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psx:substance/dextropropoxyphene/src/pmid:15973913

src2026-09-07recordconsumed

derived from · upstream

none recorded

feeds · downstream

Closure of psx:substance/dextropropoxyphene/src/pmid:15973913: 40 upstream, 159 downstream.

psx:substance/dextropropoxyphene/src/pmid:15973913
  ├─ used  src/doi:10.1016/j.yrtph.2010.12.007  Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs
  ├─ used  src/pmid:9437273  Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol
  ├─ used  src/pmid:6258941  d-Propoxyphene acts differently from morphine on opioid receptor-effector mechanisms
  ├─ used  src/pmid:2553778  Marked QRS complex abnormalities and sodium channel blockade by propoxyphene reversed with lidocaine
  ├─ used  src/pmid:10690289  Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currents
  ├─ used  src/pmid:20133509  CYP3A5 but not CYP2D6 polymorphism contributes significantly to the variability in dextropropoxyphene disposition
  ├─ used  src/pmid:6480014  Dextropropoxyphene deaths: coroner's report
  ├─ used  src/pmid:17122535  Propoxyphene (dextropropoxyphene): a critical review of a weak opioid analgesic that should remain in antiquity
  ├─ used  src/doi:10.1371/journal.pmed.1001213  Six-year follow-up of impact of co-proxamol withdrawal in England and Wales on prescribing and deaths: time-series study
  ├─ used  src/url:ab12be4656094f54  Propoxyphene synthesis history - Pohland and Sullivan 1953
  ├─ used  src/pmid:10097357  Suicides may be overreported and accidents underreported among fatalities due to dextropropoxyphene
  ├─ used  src/doi:10.1093/qjmed/hci026  Co-proxamol and suicide: preventing the continuing toll of overdose deaths
  ├─ used  src/pmid:10938209  Middle-aged men--a risk category regarding fatal poisoning due to dextropropoxyphene and alcohol in combination
  ├─ used  src/doi:10.1136/bmj.b2270  Effect of withdrawal of co-proxamol on prescribing and deaths from drug poisoning in England and Wales: time series analysis
  ├─ used  src/doi:10.1186/1472-6904-10-6  Use of analgesics in intentional drug overdose presentations to hospital before and after the withdrawal of distalgesic from the Irish market
  ├─ used  src/doi:10.1111/j.1365-2125.2008.03206.x  Co-proxamol withdrawal has reduced suicide from drugs in Scotland
  ├─ used  src/doi:10.1002/pds.3411  Propoxyphene and the risk of out-of-hospital death
  ├─ used  src/url:908b8b3708835ebc  Dextropropoxyphene legal status and 2010 US withdrawal
  ├─ used  src/pmid:16051647  Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.
  ├─ used  src/pmid:1150913  Propoxyphene bioavailability: an evaluation of ten products
  ├─ used  src/pmid:1277712  Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels
  ├─ used  src/pmid:15764408  CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement
  ├─ used  src/pmid:6480016  Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in elderly hospital patients after single and multiple doses of distalgesic
  ├─ used  src/pmid:8764759  A novel approach to the pharmacology of analgesics
  ├─ used  src/doi:10.5055/jom.2018.0466  Dextropropoxyphene effects on QTc-interval prolongation: Frequency and characteristics in relation to plasma levels
  ├─ used  src/pmid:16513452  Profound metoprolol-induced bradycardia precipitated by acetaminophen-propoxyphene
  ├─ used  src/doi:10.1111/j.1472-8206.2008.00661.x  Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumption
  ├─ used  src/doi:10.1503/cmaj.051528  Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects
  ├─ used  src/pmid:14602  Therapeutic usefulness of propoxyphene napsylate in narcotic addiction
  ├─ used  src/pmid:6122232  Propoxyphene napsylate compared to methadone for opiate dependence
  ├─ used  src/pmid:7312731  Propoxyphene dependence: an update
  ├─ used  src/pmid:6349964  Dextropropoxyphene overdosage. Pharmacological considerations and clinical management
  ├─ used  src/pmid:8335717  Simultaneous determination of dextromoramide, propoxyphene and norpropoxyphene in necropsic whole blood by liquid chromatography
  ├─ used  src/pmid:16138729  Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazine
  ├─ used  src/pmid:12774892  Interaction of alcohol and drugs in fatal poisonings
  ├─ used  src/pmid:15676043  A multicentre study of coproxamol poisoning suicides based on coroners' records in England
  ├─ used  src/pmid:3092407  Carbamazepine drug interactions
  ├─ used  src/doi:10.1176/appi.psy.50.2.169  Pharmacokinetic drug interactions of synthetic opiate analgesics
  ├─ derived_from  gen/8f13d2b4-1a32-4a35-9c03-ffe76af0e671  Generation — pipeline-v5
  └─ generated_by  pub/c8622ddf-894b-4a09-8fef-d50dc01f9bdf  Publication — backfill
├─ used  version/1  Revision 1
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  ├─ derived_from  issue/notice@88ab1a511225  Issued notice
  ├─ derived_from  issue/info_card@8aae7dadb181  Issued info_card
  ├─ derived_from  issue/emergency@f85b2d2362c9  Issued emergency
  ├─ derived_from  issue/info_card@705afe7a476d  Issued info_card
  ├─ informed_by  section/pharmacology.full@1
  ├─ informed_by  section/pharmacokinetic-detail.full@1
  ├─ informed_by  section/safety.full@1
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    ├─ used  claim/d9798522-ccb3-452f-89a0-6d179500b199  Claim in safety — inconclusive  working
    ├─ used  claim/e09ab666-b5a7-4443-a0a4-a0e0dcf2e94b  Claim in history — inconclusive  working
    ├─ used  claim/0a5fb1cc-8c2e-414d-9de6-814cfaa7e705  Claim in safety — inconclusive  working
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    ├─ used  claim/eb6e5fec-37c1-470d-9645-1918690dbc3a  Claim in history — inconclusive  working
    ├─ used  claim/0dc41457-61cd-40f9-a5b0-91437197c549  Claim in safety — inconclusive  working
    ├─ used  claim/97d98614-9d94-44de-87bb-5f1828b6b983  Claim in history — inconclusive  working
    ├─ used  claim/a3b3e14a-a354-42d2-8468-1055944dd082  Claim in safety — inconclusive  working
    ├─ used  claim/acc599bb-cfd3-4e39-8af8-fa74abea60a4  Claim in history — inconclusive  working
    ├─ used  claim/35fd0a5d-1181-499a-9201-9b7bef87b4d3  Claim in history — inconclusive  working
    ├─ used  claim/ac2256f6-3df9-42d2-b7a0-bf3af3cfed74  Claim in history — inconclusive  working
    ├─ used  claim/5b3ac629-5bdf-418e-970c-76d6b481d941  Claim in history — inconclusive  working
    ├─ used  claim/f39ca5ea-da91-40c3-a5f7-25d1c7deea55  Claim in history — inconclusive  working
    ├─ used  claim/476ec455-9abc-44f5-8042-373084694151  Claim in clinical-evidence — inconclusive  working
    └─ used  claim/465e6bad-2d1c-4f50-99b5-55dc15045fe1  Claim in safety — inconclusive  working
… closure truncated at 200 nodes

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

3911 with DOI

4 strong · 29 moderate · 6 weak

Compilations

12026-05-09T21:28:12.615Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

29last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:31:27.919Z

notice · info card · emergency

Searches

220 with no results

queries and counts on the build

Claims checked

2542 supported

2 supported · 252 not

Correspondence

0received

consent field ships in Phase 4

Edges

611

derivations recorded for this entity

Complete over 39 sources, 1 compilation, and 29 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/dextropropoxyphene/archive

2Build

one panel per compilation run

generation run 2026-05-09

62 min completedmodel pipeline-v5plan not recordedrun/5217af2c…

Selection

results seen124
selected by the model53
consumed as sources39

Verification

claims checked254
supported2
partially supported0
not supported0
inconclusive252
  • record
  • seen / partial
  • working

The model's own caveats

  • sparse_evidence
  • structural_inference

Reproduce

inputs
39 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
pipeline-v5
streams
none — agent transcripts are persisted from 2026-09 onward
22 searches — query, source, results, what was kept and why
22 searches for this run
#sourcequeryseenkeptrationale
1PubMedpropoxyphene opioid receptor binding mechanism action41Direct receptor pharmacology comparison; nicotinic receptor paper was about methadone/analogs, less directly relevant
2PubChemdextropropoxyphene11Primary chemical identity verification
3PubMedpropoxyphene mu opioid receptor binding affinity Ki11Only published systematic Ki comparison including propoxyphene at human MOR
4PubMeddextropropoxyphene sodium channel block local anesthetic11Key mechanistic paper on cardiac sodium channel blockade
5PubMeddextropropoxyphene propoxyphene pharmacology pharmacokinetics156Direct relevance to pharmacology, metabolism, and clinical use
6PubMedpropoxyphene cardiotoxicity norpropoxyphene cardiac arrhythmia QTc11Already selected; cardiotoxicity covered in Barkin review
7OpenAlexpropoxyphene cardiotoxicity norpropoxyphene cardiac withdrawal FDA52Directly relevant to cardiac risk and regulatory decisions
8ClinicalTrials.govdextropropoxyphene propoxyphene101Only trial specifically about propoxyphene napsylate safety; terminated status is significant
9OpenAlexdextropropoxyphene propoxyphene pharmacology100No propoxyphene-specific landmark papers surfaced; general opioid reviews already covered
10PubMedpropoxyphene overdose toxicity fatality death118All directly relevant to toxicity, fatality, and harm reduction
11PubMedco-proxamol dextropropoxyphene paracetamol suicide UK withdrawal65All directly relevant to regulatory history and outcome of withdrawal
12PubMedpropoxyphene dependence addiction withdrawal abuse103Dependence, tolerance, and historic opioid utility data
13WebSearchpropoxyphene dextropropoxyphene legal status UK EU Australia Canada scheduling103Confirmed multi-jurisdiction regulatory history
14WebSearchpropoxyphene Pohland 1953 synthesis history Eli Lilly first described103Key historical facts for history section
15ClinicalTrials.govpropoxyphene napsylate11Only propoxyphene-specific interventional trial found; terminated status relevant to regulatory history
16DrugCentraldextropropoxyphene pharmacokinetic parameters14Specific pharmacokinetic parameters not available from published PubMed articles
17PubMedpropoxyphene mu opioid receptor binding affinity Ki uniform11Only published systematic Ki comparison including propoxyphene at human recombinant MOR
18PubMedpropoxyphene dependence clinical trial addiction withdrawal management83Characterize dependence, withdrawal, and abuse potential
19PubMedpropoxyphene pharmacokinetics Tmax half-life plasma concentration oral dose43All provide specific pharmacokinetic data from human studies
20Multiple sourcesSMILES InChIKey CAS chemical identity verification31Chemical identity verification complete
21PubMedpropoxyphene carbamazepine inhibitor drug interaction clinical11Confirms clinically important drug interaction
22WebSearchdextropropoxyphene propoxyphene DEA Schedule IV legal status United States 2010 withdrawal103Confirmed regulatory history for US market
254 claims by section — every cited sentence, checked against its source
safety102 · 1 ok
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  • Fatalities from serotonin-syndrome have been documented with structurally related phenylpiperidine/MAOI combinationssupported

    Tramadol, meperidine, methadone, dextromethorphan are SRIs involved in serotonin toxicity with MAOIs (including fatalities). pmid:16051647

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pharmacology42 · 0 ok
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history20 · 0 ok
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summary18 · 0 ok
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pharmacokinetic-detail16 · 0 ok
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receptor-pharmacology16 · 1 ok
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  • Morphine, codeine, oxycodone, and buprenorphine lack this SRI activity and do not produce serotonin toxicity with MAOIs.supported

    Morphine, codeine, oxycodone, buprenorphine not SRIs. pmid:16051647

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neuroscience14 · 0 ok
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clinical-evidence12 · 0 ok
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comparative-pharmacology8 · 0 ok
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effects-overview4 · 0 ok
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chemistry2 · 0 ok
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3Sources

39 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
yearsourcetierstatusfeeds
2024Dextropropoxyphene legal status and 2010 US withdrawalVariousurl:908b8b3708835ebcweakconsumedcited only
2024Propoxyphene synthesis history - Pohland and Sullivan 1953Various secondary sourcesurl:ab12be4656094f54weakconsumedcited only
2018Dextropropoxyphene effects on QTc-interval prolongation: Frequency and characteristics in relation to plasma levelsKeller GA, Villa Etchegoyen C, Fernández N, et al. · Journal of Opioid Managementdoi:10.5055/jom.2018.0466moderateconsumed3 sections
2013Propoxyphene and the risk of out-of-hospital deathRay WA, Murray KT, Kawai V, Graham DJ, Cooper WO, Hall K, Stein CM · Pharmacoepidemiology and Drug Safetydoi:10.1002/pds.3411moderateconsumed3 sections
2012Six-year follow-up of impact of co-proxamol withdrawal in England and Wales on prescribing and deaths: time-series studyHawton K, Bergen H, Simkin S, Wells C, Kapur N, Gunnell D · PLoS Medicinedoi:10.1371/journal.pmed.1001213moderateconsumed3 sections
2011Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugsVolpe DA, McMahon Tobin GA, Mellon RD, et al. · Regulatory Toxicology and Pharmacologydoi:10.1016/j.yrtph.2010.12.007moderateconsumed3 sections
2010CYP3A5 but not CYP2D6 polymorphism contributes significantly to the variability in dextropropoxyphene dispositionYin OQ, Tomlinson B, Chow MS · Journal of Clinical Pharmacologypmid:20133509moderateconsumed5 sections
2010Use of analgesics in intentional drug overdose presentations to hospital before and after the withdrawal of distalgesic from the Irish marketCorcoran P, Reulbach U, Keeley HS, Perry IJ, Hawton K, Arensman E · BMC Clinical Pharmacologydoi:10.1186/1472-6904-10-6moderateconsumedcited only
2009Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumptionGaubert S, Vié M, Damase-Michel C, Pathak A, Montastruc JL · Fundamental & Clinical Pharmacologydoi:10.1111/j.1472-8206.2008.00661.xmoderateconsumed2 sections
2009Effect of withdrawal of co-proxamol on prescribing and deaths from drug poisoning in England and Wales: time series analysisHawton K, Bergen H, Simkin S, Brock A, Griffiths C, Romeri E, Smith KL, Kapur N, Gunnell D · BMJdoi:10.1136/bmj.b2270moderateconsumed1 section
2009Pharmacokinetic drug interactions of synthetic opiate analgesicsArmstrong SC, Wynn GH, Sandson NB · Psychosomaticsdoi:10.1176/appi.psy.50.2.169moderateconsumed1 section
2008Co-proxamol withdrawal has reduced suicide from drugs in ScotlandSandilands EA, Bateman DN · British Journal of Clinical Pharmacologydoi:10.1111/j.1365-2125.2008.03206.xmoderateconsumed1 section
2006Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effectsFurlan AD, et al. · Canadian Medical Association Journaldoi:10.1503/cmaj.051528strongconsumedcited only
2006Profound metoprolol-induced bradycardia precipitated by acetaminophen-propoxypheneMarraffa JM, Lang L, Ong G, Lehmann DF · Clinical Pharmacology and Therapeuticspmid:16513452weakconsumed2 sections
2006Propoxyphene (dextropropoxyphene): a critical review of a weak opioid analgesic that should remain in antiquityBarkin RL, Barkin SJ, Barkin DS · American Journal of Therapeuticspmid:17122535moderateconsumed9 sections
2005A multicentre study of coproxamol poisoning suicides based on coroners' records in EnglandHawton K, Simkin S, Gunnell D, Sutton L, Bennewith O, Turnbull P, Kapur N · British Journal of Clinical Pharmacologypmid:15676043moderateconsumed1 section
2005Acute pain management pharmacology for the patient with concurrent renal or hepatic diseaseMurphy EJ · Anaesthesia and Intensive Carepmid:15973913moderateconsumed3 sections
2005Co-proxamol and suicide: preventing the continuing toll of overdose deathsSimkin S, Hawton K, Sutton L, Gunnell D, Bennewith O · QJMdoi:10.1093/qjmed/hci026moderateconsumed2 sections
2005Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.Gillman PK · British Journal of Anaesthesiapmid:16051647strongconsumed4 sections
2005Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazineKoski A, Vuori E, Ojanperä I · Human & Experimental Toxicologypmid:16138729moderateconsumed1 section
2004CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvementSomogyi AA, Menelaou A, Fullston SV · Xenobioticapmid:15764408moderateconsumed2 sections
2003Interaction of alcohol and drugs in fatal poisoningsKoski A, Ojanperä I, Vuori E · Human & Experimental Toxicologypmid:12774892moderateconsumed1 section
2000Middle-aged men--a risk category regarding fatal poisoning due to dextropropoxyphene and alcohol in combinationJonasson U, Jonasson B, Saldeen T · Preventive Medicinepmid:10938209moderateconsumed2 sections
1999Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currentsUlens C, Daenens P, Tytgat J · Cardiovascular Researchpmid:10690289moderateconsumed4 sections
1999Suicides may be overreported and accidents underreported among fatalities due to dextropropoxypheneJonasson B, Jonasson U, Saldeen T · Journal of Forensic Sciencespmid:10097357moderateconsumed2 sections
1997Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamolLi Wan Po A, Zhang WY · BMJpmid:9437273strongconsumed5 sections
1996A novel approach to the pharmacology of analgesicsRaffa RB · The American Journal of Medicinepmid:8764759moderateconsumed1 section
1993Simultaneous determination of dextromoramide, propoxyphene and norpropoxyphene in necropsic whole blood by liquid chromatographyRop PP, Grimaldi F, Bresson M, Fornaris M, Viala A · Journal of Chromatographypmid:8335717weakconsumed1 section
1989Marked QRS complex abnormalities and sodium channel blockade by propoxyphene reversed with lidocaineWhitcomb DC, Gilliam FR, Starmer CF, Grant AO · The Journal of Clinical Investigationpmid:2553778weakconsumed5 sections
1986Carbamazepine drug interactionsBaciewicz AM · Therapeutic Drug Monitoringpmid:3092407moderateconsumed1 section
Show all 39 sources — 9 more
Sources 31 to 39
yearsourcetierstatusfeeds
1984Dextropropoxyphene deaths: coroner's reportWhittington RM · Human Toxicologypmid:6480014weakconsumed3 sections
1984Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in elderly hospital patients after single and multiple doses of distalgesicCrome P, Gain R, Ghurye R, Flanagan RJ · Human Toxicologypmid:6480016moderateconsumed2 sections
1983Dextropropoxyphene overdosage. Pharmacological considerations and clinical managementYoung RJ · Drugspmid:6349964moderateconsumed1 section
1981d-Propoxyphene acts differently from morphine on opioid receptor-effector mechanismsNeil A, Terenius L · European Journal of Pharmacologypmid:6258941moderateconsumed6 sections
1981Propoxyphene dependence: an updateCollins GB, Kiefer KS · Postgraduate Medicinepmid:7312731moderateconsumed2 sections
1981Propoxyphene napsylate compared to methadone for opiate dependenceWang RI, Kochar C, Hasegawa AT, Roh BL · Psychopharmacologypmid:6122232strongconsumed1 section
1977Therapeutic usefulness of propoxyphene napsylate in narcotic addictionJasinski DR, Pevnick JS, Clark SC, Griffith JD · Archives of General Psychiatrypmid:14602moderateconsumed1 section
1976Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levelsWelling PG, Lyons LL, Tse FL, Craig WA · Clinical Pharmacology and Therapeuticspmid:1277712moderateconsumed2 sections
1975Propoxyphene bioavailability: an evaluation of ten productsSlywka GW, Melikian AP, Whyatt PL, Meyer MC · Journal of Clinical Pharmacologypmid:1150913moderateconsumed2 sections

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-05-09revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki, prose phase)

    psx:substance/dextropropoxyphene/version/1
  2. 0022026-06-04proposal27 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    27 items in this filing

    • contraindication · psychiatric
    • contraindication · renal
    • contraindication · cardiovascular
    • contraindication · age
    • contraindication · hepatic
    • contraindication · respiratory
    • contraindication · cardiovascular
    • contraindication · other
    • contraindication · metabolic
    • dose_tier · threshold
    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · peak
    • timeline · oral · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • duration · oral · onset
    • duration · oral · peak
    • duration · oral · total
    • duration · oral · aftereffects
    psx:substance/dextropropoxyphene/proposal/contraindication/fe13e721-4645-41df-95af-7b91347f79c4
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card705afe7a476d032f9e73158d…2026-10-19 20:31Revision 1current
emergencyf85b2d2362c98030e2585598…2026-09-04 04:29Revision 1current
info_card8aae7dadb18151e84d9217ea…2026-09-04 04:29Revision 1superseded2026-10-19
notice88ab1a511225c678f3289b6e…2026-09-04 04:29Revision 1current