Fabrication of extended-release patient-tailored

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use DESVENLAFAXINE EXTENDED-RELEASE TABLETS safely and effectively. See full prescribing information for desvenlafaxine extended-tablets in a patient who is being treated with linezolid or intravenousmethylene blue (4).-----------------------WARNINGS AND PRECAUTIONS-----------------------­release tablets.DESVENLAFAXINE extended-release tablets, for oral useInitial U.S. Approval: 2008WARNING: SUICIDAL THOUGHTS AND BEHAVIORSSee full prescribing information for complete boxed warning.•••Increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants (5.1). Monitor for worsening and emergence of suicidal thoughts and behaviors (5.1).Desvenlafaxine extended-release tablets are not approved for use in pediatric patients (8.4).----------------------------INDICATIONS AND USAGE---------------------------Desvenlafaxine extended-release tablets, a serotonin and norepinephrine reuptake inhibitor (SNRI), are indicated for the treatment of major depressive disorder (MDD) (1).----------------------DOSAGE AND ADMINISTRATION----------------------­•Recommended dose: 50 mg once daily with or without food (2.1). •There was no evidence that doses greater than 50 mg per day confer any additional benefit (2.1).•Discontinuation: Reduce dose gradually whenever possible (2.1). •Take tablets whole; do not divide, crush, chew, or dissolve (2.1). •Moderate renal impairment: Maximum dose is 50 mg per day (2.2). •Severe renal impairment and end-stage renal disease (ESRD): Maximum dose is 50 mg every other day (2.2).•Moderate to severe hepatic impairment: Maximum dose is 100 mg per day (2.2).---------------------DOSAGE FORMS AND STRENGTHS---------------------­• Desvenlafaxine extended-release tablets are available as 50 mg and 100 mg (3).• Each tablet contains 75.45 mg or 150.9 mg of desvenlafaxine fumarate equivalent to 50 mg or 100 mg of desvenlafaxine (3).-------------------------------CONTRAINDICATIONS-----------------------------­• Hypersensitivity to desvenlafaxine fumarate, venlafaxine hydrochloride or any excipients in the desvenlafaxine extended-release tabletformulation (4).• Serotonin syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with desvenlafaxine extended-release tablets orwithin 7 days of stopping treatment with desvenlafaxine extended-release tablets. Do not use desvenlafaxine extended release tabletswithin 14 days of stopping an MAOI intended to treat psychiatricdisorders. In addition, do not start desvenlafaxine extended release FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: SUICIDAL THOUGHTS AND BEHAVIORS1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION2.1 General Instruction for Use2.2 Special Populations2.3 Maintenance/Continuation/Extended Treatment2.4 Discontinuing Desvenlafaxine Extended-Release Tablets2.5 Switching Patients From Other Antidepressants to DesvenlafaxineExtended-Release Tablets2.6 Switching Patients To or From a Monoamine Oxidase Inhibitor(MAOI) Intended to Treat Psychiatric Disorders3 DOSAGE FORMS AND STRENGTHS •Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including with desvenlafaxine extended-release tablets, both when taken alone, but especially when co-administered with otherserotonergic agents (including triptans, tricyclic antidepressants,fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort).If such symptoms occur, discontinue desvenlafaxine extended-releasetablets and initiate supportive treatment. If concomitant use ofdesvenlafaxine extended-release tablets with other serotonergic drugs is clinically warranted, patients should be made aware of a potentialincreased risk for serotonin syndrome, particularly during treatmentinitiation and dose increases (5.2).•Elevated Blood Pressure: Control hypertension before initiating treatment. Monitor blood pressure regularly during treatment (5.3). •Abnormal Bleeding: Desvenlafaxine extended-release tablets may increase risk of bleeding events. Caution patients about risk of bleeding associated with concomitant use of desvenlafaxine extended-releasetablets and NSAIDs, aspirin, or other drugs that affect coagulation (5.4). •Narrow-angle Glaucoma: Mydriasis has occurred with desvenlafaxine extended-release tablets. Monitor patients with raised intraocularpressure or those at risk of angle-closure glaucoma (5.5).•Activation of Mania/Hypomania: Use cautiously in patients with Bipolar Disorder. Caution patients about the risk of activation ofmania/hypomania (5.6).•Discontinuation Syndrome: Taper dose when possible and monitor for discontinuation symptoms (5.7). (5.7).•Seizure: Can occur. Use cautiously in patients with seizure disorder(5.8).•Hyponatremia: Can occur in association with SIADH (5.9). •Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur(5.10).------------------------------ADVERSE REACTIONS------------------------------­Most common adverse reactions (incidence ≥ 5% and twice the rate of placebo in the 50 or 100 mg dose groups) were: nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and specific male sexual function disorders (6.1).To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 ordrug.safety@; or FDA at 1-800-FDA-1088 or/medwatch.-----------------------USE IN SPECIFIC POPULATIONS-----------------------­• Pregnancy: Based on animal data, may cause fetal harm. (8.1).• Nursing Mothers: Discontinue drug or nursing taking into consideration importance of drug to mother (8.3).• Geriatric Use: There is an increased incidence of orthostatic hypotension in desvenlafaxine extended-release tablet treated patients ≥ 65 years (6.1 and 8.5).See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.Revised: 10/20134 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults5.2 Serotonin Syndrome5.3 Elevated Blood Pressure5.4 Abnormal Bleeding5.5 Narrow-Angle Glaucoma5.6 Activation of Mania/Hypomania5.7 Discontinuation Syndrome5.8 Seizure5.9 Hyponatremia5.10 Interstitial Lung Disease and Eosinophilic Pneumonia6 ADVERSE REACTIONS6.1 Clinical Studies Experience6.2 Postmarketing Experience7 DRUG INTERACTIONS7.1 Monoamine Oxidase Inhibitors (MAOI)7.2 Serotonergic Drugs7.3 Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, andWarfarin)7.4 Potential for Desvenlafaxine to Affect Other Drugs7.5 Other Drugs Containing Desvenlafaxine or Venlafaxine7.6 Ethanol8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal ImpairmentFULL PRESCRIBING INFORMATION8.7 Hepatic Impairment9 DRUG ABUSE AND DEPENDENCE9.1 Controlled Substance10 OVERDOSAGE10.1 Human Experience With Overdosage10.2 Management of Overdosage11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not listed.WARNING: SUICIDAL THOUGHTS AND BEHAVIORSAntidepressants increased the risk of suicidal thoughts and behavior in children,adolescents, and young adults in short-term studies. These studies did not show anincrease in the risk of suicidal thoughts and behavior with antidepressant use in patientsover age 24; there was a reduction in risk with antidepressant use in patients aged 65 andolder [see Warnings and Precautions (5.1)].In patients of all ages who are started on antidepressant therapy, monitor closely forworsening, and for emergence of suicidal thoughts and behaviors. Advise families andcaregivers of the need for close observation and communication with the prescriber [seeWarnings and Precautions (5.1)].Desvenlafaxine extended-release tablets are not approved for use in pediatric patients[see Use in Specific Populations (8.4)].1 INDICATIONS AND USAGEDesvenlafaxine extended-release tablets, a serotonin and norepinephrine reuptake inhibitor (SNRI), are indicated for the treatment of major depressive disorder (MDD) [see Clinical Studies (14) and Dosage and Administration (2.1)]. The efficacy of desvenlafaxine extended-release tablets has been established in four short-term (8-week, placebo-controlled studies) in adult outpatients who met DSM-IV criteria for major depressive disorder.2 DOSAGE AND ADMINISTRATION2.1 General Instruction for UseThe recommended dose for desvenlafaxine extended-release tablets is 50 mg once daily, with or without food.In clinical studies, doses of 50 mg to 400 mg per day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg per day and adverse reactions and discontinuations were more frequent at higher doses.When discontinuing therapy, gradual dose reduction is recommended whenever possible to minimize discontinuation symptoms [see Dosage and Administration (2.4) and Warnings and Precautions (5.7)].Desvenlafaxine extended-release tablets should be taken at approximately the same time each day. Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved.2.2 Special PopulationsPatients with renal impairmentThe maximum recommended dose in patients with moderate renal impairment (24-hr creatinine clearance [CrCl] = 30 to 50 mL/min, Cockcroft-Gault [C-G]) is 50 mg per day. The maximum recommended dose in patients with severe renal impairment (24-hr CrCl less than 30 mL/min, C-G) or end-stage renal disease (ESRD) is 50 mg every other day. Supplemental doses should not be given to patients after dialysis [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].Patients with hepatic impairmentThe recommended dose in patients with moderate to severe hepatic impairment is 50 mg per day. Dose escalation above 100 mg per day is not recommended [see Clinical Pharmacology (12.3)].2.3 Maintenance/Continuation/Extended TreatmentIt is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Patients should be periodically reassessed to determine the need for continued treatment.2.4 Discontinuing Desvenlafaxine Extended-Release TabletsSymptoms associated with discontinuation of desvenlafaxine extended-release tablets, other SNRIs and SSRIs have been reported [see Warnings and Precautions (5.7)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.2.5 Switching Patients From Other Antidepressants to Desvenlafaxine Extended-Release Tablets Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to desvenlafaxine extended-release tablets. Tapering of the initial antidepressant may be necessary to minimize discontinuation symptoms.2.6 Switching Patients To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric DisordersAt least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with desvenlafaxine extended-release tablets. Conversely, at least 7 days should be allowed after stopping desvenlafaxine extended-release tablets before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4)].Use of Desvenlafaxine Extended-Release Tablets with other MAOIs such as Linezolid or Methylene BlueDo not start desvenlafaxine extended-release tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4)].In some cases, a patient already receiving desvenlafaxine extended-release tablet therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, desvenlafaxine extended-release tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with desvenlafaxine extended-release tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with desvenlafaxine extended-release tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].3 DOSAGE FORMS AND STRENGTHSDesvenlafaxine extended-release tablets are available as:50 mg, light-pink, film-coated round shaped tablets, debossed with "T" on one side of the tablet and with "N1" on the other side.100 mg, reddish-orange, film-coated round shaped tablet, debossed with "T" on one side of the tablet and with "N2" on the other side.4 CONTRAINDICATIONS• Hypersensitivity to desvenlafaxine fumarate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine extended-release tablet formulation. Angioedema has been reported in patients treated with desvenlafaxine extended-release tablets [see Adverse Reactions (6.1)].• The use of MAOIs intended to treat psychiatric disorders with desvenlafaxine extended-release tablets or within 7 days of stopping treatment with desvenlafaxine extended-release tablets is contraindicated because of an increased risk of serotonin syndrome. The use of desvenlafaxine extended-release tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.6) and Warnings and Precautions (5.2)].Starting desvenlafaxine extended-release tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.6) and Warnings and Precautions (5.2)].5 WARNINGS AND PRECAUTIONS5.1 Suicidal Thoughts and Behaviors in Adolescents and Young AdultsPatients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled studies of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk ofsuicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.The pooled analyses of placebo-controlled studies in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term studies of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled studies in adults with MDD or other psychiatric disorders included a total of 295 short-term studies (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.Table 1Drug-Placebo Difference in Number of Cases of Suicidality per 1,000Patients TreatedAge RangeIncreases Compared to Placebo< 18 14 additional cases18 to 24 5 additional casesDecreases Compared to Placebo25 to 64 1 fewer case≥ 65 6 fewer casesNo suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about drug effect on suicide.It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance studies in adults with depression that the use of antidepressants can delay the recurrence of depression.All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [see Dosage and Administration (2.4) and Warnings and Precautions (5.7) for a description of the risks of discontinuation of desvenlafaxine extended-release tablets].Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers.Prescriptions for desvenlafaxine extended-release tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.Screening patients for bipolar disorderA major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled studies) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that desvenlafaxine extended-release tablets are not approved for use in treating bipolar depression.5.2 Serotonin SyndromeThe development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including desvenlafaxine extended-release tablets, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.The concomitant use of desvenlafaxine extended-release tablets with MAOIs intended to treat psychiatric disorders is contraindicated. Desvenlafaxine extended-release tablets should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with a MAOI such as linezolid or intravenous methylene blue in a patient taking desvenlafaxine extended-release tablets. Desvenlafaxine extended-release tablets should be discontinued before initiating treatment with the MAOI [see Contraindications (4) and Dosage and Administration (2.6)]. If concomitant use of desvenlafaxine extended-release tablets with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.Treatment with desvenlafaxine extended-release tablets and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.5.3 Elevated Blood PressurePatients receiving desvenlafaxine extended-release tablets should have regular monitoring of blood pressure since increases in blood pressure were observed in clinical studies [see Adverse Reactions (6.1)]. Pre-existing hypertensionshould be controlled before initiating treatment with desvenlafaxine extended-release tablets. Caution should be exercised in treating patients with pre-existing hypertension, cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported with desvenlafaxine extended-release tablets.Sustained blood pressure increases could have adverse consequences. For patients who experience a sustained increase in blood pressure while receiving desvenlafaxine extended-release tablets, either dose reduction or discontinuation should be considered [see Adverse Reactions (6.1)].5.4 Abnormal BleedingSSRIs and SNRIs, including desvenlafaxine extended-release tablets, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Patients should be cautioned about the risk of bleeding associated with the concomitant use of desvenlafaxine extended-release tablets and NSAIDs, aspirin, or other drugs that affect coagulation or bleeding.5.5 Narrow-Angle GlaucomaMydriasis has been reported in association with desvenlafaxine extended-release tablets; therefore, patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma (angle-closure glaucoma) should be monitored.5.6 Activation of Mania/HypomaniaDuring all MDD 2 and phase 3 studies, mania was reported for approximately 0.02% of patients treated with desvenlafaxine extended-release tablets. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other marketed antidepressants. As with all antidepressants, desvenlafaxine extended-release tablets should be used cautiously in patients with a history or family history of mania or hypomania.5.7 Discontinuation SyndromeDiscontinuation symptoms have been systematically and prospectively evaluated in patients treated with desvenlafaxine extended-release tablets during clinical studies in Major Depressive Disorder. Abrupt discontinuation or dose reduction has been associated with the appearance of new symptoms that include dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis. In general, discontinuation events occurred more frequently with longer duration of therapy.During marketing of SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), and SSRIs (Selective Serotonin Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.Patients should be monitored for these symptoms when discontinuing treatment with desvenlafaxine extended-release tablets. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate [see Dosage and Administration (2.4) and Adverse Reactions (6.1)].。

Emergency stop switches, generally referred to as E-Stops, ensure the safety of persons and machinery and provide consistent, predictable, failsafe control response. A wide range of electrical machinery must have these specialized switch controls for emergency shutdown to meet workplace safety and established international and U.S. regulatory requirements. E-Stops – critical human machine interface (HMI) devices – differ from simple stop switches (that merely turn equipment off) in that they offer “foolproof” equipment shutdown. This is accomplished through advanced switch design that requires a twist, pull, or key to release electrical contacts to allow machinery restart.E-Stops are generally designed for failsafe operation so the stop command has priority over the sustaining function. This has led to innovative switch designs that prevent “blocking” (wanton or accidental obstruction of the actuator with foreign objects) and “teasing” (which could result in premature or unreliable action). Switch companies also are developing new solutions to problems that arise when contact block and actuator are improperly installed or separated because of vibration or other malfunction. Safe Emergency StoppingAccording to international standards, the emergency stop function must be initiated by a single human action using a manually actuated control device. The E-Stop function mustbe operational at all times and designed to stop the machine without creating additional hazards.Resetting the electrical system can only be done by first releasing the E-Stop that was originally activated. If E-Stops were activated at multiple locations, all must be released before machinery restart. It should be noted that resetting E-Stops does not in itself restart the machinery; it only permits restarting through normal procedures appropriate for the machinery involved. Ergonomic, electrical, mechanical, and color requirements for E-Stops are quite specific. The E-Stop control, commonly a distinctive pushbutton switch or “mushroom type” pushbutton (although wires, ropes, bars, handles, or foot pedals are sometimes employed), must use direct mechanical actionwith mechanical latching. When the E-Stop is activated (pushed), it permanently opens the electrical contacts through a latching mechanism. To close the electrical contacts and allow machinery restart, the E-Stop actuator must be manually unlatched with a twist or a key release. Some E-Stop actuators can simply be pulled to close the electrical contacts.This approach may be less desirable from a safety standpoint than a twist or key release, which requires a more deliberate action by an operator.Designers should be aware of international and U.S. standards and regulations that impact the design and use of E-Stops.Emergency Stop SwitchesJoseph Torzillo, VP Sales, HMI ComponentsLance A. Scott, President, EAO Switch CorporationPicture Picture(grayscale)E-Stops are critical to the human machine interface (HMI).Selecting the Right E-Stopfor Your ApplicationBecause of the confusing array ofE-Stops available, it is important to understand the design basics that contribute to high-quality, ergonomic switch design. EAO is a leader in HMI Components and Systems, including innovative, rugged, reliable, and affordable E-Stops that meet or exceed international and U.S. standards. One of the first steps is determiningwhere the E-Stop fits within your machine control system and whether your particular application requires Category 0 or Category 1 type emergency shutdown. The intended application often determines the placement, size, electrical specifications, mechanical characteristics, ergonomics, color/legends, and number of E-Stops required. So a thorough understanding of the machinery and associated control systems is key to making the right E-Stop choice.A second, and equally important step, is determining what international and U.S. standards, performance ratings, and codes apply for your application. Requirements vary by industry segment, so standards for E-Stops used on transportation vehicles may differ significantly from those used on process machinery or medical equipment and will be governed by different regulatory bodies specific to those segments. Regulatory bodies may also specify size, color, legend, contact terminals, etc.It is then useful to construct or consultan existing E-Stop series selector chart (often supplied by vendors). For example, EAO provides a chart that allows easy comparison of key design factors(see Figure 2). You can select panel opening size, type of actuator, type andnumber of contact blocks, connectors,colors, and maximum electrical rating tocome up with one or more appropriatemodels.Like many vendors, EAO provides specialenclosures, switch guards, palm guards,custom labeling, and other accessories tocomplete virtually any E-Stop application.Some accessories may be specified byindustry standards, such as the SEMIstandards for semiconductor fabricationequipment that mandate the use of palmguards. EAO and other vendors also offerservices to assist customers in the design,engineering, and production of HMISystems, integrating E-Stops.Designed for rough dutyRobust, heavy-duty construction is thehallmark of the original 22.5 mm switches.Many, like the EAO Series 04 E-Stops,have stackable contact blocks, optionalkey release actuators, and mountingoptions for 22.5 mm panel openings. ThisEAO series is rated at up to 10 A, 600VAC, has silver contacts with availablegold over silver or silver over palladiumcontacts, and silver-plated screw terminalswith available quick-connect terminals.Smaller mounting footprintModern applications often demanda slimmed down E-Stop with 16 mmmounting. Innovative products, like theEAO Series 61, are now available with anactuator shape that prevents blockagefrom foreign objects, a black indicatorring visible from long distances, andavailable key release actuators. This EAOseries is rated at 5 A, 250 VAC, and has achoice of silver or gold contacts, screw orsolder quick-connect terminals.An E-Stop must be initiated by a single human action using a manual control device.A 22.5 mm switch must be durable and rugged.T oday’s applications often require a slimmer footprint.12345Figure 1 – Parts of an E-StopShort behind-panel depthNewer electronic applications are requiring E-Stops with shorter behind-panel depth. EAO’s Series 84 E-Stop,for example, features a very short behind-panel depth (18 mm maximum), single “mono-block” construction, 22.5 mm mounting, and available LED illumination that is visible from the side as well as front of the actuator. This series is rated at 3 A, 120 VAC and 1.5 A, 240 VAC, has gold contacts, quick-connect/solder printed circuit board terminals, and ribbon cable terminals.ApplicationsVirtually all industry segments – from machinery, instrumentation, medical treatment and diagnostic, lifting/ moving, and transportation – mandateE-Stops for safe operation. Designers need to have a thorough knowledge ofE-Stop fundamentals, E-Stop switch characteristics and capabilities, and the international and U.S. standards and compliance requirements that apply to their application areas.E-Stops are required on all machinery independent of the type of energy used to control the function, except for ma-chines in which an E-Stop function would not lessen the risk. An E-Stop switch is intended to be one part of a compre-hensive safety system, so the equip-ment designer must also consider safetyfunctions, such as reversal or limitationof motion, deflection, shielding, braking,or disconnecting, that are not specificallyaddressed in this paper. Primary applica-tion areas where electrical machineryis safeguarded with E-Stop technologyinclude:MetalworkingWood productionTextile productionFood processingPrintingMedical laser & x-ray equipmentPackaging equipmentSemi-fab equipmentPumpingLifting/moving equipmentPlastics & rubber processingMaterials handlingElectronic production equipmentPaper & cardboard productionInspection/testing equipmentCompressorsLaundry/dry cleaning facilitiesTransportationConstruction/building materialsX-ray EquipmentCabinet x-ray systems used fordiagnostic and therapeutic medicalapplications, industrial non-destructiveinspection and thickness gauging,security inspection of baggage, andother imaging are closely regulated foroperational safety. E-Stops are coveredby standards and regulations of theFDA Department of Health and HumanServices. The key document is CFR Title21, Part 1020 – Performance Standardsfor Ionizing Radiation Emitting Products,section 40, which requires accessibleemergency stop switches and keyedlock-out switches to disable the system.Semiconductor ManufacturingSemiconductor chips used in electricaland electronic devices are fabricatedthrough a sequence of photographicand chemical processing steps. Theprocess includes lithography, steppers,etching, and deposition equipment. Thecomplex process is governed by specificoperational and safety guidelines setdown by SEMI, a trade organization ofsuppliers of equipment and materialsused in the fabrication of semiconductordevices. SEMI S2-93 makes a cleardistinction between emergency off (EMO)switches and E-Stops, requiring the latterto be clearly distinguishable from EMOsthrough the use of color (red), actuatorshape (extended not mushroom), andlabeling (“Emergency Stop”). It alsospecifies that E-Stops should stop allhazardous mechanical motion at theequipment interface, but not shut offMedical imaging E-Stops are closely regulated.In semiconductor manufacturing, there are strictguidelines set by the SEMI trade organization.E-Stops may require shorter behind-panel depth.associated equipment.Overhead and Gantry CranesThese large lifting and moving devices may have a gantry mounted cab which includes an E-Stop on the operator console. Smaller overhead cranes usually have a wired or wireless pendant control operated from ground level. The pendant includes an E-Stop. The chief regulating body for these massive devices is the Occupational Safety and Health Administration. OSHA 29 CFR 1910.179 (a)(59) defines “emergency stop switch” as a manually or automatically operated electric switch to cut off electric power independent of the regular operating controls. Another section, 9 CFR 1910.179(a)(61) defines “main switch”as a device controlling the entire power supply to the crane.U.S. Standards for E-Stops Occupational Safety and Health Administration (OSHA) – Standards –29 CFR (Code of Federal Regulations); OSHA 1910American National Standards Institute (ANSI) – B11, Electrical and Mechanical Equipment GuidelinesANSI/NFPA (National Fire Protection Association) – 79, Electrical Standardsfor Industrial MachineryUnderwriters Laboratories Inc. (UL) –Category NISD, Emergency Stop DeviceFood and Drug Administration,Department of Health and HumanServices, Subchapter J – RadiologicalHealth: CRF Title 21, Part 1020,Performance Standards for IonizingRadiation Emitting ProductsOther Complianceand Rating BodiesMost quality E-Stop switches, includingthose made by EAO, are RoHS andREACH compliant, meet cUL (CanadianUL) requirements, and TÜV (TechnischerÜberwachungsverein, a German safetymonitoring agency), SEV (a Swissdesignation) and CE (European Union)approvals.Depending on design and applicationrequirements, many E-Stops are listedas UL category NISD emergencystop devices. This rating covers twocategories of E-Stop function as definedin ANSI/NFPA 79, Electrical Standardsfor Industrial Machinery (ANSI is theAmerican National Standards Instituteand NFPA is the National Fire ProtectionAssociation):1. Stop Category 0 – Immediate removalof power to the machine or mechanicaldisconnection (de-clutching) of hazardouselements.2. Stop Category 1 – Controlled stopwith power available to stop the machinefollowed by removal of power when thestop is achieved.The emergency stop actuator providedin these devices must be a self-latchingtype. E-Stops with this rating have beenreviewed for their functionality in additionto fire and electric shock safety.ISO 13850 (formerly EN418)Max rating: 5 A/250 VACMax rating: 3 A/250 VACE-Stops can be mounted on a console or on awireless pendant.Figure 3 – International standards that apply to Emergency Stops vs. Stop SwitchesFuture of the TechnologyThe pace of change in E-Stop technology is steady, not revolutionary. By their nature, these devices must be recognizable, reliable, and rugged. They have a straightforward function: instantly shut down equipment witha simple push of a (usually) bright red actuator. For safety, reactivation of the switch requires twisting or pulling the actuator by hand or, for even more security, unlocking it with a key beforemachinery can be restarted. Established standards, function, and familiarity dictate a certain beneficial inertia in new E-Stop developments.Many advances are driven by norm changes for E-Stops, such as DIN EN ISO 13850: 2008 that now requires mechanical latching and manual resetting of E-Stops. Most researchand development is aimed at improving the safety and reliability of the switches themselves and expanding their roles as lockout devices in some worker safety applications.One area of current interest is making sure that the E-Stop itself will “failsafe” should the actuator and contact block be separated. The contact block has normally closed contacts that allow power to flow to the machinery. Pushingan E-Stop separates the spring-loadedcontacts, and mechanical latching keepsthem open, stopping the machinery. Butwhat happens if the actuator separatesfrom the contact block or the latchingmechanism fails?Separation of the contact block from theactuator renders an E-Stop ineffective.Current solutions include mono-blockor unibody switches with a one-pieceactuator/contact block, as well asswitches with failsafe contact blocks thatautomatically cause machinery shutdownif the actuator and contact block areseparated.Other advances are application-driven.EAO’s Series 84 E-Stops, for example,were developed for hand-held enclosureswith slim behind-panel depth for roboticsapplications. These versatile E-Stopsalso are used in pendant controls forlifting and moving machinery. Applicationrequirements have also created a widevariety of available optional features andaccessories for most E-Stop products –illumination, protective rings, enclosures,guards, legend plates, etc. – that addto the functionality and safety of E-Stopinstallations.E-Stops will continue to evolve to meetnew standards and new applications.For designers, the most importantconsiderations in making the right designdecisions are a thorough understandingof E-Stop function; a grounding in thestandards, codes, and compliancesinvolved; proper selection of devicesthat meet or exceed the applicationrequirements.Once you understand the E-Stop function and relevant standards, codes, and compliances you candetermine the appropriate device.Emergency Stop Switches J. T orzillo, L. ScottEAO Switch Corporation98 Washington StreetMilford CT 06460T: (203) 877 4577F: (203) 877 3694E-mail:*******************Member of the EAO Group。

Materials Science and Engineering B132(2006)143–146Sustained-release of caffeine from a polymeric tablet matrix:An in vitro and pharmacokinetic studyDonna Tan a,Bin Zhao a,Shabbir Moochhala a,∗,Yi-Yan Yang ba Defence Medical&Environmental Research Institute,DSO National Laboratories(Kent Ridge),27Medical Drive,#12-00,Singapore117597,Republic of Singaporeb Institute of Bioengineering and Nanotechnology,31Biopolis Way,#04-01,The Nanos,Singapore138669,Republic of SingaporeAbstractCaffeine is utilized as a stimulant to impart a desired level of alertness during certain working ually,a single dose of caffeine induces 2–3h of alertness coupled with side effects whereas a longer effect of8–12h is very useful for both daily life and military action.Thus,there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix.Poly(ethylene oxide)(PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press.In vitro release profiles as well as the pharmacokinetics studies data were obtained.Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet.The PK studies showed sustained delivery of caffeine resulted in two expected phenomena:a reduction in the initial high rate of caffeine release(burst release)as well as a reduction in the change in caffeine concentration in the systemic circulation.A simple two-component system for sustained-release caffeine formulation therefore has been achieved.©2006Elsevier B.V.All rights reserved.Keywords:Pharmacokinetics;Sustained-release;Caffeine;Tablet1.IntroductionMilitary personnel involved in sustained and continuous oper-ations as well as civilian shift-workers will experience situations in which long-period of alertness is required.The use of caffeine could help alleviate cognitive performance degradation during extended wakefulness[1,2].Caffeine is a well-known and widely used stimulant for cen-tral nervous system from the group of xanthine derivatives and can be used to impart a desired level of increased alertness[2]. It is safe as a component of food at doses required to over-come sleep deprivation and has been included in diets in coffee and many soft drinks.However,a single dose of caffeine usually induces2–3h of alertness coupled with side effects.An extended duration of action of8–12h is very useful for both daily life and military action[1–3].As coffee might not be readily available to soldiers and shift-workers in such situations,therefore there is a need to develop a polymeric system to achieve a sustained-release of caffeine and prolong the stimulant action.∗Corresponding author.Tel.:+6564857201;fax:+6564857226.E-mail address:mshabbir@.sg(S.Moochhala).Tablets are among the simplest drug delivery systems and hence,the obvious choice for oral delivery of drugs.For this reason,a tablet system is being optimised for the oral sustained delivery of caffeine in the gastro-intestinal tract.Poly(ethylene)oxide(PEO)is the polymeric device used to sustain the delivery of caffeine.Its advantages as a polymer of choice are mainly because of its non-toxicity,high water-solubility,insensitivity to the pH of the biological medium[4–7], and it is safe for use in humans[5].This paper describes the fabrication method as well as in vitro and in vivo animal release profiles of the polymeric-caffeine-tablet.This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix.2.Materials and methods2.1.MaterialsPolymers,poly(ethylene oxide)with M w of8×106and 4×106;poly(ethylene glycol)(PEG)with M w8×103; poly(vinyl alcohol)(PV A)M w 3.1–5×104(87–89%0921-5107/$–see front matter©2006Elsevier B.V.All rights reserved. doi:10.1016/j.mseb.2006.02.031144 D.Tan et al./Materials Science and Engineering B132(2006)143–146hydrolyzed);ethyl cellulose(EC)(ethyl48%,viscosity 46cP);were purchased from Aldrich(Milwaukee,USA). Poly(vinyl pyrrolidone)(PVP)M w4×104;poly(dl-lactide-co-glycolide)(PLGA50:50)M w4–7.5×104;were purchased from Sigma(St Louis,USA).Poly(dl-lactic acid)(PLA)M w 1.5–2.5×104was purchased from Polyscience(Warrington, USA).As the original PLGA was not afine power,it was micro-nised with a freeze mill(SPEX6800freeze/mill,Metuchen, USA)to facilitate tablet fabrication.Poly(ethylene oxide)with M w of8×106and4×106(Aldrich waukee,USA).2.2.Tablet fabricationThe polymer,used as the dissoluble matrix material,was mixed thoroughly with caffeine powder(Sigma,St.Louis,USA) by manually grinding in a stone mortar.The resultant powder mixture is then compressed with a laboratory hydraulic press (Graseby Specac)under a pressure of38MPa for1min using two tablet punches in10-or5-mm diameter,which have convex surfaces.The total mass of each10-mm diameter tablet was maintained at360mg with different loadings of caffeine while that of the5-mm diameter tablet was kept at35mg.2.3.In vitro release studyApparatus2of the USP dissolution test(VK7000,VanKel Technology Group,Weston Parkway,USA)was employed for in vitro drug release studies.Simulated intestinalfluid(SIF, without pancreatin),which is prepared using monobasic potas-sium phosphate and sodium hydroxide(Merck,Darmstadt,Ger-many),is used as a release medium.The dissolution tests are performed in1000mL of recep-tor medium with an agitation rate of110rpm.Samples of1mL, which are replaced by an equal volume of fresh receptor medium, are periodically taken.All samples arefiltered with0.2-␮m syringefilters(Whatman,Clifton,USA)before being analysed with high performance liquid chromatography(HPLC).2.4.In vivo animal experimentsPharmacological evaluation was carried out using20male Sprague–Dawley rats weighing between220and250g.Ani-mals were catheterised via the left iliac vein and were allowed a post surgical recovery period of at least24h.They were fasted overnight with free access to water prior to dosing.Subjects were administered a single dose of either the polymeric-tablet-formulation(n=11)or the control-tablets(n=9)orally.Blood samples for measurement of plasma Caffeine concentrations were obtained predose,1–8,10,12,24,30,36and48h fol-lowing oral dosing.Plasma were immediately separated from the blood samples and frozen at−70◦C until assayed.Before the samples can be analysed for caffeine quan-tities,caffeine has to be extracted.One hundred andfifty microlitres of an internal standard(I.S.,500␮g mL−1N-acetyl-p-aminophenol in water),and an additional3mL of dichloromethane–isopropanol(88:12,v/v)were added to 150␮L of plasma.It was vortex-mixed and shaken for45min.Table1HPLC Gradient used for detection of caffeineTime(min)Flowrate(mL/min)SolventA(%)Solvent B(%)Solvent C(%)0 1.00100005 1.00950522 1.00950524 1.00095535 1.00095545 1.000604050 1.000604051 1.001000056 1.0010000 Solvent A:0.05%acetic acid;solvent B:50mM ammonium acetate;solvent C: methanol.After centrifugation for10min at11×g,the organic phase was separated and evaporated to dryness under a gentle stream of nitrogen.The extract was reconstituted with200␮L of0.05% acetic acid–methanol solution(92:8,v/v).2.5.HPLC analysisThe reconstituted sample of caffeine was analysed for caf-feine quantity using a chromatographic HPLC system(Waters 2690Separation Module)consisting of a600E multi-solvent delivery system pump,Ultra WISP715auto-injector and a UV–Vis996photodiode array detector,all were obtained from Waters Asia Ltd.An injection volume of50␮L was used.The detector was operated at a wavelength of254nm.The caffeine metabolites were separated on a SymmetryShield TM Cartridge Column RP18(250mm×4.6mm i.d.;particle size,5␮m)from Waters Asia Ltd.at22◦C and aflow rate of1mL min−1.A mobile phase comprising0.05%acetic acid,50mM ammonium acetate and methanol was used.The mobile phase consisted of 0.05%acetic acid,50mM ammonium acetate and methanol according to the following gradient program as listed in Table1.3.Results and discussion3.1.In vitro release profiles for sustained-release ofcaffeineA polymeric matrix is used to impede the diffusion of caffeine into the external environment.The efficiency of this impedance is dependent upon a variety of parameters,including polymer type,molecular weight and concentration.In the same manner, caffeine release is also effected by erosion of the tablets,which frees the caffeine from the matrices.The effect of various poly-mers on caffeine release profile was studied.Fig.1shows that PEG,PVP,PV A and EC as well as PLGA exert only a slight retardance on caffeine release.As PEG and PVP used were of low molecular weight,they would be expected to dissolve very quickly in an aqueous phase, thus removing their effects from the system.PV A and EC’s dis-solution may have caused the disintegration of the tablet(resultsD.Tan et al./Materials Science and Engineering B 132(2006)143–146145Fig.1.Cumulative caffeine release profiles of tablets containing various poly-mers:( )PEG M w 1×104;(᭹)PVP M w 4×104;( )PV A M w 3.1–5×104;( )EC,viscosity of 46cP;( )PLGA 50:50M w 4–7.5×104.The dotted line represents the release profile of pure caffeine tablets for comparison.not shown).PLGA tablets showed no satisfactory retardance although the tablet structure was maintained.This may be due to the hydrophilicity of the PGA chain segment,which would not retard the penetration of the aqueous phase.Thus,caffeine would still be able to solubilise and diffuse with ease in the presence of PLGA.Figs.2and 3show the release profiles of PEO tablets of M w of 8×106and 4×106with various percentage caffeine loading.Caffeine at 8.3%,16.7%,33.3%,50%,80%and 90%loading were fabricated with PEO as the dissoluble matrix [8].The figures show the release of caffeine from both tablets is nearly linear in the first 20h suggesting an almost constant rate of caffeine release during this period.The tablets had similar release profiles,despite differing caffeine contents.The trend is similar for the two different molecular weight PEO tablets.The tablets retained their characteristic capabilities to retard caffeine release from their matrices despite the use of varying proportions of caffeine,up to caffeine content of 80%.It can also be observed that the release of caffeine from tablets of the higher molecular weight PEO tends to be more gradual (lower rate)compared to the release rate in PEO of lowermolec-Fig.2.Release profiles of PEO M w 4×106tablets with various percentage caffeine loading:( )8.3%;( )16.7%;( )33.3%;(+)50%;(−)80%;( )90%.Fig.3.Release profiles of PEO M w 8×106tablets with various percentage caffeine loading:( )8.3%;(×)16.7%;(᭹)33.3%;( )80%;( )90%.ular weight.This is probably due to the slower dissolution and erosion,and hence release of caffeine,of the higher molecular weight polymer.The sole exceptions to the release profiles of the tablets were those with 90%caffeine-loading.These tablets tended to release their caffeine load faster than the trends of the other tablets pre-dicted.This may be explained by the dominance of the diffusion gradient created by the high caffeine content,over the retardation effect of the reduced polymer content.Since the release rates of caffeine are not significantly altered by changes in loading (up to percentage loading of 80%),it is possible to choose the most suitable percentage loading amount based upon usage of the tablet and desired overall caffeine released.3.2.In vivo tablet release profiles and pharmacokinetics analysisIt was necessary to use 5-mm diameter tablets instead of the 10-mm diameter ones studied in vitro previously because the larger tablets were too difficult for the rats used in the in vivo assays to swallow.An ideal caffeine content suitable for sustained-release for use in the animal models was determined to be 32%caffeine-loading in the PEO tablet.Sustained delivery of caffeine was expected to result in two phenomena:a reduction in the initial high rate of caffeine release (burst release),as well as the reduction in the change in caffeine concentration in the systemic circulation.The PK analysis was performed with WinNonlin ®Version 3.2(Pharsight Corporation,CA,USA).From Fig.4,it may be observed that the highest systemic concentration of caffeine attained within the first hour is 5.0␮g mL −1for negative control I (8%,w/w caffeine sucrose tablets).In contrast,the 8%(w/w)caffeine poly(ethylene oxide)tablets attained a highest systemic caffeine concentration of only 0.93␮g mL −1within 6h.This indicates a 5.4-fold decrease in the burst release.The latency to the peak concentration is 1and 5h for negative control I and 8%(w/w)caffeine PEO tablets,respectively.This is a 5-fold delay in the latency to peak concentration for the PEO tablets.However,the half-life for the 8%(w/w)caffeine PEO tablets is 1.97h and that of the negative control is 1.87h.Thus,the half-146 D.Tan et al./Materials Science and Engineering B132(2006)143–146Table2Summary of pharmacokinetics(PK)parameters of the various caffeine-loaded tabletsPolymer/%caffeine loading(w/w)Peak concentration(␮g mL−1)T max(h)AUC(h␮g mL−1)Half-life(h) Negative control I Sucrose/8 5.00120.01 1.87 Negative control II Sucrose/3223.353146.73 6.72 Sustained-release PEO/80.935 5.834 1.97Sustained-release PEO/3212.23690.8534.37Fig.4.Mean(±S.E.M.)plasma concentration of caffeine following single oral dose of the following:( )32%(w/w)caffeine-loaded sucrose tablets;(᭹) 32%(w/w)caffeine-loaded PEO tablets;(♦)8%(w/w)caffeine-loaded sucrose tablets;( )8%(w/w)caffeine-loaded PEO tablets.life is not significantly increased.Both of these tablets failed to maintain the systemic caffeine concentrations at a constant and also to sustain the release of caffeine beyond12h.In order to demonstrate the ability to maintain the systemic caffeine concentration,it is necessary to increase the amount of caffeine in the PEO tablets.In vitro studies showed that the release profile of the caffeine-loaded PEO tablets was not affected by the quantity of caffeine used,so long as this quantity did not exceed80%(w/w).As such,32%(w/w)caffeine PEO tablets were used.The caffeine load was increased to four times of that previously used,with the intention of extending the half-life of caffeine.A second negative control was also used—32% (w/w)caffeine sucrose tablets.The highest systemic concentration for the32%(w/w)caf-feine PEO tablets achieved was12.23␮g mL−1.The latency to the peak concentration was achieved at6h after dosing.This is compared to the32%(w/w)caffeine sucrose tablets where the highest systemic concentration—23.35␮g mL−1was achieved at3h after dosing.A1.90-fold decrease for initial burst release and a2-fold delay in the latency to peak concentration were obtained with the32%(w/w)caffeine PEO tablets.The half-life for the32%(w/w)caffeine PEO tablets was4.37h and that for the32%(w/w)caffeine sucrose tablets was6.72h. Table2summarizes the pharmacokinetics(PK)parameters of the caffeine-loaded tablets.The32%(w/w)caffeine PEO tablets have shown to be able to maintain a systemic caffeine concentration with a2.3-fold increase in half-life,as compared to negative control I(8%,w/w caffeine sucrose tablets),yet avoiding the burst release of caf-feine that was exhibited in negative control II(32%,w/w caffeine sucrose tablets).4.ConclusionWe have achieved a sustained-release of caffeine from our 32%(w/w)caffeine polymeric PEO tablet core.The half-life of 32%(w/w)caffeine PEO was increased2.3-fold compared to negative control I.References[1]A.P.Smith,Hum.Psychopharmacol.20(2005)441–445.[2]T.M.McLellan,G.H.Kamimori,D.M.V oss,D.G.Bell,K.G.Cole,D.Johnson,Aviat.Space Environ.Med.76(2005)647–654.[3]E.De Valck,E.De Groot,R.Cluydts,Percept.Mot.Skills96(2003)67–78.[4]nger,mun.6(1980)1–48.[5]nger,N.Peppas,J.Marcomol.Sci.Rev.Macromol.Chem.Phys.C23(1983)61–126.[6]C.G.Pitt,A.Schindler,Biodegradation of polymers,in:S.D.Bruck(Ed.),Controlled Drug Delivery,vol.I,Basic Concepts,CRC Press,Boca Raton, Florida,1983,pp.53–80.[7]R.W.Baker,Controlled Release of Biologically Active Agent,John Wileyand Sons,New York,1987,pp.84–131.[8]N.Wu,L.S.Wang,D.Tan,S.M.Moochhala,Y.Y.Yang,J.ControlledRelease102(2005)569–581.。

固定式义齿工艺流程英文回答，The fixed denture process involves several steps to ensure the creation of a high-quality and custom-fitted dental prosthetic. The process begins with a comprehensive examination and assessment of the patient's oral health, including the condition of the teeth and gums. This initial step is crucial in determining the suitability of fixed dentures for the patient.Following the assessment, the next step involves taking impressions of the patient's teeth and gums. These impressions are used to create a precise mold of thepatient's mouth, which serves as the basis for the fabrication of the fixed dentures. The use of advanced technology, such as digital scanning and 3D imaging, has significantly improved the accuracy and efficiency of this step.Once the mold is obtained, the dental laboratory fabricates the fixed dentures according to the specificrequirements of the patient. This may involve the selection of appropriate materials, such as porcelain or ceramic, to achieve the desired aesthetic and functional results. The use of high-quality materials is essential in ensuring the durability and longevity of the fixed dentures.After the fabrication of the dentures, the next step is the try-in process, where the dentures are placed in the patient's mouth to assess the fit, comfort, and aesthetics. Any necessary adjustments are made at this stage to ensure that the fixed dentures provide a natural and comfortable bite. The dentist also evaluates the patient's bite and makes any final modifications to the dentures to achieve optimal function.Once the fixed dentures are deemed satisfactory, they are securely attached to the patient's existing teeth or dental implants. The dentist ensures that the dentures are properly positioned and secured to provide stability and support for the patient's bite. Proper care and maintenance instructions are provided to the patient to ensure the longevity of the fixed dentures.Overall, the fixed denture process requires careful planning, precise fabrication, and meticulous attention to detail to achieve optimal results for the patient. By following a systematic and comprehensive approach, dental professionals can provide patients with high-quality fixed dentures that restore function, aesthetics, and confidence.中文回答，固定式义齿工艺流程包括多个步骤，以确保制作出高质量且合身的牙科假体。

英文医疗：医疗术语的英文引言："Health is not valued till sickness comes." - Thomas Fuller在现代医疗领域中，了解医学术语的英文翻译是非常重要的。

无论是医生、护士还是患者，都需要掌握这些术语以便有效地进行沟通和理解。

本文将介绍一些常见的医疗术语及其英文翻译，旨在帮助读者更好地了解医学领域。

一、常见医疗术语1. Diagnosis and Treatment（诊断与治疗）- Diagnosis（诊断）: determination of the nature of a disease or condition through examination or assessment of the signs and symptoms.- Treatment（治疗）: medical care given to a patient for an illness or injury.2. Symptoms and Signs（症状与体征）- Symptoms（症状）: subjective evidence of a disease or condition experienced by the patient.- Signs（体征）: objective evidence of a disease or condition observed by a healthcare professional.3. Medication and Prescription（药物与处方）- Medication（药物）: substance used to diagnose, cure, treat, or prevent a disease or condition.- Prescription（处方）: written order for medication or treatment from a healthcare professional to a pharmacy or patient.4. Surgery and Anesthesia（外科手术与麻醉）- Surgery（外科手术）: medical specialty that uses operative manual and instrumental techniques on a patient to investigate or treat a pathological condition.- Anesthesia（麻醉）: medical procedure used to induce a state of controlled unconsciousness, loss of sensation, or absence of reflexes for the performance of surgery or other medical procedures.5. Medical Imaging（医学影像学）- X-ray（X射线）: form of electromagnetic radiation used in medical imaging to visualize the internal structures of the body.- MRI (Magnetic Resonance Imaging)（磁共振成像）: medical imaging technique that uses a strong magnetic field and radio waves to generate images of the body's internal structures.- CT Scan (Computed Tomography)（计算机断层扫描）: medical imaging technique that uses X-rays and computer processing to create detailed cross-sectional images of the body.6. Laboratory Tests（实验室检查）- Blood Test（血液检查）: analysis of a sample of blood to measure various components, such as blood cell counts, glucose levels, and cholesterol levels.- Urine Test（尿液检查）: analysis of a urine sample to detect the presence of substances or evaluate organ function.- Biopsy（活体组织检查）: removal and examination of a sample of tissue from the body to diagnose or monitor a disease.7. Rehabilitation（康复）- Physical Therapy（物理疗法）: use of physical methods, such as exercise and massage, to improve muscle strength, mobility, and function.- Occupational Therapy（职业疗法）: therapeutic use of daily activities to enhance physical and cognitive skills for individuals with disabilities or injuries.二、总结通过本文的介绍，我们了解了一些常见的英文医疗术语及其对应的中文意思。

1000Punch materials up to1/2" (12 mm) rapidly, repeatedly and economically.Affordable. Versatile. Easy Operation. Ruggedly reliable for continuous heavy-duty punching.Totally simpleEliminate manual machine set-ups with Series 1000 Fabricators. Protect profit margins on proto-type and production runs.Hydraulic punching powerMaximum punching force is available throughout the entire stroke!With the longer effective stroke, Series 1000Fabricators rapidly and repeatedly punch through materials up to 1/2" (12 mm) thick, using fully controlled hydraulic power.Series 1000 Fabricator AdvantagesBoost Productivity — Fabricate four to ten times as many parts as conventional presses.Fast Set-Up — Eliminate lost time due to lengthy set-ups and tear-downs. Set up quickly, easily, in just minutes.Minimize Inventory — Profitable short runs let you cut inventory and space needs.Reduce Material Handling — Fabricate parts up to 72” (1825 mm) long without removing or repo-sitioning. Optional 120”/144” (3050 mm/3660 mm)axis for more capability. Handling time reduced by as much as 50 percent.“C” Frame Design with Rear Address Gauging —Fabricate material twice as wide as the y-axis.No Clamps — No clamps to interfere with work surface. Programmed control change positions are not required.Easy Operation — Operator simply positions mater-ial against the CNC-positioned gauge points, and uses a footswitch to initiate the punch cycle. Upon punch-stroke completion, the gauging advances automatically to the next programmed position.Hydraulic Punching with Positive Stripping — Full tonnage capacity and safety control throughentire punching stroke.Series 1000 Fabricators are designed and built to operate on heavy sheet and plate. Punch up to 5"(125 mm) diameter holes.Punch material up to 1/2" (12 mm) thick.SimpleCanned Cycle ProgrammingSix canned cyclessimplify programming. Enter the coordinates and pattern from the part drawing and the Panelgage 1000M control establishes the locationof each punch cycle.Bolt Hole Circle•X, Y of circle center Line at an Angle:• X, Y of starting hole •Angle•Hole spacing •Number of holes •X, Y of starting hole •Starting angle •Hole spacing •Length•X, Y of starting hole •Hole spacing •X length • Y lengthPanelgage 1000M CNC ControlOperator-friendly, machine-mounted control requires no special training for programmers. With only part dimensions, an operator uses a simple touchscreen to setup for a complete part.•Multiple part program storage in nonvolatile memory•Software provided for additional storage/backup —easily added to your PC•Full program review, edit and manual display •Conversation-type, plain English programming •English-metric operation •On-board diagnostics •Position display•Manual operation with “Go To” position•Electronic zeroing on standard and extended material stops •OffsetsStandard Tooling — Whitney 28XX punches and dies save up to 50 percent in tooling costs.Rapid Tool Change — Changes completed in 15 seconds for round or shaped holes up to 5" (125 mm) diameter.Accuracy — Gauge positioning accuracy is ±.005"with a repeat accuracy of ±.003".Overload Protection — Hydraulic punching system is protected from overload and automatically reset.IncreaseLow CostQuick-set stroke lengthSimply turning the cam on an adjustable limit switch assembly lets you work with the most efficient stroke length for every job.Adjustable limit switch assembly set for material up to 1/8" (3 mm) thick.Adjustable limit switch assembly set formaterial 10 ga. through 1/4". This position is also used for material 1/4" to 1/2" (6 mm to 12 mm) thick.•Reduce set-up times.•Convert quickly from thin-gauge to thick materials.•Use maximum machine hit rates without lengthy adjustments.Stripper plate versatilityStandard stripper plate with insert for material to 1/8" (3 mm).Standard stripper plate without insert for 10 ga. through 1/4" (3.5 mm through 6 mm)material.An optional stripper is available for material 1/4" to 1/2" thick.Pressure control switchFor reversing underpressure to countersink,extrude, coin, louvre and knockout.Standard EquipmentSeries 1000 CNC Fabricators meet application needs.Model Punching Force Throat Depth153050 tons30"(450 kN)(760 mm)154850 tons48"(450 kN)(1220 mm)Series 1000 Fabricatorsuse standard 28XX punches and dies with either flat face, 1/8" (3 mm)shear, or 7/16" max-shear.This economical tooling allows for rapid toolchanges, and is self-align-ing with shaped sizes keyed for orientation.Positive stripping allows the workpiece to strip free for instantaneous positioning without low-ering punching tonnage..001" TIR concentricityAll 28XX punches and dies are concentric to .001 TIR.On all punches, the punch tip is concentric with the punch shank. On all dies, the hole in the die is concentric with the outer diameter of the die. Shaped tooling is pinned for proper alignment. Custom pin location is available.Optional urethane stripper sleevesUrethane stripper sleeves are available for punching close-center holes in light gauge metal and for many other special applications. No marking or deformity of material occurs.Strippers are sup-plied with only a small hole. The first punch stroke produces a snug fit of the stripper to its punch.Economical. Accurate. Fast and easy tool changing.Tool changing is easy with economical 28XX style quick-change tooling.Tool and die standard sizesCountersinking in one strokeEliminate costly secondary opera-tions when coun-tersinking andextruding by using special tools and techniques. One stroke of a Series 1000 can produce partial, full or formed counter-sinks, pierce andextrude holes, countersink both sides of a hole,or pierce and form holes.The special tooling is designed for use on hydraulic presses equipped with pressure adjustment controls.The basic countersinks: partial (A), full (B), and formed (C). They vary widely in size and angle,but all can be produced in one press stroke.A full countersink (see photo above) is widely used in approximately 3/16" to 1/2" (5 mm to 12 mm) material. It requires a pre-punched hole larger than the pilot on the countersink punch.A standard die and a countersink punch with a pilot is used to extrude the metal back into the hole. No material-thickening or burr is produced.For complete information on standards and special-purpose toolssee the Whitney 28XX Punch & Die Catalog.An increase of two to three times punchingcapacity is available from Series 1000 Fabricators by using special tooling to increase the tonnage capabilities.For example, a 30 ton Series 1000 can punch up to a 2" (50 mm) diameter hole through4 ga. (5.7 mm) thick mild steel using a standard 2" (50 mm) punch with a 1/8" (3 mm) concave shear. Using a punch with 7/16" (11 mm) highcapacity concave shear the same machine can punch up to a 5" (127 mm) diameter hole in 5 ga. (5.3 mm) material.This means a 30 ton (275 kN) press can be tooled up to produce holes which normally require an 80 ton (730 kN) capacity mechanical press. A 50 ton (455 kN) press can be tooled up to produce holes which normally require a 100 ton (910 kN) capacity mechanical press.Sheared tooling increases press capacityComparison ChartStandard Round vs. High Capacity Round with Concave ShearOff-line Program Software•Do remote programming on your PC•Full color graphic representation •Editing•Copying•Convert Panelgage 2 and Panelgage 2E programs •Upload and Download •Generate Tool List•Save/Restore machine parameters•Create part program back-up files •English/metric conversionPunching shaped materialsSeries 1000 Fabricators can be supplied with special toolingaccessories to punch a wide range of shapes other than flat stock. Angles, channels and special extrusions can all beprocessed.Special attachments, designed by Whitney engineers, help the Series 1000 Fabricators meet virtually any punching requirement.Angle/channel iron punching assemblyPunch both angle and channel iron on the Series 1000 with the Angle Iron Attachment. Fabricate angle up to 3" x 3"(75 mm x 75 mm) and channel iron up to 3" x 12" x 20.7 lbs./ft.(75 mm x 305 mm x 9.4 kg/m). Consult Whitney for angle and channel iron over 3" (75 mm).The attachment is easily installed without modifications to the press. Package includes special strippers and punch adapter with point of operation guarding.Brush top tablesBrush top tables provide easy material movement and eliminate marks andscratches on polished, painted or anodized materials. The brushes maintain smoothworkpiece support during thefabrication process.Optional EquipmentTool BoxTool box organizes strippers, die adapters,punches and dies for easy use and offers convenient storage.Optional EquipmentOptional EquipmentCenter PunchThe center punch is used primarily for layout of drilled holes. This can also be used to layout shear,bend lines and optional equipment added later.Extended Gauge Point84510351L E D O M R O T A C I R B A F Punching Force50 Tons (445 kN)50 Tons (445 kN)Punching Capacity: A36 - 60,000 psi shear strength s s e n k c i h T l a i r e t a M r e t e m a i D e l o H Std. Tooling Max. Shear Std. Tooling Max. Shear Std. Tooling Max. Shear 1" (25 mm)5/16" (8 mm)5/16" (8 mm)1/2" (12 mm)1/2" (12 mm)1/2" (12 mm)1/2" (12 mm)2" (50 mm) 4 ga. (5.7 mm)1/4" (6 mm)5/16" (8 mm)3/8" (9 mm)5/16" (8 mm)3/8" (9 mm)3" (75 mm)8 ga. (4 mm)1/4" (6 mm) 4 ga. (5.7 mm)3/8" (9 mm) 4 ga. (5.7 mm)3/8" (9 mm)4" (100 mm)10 ga. (3.5 mm)7/32" (5.6 mm) 6 ga. (5 mm)5/16" (8 mm) 6 ga. (5 mm)5/16" (8 mm)5" (125 mm)11 ga. (3 mm)5 ga. (5.3 mm)8 ga. (4 mm)9/32" (7 mm)8 ga. (4 mm)9/32" (7 mm)Positioning Accuracy +.005" (.125 mm)+.005" (.125 mm)(CNC gauging)Throat Depth)m m 0221( "84)m m 067( "03Positioning Area Max.Standard "27 x "84"27 x "03(760 mm x 1825 mm)(1220 mm x 1825 mm)Optional30" x 120" or 144"48" x 120" or 144"(760 mm x 3050 mm(1220 mm x 3050 mm)m m 0663 r o )m m 0663 r o Punching Stroke Normal)m m 21( "2/1)m m 21( "2/1Adjustable — Minimum)m m 6( "8/3)m m 6( "8/3— Maximum )m m 05( "2)m m 05( "2Hydraulic Power Unit PH 02PH 02Machine Shipping Weight12,410 lbs. (5641 kg)17,120 lbs. (7782 kg)MODEL A BC DEF153033" (838 mm)154830" (762 mm) 48" (1219 mm)80" (2032 mm) 80" (2032 mm)33" (838 mm)16-1/2" (419 mm)16-1/2" (419 mm)95" (2413 mm) 111" (2819 mm)78" (1981 mm) 94" (2388 mm)*Number of optional support tables required varies with machine model and length of gauging system x-axis. Tables available with ball or brush transfer tops. NOTE: Because Whitney is continually improving its products, specifications are subject to change without notice.。

ERP专业词汇集合ERP专业词汇1 ABM Activity-based Management 基于作业活动管理2 AO Application Outsourcing 应用程序外包3 APICS American Production and Inventory Control Society,Inc 美国生产与库存管理协会4 APICS Applied Manufacturing Education Series 实用制造管理系列培训教材5 APO Advanced Planning and Optimization 先进计划及优化技术6 APS Advanced Planning and Scheduling 高级计划与排程技术7 ASP Application Service/Software Provider 应用服务/软件供应商8 ATO Assemble To Order 定货组装9 ATP Available To Promise 可供销售量(可签约量)10 B2B Business to Business 企业对企业(电子商务)11 B2C Business to Consumer 企业对消费者(电子商务)12 B2G Business to Government 企业对政府(电子商务)13 B2R Business to Retailer 企业对经销商(电子商务)14 BIS Business Intelligence System 商业智能系统15 BOM Bill Of Materials 物料清单16 BOR Bill Of Resource 资源清单17 BPR Business Process Reengineering 业务/企业流程重组18 BPM Business Process Management 业务/企业流程管理19 BPS Business Process Standard 业务/企业流程标准20 C/S Client/Server(C/S)\Browser/Server(B/S) 客户机/服务器\浏览器/服务器21 CAD Computer-Aided Design 计算机辅助设计22 CAID Computer-Aided Industrial Design 计算机辅助工艺设计23 CAM Computer-Aided Manufacturing 计算机辅助制造24 CAPP Computer-Aided Process Planning 计算机辅助工艺设计25 CASE Computer-Aided Software Engineering 计算机辅助软件工程26 CC Collaborative Commerce 协同商务27 CIMS Computer Integrated Manufacturing System 计算机集成制造系统28 CMM Capability Maturity Model 能力成熟度模型29 COMMS Customer Oriented Manufacturing Management System 面向客户制造管理系统30 CORBA Common Object Request Broker Architecture 通用对象请求代理结构31 CPC Collaborative Product Commerce 协同产品商务32 CPIM Certified Production and Inventory Management 生产与库存管理认证资格33 CPM Critical Path Method 关键线路法34 CRM Customer Relationship Management 客户关系管理35 CRP capacity requirements planning 能力需求计划36 CTI Computer Telephony Integration 电脑电话集成(呼叫中心)37 CTP Capable to Promise 可承诺的能力38 DCOM Distributed Component Object Model 分布式组件对象模型39 DCS Distributed Control System 分布式控制系统40 DMRP Distributed MRP 分布式MRP41 DRP Distribution Resource Planning 分销资源计划42 DSS Decision Support System 决策支持系统43 DTF Demand Time Fence 需求时界44 DTP Delivery to Promise 可承诺的交货时间45 EAI Enterprise Application Integration 企业应用集成46 EAM Enterprise Assets Management 企业资源管理47 ECM Enterprise Commerce Management 企业商务管理48 ECO Engineering Change Order 工程变更订单49 EDI Electronic Data Interchange 电子数据交换50 EDP Electronic Data Processing 电子数据处理51 EEA Extended Enterprise Applications 扩展企业应用系统52 EIP Enterprise Information Portal 企业信息门户53 EIS Executive Information System 高层领导信息系统54 EOI Economic Order Interval 经济定货周期55 EOQ Economic Order Quantity 经济订货批量(经济批量法)56 EPA Enterprise Proficiency Analysis 企业绩效分析57 ERP Enterprise Resource Planning 企业资源计划58 ERM Enterprise Resource Management 企业资源管理59 ETO Engineer To Order 专项设计，按订单设计60 FAS Final Assembly Schedule 最终装配计划61 FCS Finite Capacity Scheduling 有限能力计划62 FMS Flexible Manufacturing System 柔性制造系统63 FOQ Fixed Order Quantity 固定定货批量法64 GL General Ledger 总账65 GUI Graphical User Interface 图形用户界面66 HRM Human Resource Management 人力资源管理67 HRP Human Resource Planning 人力资源计划68 IE Industry Engineering/Internet Exploration 工业工程/浏览器69 ISO International Standard Organization 国际标准化组织70 ISP Internet Service Provider 互联网服务提供商71 ISPE International Society for Productivity Enhancement 国际生产力促进会72 IT/GT Information/Group Technology 信息/成组技术73 JIT Just In Time 准时制造/准时制生产74 KPA Key Process Areas 关键过程域75 KPI Key Performance Indicators 关键业绩指标76 LP Lean Production 精益生产77 MES Manufacturing Executive System 制造执行系统78 MIS Management Information System 管理信息系统79 MPS Master Production Schedule 主生产计划80 MRP Material Requirements Planning 物料需求计划81 MRPII Manufacturing Resource Planning 制造资源计划82 MTO Make To Order 定货(订货)生产83 MTS Make To Stock 现货(备货)生产84 OA Office Automation 办公自动化85 OEM Original Equipment Manufacturing 原始设备制造商86 OPT Optimized Production Technology 最优生产技术87 OPT Optimized Production Timetable 最优生产时刻表88 PADIS Production And Decision Information System 生产和决策管理信息系统89 PDM Product Data Management 产品数据管理90 PERT Program Evaluation Research Technology 计划评审技术91 PLM Production Lifecycle Management 产品生命周期管理92 PM Project Management 项目管理93 POQ Period Order Quantity 周期定量法94 PRM Partner Relationship Management 合作伙伴关系管理95 PTF Planned Time Fence 计划时界96 PTX Private Trade Exchange 自用交易网站97 RCCP Rough-Cut Capacity Planning 粗能力计划98 RDBM Relational Data Base Management 关系数据库管理99 RPM Rapid Prototype Manufacturing 快速原形制造100 RRP Resource Requirements Planning 资源需求计划101 SCM Supply Chain Management 供应链管理102 SCP Supply Chain Partnership 供应链合作伙伴关系103 SFA Sales Force Automation 销售自动化104 SMED Single-Minute Exchange Of Dies 快速换模法105 SOP Sales And Operation Planning 销售与运作规划106 SQL Structure Query Language 结构化查询语言107 TCO Total Cost Ownership 总体运营成本108 TEI Total Enterprise Integration 全面企业集成109 TOC Theory Of Constraints/Constraints managemant 约束理论/约束管理110 TPM Total Productive Maintenance 全员生产力维护111 TQC Total Quality Control 全面质量控制112 TQM Total Quality Management 全面质量管理113 WBS Work Breakdown System 工作分解系统114 XML eXtensible Markup Language 可扩展标记语言115 ABC Classification(Activity Based Classification) ABC分类法116 ABC costing 作业成本法117 ABC inventory control ABC 库存控制118 abnormal demand 反常需求119 acquisition cost ,ordering cost 定货费120 action message 行为/活动(措施)信息121 action report flag 活动报告标志122 activity cost pool 作业成本集123 activity-based costing(ABC) 作业基准成本法/业务成本法124 actual capacity 实际能力125 adjust on hand 调整现有库存量126 advanced manufacturing technology 先进制造技术127 advanced pricing 高级定价系统128 AM Agile Manufacturing 敏捷制造129 alternative routing 替代工序(工艺路线)130 Anticipated Delay Report 拖期预报131 anticipation inventory 预期储备132 apportionment code 分摊码133 assembly parts list 装配零件表134 automated storage/retrieval system 自动仓储/检索系统135 Automatic Rescheduling 计划自动重排136 available inventory 可达到库存137 available material 可用物料138 available stock 达到库存139 available work 可利用工时140 average inventory 平均库存141 back order 欠交(脱期)订单142 back scheduling 倒排(序)计划/倒序排产? 143 base currency 本位币144 batch number 批号145 batch process 批流程146 batch production 批量生产147 benchmarking 标杆瞄准(管理)148 bill of labor 工时清单149 bill of lading 提货单150 branch warehouse 分库151 bucketless system 无时段系统152 business framework 业务框架153 business plan 经营规划154 capacity level 能力利用水平155 capacity load 能力负荷156 capacity management 能力管理157 carrying cost 保管费158 carrying cost rate 保管费率159 cellular manufacturing 单元式制造160 change route 修改工序161 change structure 修改产品结构162 check point 检查点163 closed loop MRP 闭环MRP164 Common Route Code(ID) 通用工序标识165 component-based development 组件(构件)开发技术166 concurrent engineering 并行(同步)工程167 conference room pilot 会议室模拟168 configuration code 配置代码169 continuous improvement 进取不懈170 continuous process 连续流程171 cost driver 作业成本发生因素172 cost driver rate 作业成本发生因素单位费用173 cost of stockout 短缺损失174 cost roll-up 成本滚动计算法175 crew size 班组规模176 critical part 急需零件177 critical ratio 紧迫系数178 critical work center 关键工作中心179 CLT Cumulative Lead Time 累计提前期180 current run hour 现有运转工时181 current run quantity 现有运转数量182 customer care 客户关怀183 customer deliver lead time 客户交货提前期184 customer loyalty 客户忠诚度185 customer order number 客户订单号186 customer satisfaction 客户满意度187 customer status 客户状况188 cycle counting 周期盘点189 DM Data Mining 数据挖掘190 Data Warehouse 数据仓库191 days offset 偏置天数192 dead load 空负荷193 demand cycle 需求周期194 demand forecasting 需求预测195 demand management 需求管理196 Deming circle 戴明环197 demonstrated capacity 实际能力198 discrete manufacturing 离散型生产199 dispatch to 调度200 DRP Distribution Requirements Planning 分销需求计划201 drop shipment 直运202 dunning letter 催款信203 ECO workbench ECO工作台204 employee enrolled 在册员工205 employee tax id 员工税号206 end item 最终产品207 engineering change mode flag 工程变更方式标志208 engineering change notice 工程变更通知209 equipment distribution 设备分配210 equipment management 设备管理211 exception control 例外控制212 excess material analysis 呆滞物料分析213 expedite code 急送代码214 external integration 外部集成215 fabrication order 加工订单216 factory order 工厂订单217 fast path method 快速路径法218 fill backorder 补足欠交219 final assembly lead time 总装提前期220 final goods 成品221 finite forward scheduling 有限顺排计划222 finite loading 有限排负荷223 firm planned order 确认的计划订单224 firm planned time fence 确认计划需求时界225 FPR Fixed Period Requirements 定期用量法226 fixed quantity 固定数量法227 fixed time 固定时间法228 floor stock 作业现场库存229 flow shop 流水车间230 focus forecasting 调焦预测231 forward scheduling 顺排计划232 freeze code 冻结码233 freeze space 冷冻区234 frozen order 冻结订单235 gross requirements 毛需求236 hedge inventory 囤积库存237 in process inventory 在制品库存238 in stock 在库239 incrementing 增值240 indirect cost 间接成本241 indirect labor 间接人工242 infinite loading 无限排负荷243 input/output control 投入/产出控制244 inspection ID 检验标识245 integrity 完整性246 inter companies 公司内部间247 interplant demands 厂际需求量248 inventory carry rate 库存周转率249 inventory cycle time 库存周期250 inventory issue 库存发放251 inventory location type 仓库库位类型252 inventory scrap 库存报废量253 inventory transfers 库存转移254 inventory turns/turnover 库存(资金)周转次数255 invoice address 发票地址256 invoice amount gross 发票金额257 invoice schedule 发票清单258 issue cycle 发放周期259 issue order 发送订单260 issue parts 发放零件261 issue policy 发放策略262 item availability 项目可供量263 item description 项目说明264 item number 项目编号265 item record 项目记录266 item remark 项目备注267 item status 项目状态268 job shop 加工车间269 job step 作业步骤270 kit item 配套件项目271 labor hour 人工工时272 late days 延迟天数273 lead time 提前期274 lead time level 提前期水平275 lead time offset days 提前期偏置(补偿)天数276 least slack per operation 最小单个工序平均时差277 line item 单项产品278 live pilot 应用模拟279 load leveling 负荷量280 load report 负荷报告281 location code 仓位代码282 location remarks 仓位备注283 location status 仓位状况284 lot for lot 按需定货(因需定量法/缺补法)285 lot ID 批量标识286 lot number 批量编号287 lot number traceability 批号跟踪288 lot size 批量289 lot size inventory 批量库存290 lot sizing 批量规划291 low level code 低层(位)码292 machine capacity 机器能力293 machine hours 机时294 machine loading 机器加载295 maintenance ,repair,and operating supplies 维护修理操作物料296 make or buy decision 外购或自制决策297 management by exception 例外管理法298 manufacturing cycle time 制造周期时间299 manufacturing lead time 制造提前期300 manufacturing standards 制造标准301 master scheduler 主生产计划员302 material 物料303 material available 物料可用量304 material cost 物料成本305 material issues and receipts 物料发放和接收306 material management 物料管理307 material manager 物料经理308 material master,item master 物料主文件309 material review board 物料核定机构310 measure of velocity 生产速率水平311 memory-based processing speed 基于存储的处理速度312 minimum balance 最小库存余量313 Modern Materials Handling 现代物料搬运314 month to date 月累计315 move time , transit time 传递时间316 MSP book flag MPS登录标志317 multi-currency 多币制318 multi-facility 多场所319 multi-level 多级320 multi-plant management 多工厂管理321 multiple location 多重仓位322 net change 净改变法323 net change MRP 净改变式MRP324 net requirements 净需求325 new location 新仓位326 new parent 新组件327 new warehouse 新仓库328 next code 后续编码329 next number 后续编号330 No action report 不活动报告331 non-nettable 不可动用量332 on demand 急需的333 on-hand balance 现有库存量334 on hold 挂起335 on time 准时336 open amount 未清金额337 open order 未结订单/开放订单338 order activity rules 订单活动规则339 order address 订单地址340 order entry 订单输入341 order point 定货点342 order point system 定货点法343 order policy 定货策略344 order promising 定货承诺345 order remarks 定货备注346 ordered by 定货者347 overflow location 超量库位348 overhead apportionment/allocation 间接费分配349 overhead rate,burden factor,absorption rate 间接费率350 owner's equity 所有者权益351 parent item 母件352 part bills 零件清单353 part lot 零件批次354 part number 零件编号355 people involvement 全员参治356 performance measurement 业绩评价357 physical inventory 实际库存358 picking 领料/提货359 planned capacity 计划能力360 planned order 计划订单361 planned order receipts 计划产出量362 planned order releases 计划投入量363 planning horizon 计划期/计划展望期364 point of use 使用点365 Policy and procedure 工作准则与工作规程366 price adjustments 价格调整367 price invoice 发票价格368 price level 物价水平369 price purchase order 采购订单价格370 priority planning 优先计划371 processing manufacturing 流程制造372 product control 产品控制373 product family 产品系列374 product mix 产品搭配组合375 production activity control 生产作业控制376 production cycle 生产周期377 production line 产品线378 production rate 产品率379 production tree 产品结构树380 PAB Projected Available Balance 预计可用库存(量) 381 purchase order tracking 采购订单跟踪382 quantity allocation 已分配量383 quantity at location 仓位数量384 quantity backorder 欠交数量385 quantity completion 完成数量386 quantity demand 需求量387 quantity gross 毛需求量388 quantity in 进货数量389 quantity on hand 现有数量390 quantity scrapped 废品数量391 quantity shipped 发货数量392 queue time 排队时间393 rated capacity 额定能力394 receipt document 收款单据395 reference number 参考号396 regenerated MRP 重生成式MRP397 released order 下达订单398 reorder point 再订购点399 repetitive manufacturing 重复式生产(制造)400 replacement parts 替换零件401 required capacity 需求能力402 requisition orders 请购单403 rescheduling assumption 重排假设404 resupply order 补库单405 rework bill 返工单406 roll up 上滚407 rough cut resource planning 粗资源计划408 rounding amount 舍入金额409 run time 加工(运行)时间410 safety lead time 安全提前期411 safety stock 安全库存412 safety time 保险期413 sales order 销售订单414 scheduled receipts 计划接收量(预计入库量/预期到货量) 415 seasonal stock 季节储备416 send part 发送零件417 service and support 服务和支持418 service parts 维修件419 set up time 准备时间420 ship address 发运地址421 ship contact 发运单联系人422 ship order 发货单423 shop calendar 工厂日历(车间日历)424 shop floor control 车间作业管理(控制)425 shop order , work order 车间订单426 shrink factor 损耗因子(系数)427 single level where used 单层物料反查表428 standard cost system 标准成本体系429 standard hours 标准工时430 standard product cost 标准产品成本431 standard set up hour 标准机器设置工时432 standard unit run hour 标准单位运转工时433 standard wage rate 标准工资率434 status code 状态代码435 stores control 库存控制436 suggested work order 建议工作单437 supply chain 供应链438 synchronous manufacturing 同步制造/同期生产439 time bucket 时段(时间段)440 time fence 时界441 time zone 时区442 top management commitment 领导承诺443 total lead time 总提前期444 transportation inventory 在途库存445 unfavorable variance, adverse 不利差异446 unit cost 单位成本447 unit of measure 计量单位448 value chain 价值链449 value-added chain 增值链450 variance in quantity 量差451 vendor scheduler,supplier scheduler 采购计划员/供方计划员452 vendor scheduling 采购计划法453 Virtual Enterprise(VE)/ Organization 虚拟企业/公司454 volume variance 产量差异455 wait time 等待时间456 where-used list 反查用物料单457 work center capacity 工作中心能力458 workflow 工作流459 work order 工作令460 work order tracking 工作令跟踪461 work scheduling 工作进度安排462 world class manufacturing excellence 国际优秀制造业463 zero inventories 零库存464465 Call/Contact/Work/Cost center 呼叫/联络/工作/成本中心466 Co/By-product 联/副产品467 E-Commerce/E-Business/E-Marketing 电子商务/电子商务/电子集市468 E-sales/E-procuement/E-partner 电子销售/电子采购/电子伙伴469 independent/dependent demand 独立需求/相关需求件470 informal/formal system 非/规范化管理系统471 Internet/Intranet/Extranet 互联网/企业内部网/企业外联网472 middle/hard/soft/share/firm/group ware 中间/硬/软/共享/固/群件473 pegging/kitting/netting/nettable 追溯(反查)/配套出售件/净需求计算474 picking/dispatch/disbursement list 领料单(或提货单)/派工单/发料单475 preflush/backflush/super backflush 预冲/倒冲法/完全反冲476 yield/scrap/shrinkage (rate) 成品率/废品率/缩减率477 scrap/shrinkage factor 残料率（废品系数）/损耗系数478479 costed BOM 成本物料清单480 engineering BOM 设计物料清单481 indented BOM 缩排式物料清单482 manufacturing BOM 制造物料清单483 modular BOM 模块化物料清单484 planning BOM 计划物料清单485 single level BOM 单层物料清单486 summarized BOM 汇总物料清单487488 account balance 账户余额489 account code 账户代码490 account ledger 分类账491 account period 会计期间492 accounts payable 应付账款493 accounts receivable 应收账款494 actual cost 实际成本495 aging 账龄496 balance due 到期余额497 balance in hand 现有余额498 balance sheet 资产负债表499 beginning balance 期初余额500 cash basis 现金收付制501 cash on bank 银行存款502 cash on hand 现金503 cash out to 支付给504 catalog 目录505 category code 分类码506 check out 结帐507 collection 催款508 cost simulation 成本模拟509 costing 成本核算510 current assets 流动资产511 current liabilities 流动负债512 current standard cost 现行标准成本513 detail 明细514 draft remittance 汇票汇出515 end of year 年末516 ending availables 期末可供量517 ending balance 期末余额518 exchange rate 汇率519 expense 费用520 financial accounting 财务会计521 financial entity 财务实体522 financial reports 财务报告523 financial statements 财务报表524 fiscal period 财务期间525 fiscal year 财政年度526 fixed assets 固定资产527 foreign amount 外币金额528 gains and loss 损益529 in balance 平衡530 income statement 损益表531 intangible assets 无形资产532 journal entry 分录533 management accounting 管理会计534 manual reconciliation 手工调账535 notes payable 应付票据536 notes receivable 应收票据537 other receivables 其他应收款538 pay aging 付款账龄539 pay check 工资支票540 pay in 缴款541 pay item 付款项目542 pay point 支付点543 pay status 支付状态544 payment instrument 付款方式545 payment reminder 催款单546 payment status 付款状态547 payment terms 付款期限548 period 期间549 post 过账550 proposed cost 建议成本551 simulated cost 模拟成本552 spending variance,expenditure variance 开支差异553 subsidiary 明细账554 summary 汇总555 tax code 税码556 tax rate 税率557 value added tax 增值税558559 as of date , stop date 截止日期560 change lot date 修改批量日期561 clear date 结清日期562 date adjust 调整日期563 date available 有效日期564 date changed 修改日期565 date closed 结束日期566 date due 截止日期567 date in produced 生产日期568 date inventory adjust 库存调整日期569 date obsolete 作废日期570 date received 收到日期571 date released 交付日期572 date required 需求日期573 date to pull 发货日期574 earliest due date 最早订单完成日期575 effective date 生效日期576 engineering change effect date 工程变更生效日期577 engineering stop date 工程停止日期578 expired date 失效日期，报废日期579 from date 起始日期580 last shipment date 最后运输日期581 need date 需求日期582 new date 新日期583 pay through date 付款截止日期584 receipt date 收到日期585 ship date 发运日期586587 allocation 已分配量588 alphanumeric 字母数字589 approver 批准者590 assembly 装配(件)591 backlog 未结订单/拖欠订单592 billing 开单593 bill-to 发票寄往地594 bottleneck 瓶颈资源595 bulk 散装596 buyer 采购员597 component 子件/组件598 customer 客户599 delivery 交货600 demand 需求601 description 说明602 discrete 离散603 ergonomics 工效学(人类工程学) 604 facility 设备、功能605 feature 基本组件/特征件606 forecast 预测607 freight 运费608 holidays 例假日609 implement 实施610 ingredient 配料、成分611 inquire 查询612 inventory 库存613 item 物料项目614 job 作业615 Kanban 看板616 level 层次(级)617 load 负荷618 locate 定位619 logistics 后勤保障体系；物流管理620 lot 批次621 option 可选件622 outstanding 逾期未付623 overhead 制造费用624 override 覆盖625 overtime 加班626 parent 双亲(文件)627 part 零件628 phantom 虚拟件629 plant 工厂，场所630 preference 优先权631 priority 优先权(级)632 procurement 采购633 prototyping 原形测试634 queue 队列635 quota 任务额，报价636 receipt 收款、收据637 regeneration 全重排法638 remittance 汇款639 requisition 请购单640 returned 退货641 roll 滚动642 routing 工艺线路643 schedule 计划表644 shipment 发运量645 ship-to 交货地646 shortage 短缺647 shrink 损耗648 spread 分摊649 statement 报表650 subassembly 子装配件651 supplier 供应商652 transaction 事务处理653 what-if 如果怎样-将会怎样654655 post-deduct inventory transaction processing 后减库存处理法656 pre-deduct inventory transaction processing 前减库存处理法657 generally accepted manufacturing practices 通用生产管理原则658 direct-deduct inventory transaction processing 直接增减库存处理法659 Pareto Principle 帕拉图原理660 Drum-buffer-rope 鼓点-缓冲-绳子661663 Open Database Connectivity 开放数据库互连664 Production Planning 生产规划编制665 Work in Process 在制品666 accelerated cost recovery system 快速成本回收制度667 accounting information system 会计信息系统668 acceptable quality kevel 可接受质量水平669 constant purchasing power accounting 不买够买力会计670 break-even analysis 保本分析671 book value 帐面价值672 cost-benefit analysis 成本效益分析673 chief financial office 财务总监674 degree of financial leverage 财务杠杆系数675 degree of operating leverage 经济杠杆系数676 first-in , first-out 先进先出法677 economic lot size 经济批量678 first-in ,still-here 后进先出法679 full pegging 完全跟踪680 linear programming 线性规划681 management by objective 目标管理682 value engineering 价值工程683 zero based budgeting 零基预算684 CAQ computer aided quality assurance 计算机辅助质量保证685 DBMS database management system 数据库管理系统686 IP Internet Protocol 网际协议687 TCP Transmission Control Protocol 传输控制协议689690 API Advanced Process Industry 高级流程工业691 A2A Application to Application 应用到应用(集成)692 article 物品693 article reserves 物品存储694 assembly order 装配订单695 balance-on-hand-inventory 现有库存余额696 bar code 条形码697 boned warehouse 保税仓库698 CPA Capacity Requirements Planning 能力需求计划699 change management 变革管理700 chill space 冷藏区701 combined transport 联合运输702 commodity inspection 进出口商品检验703 competitive edge 竞争优势704 container 集装箱705 container transport 集装箱运输706 CRP Continuous Replenishment Program 连续补充系数707 core competence 核心才能708 cross docking 直接换装709 CLV Customer Lifetime Value 客户生命周期价值710 CReM Customer Relationship Marketing 客户关系营销711 CSS Customer Service and Support 客户服务和支持712 Customer Service Representative 客户服务代表713 customized logistics 定制物流714 customs declaration 报关715 cycle stock 经常库存716 data cleansing 数据整理717 Data Knowledge and Decision Support 数据知识和决策支持718 data level integration 数据层集成719 data transformation 数据转换720 desktop conferencing 桌面会议721 distribution 配送722 distribution and logistics 分销和后勤723 distribution center 配送中心724 distribution logistics 销售物流725 distribution processing 流通加工726 distribution requirements 分销量727 DRP distribution resource planning 配送/分销资源计划728 door-to-door 门到门729 drop and pull transport 甩挂运输730 DEM Dynamic Enterprise Module 动态企业建模技术731 ECR Efficient Consumer Response 有效顾客反应732 e-Government Affairs 电子政务733 EC Electronic Commerce 电子商务734 Electronic Display Boards 电子公告板735 EOS Electronic order system 电子订货系统736 ESD Electronic Software Distribution 电子软件分发737 embedding 插入738 employee category 员工分类739 empowerment 授权740 engineering change effect work order 工程变更生效单741 environmental logistics 绿色物流742 experiential marketing 直效行销(又称体验行销)743 export supervised warehouse 出口监管仓库744 ERP Extended Resource Planning 扩展资源计划745 field sales/cross sale/cross sell 现场销售/交叉销售/连带销售746 franchising 加盟连销权747 FCL Full Container Load 整箱货748 Global Logistics Management 全球运筹管理749 goods collection 集货750 goods shed 料棚751 goods shelf 货架752 goods stack 货垛753 goods yard 货场754 handing/carrying 搬运755 high performance organization 高绩效组织756 inland container depot 公路集装箱中转站757 inside sales 内部销售758 inspection 检验759 intangible loss 无形消耗760 internal logistics 企业物流761 international freight forwarding agent 国际货运代理762 international logistics 国际物流763 invasive integration 侵入性集成764 joint distribution 共同配送765 just-in-time logistics 准时制物流766 KM Knowledge Management 知识管理767 lead (customer) management 潜在客户管理768 learning organization 学习型组织769 LCL less than container load 拼装货770 load balancing 负载平衡771 loading and unloading 装载772 logistics activity 物流活动773 logistics alliance 物流联盟774 logistics center 物流中心775 logistics cost 物流成本776 logistics cost control 物流成本管理777 logistics documents 物流单证778 logistics enterprise 物流企业779 logistics information 物流信息780 logistics management 物流管理781 logistics modulus 物流模数782 logistics network 物流网络783 logistics operation 物流作业784 LRP Logistics Resource Planning 物流资源计划785 logistics strategy 物流战略786 logistics strategy management 物流战略管理787 logistics technology 物流技术788 MES Manufacture Execute System 制造执行系统789 mass customization 大规模定制790 NPV Net Present Value 净现值791 neutral packing 中性包装792 OLAP On-line Analysis Processing 联机/在线分析系统793 OAG Open Application Group 开放应用集成794 order picking 拣选795 outsourcing 外包796 package/packaging 包装797 packing of nominated brand 定牌包装798 palletizing 托盘包装799 PDA Personal Digital Assistant 个人数据助理800 personalization 个性化801 PTF Planning time fence 计划时界802 POS Point Of Sells 电子收款机803 priority queuing 优先排队804 PBX Private Branch Exchange 专用分组交换机805 production logistics 生产物流806 publish/subscribe 发布/订阅807 quality of working life 工作生活品质808 Quick Response 快速反映809 receiving space 收货区810 REPs Representatives 代表或业务员811 return logistics 回收物流812 ROI Return On Investment 投资回报率813 RM Risk Management 风险管理814 sales package 销售包装815 scalability 可扩充性816 shipping space 发货区817 situational leadership 情境领导818 six sigma 六个标准差819 sorting/stacking 分拣/堆拣820 stereoscopic warehouse 立体仓库821 storage 保管822 stored procedure 存储过程823 storehouse 库房824 storing 储存825 SRM Supplier Relationship Management 供应商关系管理826 tangible loss 有形消耗827 team building 团队建立828 TEM Technology-enabled Marketing 技术辅助式营销829 TES Technology-enabled Selling 技术辅助式销售830 TSR TeleSales Service Representative 销售服务代表831 TPL Third-Part Logistics 第三方物流832 through transport 直达运输833 unit loading and unloading 单元装卸834 Value Management 价值管理835 value-added logistics service 增值物流服务836 Value-chain integration 价值链集成837 VMI Vender Managed Inventory 卖方主导型库存管理/供应商管理仓库838 virtual logistics 虚拟物流839 virtual warehouse 虚拟仓库840 vision 远景管理841 volume pricing model 批量定价模型842 warehouse 仓库843 waste material logistics 废弃物物流844 workflow management 工作流管理845 zero latency 零等待846 ZLE Zero Latency Enterprise 零等待企业847 ZLP Zero Latency Process 零等待过程848 zero-inventory technology 零库存技术。

Comparison of Quality of Care for Patients in the Veterans Health Administration and Patients in a National SampleSteven M.Asch,MD,MPH;Elizabeth A.McGlynn,PhD;Mary M.Hogan,PhD;Rodney A.Hayward,MD;Paul Shekelle,MD,MPH; Lisa Rubenstein,MD;Joan Keesey,BA;John Adams,PhD;and Eve A.Kerr,MD,MPHBackground:The Veterans Health Administration(VHA)has introduced an integrated electronic medical record,performance measurement,and other system changes directed at improving care.Recent comparisons with other delivery systems have been limited to a small set of indicators.Objective:To compare the quality of VHA care with that of care in a national sample by using a comprehensive quality-of-care measure.Design:Cross-sectional comparison.Setting:12VHA health care systems and12communities. Patients:596VHA patients and992patients identified through random-digit dialing.All were men older than35years of age.Measurements:Between1997and2000,quality was measured by using a chart-based quality instrument consisting of348indi-cators targeting26conditions.Results were adjusted for cluster-ing,age,number of visits,and medical conditions. Results:Patients from the VHA scored significantly higher for adjusted overall quality(67%vs.51%;difference,16percentage points[95%CI,14to18percentage points]),chronic disease care (72%vs.59%;difference,13percentage points[CI,10to17 percentage points]),and preventive care(64%vs.44%;differ-ence,20percentage points[CI,12to28percentage points]),but not for acute care.The VHA advantage was most prominent in processes targeted by VHA performance measurement(66%vs. 43%;difference,23percentage points[CI,21to26percentage points])and least prominent in areas unrelated to VHA perfor-mance measurement(55%vs.50%;difference,5percentage points[CI,0to10percentage points]).Limitations:Unmeasured residual differences in patient charac-teristics,a lower response rate in the national sample,and differ-ences in documentation practices could have contributed to some of the observed differences.Conclusions:Patients from the VHA received higher-quality care according to a broad measure.Differences were greatest in areas where the VHA has established performance measures and actively monitors performance.Ann Intern Med.2004;141: For author affiliations,see end of text.A s methods for measuring the quality of medical carehave matured,widespread quality problems have be-come increasingly evident(1,2).The solution to these problems is much less obvious,however,particularly with regard to large delivery systems.Many observers have sug-gested that improved information systems,systematic per-formance monitoring,and coordination of care are neces-sary to enhance the quality of medical care(3).Although the use of integrated information systems(including elec-tronic medical records)and performance indicators has be-come more common throughout the U.S.health care sys-tem,most providers are not part of a larger integrated delivery system and continue to rely on traditional infor-mation systems(4).An exception is the Veterans Health Administration (VHA).As the largest delivery system in the United States, the VHA has been recognized as a leader in developing a more coordinated system of care.Beginning in the early 1990s,VHA leadership instituted both a sophisticated electronic medical record system and a quality measure-ment approach that holds regional managers accountable for several processes in preventive care and in the manage-ment of common chronic conditions(5,6).Other changes include a system-wide commitment to quality improve-ment principles and a partnership between researchers and managers for quality improvement(7).As Jha and colleagues(8)have shown,since these changes have been implemented,VHA performance has outpaced that of Medicare in the specific areas targeted. Nevertheless,whether this improvement has extended be-yond the relatively narrow scope of the performance mea-sures is unknown.Beyond that study,the data comparing VHA care with other systems of care are sparse and mixed. For example,patients hospitalized at VHA hospitals were more likely than Medicare patients to receive angiotensin-converting enzyme inhibitors and thrombolysis after myo-cardial infarction(9).On the other hand,VHA patients were less likely to receive angiography when indicated and had higher mortality rates after coronary artery bypass grafting than patients in community hospitals(10,11). Kerr and colleagues found that care for diabetes was better in almost every dimension in the VHA system than in commercial managed care(12).More extensive compari-sons,especially of outpatient care,are lacking.To address these issues,a more comprehensive assessment of quality is needed.Using a broad measure of quality of care that is based on medical record review and was developed outside theImproving Patient Care is a special section within Annals supported in part by the U.S.Department of Health and Human Services(HHS)Agency for Healthcare Research and Quality (AHRQ).The opinions expressed in this article are those of the authors and do not represent the position or endorsement of AHRQ or HHS.Improving Patient CareVHA,we compared the quality of outpatient and inpatient care among2samples:1)a national sample of patients drawn from12communities and2)VHA patients from26 facilities in12health care systems located in the southwest-ern and midwestern United States(13).We analyzed per-formance in the years after the institution of routine per-formance measurement and the electronic medical record. Using the extensive set of quality indicators included in the measurement system,we compared the overall quality of care delivered in the VHA system and in the United States, as well as the quality of acute,chronic,and preventive care across26conditions.In addition,we evaluated whether VHA performance was better in the specific areas targeted by the VHA quality management system.M ETHODSDevelopment of Quality IndicatorsFor this study,we used quality indicators from RAND’s Quality Assessment Tools system,which is de-scribed in more detail elsewhere(14–17).The indicators included in the Quality Assessment Tools system are pro-cess quality measures,are more readily actionable than out-comes measures,require less risk adjustment,and follow the structure of national guidelines(18,19).After review-ing established national guidelines and the medical litera-ture,we chose a subset of quality indicators from the Qual-ity Assessment Tools system that represented the spectrum of outpatient and inpatient care(that is,screening,diagno-sis,treatment,and follow-up)for acute and chronic con-ditions and preventive care processes representing the lead-ing causes of morbidity,death,and health care use among older male patients.The Appendix Table(available at www )lists the full indicator set,which was deter-mined by four9-member,multispecialty expert panels. These panels assessed the validity of the proposed indica-tors using the RAND/University of California,Los Ange-les–modified Delphi method.The experts rated the indi-cators on a9-point scale(1ϭnot valid;9ϭvery valid), and we accepted indicators that had a median validity score of7or higher.This method of selecting indicators is reli-able and has been shown to have content,construct,and predictive validity(20–23).Of the439indicators in the Quality Assessment Tools system,we included348indica-tors across26conditions in our study and excluded91 indicators that were unrelated to the target population(for example,those related to prenatal care and cesarean sec-tions).Of the348indicators,21were indicators of overuse (for example,patients with moderate to severe asthma should not receive␤-blocker medications)and327were indicators of underuse(for example,patients who have been hospitalized for heart failure should have follow-up contact within4weeks of discharge).Two physicians independently classified each indicator according to the type of care delivered;the function of the indicated care(screening,diagnosis,treatment,and follow-up);and whether the indicator was supported by a ran-domized,controlled trial,another type of controlled trial, or other evidence.Type of care was classified as acute(for example,in patients presenting with dysuria,presence or absence of fever andflank pain should be elicited),chronic (for example,patients with type2diabetes mellitus in whom dietary therapy has failed should receive oral hypo-glycemic therapy),or preventive(for example,all patients should be screened for problem drinking).In addition,we further classified the indicators into3mutually exclusive categories according to whether they corresponded to the VHA performance indicators that were in use infiscal year 1999.Twenty-six indicators closely matched the VHA in-dicators,152involved conditions that were targeted by the VHA indicators but were not among the26matches,and 170did not match the VHA measures or conditions.We performed a similar process to produce a list of15indica-tors that matched contemporaneous Health Plan Employer Data and Information Set(HEDIS)performance measures (24).Table1shows the conditions targeted by the indica-tors,and Table2gives an example indicator for each of the conditions or types of care for which condition-or type-specific comparisons were possible.Identifying ParticipantsPatients were drawn from2ongoing quality-of-care studies:a study of VHA patients and a random sample of adults from12communities(13).The VHA patients were drawn from26clinical sites in12health care systems lo-Table1.Conditions and Number of Indicators Used inComparisons*Targeted within the Veterans Health Administration indicator set.Improving Patient CareQuality of Care in the Veterans Health Administrationcated in2Veterans Integrated Service Networks in the midwestern and southwestern United States.These net-works closely match the overall Veterans Affairs system with regard to medical record review and survey-based quality measures(25,26).We selected patients who had had at least2outpatient visits in each of the2years be-tween1October1997and30September1999.A total of 106576patients met these criteria.We randomly sampled 689,oversampling for chronic obstructive pulmonary dis-ease(COPD),hypertension,and diabetes,and were able to locate records for664patients(a record location rate of 96%).Because of resource constraints,we reviewed a ran-dom subset of621of these records.Since this sample con-tained only20women and4patients younger than35 years of age,we further restricted the sample to men older than35years of age.Thus,we included596VHA patients in the analysis.All of these patients had complete medical records.The methods we used to obtain the national sample have been described elsewhere(13)and are summarized here.As part of a nationwide study,residents of12large metropolitan areas(Boston,Massachusetts;Cleveland, Ohio;Greenville,South Carolina;Indianapolis,Indiana; Lansing,Michigan;Little Rock,Arkansas;Miami,Florida; Newark,New Jersey;Orange County,California;Phoenix, Arizona;Seattle,Washington;and Syracuse,New York) were contacted by using random-digit dialing and were asked to complete a telephone survey(27).To ensure com-parability with the VHA sample,we included only men older than35years of age.Between October1998and August2000,we telephoned4086of these participants and asked for permission to obtain copies of their medical records from all providers(both individual and institu-tional)that they had visited within the past2years.We received verbal consent from3138participants(77%of those contacted by telephone).We mailed consent forms and received written permission from2351participants (75%of those who had given verbal permission).We re-ceived at least1medical record for2075participants(88% of those who had returned consent forms).We excluded participants who had not had at least2medical visits in the past2years to further ensure comparability with the VHA sample.Thus,ourfinal national sample included992per-sons.The rolling abstraction period(October1996to Au-gust2000)substantially overlapped the VHA sampling pe-riod.The average overlap was70%,and all records had at least1year of overlap.Seven hundred eight(71%)of the 992persons in the national sample had complete medical records.On the basis of data from the original telephone survey,we determined that participants in the national sample were more likely to be older,white,and better educated;to have higher income levels;and to have less than excellent health compared with eligible nonpartici-pants(13).Chart AbstractionWe sent photocopies of all of the medical records to1 of2central areas for abstraction.For VHA patients,we abstracted data on all care received between October1997 and September1999;for patients in the national sample, we abstracted data on all care received in the2years before the date of recruitment.We used computer-assisted ab-straction software on a Microsoft Visual Basic6.0platform (Microsoft Corp.,Seattle,Washington),which allowed us to tailor the manual chart abstraction to the specific record being reviewed and provided interactive data quality checks (consistency,range),calculations(for example,high blood pressure),and classifications(for example,drug class). Twenty trained registered nurse abstractors collected the data.To assess interrater reliability,we reabstracted charts for4%of the participants selected at random.According to the␬statistic,average reliability in the national sample was substantial to almost perfect(28)at3levels:presence of a condition(␬ϭ0.83),indicator eligibility(␬ϭ0.76), and indicator scoring(␬ϭ0.80)(13).Statistical AnalysisAll analyses were conducted by using SAS,version8.2 (SAS Institute,Cary,North Carolina).The unit of analysis was adherence to a given indicator in a given patient.For each indicator,we determined the criteria that made par-ticipants eligible for the process specified in the indicator (yes or no).We then determined whether participants had received the specified process each time an indication was noted in their medical record(yes,no,or proportion).We determined aggregate indicator scores for each summary category(that is,acute,chronic,and preventive care;Table2.Example Indicators of Quality ofCare**A full list of the indicators is included in the Appendix Table(available at).COPDϭchronic obstructive pulmonary disease;CTϭcom-puted tomography;MIϭmyocardial infarction;MRIϭmagnetic resonance im-aging.Improving Patient Care Quality of Care in the Veterans Health Administrationscreening;diagnosis;treatment;and follow-up)by dividing all instances in which participants received recommended care by the total number of instances in which the care should have been received.We constructed the scores as proportions ranging from 0%to 100%,adjusting for clus-tering of indicators within patients.Because of clustering of the data,we used the bootstrap method to estimate standard errors for all of these scores (29).We applied sampling weights to represent the original populations from which the 2samples were drawn and to adjust for nonresponse.We also used weights to standard-ize the patients for characteristics common among the VHA population:COPD;hypertension;diabetes;and age categories ranging from 35to 50years of age,51to 65years of age,and older than 65years of age.Sampling weights were applied at the individual level;indicators were implicitly weighted on the basis of prevalence of eligibility.Although we report weighted results because we believe they are most representative,weighting did not affect the direction or significance of any reported results.We used t -tests or chi-square tests with bootstrapped standard errors to compare the standardized VHA and na-tional samples according to population characteristics;ag-gregate quality of care;subsets of indicators related to acute,chronic,and preventive care;subsets of indicators related to function of care;subsets of indicators supported by randomized,controlled trials;subsets of indicators sim-ilar to those used by the VHA in its performance measure-ment system;and chronic conditions that affected more than 50patients from both samples,including COPD,coronary artery disease,depression,diabetes,hyperlipid-emia,headache,hypertension,and osteoarthritis.We used logistic regression to compare the rates at which the respec-tive samples received the care specified in the indicators.This allowed us to adjust for factors beyond the standard-ization,including age as an integer variable,number of chronic and acute conditions,and number of outpatient visits.We calculated adjusted scores after taking into ac-count clustering of indicators at the individual patient level.For the logistic regression models,standard errors and confidence intervals were adjusted for the clustering ofindicators within patients by using the sandwich estimator (30).To test the sensitivity of our results to geography and insurance,we also estimated models confining the national sample to the 6communities nearest the 2VHA regions and to respondents with insurance.To test the sensitivity of our results to completeness of documentation,we esti-mated models restricted to patients with complete records and to the subset of indicators with high likelihood (labo-ratory tests and radiology)and less likelihood (counseling and education)of complete documentation.Since the number of visits could represent an intervening variable between the comparison samples and quality,we also ran models that did not adjust for the number of visits.Finally,to test the sensitivity of our results to the type of indicator set used,we compared the adjusted performance of the VHA and the community on the subset of indicators that matched the widely accepted HEDIS indicator set.Role of the Funding SourceThe funding agencies (Veterans Affairs Health Services Research and Development Service,the Robert Wood Johnson Foundation,the Centers for Medicare &Medic-aid Services,the Agency for Healthcare Research and Qual-ity,and the California HealthCare Foundation)did not participate in the data collection or analysis or in interpre-tation of the results.Veterans Affairs officials received ad-vance copies of the manuscript for comment.R ESULTSCharacteristics of the Study SamplesTable 3presents the characteristics of the VHA and national samples,with and without weighting for sam-pling,nonresponse,and standardization for age categories and the prevalence of COPD,hypertension,and diabetes in the VHA sample.After standardization,there were no statistically significant differences in the age of the partici-pants or the number of chronic conditions,although pa-tients in the national sample had slightly more acute con-ditions.There were also no significant differences in the rates of chronic conditions between the 2samples,with theTable 3.Veterans Health Administration and National SampleCharacteristics**COPD ϭchronic obstructive pulmonary disease;VHA ϭVeterans Health Administration.Improving Patient CareQuality of Care in the Veterans Health Administrationexception that VHA patients had a somewhat higher prev-alence of osteoarthritis.Patients from the VHA also had asignificantly greater number of outpatient visits per year(9.2vs.7.9;PϽ0.001).Comparisons of Quality of CareTable4presents the results of our analyses comparingthe quality of care between the standardized VHA andnational samples,adjusting for age and for the number ofchronic conditions,acute conditions,and outpatient visits.Sixteen of the348indicators had no eligible patients ineither sample,leaving294indicators and596patients onwhich to base the VHA scores and330indicators and992patients on which to base the national scores.Overall,VHA patients were more likely than patients in the na-tional sample to receive the care specified by the indicators(67%vs.51%;difference,16percentage points[CI,14to18percentage points]).Performance in the VHA outpacedthat of the national sample for both chronic care(72%vs.59%;difference,13percentage points[CI,10to17per-centage points])and preventive care(64%vs.44%;differ-ence,20percentage points[CI,12to28percentagepoints]),but not for acute care(53%vs.55%;difference,Ϫ2percentage points[CI,Ϫ9toϪ4percentage points]). In particular,the VHA sample received significantly bettercare for depression,diabetes,hyperlipidemia,and hyper-tension.The VHA also performed consistently betteracross the entire spectrum of care,including screening,di-agnosis,treatment,and follow-up.These differences in quality of care held true when we considered only those indicators(nϭ72)supported by randomized,controlled trials(57%vs.45%;difference,12percentage points[CI, 3to20percentage points]).Associations with Performance MeasurementTo test the association between performance and per-formance measurement within the VHA,we restricted the analysis of overall quality to processes and conditions spe-cifically addressed by the VHA performance measurement set.When we restricted the analysis to specific indicators that closely matched the performance measures targeted by the VHA,VHA patients had a substantially greater chance of receiving the indicated care than did patients in the national sample(adjusted scores,67%vs.43%;difference, 24percentage points[CI,21to26percentage points]). Patients from the VHA were also more likely than national patients to receive care in the conditions or areas specified by the VHA indicator set,even when the processes covered by the indicators were substantially different(70%vs. 58%;difference,12percentage points[CI,10to15per-centage points]).The difference between VHA patients and national patients in conditions or areas not covered by the VHA performance measurement system barely reached conventional levels of statistical significance(55%vs.50%; difference,5percentage points[CI,0to10percentage points]).Table4.Adjusted Adherence to Indicators byCategory**Adjusted for age,number of chronic conditions,number of acute conditions,and number of outpatient visits.COPDϭchronic obstructive pulmonary disease;VHAϭVeterans Health Administration.†Number of unique indicators in category with at least1eligible patient.‡The number of eligible events is the number of times indicators in the category were triggered.Improving Patient Care Quality of Care in the Veterans Health AdministrationSensitivity AnalysesConfining the analyses to patients in both samples who had complete records did not change the direction or significance of any reported results.The VHA advantage was largest in indicators most likely to have possible un-derdocumentation(adjusted performance for counseling and education,45%vs.26%;difference,19percentage points[CI,14to30percentage points]),but even in lab-oratory tests and radiology,an area that would be less sen-sitive to documentation differences,there was also a sub-stantial difference(67%vs.52%;difference,15percentage points[CI,11to19percentage points]).Confining the analysis to the6nationally sampled metropolitan areas closest to the2VHA regions also did not change the di-rection or significance of any result,nor did excluding un-insured patients from the national sample.Models that did not adjust for the number of visits had the same VHA effects as those that did adjust for number of visits.Patients from the VHA also still received more indicated care(ad-justed rates,60%vs.39%;difference,21percentage points [CI,16to26percentage points])when the analyses were confined to the overlap of our indicator set and HEDIS measures,the most commonly used national performance indicator set for managed care.D ISCUSSIONUsing the RAND Quality Assessment Tools broad measure of quality of care,we found that adherence to recommended processes of care in2VHA regions typically exceeded that in a comparable national sample in12com-munities.Thesefindings persisted when we adjusted the samples for age,number of acute and chronic conditions, and number of outpatient visits and when we examined only processes supported by randomized,controlled trials. In addition,we found that the differences between the VHA and national sample were greatest in processes sub-ject to the VHA performance measurement system.The “halo effect”of better VHA care extended to measures of processes in the same condition or area that were not spe-cifically measured by the VHA performance system;how-ever,this effect decreased greatly in unrelated areas.Acute care,COPD care,osteoarthritis care,and coronary artery disease care were exceptions to the pattern of better care in the VHA,although our power to distinguish quality dif-ferences was limited by the small number of patients with COPD in the national sample(nϭ62).To date,the VHA has not targeted acute care or os-teoarthritis care as part of its intensive performance mea-surement system(6).Coronary artery disease,on the other hand,has been the subject of quality improvement efforts both inside and outside the VHA,including those spon-sored by the American Heart Association(31–33).Indeed, many previous comparisons between VHA and national samples outside the VHA performance set have involved patients with coronary artery disease and have yielded mixed results(10).That we found little difference between the care provided to patients with coronary artery disease in the VHA and in a national sample is consistent with otherfindings and could be the result of comparable qual-ity measurement programs for this condition in the United States and in the VHA.On the other hand,predominantly outpatient-based quality improvement efforts for diabetes have also been implemented in both the VHA system and other institutions,and our analyses showed that the VHA outperformed the national sample for diabetes care.The difference may be due to more effective outpatient VHA quality improvement for diabetes,but further research is needed to investigate the roots of this discrepancy.Although our study is one of the most comprehensive comparisons between VHA patients and national patients, it has limitations.First,our analysis is based on a compar-ison of2different study samples.Although we used robust statistical techniques to account for any differences be-tween the samples,we could not adjust for the somewhat different geographic distributions or abstraction periods, although there was a great deal of overlap in both areas. Furthermore,in other analyses,we have not observed any large geographic variations in the aggregate indicator scores for the national sample,and our results did not change when we confined the national sample to the6communi-ties closest to the2Veterans Affairs regions(34).Our study also relied on patient recollection of provider visits in the national sample.It is possible that patients received care from additional providers but did not recall or that we did not receive all available charts.However,we found that confining our analyses to patients with complete records did not change the results,and persons with missing charts were likely to have higher quality scores(13).We lack data on whether patients in the national sample were also re-ceiving care at the VHA,or vice versa.Other studies have found evidence of co-management between VHA and non-VHA providers(35).To the extent that this co-manage-ment occurred,it would probably lead to an underestimate of the differences between the2groups.An additional limitation of our study is that there were too few men younger than35years of age and too few women in our VHA sample to analyze care for these subgroups.For women,limited data from other studies indicate a VHA advantage in breast cancer screening(7).While the Quality Assessment Tools system is quite broad,it cannot represent all of medical care,and there are probably gaps in the indicator st,the evidence grading system for Quality Assessment Tools is based on a simple measure of research design.More precise evidence categories might have altered our analysis of the effect of level of evidence on the com-parison between the VHA and national samples,but it is difficult to tell whether the differences would be accentu-ated or diminished.Several unmeasured patient characteristics could have biased our results.The response rate was lower in the na-tional sample than in the VHA sample,underrepresentingImproving Patient CareQuality of Care in the Veterans Health Administration。