{"id":"https://openalex.org/W7224516480","doi":"https://doi.org/10.1177/10600280261496561","title":"Efficacy, Safety, and Impact of Combined Extended-Release Tramadol Hydrochloride and Acetaminophen on Inflammatory Mediators in Malignant Lymphoma-Associated Pain","display_name":"Efficacy, Safety, and Impact of Combined Extended-Release Tramadol Hydrochloride and Acetaminophen on Inflammatory Mediators in Malignant Lymphoma-Associated Pain","publication_year":2026,"publication_date":"2026-10-29","ids":{"openalex":"https://openalex.org/W7224516480","doi":"https://doi.org/10.1177/10600280261496561","pmid":"https://pubmed.ncbi.nlm.nih.gov/42954666"},"language":"en","primary_location":{"id":"doi:10.1177/10600280261496561","doi":"https://doi.org/10.1177/10600280261496561","is_oa":false,"landing_page_url":"https://doi.org/10.1177/10600280261496561","pdf_url":null,"source":{"id":"https://openalex.org/S113426163","display_name":"Annals of Pharmacotherapy","issn_l":"0012-6578","issn":["0012-6578","1060-0280","1542-6270"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320017","host_organization_name":"SAGE Publishing","host_organization_lineage":["https://openalex.org/P4310320017"],"host_organization_lineage_names":["SAGE Publishing"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Pharmacotherapy","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5160143914","display_name":"Xiaohua Qi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I9916479","display_name":"Air Force Medical University","ror":"https://ror.org/00ms48f15","country_code":"CN","type":"education","lineage":["https://openalex.org/I9916479"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiaohua Qi","raw_affiliation_strings":["Department of Hematology, The First Affiliated Hospital of Air Force Military Medical University, Xi\u2019an, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Hematology, The First Affiliated Hospital of Air Force Military Medical University, Xi\u2019an, China","institution_ids":["https://openalex.org/I9916479"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102233176","display_name":"Li Zhu","orcid":"https://orcid.org/0009-0003-5073-2402","observed_orcids":["https://orcid.org/0009-0003-5073-2402"]},"institutions":[{"id":"https://openalex.org/I9916479","display_name":"Air Force Medical University","ror":"https://ror.org/00ms48f15","country_code":"CN","type":"education","lineage":["https://openalex.org/I9916479"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Li Zhu","raw_affiliation_strings":["Department of Hematology, The First Affiliated Hospital of Air Force Military Medical University, Xi\u2019an, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Hematology, The First Affiliated Hospital of Air Force Military Medical University, Xi\u2019an, China","institution_ids":["https://openalex.org/I9916479"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160127740","display_name":"Jianzhen Li","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I9916479","display_name":"Air Force Medical University","ror":"https://ror.org/00ms48f15","country_code":"CN","type":"education","lineage":["https://openalex.org/I9916479"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jianzhen Li","raw_affiliation_strings":["Department of Nursing, The First Affiliated Hospital of Air Force Military Medical University, Xi\u2019an, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Nursing, The First Affiliated Hospital of Air Force Military Medical University, Xi\u2019an, China","institution_ids":["https://openalex.org/I9916479"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5160075076","display_name":"Yan Li","orcid":"https://orcid.org/0009-0001-3763-212X","observed_orcids":["https://orcid.org/0009-0001-3763-212X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Yan Li","raw_affiliation_strings":["Department of Hematology, Xi\u2019an No.3 Hospital, China"],"raw_orcid":"https://orcid.org/0009-0001-3763-212X","affiliations":[{"raw_affiliation_string":"Department of Hematology, Xi\u2019an No.3 Hospital, China","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5160075076"],"corresponding_institution_ids":[],"apc_list":{"value":4400,"currency":"USD","value_usd":4400},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.89387628,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"10600280261496561","last_page":"10600280261496561"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11199","display_name":"Pain Management and Opioid Use","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/2703","display_name":"Anesthesiology and Pain Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11199","display_name":"Pain Management and Opioid Use","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/2703","display_name":"Anesthesiology and Pain Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.0015999999595806003,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10189","display_name":"Anesthesia and Pain Management","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/paracetamol","display_name":"paracetamol","score":0.9990000128746033},{"id":"https://openalex.org/keywords/combination-analgesics","display_name":"analgesic combination","score":0.9330000281333923},{"id":"https://openalex.org/keywords/pain-mediators","display_name":"pain mediators","score":0.7129999995231628},{"id":"https://openalex.org/keywords/pro-inflammatory-cytokines","display_name":"inflammatory cytokines","score":0.8009999990463257},{"id":"https://openalex.org/keywords/substance-p","display_name":"substance P","score":0.953000009059906},{"id":"https://openalex.org/keywords/prostaglandin-e2","display_name":"prostaglandin E2","score":1.0},{"id":"https://openalex.org/keywords/endothelin-1","display_name":"endothelin-1","score":0.9959999918937683},{"id":"https://openalex.org/keywords/serotonin","display_name":"serotonin","score":0.7820000052452087},{"id":"https://openalex.org/keywords/interleukin-6","display_name":"interleukin-6","score":0.7940000295639038},{"id":"https://openalex.org/keywords/tnf-alpha","display_name":"TNF-\u03b1","score":0.9629999995231628},{"id":"https://openalex.org/keywords/quality-of-life","display_name":"quality of life","score":0.9409999847412109},{"id":"https://openalex.org/keywords/analgesic-efficacy","display_name":"analgesic efficacy","score":0.753000020980835},{"id":"https://openalex.org/keywords/adverse-events","display_name":"adverse events","score":0.7900000214576721},{"id":"https://openalex.org/keywords/cancer-pain-management","display_name":"cancer pain management","score":0.7609999775886536},{"id":"https://openalex.org/keywords/analgesic-safety","display_name":"analgesic safety","score":0.4169999957084656}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.9638000130653381},{"id":"https://openalex.org/C2779777798","wikidata":"https://www.wikidata.org/wiki/Q407592","display_name":"Tramadol","level":3,"score":0.777999997138977},{"id":"https://openalex.org/C2778722691","wikidata":"https://www.wikidata.org/wiki/Q57055","display_name":"Acetaminophen","level":2,"score":0.7739999890327454},{"id":"https://openalex.org/C2780820201","wikidata":"https://www.wikidata.org/wiki/Q173235","display_name":"Analgesic","level":2,"score":0.738099992275238},{"id":"https://openalex.org/C42219234","wikidata":"https://www.wikidata.org/wiki/Q131130","display_name":"Anesthesia","level":1,"score":0.5325999855995178},{"id":"https://openalex.org/C2776999253","wikidata":"https://www.wikidata.org/wiki/Q1304270","display_name":"Combination therapy","level":2,"score":0.4799000024795532},{"id":"https://openalex.org/C2910896220","wikidata":"https://www.wikidata.org/wiki/Q407592","display_name":"Tramadol Hydrochloride","level":4,"score":0.47209998965263367},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.4277999997138977},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.37689998745918274},{"id":"https://openalex.org/C2779951463","wikidata":"https://www.wikidata.org/wiki/Q7268788","display_name":"Quality of life (healthcare)","level":2,"score":0.3741999864578247},{"id":"https://openalex.org/C14184104","wikidata":"https://www.wikidata.org/wiki/Q1362526","display_name":"Visual analogue scale","level":2,"score":0.31630000472068787},{"id":"https://openalex.org/C2779252780","wikidata":"https://www.wikidata.org/wiki/Q582687","display_name":"Antipyretic","level":3,"score":0.29980000853538513},{"id":"https://openalex.org/C15490471","wikidata":"https://www.wikidata.org/wiki/Q2734305","display_name":"Nociception","level":3,"score":0.2985000014305115},{"id":"https://openalex.org/C17991360","wikidata":"https://www.wikidata.org/wiki/Q21173843","display_name":"Tumor necrosis factor alpha","level":2,"score":0.29179999232292175},{"id":"https://openalex.org/C2779837120","wikidata":"https://www.wikidata.org/wiki/Q579348","display_name":"Prostaglandin E1","level":2,"score":0.29109999537467957},{"id":"https://openalex.org/C2779826273","wikidata":"https://www.wikidata.org/wiki/Q244408","display_name":"Diclofenac","level":2,"score":0.2858999967575073},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2540999948978424},{"id":"https://openalex.org/C46762472","wikidata":"https://www.wikidata.org/wiki/Q178648","display_name":"Peripheral","level":2,"score":0.2517000138759613},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.2513999938964844}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1177/10600280261496561","doi":"https://doi.org/10.1177/10600280261496561","is_oa":false,"landing_page_url":"https://doi.org/10.1177/10600280261496561","pdf_url":null,"source":{"id":"https://openalex.org/S113426163","display_name":"Annals of Pharmacotherapy","issn_l":"0012-6578","issn":["0012-6578","1060-0280","1542-6270"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320017","host_organization_name":"SAGE Publishing","host_organization_lineage":["https://openalex.org/P4310320017"],"host_organization_lineage_names":["SAGE Publishing"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Pharmacotherapy","raw_type":"journal-article"},{"id":"pmid:42954666","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42954666","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Annals of pharmacotherapy","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":1.0,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":38,"referenced_works":["https://openalex.org/W1991925106","https://openalex.org/W2123657472","https://openalex.org/W2133988714","https://openalex.org/W3107716656","https://openalex.org/W3129333098","https://openalex.org/W3137886769","https://openalex.org/W4229075591","https://openalex.org/W4291632973","https://openalex.org/W4309361964","https://openalex.org/W4389799527","https://openalex.org/W4391882337","https://openalex.org/W4396765581","https://openalex.org/W4402348481","https://openalex.org/W4402694800","https://openalex.org/W4403639456","https://openalex.org/W4404568540","https://openalex.org/W4406847356","https://openalex.org/W4408344589","https://openalex.org/W4409205506","https://openalex.org/W4410513923","https://openalex.org/W4411553816","https://openalex.org/W4412154452","https://openalex.org/W4412158724","https://openalex.org/W4412652375","https://openalex.org/W4413139756","https://openalex.org/W4413312135","https://openalex.org/W4414717378","https://openalex.org/W4414779694","https://openalex.org/W4414909367","https://openalex.org/W4415436709","https://openalex.org/W4416202717","https://openalex.org/W4417269027","https://openalex.org/W7116896502","https://openalex.org/W7125944211","https://openalex.org/W7135180242","https://openalex.org/W7143296426","https://openalex.org/W7151268147","https://openalex.org/W7155060836"],"related_works":["https://openalex.org/W2135403426","https://openalex.org/W4417269027","https://openalex.org/W2067066717","https://openalex.org/W2117636258","https://openalex.org/W7127653258","https://openalex.org/W2016973199","https://openalex.org/W2181852399","https://openalex.org/W2390616738","https://openalex.org/W2029133283","https://openalex.org/W2416995866"],"abstract_inverted_index":{"Background:":[0],"Malignant":[1],"lymphoma-associated":[2,92],"pain":[3,75,93,129,139,216,329,421],"significantly":[4,181,251,347],"impairs":[5],"quality":[6,173,304],"of":[7,23,43,60,69,120,174,215,225,248,289,305,314,327,333,351,375,417],"life":[8,249,306],"and":[9,21,41,64,77,131,172,187,196,222,285,294,300,318,331,379,431],"is":[10,321,361],"linked":[11],"to":[12,37,65,100,364,419],"systemic":[13,78,385],"inflammatory":[14,79,151,335],"responses.":[15],"This":[16,34,359],"study":[17,35,84],"evaluated":[18],"the":[19,39,58,67,212,254,312,324,334,339,342,349,362,372,384,400,414],"efficacy":[20,40,190,299,374,430],"safety":[22,42],"combining":[24],"extended-release":[25,46,292],"tramadol":[26,44,107,197,290],"hydrochloride":[27,45,291],"with":[28,31,50,54,90,193,308,323,424],"acetaminophen":[29,51,103,194,295],"compared":[30,192,307],"monotherapy.":[32],"Objective:":[33],"aimed":[36],"evaluate":[38],"tablets":[47,293],"in":[48,57,184,211,253,303,311,367,395,422],"combination":[49,112,178,255,288,343,377],"versus":[52],"monotherapy":[53,310],"either":[55,309],"agent":[56],"treatment":[59,71,313,340],"malignant":[61,91,315,425],"lymphoma-related":[62,316],"pain,":[63,317],"investigate":[66],"effects":[68,382],"these":[70],"regimens":[72],"on":[73,383,399],"peripheral":[74,137,328],"mediators":[76,140,217,330],"cytokines.":[80],"Methods:":[81],"A":[82],"comparative":[83],"was":[85,268],"conducted":[86],"involving":[87],"165":[88],"patients":[89,423],"(January":[94],"2024-December":[95],"2025).":[96],"Patients":[97],"were":[98],"assigned":[99],"3":[101],"groups:":[102],"(n":[104,108,114],"=":[105,109,115],"53),":[106],"55),":[110],"or":[111],"therapy":[113,209],"57),":[116],"receiving":[117],"28":[118],"days":[119],"treatment.":[121],"Primary":[122],"outcomes":[123,135],"included":[124,136],"Numerical":[125],"Rating":[126],"Scale":[127],"(NRS)":[128],"scores":[130,186],"analgesic":[132,189,298],"efficacy.":[133],"Secondary":[134],"blood":[138],"(substance":[141],"P":[142,201,240,258,273],"[SP],":[143],"prostaglandin":[144],"E2":[145],"[PGE2],":[146],"endothelin-1":[147],"[ET-1],":[148],"5-hydroxytryptamine":[149],"[5-HT]),":[150],"cytokines":[152,226],"(interleukin":[153],"[IL]-2,":[154],"IL-4,":[155,237],"IL-6,":[156,229],"IL-10,":[157],"tumor":[158],"necrosis":[159],"factor-":[160],"\u03b1":[161,163,231],"[TNF-":[162],"]":[164,165],",":[166,232,279],"interferon-":[167],"\u03b3":[168],"[IFN-":[169],"\u03b3\u03b3":[170,234],"]),":[171],"life.":[175],"Results:":[176],"The":[177,287],"group":[179,256],"demonstrated":[180],"greater":[182,301],"reductions":[183],"NRS":[185],"superior":[188,297],"(91.23%)":[191],"(71.70%)":[195],"(78.18%)":[198],"groups":[199,271],"(":[200,239,257],"<":[202,241,259],"0":[203,242,260,275],".":[204,207,243,246,261,264,276],"05":[205,244,262,277],")":[206,245,263,278],"Combination":[208],"resulted":[210],"greatest":[213],"reduction":[214],"(SP,":[218],"PGE2,":[219],"ET-1,":[220],"5-HT)":[221],"significant":[223],"modulation":[224,332],"(lower":[227],"IL-2,":[228],"TNF-":[230],"IFN-":[233],";":[235],"higher":[236],"IL-10)":[238],"Quality":[247],"improved":[250],"more":[252],"Adverse":[265],"event":[266],"incidence":[267],"comparable":[269],"across":[270],"(18.87%-22.81%;":[272],">":[274],"indicating":[280],"favorable":[281,356],"clinical":[282,373,396],"safety.":[283],"Conclusion":[284],"Relevance:":[286],"provides":[296],"improvement":[302],"its":[319,380,428],"mechanism":[320],"associated":[322],"synergistic":[325],"downregulation":[326],"cytokine":[336],"profile.":[337],"During":[338],"period,":[341],"regimen":[344,378,406],"did":[345],"not":[346],"increase":[348],"risk":[350],"adverse":[352],"reactions,":[353],"demonstrating":[354],"a":[355,390],"benefit-risk":[357],"ratio.":[358],"report":[360],"first":[363],"simultaneously":[365],"confirm,":[366],"this":[368,376,403,405],"patient":[369],"population,":[370],"both":[371],"modulatory":[381],"pain-inflammation":[386],"network,":[387],"thereby":[388],"providing":[389],"strategy":[391],"for":[392,413],"enhanced":[393],"analgesia":[394],"practice.":[397],"Based":[398],"data":[401],"from":[402],"study,":[404],"may":[407],"serve":[408],"as":[409],"an":[410],"effective":[411],"option":[412],"short-term":[415],"management":[416],"moderate":[418],"severe":[420],"lymphoma;":[426],"however,":[427],"long-term":[429],"broad":[432],"applicability":[433],"require":[434],"further":[435],"investigation.":[436]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-30T00:00:00"}