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  1. Article: Combination opioid analgesics.

    Smith, Howard S

    Pain physician

    2008  Volume 11, Issue 2, Page(s) 201–214

    Abstract: ... sensations. Combination opioid analgesics are one avenue which may give rise to "pain pills" with improved ... of this article - reasons for combining an opioid with a second agent to produce a combination opioid analgesic ... of oxidative and conjugative enzymes). Investigators have concentrated on ways to alter existing analgesics or ...

    Abstract Although there is no "ideal analgesic," scientists and clinicians alike continue to search for compounds with qualities which may approach the "ideal analgesic." Characteristics of an "ideal" analgesic may include: the agent is a full agonist providing optimal/maximal analgesia for a wide range/variety of pain states (e.g., broad spectrum analgesic activity), it does not exhibit tolerance, it produces no unwanted effects and minimal adverse effects, it has no addictive potential, it does not facilitate pain/hyperalgesia, it has a long duration, it has high oral bioavailability, it is not vulnerable to important drug interactions, it is not significantly bound to plasma proteins, it has no active metabolites, it has linear kinetics, and it is eliminated partly by hydrolysis to an inactive metabolite (without involvement of oxidative and conjugative enzymes). Investigators have concentrated on ways to alter existing analgesics or to combine existing analgesic compounds with compounds which may improve efficacy over time or minimize adverse effects. The addition of an analgesic with a second agent (which may or may not also be an analgesic) to achieve a "combination analgesic" is a concept which has been exploited for many years. Although there may be many reasons to add 2 agents together in efforts to achieve analgesia, for purposes of this article - reasons for combining an opioid with a second agent to produce a combination opioid analgesic may be classified into 6 major categories: 1.) combinations to prolong analgesic duration; 2.) combinations to enhance or optimize analgesic efficacy (e.g., analgesic synergy); 3.) combinations to diminish or minimize adverse effects; 4.) combinations to diminish opioid effects which are not beneficial (or contrariwise to or enhance beneficial opioid effects); 5.) combinations to reduce opioid tolerance/opioid-induced hyperalgesia; and 6.) combinations to combat dependency issues/addiction potential/craving sensations. Combination opioid analgesics are one avenue which may give rise to "pain pills" with improved analgesic profiles over existing analgesic medications.
    MeSH term(s) Analgesics, Opioid/therapeutic use ; Animals ; Drug Therapy, Combination ; Humans ; Pain/drug therapy
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2008-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2146393-1
    ISSN 1533-3159
    ISSN 1533-3159
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Opioid Analgesic Reduction Study (OARS)—a comparison of opioid vs. non-opioid combination analgesics for management of post-surgical pain

    Cecile A. Feldman / Janine Fredericks-Younger / Shou-En Lu / Paul J. Desjardins / Hans Malmstrom / Michael Miloro / Gary Warburton / Brent Ward / Vincent Ziccardi / Daniel Fine

    Trials, Vol 23, Iss 1, Pp 1-

    a double-blind randomized clinical trial

    2022  Volume 20

    Abstract: ... been designed to evaluate whether a combination of over-the-counter non-opioid-containing analgesics is ... Dentists are among the leading prescribers of opioid analgesics. Opioid-seeking behaviors have been linked ... not inferior to the most prescribed opioid analgesic. The impacted 3rd molar extraction model is being ...

    Abstract Abstract Background Everyday people die unnecessarily from opioid overdose-related addiction. Dentists are among the leading prescribers of opioid analgesics. Opioid-seeking behaviors have been linked to receipt of initial opioid prescriptions following the common dental procedure of third molar extraction. With each opioid prescription, a patient’s risk for opioid misuse or abuse increases. With an estimated 56 million tablets of 5 mg hydrocodone annually prescribed after third molar extractions in the USA, 3.5 million young adults may be unnecessarily exposed to opioids by dentists who are inadvertently increasing their patient’s risk for addiction. Methods A double-blind, stratified randomized, multi-center clinical trial has been designed to evaluate whether a combination of over-the-counter non-opioid-containing analgesics is not inferior to the most prescribed opioid analgesic. The impacted 3rd molar extraction model is being used due to the predictable severity of the post-operative pain and generalizability of results. Within each site/clinic and gender type (male/female), patients are randomized to receive either OPIOID (hydrocodone/acetaminophen 5/300 mg) or NON-OPIOID (ibuprofen/acetaminophen 400/500 mg). Outcome data include pain levels, adverse events, overall patient satisfaction, ability to sleep, and ability to perform daily functions. To develop clinical guidelines and a clinical decision-making tool, pain management, extraction difficulty, and the number of tablets taken are being collected, enabling an experimental decision-making tool to be developed. Discussion The proposed methods address the shortcomings of other analgesic studies. Although prior studies have tested short-term effects of single doses of pain medications, patients and their dentists are interested in managing pain for the entire post-operative period, not just the first 12 h. After surgery, patients expect to be able to perform normal daily functions without feeling nauseous or dizzy and they desire a restful sleep at ...
    Keywords Opioids ; Acute pain ; Opioid-related side effects ; Pain management ; Combination analgesics ; Over-the-counter analgesics ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The Opioid Analgesic Reduction Study (OARS)-a comparison of opioid vs. non-opioid combination analgesics for management of post-surgical pain: a double-blind randomized clinical trial.

    Feldman, Cecile A / Fredericks-Younger, Janine / Lu, Shou-En / Desjardins, Paul J / Malmstrom, Hans / Miloro, Michael / Warburton, Gary / Ward, Brent / Ziccardi, Vincent / Fine, Daniel

    Trials

    2022  Volume 23, Issue 1, Page(s) 160

    Abstract: ... to evaluate whether a combination of over-the-counter non-opioid-containing analgesics is not inferior ... among the leading prescribers of opioid analgesics. Opioid-seeking behaviors have been linked to receipt of initial ... to the most prescribed opioid analgesic. The impacted 3rd molar extraction model is being used due ...

    Abstract Background: Everyday people die unnecessarily from opioid overdose-related addiction. Dentists are among the leading prescribers of opioid analgesics. Opioid-seeking behaviors have been linked to receipt of initial opioid prescriptions following the common dental procedure of third molar extraction. With each opioid prescription, a patient's risk for opioid misuse or abuse increases. With an estimated 56 million tablets of 5 mg hydrocodone annually prescribed after third molar extractions in the USA, 3.5 million young adults may be unnecessarily exposed to opioids by dentists who are inadvertently increasing their patient's risk for addiction.
    Methods: A double-blind, stratified randomized, multi-center clinical trial has been designed to evaluate whether a combination of over-the-counter non-opioid-containing analgesics is not inferior to the most prescribed opioid analgesic. The impacted 3rd molar extraction model is being used due to the predictable severity of the post-operative pain and generalizability of results. Within each site/clinic and gender type (male/female), patients are randomized to receive either OPIOID (hydrocodone/acetaminophen 5/300 mg) or NON-OPIOID (ibuprofen/acetaminophen 400/500 mg). Outcome data include pain levels, adverse events, overall patient satisfaction, ability to sleep, and ability to perform daily functions. To develop clinical guidelines and a clinical decision-making tool, pain management, extraction difficulty, and the number of tablets taken are being collected, enabling an experimental decision-making tool to be developed.
    Discussion: The proposed methods address the shortcomings of other analgesic studies. Although prior studies have tested short-term effects of single doses of pain medications, patients and their dentists are interested in managing pain for the entire post-operative period, not just the first 12 h. After surgery, patients expect to be able to perform normal daily functions without feeling nauseous or dizzy and they desire a restful sleep at night. Parents of young people are concerned with the risks of opioid use and misuse, related either to treatments received or to subsequent use of leftover pills. Upon successful completion of this clinical trial, dentists, patients, and their families will be better able to make informed decisions regarding post-operative pain management.
    Trial registration: ClinicalTrials.gov NCT04452344 . Registered on June 20, 2020.
    MeSH term(s) Analgesics/therapeutic use ; Analgesics, Non-Narcotic/therapeutic use ; Analgesics, Opioid/therapeutic use ; Double-Blind Method ; Drug Combinations ; Female ; Humans ; Male ; Multicenter Studies as Topic ; Pain, Postoperative/diagnosis ; Pain, Postoperative/drug therapy ; Pain, Postoperative/etiology ; Randomized Controlled Trials as Topic ; Young Adult
    Chemical Substances Analgesics ; Analgesics, Non-Narcotic ; Analgesics, Opioid ; Drug Combinations
    Language English
    Publishing date 2022-02-17
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-022-06064-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Nonopioid Combination Formulations.

    Kita, Ashley E / Boisoneau, David / Lambert, David

    Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

    2022  Volume 166, Issue 4, Page(s) 791

    MeSH term(s) Analgesics, Non-Narcotic ; Analgesics, Opioid ; Humans
    Chemical Substances Analgesics, Non-Narcotic ; Analgesics, Opioid
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 392085-9
    ISSN 1097-6817 ; 0161-6439 ; 0194-5998
    ISSN (online) 1097-6817
    ISSN 0161-6439 ; 0194-5998
    DOI 10.1177/01945998211027349
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: HTX-011 in Combination with Multimodal Analgesic Regimen Minimized Severe Pain and Opioid Use after Total Knee Arthroplasty in an Open-Label Study.

    Lee, Gwo-Chin / Berkowitz, Richard / Hacker, Scott / Hu, Jia / Rechter, Alan

    The journal of knee surgery

    2022  Volume 36, Issue 9, Page(s) 925–932

    Abstract: ... release polymer. In a prior randomized controlled trial (RCT), HTX-011 reduced pain and opioid use ... acetaminophen and celecoxib until discharge. Opioid rescue was allowed upon patient request for additional pain ... control. Pain scores, opioid consumption, discharge readiness, and adverse events were recorded. Fifty-one ...

    Abstract Total knee arthroplasty (TKA) can be associated with significant postoperative pain despite multimodal analgesic (MMA) protocols, and most patients require the use of opioids postoperatively. HTX-011 is a dual-acting local anesthetic containing bupivacaine and low-dose meloxicam in an extended-release polymer. In a prior randomized controlled trial (RCT), HTX-011 reduced pain and opioid use through 72 hours after TKA compared with bupivacaine hydrochloride. This open-label study (NCT03974932) evaluated the efficacy and safety of HTX-011 combined with an MMA regimen in patients undergoing TKA under spinal anesthesia. All patients received intraoperative HTX-011 (400 mg bupivacaine/12 mg meloxicam) in combination with an MMA regimen consisting of preoperative acetaminophen, celecoxib, and pregabalin and postoperative acetaminophen and celecoxib until discharge. Opioid rescue was allowed upon patient request for additional pain control. Pain scores, opioid consumption, discharge readiness, and adverse events were recorded. Fifty-one patients were treated. Compared with the prior RCT, HTX-011 with this MMA regimen further lowered pain scores and reduced opioid use. Mean patient-reported pain scores remained in the mild range, and 82% of patients or more did not experience severe pain at any individual time point through 72 hours after surgery. Mean total opioid consumption was low over 72 hours: 24.8 morphine milligram equivalents (1-2 tablets of oxycodone 10 mg/day). Approximately 60% of patients were ready for discharge by 12 hours, and 39% were discharged without an opioid prescription and did not call back for pain management. The treatment regimen was well tolerated, and no added risk was observed with the addition of MMA. HTX-011 with an MMA regimen reduced postoperative pain and opioid use following TKA.
    MeSH term(s) Humans ; Analgesics, Opioid ; Arthroplasty, Replacement, Knee/adverse effects ; Acetaminophen/therapeutic use ; Meloxicam/therapeutic use ; Celecoxib/therapeutic use ; Analgesics/therapeutic use ; Bupivacaine/therapeutic use ; Pain, Postoperative/drug therapy ; Pain, Postoperative/etiology ; Anesthetics, Local/therapeutic use ; Opioid-Related Disorders
    Chemical Substances Analgesics, Opioid ; Acetaminophen (362O9ITL9D) ; Meloxicam (VG2QF83CGL) ; Celecoxib (JCX84Q7J1L) ; Analgesics ; Bupivacaine (Y8335394RO) ; Anesthetics, Local
    Language English
    Publishing date 2022-06-10
    Publishing country Germany
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2075354-8
    ISSN 1938-2480 ; 1538-8506 ; 0899-7403
    ISSN (online) 1938-2480
    ISSN 1538-8506 ; 0899-7403
    DOI 10.1055/s-0042-1747945
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Naldemedine-laxative combination: retrospective inpatient study.

    Takemura, Miho / Niki, Kazuyuki / Miyaguchi, Sho / Ueda, Mikiko

    BMJ supportive & palliative care

    2024  Volume 13, Issue e3, Page(s) e816–e819

    Abstract: Objectives: The initiation of peripherally acting μ-opioid receptor antagonists (PAMORAs ... in combination with other laxatives in the acute care setting.: Methods: This retrospective study evaluated 93 ... only group.: Conclusions: The introduction of naldemedine alone or in combination with MgO should be ...

    Abstract Objectives: The initiation of peripherally acting μ-opioid receptor antagonists (PAMORAs) should be considered 2 weeks after conventional laxatives have failed to achieve an adequate response, and affected patients should be evaluated every 2 weeks thereafter. However, this guidance is difficult to implement in acute care hospitals. This study aimed to examine how naldemedine (PAMORA) should be introduced in combination with other laxatives in the acute care setting.
    Methods: This retrospective study evaluated 93 inpatients who received at least four doses of naldemedine. We investigated changes in the average daily defecation counts during the first 7 days after compared with before naldemedine administration and the incidence of diarrhoea.
    Results: Daily defecation counts during the first 7 days after compared with before naldemedine administration were greater in both the naldemedine, magnesium oxide (MgO) and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. The incidence rates of diarrhoea were significantly higher in the naldemedine, MgO, and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group.
    Conclusions: The introduction of naldemedine alone or in combination with MgO should be considered.
    MeSH term(s) Humans ; Laxatives/therapeutic use ; Retrospective Studies ; Magnesium Oxide/therapeutic use ; Inpatients ; Analgesics, Opioid/therapeutic use ; Constipation/epidemiology ; Constipation/drug therapy ; Naltrexone/therapeutic use ; Naltrexone/analogs & derivatives ; Narcotic Antagonists/therapeutic use ; Diarrhea
    Chemical Substances naldemedine (03KSI6WLXH) ; Laxatives ; Magnesium Oxide (3A3U0GI71G) ; Analgesics, Opioid ; Naltrexone (5S6W795CQM) ; Narcotic Antagonists
    Language English
    Publishing date 2024-01-08
    Publishing country England
    Document type Journal Article
    ISSN 2045-4368
    ISSN (online) 2045-4368
    DOI 10.1136/spcare-2022-003685
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: In Response to: "Nonopioid Combination Formulations".

    Anne, Samantha / Mims, James Whit / Tunkel, David

    Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

    2022  Volume 166, Issue 4, Page(s) 791–792

    MeSH term(s) Analgesics, Non-Narcotic ; Analgesics, Opioid/therapeutic use ; Humans
    Chemical Substances Analgesics, Non-Narcotic ; Analgesics, Opioid
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 392085-9
    ISSN 1097-6817 ; 0161-6439 ; 0194-5998
    ISSN (online) 1097-6817
    ISSN 0161-6439 ; 0194-5998
    DOI 10.1177/01945998211027354
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Tricyclic Antidepressants in Nociceptive and Neuropathic Pain: A Review of Their Analgesic Properties in Combination With Opioids.

    Reinert, Justin P / Veronin, Michael A / Medina, Christopher

    The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians

    2022  Volume 39, Issue 1, Page(s) 35–40

    Abstract: Objectives: ...

    Abstract Objectives:
    Language English
    Publishing date 2022-12-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 54478-4
    ISSN 8755-1225
    ISSN 8755-1225
    DOI 10.1177/87551225221139699
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: HTX-011 in Combination with Multimodal Analgesic Regimen Minimized Severe Pain and Opioid Use after Total Knee Arthroplasty in an Open-Label Study

    Lee, Gwo-Chin / Berkowitz, Richard / Hacker, Scott / Hu, Jia / Rechter, Alan

    The Journal of Knee Surgery

    2022  Volume 36, Issue 09, Page(s) 925–932

    Abstract: ... release polymer. In a prior randomized controlled trial (RCT), HTX-011 reduced pain and opioid use ... acetaminophen and celecoxib until discharge. Opioid rescue was allowed upon patient request for additional pain ... control. Pain scores, opioid consumption, discharge readiness, and adverse events were recorded. Fifty-one ...

    Abstract Total knee arthroplasty (TKA) can be associated with significant postoperative pain despite multimodal analgesic (MMA) protocols, and most patients require the use of opioids postoperatively. HTX-011 is a dual-acting local anesthetic containing bupivacaine and low-dose meloxicam in an extended-release polymer. In a prior randomized controlled trial (RCT), HTX-011 reduced pain and opioid use through 72 hours after TKA compared with bupivacaine hydrochloride. This open-label study (NCT03974932) evaluated the efficacy and safety of HTX-011 combined with an MMA regimen in patients undergoing TKA under spinal anesthesia. All patients received intraoperative HTX-011 (400 mg bupivacaine/12 mg meloxicam) in combination with an MMA regimen consisting of preoperative acetaminophen, celecoxib, and pregabalin and postoperative acetaminophen and celecoxib until discharge. Opioid rescue was allowed upon patient request for additional pain control. Pain scores, opioid consumption, discharge readiness, and adverse events were recorded. Fifty-one patients were treated. Compared with the prior RCT, HTX-011 with this MMA regimen further lowered pain scores and reduced opioid use. Mean patient-reported pain scores remained in the mild range, and 82% of patients or more did not experience severe pain at any individual time point through 72 hours after surgery. Mean total opioid consumption was low over 72 hours: 24.8 morphine milligram equivalents (1–2 tablets of oxycodone 10 mg/day). Approximately 60% of patients were ready for discharge by 12 hours, and 39% were discharged without an opioid prescription and did not call back for pain management. The treatment regimen was well tolerated, and no added risk was observed with the addition of MMA. HTX-011 with an MMA regimen reduced postoperative pain and opioid use following TKA.
    Keywords HTX-011 ; multimodal analgesia ; postoperative pain ; total knee arthroplasty
    Language English
    Publishing date 2022-06-10
    Publisher Thieme Medical Publishers, Inc.
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2075354-8
    ISSN 1938-2480 ; 1538-8506 ; 0899-7403
    ISSN (online) 1938-2480
    ISSN 1538-8506 ; 0899-7403
    DOI 10.1055/s-0042-1747945
    Database Thieme publisher's database

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  10. Article ; Online: The combination of opioid and neurotensin receptor agonists improves their analgesic/adverse effect ratio.

    Eiselt, Emilie / Côté, Jérôme / Longpré, Jean-Michel / Blais, Véronique / Sarret, Philippe / Gendron, Louis

    European journal of pharmacology

    2019  Volume 848, Page(s) 80–87

    Abstract: ... where they modulate nociceptive responses. Nowadays, opioid analgesics like morphine remain the most prescribed drugs ... would require lower doses to produce significant analgesic effects, hence decreasing opioid-induced ... Opioid and neurotensin (NT) receptors are expressed in both central and peripheral nervous systems ...

    Abstract Opioid and neurotensin (NT) receptors are expressed in both central and peripheral nervous systems where they modulate nociceptive responses. Nowadays, opioid analgesics like morphine remain the most prescribed drugs for the treatment of moderate to severe pain. However, despite their daily used, opioids can produce life-threatening side effects, such as constipation or respiratory depression. Besides, NT analogs exert strong opioid-independent analgesia. Here, we thus hypothesized that the combined use of opioid and NT agonists would require lower doses to produce significant analgesic effects, hence decreasing opioid-induced adverse effects. We used isobologram analyses to determine if the combination of a NT brain-penetrant analog, An2-NT(8-13) with morphine results in an inhibitory, synergistic or additive analgesic response. We found that intravenous administration of An2-NT(8-13) reduced by 90% the nocifensive behaviors induced by formalin injection, at the dose of 0.018 mg/kg. Likewise, subcutaneous morphine reduced pain by 90% at 1.8 mg/kg. Importantly, isobologram analyses revealed that the co-injection of An2-NT(8-13) with morphine induced an additive analgesic response. We finally assessed the effects of morphine and An2-NT(8-13) on the gastrointestinal tract motility using the charcoal meal test. As opposed to morphine which significantly reduced the intestinal motility at the analgesic effective dose of 1.8 mg/kg, An2-NT(8-13) did not affect the charcoal meal intestinal transit at 0.018 mg/kg. Interestingly, at the dose providing 90% pain relief, the co-administration of morphine with An2-NT(8-13) had a reduced effect on constipation. Altogether, these results suggest that combining NT agonists with morphine may improve its analgesic/adverse effect ratio.
    MeSH term(s) Analgesics, Opioid/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Male ; Morphine/administration & dosage ; Neurotensin/administration & dosage ; Pain Measurement/drug effects ; Pain Measurement/methods ; Peptide Fragments/administration & dosage ; Peptides/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurotensin/agonists ; Receptors, Neurotensin/metabolism ; Receptors, Opioid, mu/agonists ; Receptors, Opioid, mu/metabolism
    Chemical Substances Analgesics, Opioid ; Angiopep-2 ; Peptide Fragments ; Peptides ; Receptors, Neurotensin ; Receptors, Opioid, mu ; Neurotensin (39379-15-2) ; neurotensin (8-13) (60482-95-3) ; Morphine (76I7G6D29C)
    Language English
    Publishing date 2019-01-29
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2019.01.048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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