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Methadone treatment for analgesic therapy in patients with acute or chronic pain should only be initiated if the potential analgesic or palliative care benefit of treatment with methadone is considered and outweighs the risks buy cialis jelly online now. Conditions For Distribution And Use Of Methadone Products For The Treatment Of Opioid Addiction Code of Federal Regulations discount cialis jelly online mastercard, Title 42 discount cialis jelly express, Sec 8 Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by opioid treatment programs (and agencies, practitioners or institutions by formal agreement with the program sponsor) certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority. Certified treatment programs shall dispense and use methadone in oral form only and according to the treatment requirements stipulated in the Federal Opioid Treatment Standards (42 CFR 8. See below for important regulatory exceptions to the general requirement for certification to provide opioid agonist treatment. Failure to abide by the requirements in these regulations may result in criminal prosecution, seizure of the drug supply, revocation of the program approval, and injunction precluding operation of the program. Long-acting opioid analgesics 59 of 74 Final Update 6 Report Drug Effectiveness Review Project Active Trade ingredient name(s) Boxed warnings Morphine Avinza WARNING: AVINZA capsules are a modified-release formulation of morphine sulfate indicated for once daily administration for the relief of moderate to severe pain requiring continuous, around-the-clock opioid therapy for an extended period of time. THE CAPSULE BEADS ARE NOT TO BE CHEWED, CRUSHED, OR DISSOLVED DUE TO THE RISK OF RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE. PATIENTS MUST NOT CONSUME ALCOHOLIC BEVERAGES WHILE ON AVINZA THERAPY. ADDITIONALLY, PATIENTS MUST NOT USE PRESCRIPTION OR NON-PRESCRIPTION MEDICATIONS CONTAINING ALCOHOL WHILE ON AVINZA THERAPY. CONSUMPTION OF ALCOHOL WHILE TAKING AVINZA MAY RESULT IN THE RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE. This should be considered when prescribing or dispensing KADIAN in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Ingestion of these capsules or of the pellets within the capsules may cause fatal respiratory depression when administered to patients not already tolerant to high doses of opioids. The pellets in the capsules are not to be chewed, crushed or dissolved due to the risk of rapid release and absorption of a potentially fatal dose of morphine Morphine Oramorph NOTE: THE SUSTAINED RELEASE OF MORPHINE FROM SR ORAMORPH SR SHOULD BE TAKEN INTO CONSIDERATION IN THE EVENT OF AN OVERDOSAGE. Long-acting opioid analgesics 60 of 74 Final Update 6 Report Drug Effectiveness Review Project Active Trade ingredient name(s) Boxed warnings Morphine sulfate Embeda™ WARNING See full prescribing information for complete boxed and naltrexone warning. The pellets in the capsules are not to be crushed, dissolved, or chewed. Misuse or abuse of EMBEDA™ by tampering with the formulation, crushing or chewing the pellets, causes the rapid release and absorption of both morphine and naltrexone. The resulting morphine dose may be fatal, particularly in opioid-naïve individuals. In opioid-tolerant individuals, the absorption of naltrexone may increase the risk of precipitating withdrawal. Long-acting opioid analgesics 61 of 74 Final Update 6 Report Drug Effectiveness Review Project Active Trade ingredient name(s) Boxed warnings Oxycodone OxyContin WARNING: IMPORTANCE OF PROPER PATIENT SELECTION AND POTENTIAL FOR ABUSE OxyContin contains oxycodone which is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine. This should be considered when prescribing or dispensing OxyContin in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for one week or longer. OxyContin 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in opioid-tolerant patients, as they may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory-depressant or sedating effects of opioids. Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e. Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse, abuse and addiction. Taking cut, broken, chewed, crushed or dissolved OxyContin tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone. Patients receiving OxyContin and a CYP3A4 inhibitor should be carefully monitored for an extended period of time and dosage adjustments should be made if warranted. Long-acting opioid analgesics 62 of 74 Final Update 6 Report Drug Effectiveness Review Project Active Trade ingredient name(s) Boxed warnings Oxymorphone Opana ER WARNING: POTENTIAL FOR ABUSE, IMPORTANCE OF PROPER PATIENT SELECTION AND LIMITATIONS OF USE Potential for Abuse OPANA ER contains oxymorphone, which is a morphine-like opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing OPANA ER in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Proper Patient Selection OPANA ER is an extended-release oral formulation of oxymorphone indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Limitations of Use OPANA ER is NOT intended for use as an as needed analgesic. Taking broken, chewed, dissolved, or crushed OPANA ER TABLETS leads to rapid release and absorption of a potentially fatal dose of oxymorphone. Patients must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on OPANA ER therapy. The co-ingestion of alcohol with OPANA ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone. Long-acting opioid analgesics 63 of 74 Final Update 6 Report Drug Effectiveness Review Project References 1. Long-acting opioid analgesics 64 of 74 Final Update 6 Report Drug Effectiveness Review Project Appendix C. Excluded trials Update 6 The following full-text publications were considered for inclusion but failed to meet the criteria for this report. See previous versions of the report on the Drug Effectiveness Review Project website for studies excluded previously. Exclusion codes: 3=ineligible intervention, 4=ineligible population Exclusion Excluded trials code Active-control trials Karlsson M, Berggren A-C. Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: a 12-week, randomized, 3 open-label, controlled, parallel-group noninferiority study. Mar 2009;31(3):503-513 Shram MJ, Sathyan G, Khanna S, et al. Evaluation of the abuse potential of extended release hydromorphone versus immediate release hydromorphone. Placebo-controlled trials Corsinovi L, Martinelli E, Fonte G, et al. Efficacy of oxycodone/acetaminophen and codeine/acetaminophen vs. Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with 3 moderate to severe chronic pain. Dec 2008;9(12):1144-1154 Long-acting opioid analgesics 70 of 74 Final Update 6 Report Drug Effectiveness Review Project Appendix E. Strength of evidence Table 1: Comparative effectiveness of long-acting opioids for pain relief and quality of life Strength of Domains pertaining to strength of evidence Magnitude of effect evidence Number of Risk of High, studies; bias moderate, Number of (design/ Summary effect size low, subjects quality) Consistency Directness Precision (95% CI) insufficient Transdermal fentanyl vs.

Treatment of duodenal ulcer with omeprazole or ranitidine in a Brazilian population: a multicenter double-blind generic 20mg cialis jelly amex, parallel group study order cialis jelly online pills. Comparison of omeprazole with ranitidine for treatment of symptoms associated with gastroesophageal reflux disease and uncomplicated duodenal ulcer buy cialis jelly canada. Duodenal ulcer healing with 1-week eradication triple therapy followed, or not, by anti-secretory treatment: a multicentre double-blind placebo-controlled trial. Double-blind comparison of omeprazole 20 mg OM and ranitidine 300 mg NOCTE in duodenal ulcer: a Taiwan multi-centre study. Wilairatana S, Kurathong S, Atthapaisalsarudee C, Saowaros V, Leethochawalit M. Omeprazole or cimetidine once daily for the treatment of duodenal ulcers? Healing of gastric ulcers with esomeprazole versus ranitidine in patients who continued to receive NSAID therapy: a randomized trial. Omeprazole heals duodenal, but not gastric ulcers more rapidly than ranitidine. Omeprazole and cimetidine in the treatment of ulcers of the body of the stomach: a double blind comparative trial. Proton pump inhibitors Page 82 of 121 Final Report Update 5 Drug Effectiveness Review Project 139. Gastric ulcer healing and basic fibroblast growth factor: effects of lansoprazole and famotidine. Comparison of lansoprazole and famotidine for gastric ulcer by endoscopic ultrasonography: a preliminary trial. Aoyama N, Kinoshita Y, Misaki F, Himeno S, Kasuga M, Chiba T. Evaluation of gastric ulcer healing by lansoprazole by measurement of ulcer diameter. Histological aspects and healing rates of gastric ulcers treated with omeprazole 20 mg once daily or ranitidine 150 mg B. Walan A, Bader JP, Classen M, Lamers BHW, Piper DW, Rutgersson K. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. Short report: Treatment of gastric ulcer with lansoprazole or ranitidine: a multicentre clinical trial. Pantoprazole is superior to ranitidine in the treatment of acute gastric ulcer. Effect of omeprazole and cimetidine on prepyloric gastric ulcer: double blind comparative trial. Randomised, double blind comparison of omeprazole and cimetidine in the treatment of symptomatic gastric ulcer. Relapse of gastric ulcers after healing with omeprazole and cimetidine. Kovacs TO, Campbell D, Richter J, Haber M, Jennings DE, Rose P. Double blind comparison of lansoprazole 15 mg, lansoprazole 30 mg and placebo as maintenance therapy in patients with healed duodenal ulcers resistant to H2 receptor antagonists. Different doses of omeprazole in the maintenance treatment of patients with peptic ulcers resistant to H2-blockers. Current Therapeutic Research, Clinical & Experimental. Kovacs TO, Campbell D, Haber M, Rose P, Jennings DE, Richter J. Double blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in the maintenance of healed gastric ulcer. Agrawal NM, Campbell DR, Safdi MA, Lukasik Nl, Huang B, Haber MM. Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti inflammatory drug associated gastric ulcers results of a double blind, randomized, multicenter study. Proton pump inhibitors Page 83 of 121 Final Report Update 5 Drug Effectiveness Review Project 154. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID induced Ulcer Management (OMNIUM) Study Group. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial Ranitidine versus Omeprazole for NSAID associated Ulcer Treatment (ASTRONAUT) Study Group. Gastroduodenal ulcers associated with the use of non-steroidal anti-inflammatory drugs: a systematic review of preventive pharmacological interventions. Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol. Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole versus omeprazole. Rostom A, Wells G, Tugwell P, Welch V, Dube C, McGowan J. Cochrane Database of Systematic Reviews [computer file]. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole. Bianchi Porro G, Lazzaroni M, Imbesi V, Montrone F, Santagada T. Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti- inflammatory drugs: A prospective, placebo-controlled, double-blind, parallel-group study. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. Primary prevention of diclofenac associated ulcers and dyspepsia by omeprazole or triple therapy in Helicobacter pylori positive patients: a randomised, double blind, placebo controlled, clinical trial. Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients. Prevention of ulcers by esomeprazole in at- risk patients using non-selective NSAIDs and COX-2 inhibitors. Ulcer recurrence in high-risk patients receiving nonsteroidalanti-inflammatory drugs plus low-dose aspirin: results of a post HOC subanalysis. Proton pump inhibitors Page 84 of 121 Final Report Update 5 Drug Effectiveness Review Project 167.

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The ULTRA study of 78 low-dose transdermal estrogen reported no significant improvements in the SF-36 subscales of 29 physical and mental function purchase 20 mg cialis jelly fast delivery. The findings of Dayal and colleagues were similar in that conjugated equine estrogen did not improve vitality order line cialis jelly, general health status cheap cialis jelly uk, or quality of life at 12- week follow-up. A third study of women over 70 years randomized to oral estradiol or placebo 26 also did not report significant changes in a “SF-36 score. What is the comparative effectiveness of different hormone therapy preparations when used by postmenopausal women or women in the menopausal transition stage for preventing low bone density and fractures? Outcomes include bone density measurements at lumbar spine, forearm, and hip sites and/or fracture data from one or more sites. Numbers of included studies are summarized in Table 7 below; trials are described in Evidence Tables 5 (head-to-head trials) and 6 (placebo- controlled trials), and quality ratings are presented in Appendix F. Quality ratings of studies added for Update #3 are shown in Appendix G. Hormone therapy Page 40 of 110 Final Report Update 3 Drug Effectiveness Review Project Table 7. Number of studies of estrogens with bone density or fracture outcomes Total Bone Density Fractures Head-to-head comparisons CEE and transdermal estradiol (E2) 3 3 0 Transdermal estradiol (E2) and estradiol 1 1 0 valerate (E2V) Placebo comparisons Estradiol (E2) Oral 16 16 1 Transdermal 15 15 2 Estradiol valerate (E2V) 5 5 1 Conjugated equine estrogen (CEE) 29 26 8 Conjugated synthetic estrogen 1 1 0 Esterified estrogen (EE) 1 1 0 Estropipate 0 0 0 Characteristics of the trials included: • Three trials with bone density outcomes compared estrogens head-to-head. Treatment refers to studies of women with pre-existing fractures or a diagnosis of osteoporosis at baseline. Bone density Head-to-head comparisons We identified no new head-to-head trials with bone density or fracture outcomes in this update. Four head-to-head trials compared different estrogen preparations, including three trials 108-110 of CEE compared to transdermal E2, and one trial of transdermal E2 compared to estradiol 111 valerate (Table 8 and Evidence Table 5). Hormone therapy Page 41 of 110 Final Report Update 3 Drug Effectiveness Review Project Table 8. Head-to-head trials with bone density outcomes Population Study/year Study design characteristics Interventions Main outcomes/results Oral CEE compared with transdermal E2 Castelo- Open label Postmenopausal CEE: 0. Oral CEE compared oral E2 Castelo- Blinding unclear Postmenopausal CEE: 0. N=73 Mean age 51 (45- days); E2V: 2 mg/day No significant differences between treatment 2 years 54 years) (11 days); groups at any site. In one trial, women using either CEE for 30 days or transdermal E2 for 25 days/month had an increase in lumbar spine 108 bone mineral content compared to placebo (CEE: +4. Use of CEE for 25 days/month did not show a significant change (+1. Similar results were 109 found when using these regimens in 118 women with prior hysterectomies. Increases in bone mineral density (BMD) occurred in all treatment groups after one year, and the increases did not differ significantly between the CEE and E2 groups. The addition of alendronate to either form of hormone therapy increased BMD significantly more than did 110 hormone therapy alone. One study of 73 healthy postmenopausal women age 45 to 54 years compared the effects 111 of oral E2 and E2V on forearm and spinal BMD. Both groups significantly gained bone density compared to placebo, and no significant differences between groups were found at any site. Placebo comparisons Sixty-four RCTs comparing an eligible estrogen preparation with placebo and reporting BMD outcome data met criteria for this review. New studies added for Update #3 are shown in Table 9. Characteristics of the trials include: • Trials were conducted predominantly in the U. For trials including both types, the data was not separately reported so comparisons could not be made. Hormone therapy Page 43 of 110 Final Report Update 3 Drug Effectiveness Review Project Table 9. Placebo controlled trials with bone density outcomes (new for Update #3) Study Design; Study/year Number; Population (quality) Duration characteristics Interventions Main outcomes/results Oral estrogens Conjugated equine estrogen Reid, 2004 Double-blind Postmenopausal; CEE 0. Femoral neck: No change from baseline in placebo group. Trend for increased BMD in E2 or E2 + MPA groups, but not significant All 3 progestin treatments were similar to placebo Hormone therapy Page 44 of 110 Final Report Update 3 Drug Effectiveness Review Project Study Design; Study/year Number; Population (quality) Duration characteristics Interventions Main outcomes/results Warming, Double-blind; Postmenopausal; E2 1 mg + 1mg Difference between HRT and placebo after 2 years: 2004 N=240; 0/240 drospirenone, Spine: 7% (p<0. At 36 months, combination therapy had a significantly greater increase in total hip BMD than those on either ALN or HRT alone (p<. Conjugated synthetic estrogen combination Lindsay, Double-blind Postmenopausal Conjugated estrogens % of patients who did not lose >2% of spine BMD at 2005 Multicenter; Mean age 51. Placebo: 30%; 27% who did not lose >2% in 12 months lost >2% at 24 months. Transdermal estrogens Estradiol patch Ettinger, 2004 Double-blind Postmenopausal; estradiol patch releasing Lumbar spine BMD: Increased 2. N=417; Mean 67 ±5 years; (replaced once/week) Between group difference at 2 years: 2. Hormone therapy Page 45 of 110 Final Report Update 3 Drug Effectiveness Review Project Study Design; Study/year Number; Population (quality) Duration characteristics Interventions Main outcomes/results Estradiol patch/levonorgestrel Warming, Double-blind Postmenopausal, 45 micrograms estradiol Difference in BMD, HRT vs. One trial did not report treatment and placebo group differences, but stated that forearm bone density in the treatment group was statistically 125 significantly increased from baseline while the placebo group showed no change. Another trial reported a trend in E2 groups towards increased bone density, however statistical 126 significance was not reached for between group comparisons. All 15 trials of transdermal E2 reported statistically significant improvements in bone 127-139 density compared to placebo. Only three trials did not use concomitant 129, 134, 138, 140, 141 progestin/progesterone. Five trials of E2V with concomitant progestin/progesterone reported bone density 111, 142-145 outcomes. Four of the five trials noted improvement in treatment groups compared to 111, 142-144 145 placebo, and one did not. All trials reported significant within-group changes in bone density at multiple sites for various doses with higher doses showing greater changes. In a good-quality trial comparing combination treatment with CEE (with or without medroxyprogesterone) plus alendronate to either treatment alone, patients on combination therapy had a significantly greater increase in total hip BMD than those 170, 171 151 on either ALN or HRT alone after 3 years (p<. A more recent substudy of the Women’s HOPE trial found that most women on lower doses of CE with or without medroxyprogesterone (0. Similar improvements were found in the lumbar spine. In subjects with 6-year follow-up BMD data (n=443), the percentage increase in lumbar spine BMD was 7. The CEE-only study of the WHI produced modest but consistent positive effects on bone 173 mineral density. Hormone therapy Page 46 of 110 Final Report Update 3 Drug Effectiveness Review Project 174 One study of esterified estrogen examined dosages of 0.

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Thefour parasitesgroupinto two clusters cheap 20 mg cialis jelly visa, shown in figure 11 cialis jelly 20mg mastercard. If a phylogenetic anal- ysis provides the same classification purchase cialis jelly discount, then immunological distance in- creases with phylogenetic distance. The parasites may, for example, ac- cumulate genetic differences randomly throughout their genomes. Par- asites that diverged from a more distant common ancestor have more genetic differences both inside and outside the tested antigenic regions, with no concentration of differences in the antigenic sites. Alternatively, natural selection on the antigenic sites may be driving apart the clusters. Then both antigenic and nonantigenic sites provide the same phyloge- netic pattern,clustering P1/P3 versus P2/P4,butthedifferences between the clusters would likely be concentrated disproportionately in the anti- genic sites. Acorrespondence generally occurs between phylogenetic distance and the differences measured on particular characters, reflecting the natural tendency for similarity by common descent. Sometimes a par- ticular force disrupts this natural concordance. In this case, broad similarity over the nucleotide or amino acid sequence phylogenetically groups P1 with P2 and P3 with P4. T heim m unological test, which focuses on only a narrow subset 180 CHAPTER 11 P1 P3 P2 P4 Figure 11. The white lineages have the antigenic properties of the P1/P3 im- munological grouping, and the black lineages have the antigenic properties of the P2/P4 immunological grouping shown in fig. Thewhitelineages share the P1/P3 immunological grouping and the black lineages share the P2/P4 immunological grouping shown in fig. The gray lineages show that the immunological type for the ancestors of each phy- logenetic group cannot be resolved. The pattern shows recurrent evolution of an antigenic type. Many processes can generate the discordant pattern of figure 11. Suppose, for example, that only two variants can occur at a particular epitope because of conformational constraints on the function of the parasite molecule. If an epidemic begins with a parasite in state one, then host immunity will eventually favor the spread of state two. Con- versely, an initial epidemic beginning with state two leads eventually to replacement by state one. Pairs of closely related lineages will often be of opposite state. ANTIGENICITY AND PHYLOGENY 181 Functional hypotheses can often be tested by comparison of the pre- dicted and observed phylogenetic patterns. For example, the functional constraint that an epitope can exist only in two alternative, antigeni- cally distinct states predicts a discordant pattern between phylogenetic and immunological classifications. Alternatively, an observed discor- dance between phylogenetic and immunological classifications may lead to a functional or process-oriented hypothesis. That hypothesis can be tested by using other methods to infer function or process—for exam- ple, whether an observed epitope is indeed constrained to two alterna- tive states by structural and functional attributes. This group includes well-known patho- gens such as yellow fever, dengue fever, and West Nile virus. These viruses span a diverse group, with nucleotide sequence identities of 69% or higher within the fourteen phylogenetic clades and lower percentages of identities between clades. The flavivirus clades identified by molecular phylogeny correspond closely to the antigenic classification by Calisher et al. Two factors probably contribute to the close match between antigenic classification and molecular phylogeny. First, distinct clades have fairly large nucleotide sequence differences. Thus, both phylogenetic and antigenic groupings measure broad-scale divergence. Second, the antigenic analysis used polyclonal antisera, so that each test agent averaged broadly over many antigenic sites. The phylogenetic analysis separated three clusters: classical swine types on 182 CHAPTER 11 swine avian avian-like swine 1 2 3 4 5 6 7 8 Figure 11. The isolates were obtained from swine (sw), turkey (ty), and duck (dk). The avian isolates were closer to the swine isolates on the right (avian-like swine) than to the swine isolates on the left when measured by nucleotide distances (data not shown). The matrix above the tree shows the intensity of reaction for each isolate to eight monoclonal antibodies. The immunological reactivities divide the swine and avian-like swine into distinct clusters, matching the phylogenetic classification. The avi- an isolates are immunologically relatively distant from the other clus- ters and from each other, creating dissonance between phylogeny and antigenicity. It may be that the avian isolates have differentiated more strongly at the sites recognized by some of the monoclonal antibod- ies than they have when averaged over the entire sequenced region. It would be interesting to know more about the sites to which the different ANTIGENICITY AND PHYLOGENY 183 monoclonal antibodies bind. Perhaps some of those sites are influenced by selective pressures for attachment to host cells or for avoidance of host defense that differ between birds and pigs. Isolates obtained in a particular year tend to trace their ancestry back to a common progenitor lineage just a few years into the past (Bush et al. Thus, the temporal sequence of the population is dominated by lineal replacements rather than bifurcating divergence. Immune selective pres- sure on hemagglutinin appears to drive the lineal replacements—put another way, immunological pressure drives change in the population- wide pattern of phylogenetic descent. Thus, the phylogenetic pattern of change may match the immunological pattern of change. Concor- dance probably depends on the percentage of amino acid substitutions explained by antibody pressure and the degree to which the antibody panel used for classification measures aggregate divergence. The phylogenetic distance between isolates does not predict well the strength of shared immunological response (Vogel et al. Vaccines must stimulate an immune response against most viral ge- notypes in order to provide sufficient protection. A candidate vaccine might, for example, include isolates from each of the common phyloge- netic lineages. This provides good coverage of diverse pathogens when antigenicity corresponds to phylogeny. However, phylogeny does not predict antigenicity for HIV.

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