was used. The simplest method to assess energy requirements is to use population estimates of calories required per kilogram of body weight. This method assumes standard values for the energy requirements associated with various disease states or clinical conditions, as well as the additional requirements for repletion of a malnourished individual. It does not take into consideration age- or gender-related differences in energy needs. Caloric requirements increase with fever, sepsis, major surgery, trauma, burns, and long-term growth failure, and in the presence of chronic conditions such as bronchopulmonary dysplasia, congenital heart disease, and cystic fibrosis. Clinical judgment and close monitoring are essential to ensure that the desired nutrition therapy outcomes are attained. These equations were derived from oxygen (O2) consumption measurements made on normally nourished individuals who were in a fasting and resting state. Numerous equations and "stress" factors have been published, but none has been shown to be superior in all situations. Measuring energy expenditure with indirect calorimetry is potentially more accurate, especially for the stressed, hospitalized, and ventilated patient, but it is neither appropriate nor available for all patients. Regardless of the method chosen, careful monitoring of the response to nutrition intervention is imperative. Mechanically ventilated patients are technically easier to study because the indirect calorimeter circuit can be integrated into the ventilator circuit. The patient must be at complete rest for 1 hour, must not receive bolus feedings either by feeding tube or orally for 4 hours, should have no changes in substrate delivery for 12 hours, must be on a fraction of inspired O2 of less than 0. Unfortunately, many of the patients in whom indirect calorimetry would be most useful will not meet these requirements. It is often extrapolated to a 24-hour period to approximate daily energy requirements. Protein needs in kidney failure are variable and 2361 affected by the various kidney replacement therapies available. The application of these guidelines requires both clinical judgment and frequent monitoring of kidney and liver function, serum chemistries, clinical condition, and nutrition outcomes (see Chap. Nitrogen is found only in protein and at a relatively constant ratio of 1 g nitrogen per 6. This ratio may vary somewhat for enteral and parenteral feeding formulations, depending on the biologic value of the protein source. Adequacy of protein intake can be assessed clinically by measuring urinary nitrogen excretion and comparing it with nitrogen intake-a nitrogen balance study. As the stress level increases, a concomitant increase in protein catabolism results in an increase in urinary nitrogen excretion. Usually the amount of urea nitrogen is measured in a 24-hour urine urea collection. In healthy individuals, the quantity of urine urea nitrogen accounts for 80% to 90% of the total urine nitrogen excreted. Nitrogen output (g/ day) can be approximated as 24-hour urine urea nitrogen + 4, where 4 is a factor representing usual skin, fecal, and respiratory nitrogen losses. Overall, fat should represent no more than 10% to 35% of total calories, with the recommendation that saturated fatty acids, trans fatty acids, and dietary cholesterol intake be kept as low as possible while consuming a nutritionally adequate diet. An additional 50 mL/kg per day should be provided for each kilogram of body weight between 11 kg and 20 kg, and 20 mL/kg per day for each kilogram above 20 kg. Thus daily fluid needs for a child weighing 8 kg would be at least 800 mL/day, whereas at least 1,350 mL/day would be needed for a 17-kg child. Monitoring of urine output and specific gravity as well as serum electrolytes and weight changes can be used to assess fluid status. A urine output of at least 1 mL/kg per hour (in children) and approximately 50 mL per hour (in adults) is considered adequate to ensure tissue perfusion. Urine output should be higher if large fluid volumes or high renal solute loads. Concomitant diuretic therapy as a result of increased solute excretion limits the usefulness of urine specific gravity as an index of fluid status. Some evidence also suggests that fiber has a role in the prevention of colon cancer and promotion of weight control through its effect on satiety. Men and women 50 years of age and younger should ingest 38 g/day and 25 g/day, respectively, of total fiber. For men and women older than 50 years of age, the recommended intakes are 30 g/day and 21 g/day, respectively. However, many water-soluble micronutrients are excreted more rapidly via the kidneys when administered intravenously. Sodium, potassium, magnesium, and phosphorus are particularly dependent on kidney function, and in the setting of kidney failure, intake will likely need to be restricted. Patients who are severely malnourished will have increased electrolyte requirements during early refeeding owing to preexisting deficiencies and/or rapid intracellular uptake with anabolism. Failure to provide adequate electrolytes during refeeding has resulted in death from the refeeding syndrome. Data represent either the recommended dietary allowance or the adequate intake for each nutrient where established. For example, with diuretics, urine sodium, potassium, and magnesium wasting may occur, causing a reduction in their respective serum concentrations (see Chaps. Corticosteroids and cyclosporine are known to cause hyperglycemia, whereas other drugs are prescribed to pharmacologically lower blood glucose concentrations, for example, insulin and oral hypoglycemics (see Chap. For example, sulfasalazine therapy causes a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamin concentrations. Functional tests and simple, noninvasive tests for body composition analysis hold promise for the future. However, until better methods of assessment become available clinically and are demonstrated to be cost-effective, the currently available battery of tests will continue to be the mainstay of nutrition assessment. Information in this chapter can be used to establish empiric goals for a nutrition care plan. However, as with other forms of therapy, continuous monitoring and reassessment are required to determine if these goals are appropriate for an individual patient. Lipid emulsion (10%) is used as the vehicle for the anesthetic agent propofol and may contribute a large amount of fat calories when continuous propofol infusions are used. In these instances, nutrition-support regimens must be adjusted to accommodate the calories and other nutrients delivered through these therapies. Most of the currently available markers of nutrition status were first used in epidemiologic studies to define large populations suffering from malnutrition caused by famine. The response of the various nutrition status markers to nutrition therapy and the correlation between improvement in these markers and decreased morbidity and mortality further support their validity. However, when applied to an individual, most of these markers lack specificity and sensitivity, which makes the development of a clinically useful, cost-effective approach to individual patient nutrition assessment challenging. The importance of the nutrition-focused history and physical examination in both nutrition screening and nutrition assessment cannot be overemphasized. The least amount of objective data that can further substantiate the clinical impression and provide a baseline for subsequent monitoring are those markers that show the best correlation with outcome: weight and serum albumin concentration. The cost-effectiveness of the addition of further biochemical parameters is yet to be determined. Once a nutrition intervention has been initiated, periodic reassessment of nutrition status is critical to determine the accuracy of the initial estimate of nutrition requirements. Indications and limitations of the use of subjective global assessment in clinical practice: An update. The mini nutritional assessment as an assessment tool in elders in long-term care. Prediction of height from knee height in children with cerebral palsy and non-disabled children. Prediction of stature from knee height for black and white adults and children with application to mobilityimpaired or handicapped persons. Growth in weight, recumbent length, and head circumference for preterm low-birthweight infants during the first three years of life using gestation-adjusted ages. Albumin and prealbumin concentrations in patients receiving postoperative parenteral nutrition. The Science and Practice of Nutrition Support: A Case-Based Core Curriculum, America Society for Parenteral and Enteral Nutrition. Neurologic symptoms due to possible chromium deficiency in long-term parenteral nutrition that closely mimic metronidazole-induced syndromes. Whole-blood manganese levels and brain manganese accumulation in children receiving longterm home parenteral nutrition. Brain manganese deposition and blood levels in patients undergoing home parenteral nutrition. The effect of selenium supplementation on skeletal and cardiac muscle in selenium-depleted patients. Molybdenum requirements in low-birth-weight infants receiving parenteral and enteral nutrition. Lactic acidosis traced to thiamin deficiency related to nationwide shortage of multivitamins for total parenteral nutrition-United States, 1997. Prevention of rickets and vitamin D deficiency: New guidelines for vitamin D intake. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Serum phospholipid fatty acids in severely injured patients on total parenteral nutrition with medium chain/long chain triglyceride emulsions. Effect of early introduction of formula versus fat-free parenteral nutrition on essential fatty acid status of preterm infants. Comparison of forearm muscle dynamometry with nutritional prognostic index, as a preoperative indicator in cancer patients. Does admission grip strength predict length of stay in hospitalized older patients Dual-energy x-ray absorptiometry and body composition: Difference between devices and comparison with reference models. Body composition assessment in adults with cystic fibrosis: Comparison of dual-energy xray absorptiometry with skinfolds and bioelectrical impedance analysis. Determination of body composition in children with cerebral palsy: Bioelectrical impedance analysis and anthropometry vs dual-energy x-ray absorptiometry. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids, 2005. Is there a role for nonprotein calories in developing and evaluating the nutrient prescription Monitoring energy metabolism with indirect calorimetry: Instruments, interpretation, and clinical application. The use of a handheld calorimetry unit to estimate energy expenditure during different physiological conditions. Comparison of three methods for the estimation of total nitrogen losses in hospitalized patients. Position of the American Dietetic Association: Health implications of dietary fiber.

Patients who respond slowly to induction therapy are at higher risk of relapse if they are not treated on more aggressive regimens medications xr cheap mesalamine 800 mg on line. Consolidation may be intensified for slow early responders or high-risk patients to include cyclophosphamide treatment uterine cancer cheap mesalamine 800 mg with mastercard, low-dose cytarabine 72210 treatment buy mesalamine 800mg line, and pegaspargase osteoporosis treatment buy discount mesalamine 800 mg online. Delayed Intensification/Interim Maintenance One or two delayed intensification phases separated by low-intensity interim maintenance cycles have been added to maintain remission and to decrease cumulative toxicity symptoms for mono buy 800mg mesalamine with mastercard. Delayed intensification usually consists of dexamethasone symptoms 5dpo mesalamine 400mg online, vincristine, doxorubicin, pegaspargase, cyclophosphamide, thioguanine or mercaptopurine, low-dose cytarabine, and intrathecal methotrexate. Interim maintenance usually consists of dexamethasone, vincristine, weekly methotrexate, mercaptopurine, and intrathecal methotrexate. The antimetabolite-based regimens may have a reduced risk of late toxicities, but the more intensive regimens appear to result in better survival for some patients, especially those with higher-risk disease. Based on the results of studies that show a trend toward an increase in late relapse (excluding isolated testicular relapse) among male children treated for 2 years versus 3 years, some centers treat female children for 2 years while males receive maintenance to complete a total of 3 years of therapy. Interpatient variability in the pharmacokinetics of oral methotrexate and mercaptopurine may also be an important determinant of the effectiveness and toxicity of maintenance therapy. Patients who take their oral methotrexate and mercaptopurine on an evening versus a morning schedule appear to have a superior outcome. Mercaptopurine cannot be given with milk or milk products because of the presence of xanthine oxidase. To account for the interpatient variability, most clinicians will titrate the dose of either agent to maintain an absolute neutrophil count of 750 to 1,500 cells/mm3. Some protocols circumvent bioavailability and poor adherence issues by administering methotrexate intravenously or intramuscularly. Genetic polymorphisms may affect drug metabolism, receptor expression, drug transportation, drug disposition, and pharmacologic response. Maintenance Therapy Maintenance therapy allows long-term drug exposure to slowly dividing cells, allows the immune system time to eradicate leukemia cells, and promotes apoptosis (programmed cell death). The goal of maintenance therapy is to further eradicate residual leukemic cells and prolong remission duration. Maintenance therapy usually consists of daily mercaptopurine and weekly methotrexate for 12-week courses, at doses that produce relatively little myelosuppression, with monthly "pulses" of vincristine and a steroid for 5 days per month. Lack of pharmacokinetic data for chemotherapy in infants has contributed to toxicity from inappropriate dosing of doxorubicin and vincristine. To reduce neuropsychological complications, most protocols avoid cranial irradiation. High treatment-related mortality in this group may offset any benefit from a lower relapse rate. Whether this approach will reduce treatment-related mortality and result in more favorable outcomes is currently unknown. The National Marrow Donor Program and the American Society for Blood and Marrow Transplantation have developed guidelines for transplant consultation based on current clinical practice and evidence-based medicine. Complete remission is achieved in 70% to 90% of adults with a four-drug regimen containing daunorubicin or doxorubicin, vincristine, Lasparaginase, and prednisone. The value of adding more drugs to the basic three- or four-drug induction regimen is unclear. Equally unclear is the value of higher doses of standard combinations of drugs for remission induction. The response to therapy and durability of response seem less than in younger adults or children. Treatment-related mortality rates during remission induction therapy are also higher in this population. Older patients are more likely to be Ph+ positive, with the Ph+ present in more than 50% patients age 55 years and older. Responses are achieved, although are short-lived, with relapses occurring within 6 months. Several studies reported a decrease in the incidence of febrile neutropenia, duration of hospitalization, and duration of antibiotic use, although the effects on these end points are inconsistent among trials. The Childhood Cancer Survivor Study tracks the health status of adults treated for childhood cancer between 1970 and 1986 and has yielded invaluable 2267 information on how to monitor adult survivors. Cranial irradiation has also been found to cause learning deficits, especially in patients younger than 5 years of age at the time of treatment. Patients who received cranial radiation as children also have higher unemployment rates and lower marital rates among females two decades after diagnosis. Thrombocytopenia (severe, <50,000 cells/mm3) is present in approximately 50% of cases. Coagulation: elevated prothrombin time, partial thrombo- plastin time, D-dimers; hypofibrinogenemia. In addition to clinical presentation, laboratory and pathology evaluations are required for a definitive diagnosis of leukemia. The most important test is a bone marrow aspirate and biopsy, which is submitted to hematopathology for testing and evaluation. Cytogenetic analysis of the marrow to determine the presence of nonrandom numerical and structural chromosomal abnormalities in leukemic cells is also helpful for diagnosis, establishing prognosis, and evaluating response to therapy. Recently, technically difficult cytogenetic analysis has been supplemented with fluorescent in situ hybridization that allows for quick, sensitive analysis of samples that might be inadequate for karyotyping. The results of some of these molecular tests correlate with prognosis and are discussed in Risk Classification below. Other Diagnostic Tests Bone marrow biopsy and aspirate: send for morphologic examination, cytochemical staining, immunophenotyping, and cytogenetic (chromosome) analysis. At diagnosis the marrow is typically hypercellular, with normal erythropoiesis being replaced by leukemic blasts. This is typically performed once there is clearance of blasts from the peripheral blood. Identification of these risk factors may allow the clinician to better understand the disease and to tailor treatment according to risk of disease recurrence. For example, if a patient has many clinical and laboratory features that are associated with a good response to chemotherapy ("good-risk"), then the clinician may choose to give less-intensive therapy to reduce the risk of long-term toxic effects. The duration of remission is also shorter in older patients as compared to younger patients. Other patient-specific prognostic factors include concurrent infection and any major organ impairment. Symptoms the patient may report weight loss, malaise, fatigue, and palpitations and dyspnea on exertion. There are proposed algorithms for patient management based on the presence or absence of these abnormalities but they are not currently incorporated into standard practice. With continued improvement of supportive care for patients undergoing chemotherapy, more intensive treatment regimens are being given in an effort to reduce the high rate of leukemic relapse and increase the proportion of long-term survivors. The most common regimen ("7+3") combines daunorubicin administered as a short infusion of 45 to 60 mg/m2 per day on days 1 to 3, along with cytarabine administered as a continuous 24-hour infusion of 100 mg/ m2 per day on days 1 to 7. The remission rate decreases to 40% to 50% in patients older than 60 years of age. As discussed later, the occurrence of leukemic relapse in the bone marrow significantly reduces the likelihood of curing the disease. Most patients who will die from acute leukemia die within the first 6 years; the survival curve (percentage alive versus time) beyond the sixth year after therapy does not continue to decline as rapidly ("survival plateau"), and at this time patients can be considered "cured. Other clinical trials have evaluated idarubicin or mitoxantrone as alternatives to daunorubicin in combination with standard continuous infusion cytarabine. Some clinicians believe that idarubicin is superior in attaining a complete remission following one cycle of induction compared to alternative anthracyclines or anthracenediones. Randomized trials in the elderly show similar remission rates with all anthracyclines and anthracenediones. Other strategies that have been evaluated include adding another agent such as etoposide to the induction regimen. These results have been confirmed in other studies, but as yet are to be adopted in the United States as part of standard therapy. Several groups, including the Southwest Oncology Group and the Australian Leukemia Study Group, have evaluated the impact of adding high-dose cytarabine to induction therapy. In summary, the role of high-dose cytarabine during induction remains controversial. If used during induction, high-dose cytarabine is more appropriate in younger patients than in elderly patients because of poor tolerance by elderly patients. In patients 60 years of age and older with good performance status, the conventional 7+3 regimen should be used or the patient should be enrolled in available clinical trials. Older patients (60 years) with an antecedent hematologic disorder or those with significant comorbidities unrelated to leukemia should be offered a clinical trial or best supportive care because of the dismal outcomes associated with conventional chemotherapy. Methotrexate 12 to 15 mg, with or without cytarabine, should be administered intrathecally twice a week until clearance of leukemic blasts from the cerebrospinal fluid, and then monthly for about 6 months. Relapse is presumably a consequence of the presence of residual, but clinically undetectable, leukemic cells after remission induction therapy. The goal of intensive postremission therapy is to eradicate these residual leukemic cells and to prevent the emergence of drugresistant disease. The need for postremission therapy is based on postmortem analysis and cell kinetic data suggesting that nearly 109 residual leukemic cells remain after effective remission induction therapy. Results of randomized trials in adults clearly show that postremission therapy following remission induction therapy prolongs survival versus no therapy, although the exact duration of postremission therapy is controversial. High-dose cytarabine appears to be a key part of postremission therapy, particularly if not used in induction therapy. However, 2270 many questions remain, such as the optimal dose (g/m2), number of doses per cycle, and number of cycles of high-dose cytarabine. As clinicians have gained more experience in this intensive form of therapy and been provided with more effective immunosuppressive and antibiotic regimens, transplant-related mortality rates have decreased and survival rates have increased. However, the optimal dose of high-dose cytarabine, the number of doses per cycle, and the number of cycles to give remain unknown. Much controversy surrounds this treatment approach, specifically the appropriateness, timing, treatment design, and donor selection. Interestingly, the response rates in the conventional chemotherapy arm in this trial were lower than those reported in other studies, which may account for the survival benefit in the transplant group. One trial design issue that might explain this lack of survival benefit was the low percentage of patients who progressed to transplantation when randomized, thus diluting the effect of transplantation. Several comparative trials of bone marrow versus peripheral blood have been completed in patients with hematologic malignancies, and a meta-analysis of nine randomized trials demonstrated a lower relapse rate for those patients receiving peripheral blood stem cells. The optimal treatment of choice in patients with intermediate-risk cytogenetics is not clear and is based on clinician preference. Many centers consider a relapse probability of 40% to 50% sufficiently high so as to warrant the risk of transplantation-related mortality. In compressed or intensified treatment regimens, the second course of therapy is given 6 days after the first, without waiting for marrow recovery to occur. Typically a bone marrow biopsy is performed 7 to 10 days after the completion of chemotherapy (or day 14 from the start of chemotherapy) to document disease eradication. The second course may be identical to the initial induction regimen, or include high-dose cytarabine and asparaginase, or mitoxantrone and cytarabine. Neonates with Down syndrome may develop transient myeloproliferative disease that usually spontaneously resolves without treatment within a few months. The difficulty lies in the ability to reliably identify these patients at diagnosis. The quality-of-life of each group was similar, with patients in each group spending approximately 50% of the study time in the hospital. Thus chemotherapy is a viable treatment option for elderly patients, although the best chemotherapy regimen and overall treatment approach are controversial. One approach is to attenuate the dose of chemotherapy, preferably with oral agents where possible, or lower doses of intravenous agents. Agents used in this strategy include oral etoposide, low-dose subcutaneous cytarabine, and other oral agents such as thioguanine and idarubicin (oral idarubicin is not currently commercially available in the United States). Lowdose cytarabine produced a greater number of complete remissions compared to placebo, and prolonged 1-year survival. More elderly patients than younger patients will require two courses of remission induction therapy to achieve a complete remission. In an effort to improve response rates, some trials have attempted to determine the optimal anthracycline and the appropriate dose. In the elderly, attenuated-dose cytarabine during remission induction decreases remission and survival rates while decreasing treatment-related mortality rates, which raises the concern that attenuated-dose cytarabine during postremission therapy may cause similar outcomes. An alternative approach to intensive postconsolidation therapy is the administration of multiple courses of chemotherapy in the ambulatory setting. The Acute Leukemia French Association recently demonstrated improved overall survival among patients receiving six monthly courses of outpatient chemotherapy (daunorubicin or idarubicin day 1; low-dose subcutaneous cytarabine for 5 days) compared to intensive consolidation (daunorubicin or idarubicin days 1 to 4; cytarabine continuous infusion). Results with interleukin-2 as a means to enhance the antileukemic activity of immune cells are promising. Whether they can modify the course of disease resulting in prolonged survival is unclear. Gemtuzumab ozogamicin is an immunoconjugate that consists of a monoclonal antibody linked to calicheamicin, a potent antineoplastic agent.

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