{ "$schema_version": "5.4", "review_mode": "revision", "claim_restatement": { "index_wording": "Helicobacter pylori infection is a primary cause of peptic ulcer disease", "entry_form": "claim", "gradeable_restatement": "Helicobacter pylori infection is a major upstream cause of human peptic ulcer disease.", "restatement_required": false, "split_into": [], "parent_claim": null, "scope_clarification": "The original claim is already gradeable. A primary cause means a major, nonexclusive upstream contributor, not a fixed attributable fraction or the most frequent cause in every population. The prior outcome-undefined susceptibility qualifier is removed; no future ulcer or treatment response defines eligibility. This is an explicit correction, not a new post-hoc responder subgroup.", "scope_qualifiers": [ { "qualifier": "in susceptible hosts", "determinable_before_outcome": false, "determined_from": "nothing independent of the outcome: susceptibility was identifiable only after ulcers appeared", "action": "deleted", "history": "Present in edition A (pre-critique); deleted by edition B; deletion retained by red-team pass-01." } ], "red_team_note": "Pass-01 (2026-09-27) checked Step 0: \"a primary cause\" in the index wording is rendered as \"a major upstream cause\" — a nonexclusive causal claim in the strong form the field defends. Held." }, "hypothesis": { "name": "Helicobacter pylori as a primary cause of peptic ulcer disease", "central_claim": "Helicobacter pylori infection is a major upstream cause of human peptic ulcer disease.", "proposed_mechanism": "Persistent gastric infection initiates inflammatory mucosal injury and alters gastric physiology; the resulting host-pathogen interaction contributes to gastric and duodenal ulceration and recurrence.", "claimed_scope": "disease-class", "claimed_level": [ "initiation", "maintenance", "response" ], "is_conjunctive": false, "conjunctive_note": "Three supporting dimensions of the same causal proposition are assessed separately; universal causation is not added." }, "rubric_routing": { "primary_rubric": "04-microbiome-systemic.md", "secondary_rubrics": [], "index_notes_applied": [ "No Helicobacter pylori or peptic-ulcer entry exists in hypothesis-index.md (v3.0 index in the v5.4 packet); no aggregation rule is prescribed. A stub entry is proposed in redteam/pass-01-2026-09-27.md for the owner." ], "rubric_fit_note": "No supplied rubric fits well. H. pylori is a single named gastric pathogen causing local disease; rubric 04 (microbiome/systemic) is the closest and is used for its explicit eradication and hard-endpoint provision; its consortium, cage and transfer requirements are not applied literally to clinical eradication trials. Rubric 05 (immunology) was considered and rejected: it governs immune-pathway claims, not infection-to-disease causation. Universal ladder definitions carry the upper rungs. (Edition B note retained: Partial fit: this is a defined gastric pathogen causing local disease, not an unspecified microbial community causing systemic disease. Use the explicit v5 eradication/hard-endpoint provision and universal ladder. FMT, consortium and cage requirements are not applied literally to clinical eradication trials. Nonmicrobial rival models use the universal framework.)" }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "H. pylori infection is a major upstream causal contributor to human peptic ulcer disease rather than a bystander of established mucosal damage.", "subclaim_type": "primacy", "claimed_scope": "Human gastric and duodenal peptic ulcer disease; a major nonexclusive cause, with populations defined before outcomes are observed.", "key_evidence_anchor": "Ulcer recurrence and rebleeding after removal (randomized trials and their Cochrane syntheses), prevention of incident and complicated ulcers in NSAID-naive patients, infection preceding ulcer in stored sera, population-scale mass eradication, and experimentally induced ulceration.", "rationale": "Removal prevents recurrence and rebleeding across many randomized trials [1-3, 15, 16]; removal before NSAID exposure prevents incident and complicated ulcers [4, 18]; infection precedes ulcer by a decade or more with a gradient [17]; population mass eradication was followed by a large fall in peptic ulcer disease [19]; organism addition produces gastritis in people [13, 23] and ulcers in gerbils [7]. The one unresolved within-scope failed prediction is HEAT's later period [6, 14], a single imprecise window in established aspirin users; it is carried as the named exception. Edition B's other SC1 blockers (a stress association; the absence of a validated susceptibility rule) do not bind a nonexclusive major-cause claim.", "governing_rubric": "04-microbiome-systemic.md", "hsef_level": "Θ", "confidence": "High", "governing_cap_or_threshold": "Θ met (rubric 04: \"Requires high reproducibility, narrow causal attribution, and robust mechanistic pathway.\"; universal: \"High predictive accuracy with minimal unresolved exceptions\"). Ω blocked: infection is neither necessary for every ulcer nor sufficient in every infected person [9, 12, 17, 21].", "scope": "Human gastric and duodenal peptic ulcer disease; a major nonexclusive cause, with populations defined before outcomes are observed.", "operational_scope": { "eligibility_is_outcome_independent": true, "baseline_infection": "Objective infection assessment before intervention or outcome ascertainment; retain the trial-specific diagnostic method.", "baseline_covariates": [ "Existing ulcer and ulcer site", "NSAID/aspirin exposure", "Age and clinical setting" ], "candidate_effect_modifiers": "CagA status, acid-output phenotype and host genotype are candidates for prospective stratification, not validated eligibility cutoffs in this dossier.", "forbidden_selection": "Do not select susceptibility using future ulceration, later treatment benefit or successful post-randomization eradication.", "falsifier": "In prospectively defined infection-positive populations, repeated, adequately powered, well-controlled comparisons show that durable removal does not reduce adjudicated ulcer outcomes over a prespecified interval, with confidence intervals excluding a prespecified clinically meaningful reduction. Such a result contradicts that population-and-time prediction; repeated failures across the principal settings would challenge the broad major-cause account. Affected participants must not be excluded afterward as not susceptible. A single context-specific null does not erase positive evidence elsewhere.", "registration_status": "Operational clarification made during this revision; not falsely attributed to an earlier preregistration.", "ulcer_status_at_entry": "Separate established-ulcer recurrence cohorts from populations without an ulcer at entry.", "endpoint": "Endoscopically confirmed ulcer incidence/recurrence or adjudicated peptic ulcer bleeding; gastritis is supportive only.", "follow_up": "Prespecify each endpoint and horizon; do not infer indefinite benefit from short follow-up." }, "pass01_prior_level": "Η", "dissent_edition_B": "Edition B held SC1 at Η: HEAT durability unexplained in the investigators' own account, plus stress-associated residual risk and no prospectively validated susceptibility rule. Recorded, not adopted: see pass-01 finding F1." }, { "id": "SC2", "statement": "Eradication treatment materially reduces subsequent ulcer recurrence in patients with infection and an ulcer documented before treatment.", "subclaim_type": "necessity", "claimed_scope": "Patients with objectively documented H. pylori infection and gastric or duodenal ulcer before treatment, followed after healing for approximately one to two years in the recurrence-trial settings; ongoing NSAID exposure is a separately reported limitation.", "key_evidence_anchor": "Randomized eradication comparisons with endoscopic recurrence after treatment cessation. Cochrane syntheses [15, 16].", "rationale": "Large, replicated recurrence differences after treatment cessation support this specified reversibility prediction. Baseline ulcer status defines the study population; future recurrence and successful eradication are not used to select randomized comparison groups. This score does not extend to lifelong prevention or to HEAT primary prevention. Pass-01: replication now rests on the Cochrane synthesis of randomized trials for both duodenal and gastric recurrence [15] and on rebleeding, a hard endpoint [16]; Cochrane rates the recurrence evidence very low quality on trial conduct, which bears on the precision of the effect, not its direction.", "governing_rubric": "04-microbiome-systemic.md", "hsef_level": "Θ", "confidence": "High", "governing_cap_or_threshold": "Θ met for the recurrence scope. Ω blocked: sufficiency not shown — roughly half to three-quarters of persistently infected gastric-ulcer patients recurred within follow-up [2, 3], not all — and no second system reproduces recurrence.", "scope": "Patients with objectively documented H. pylori infection and gastric or duodenal ulcer before treatment, followed after healing for approximately one to two years in the recurrence-trial settings; ongoing NSAID exposure is a separately reported limitation.", "operational_scope": { "eligibility_is_outcome_independent": true, "baseline_infection": "Objective infection assessment before intervention or outcome ascertainment; retain the trial-specific diagnostic method.", "baseline_covariates": [ "Existing ulcer and ulcer site", "NSAID/aspirin exposure", "Age and clinical setting" ], "candidate_effect_modifiers": "CagA status, acid-output phenotype and host genotype are candidates for prospective stratification, not validated eligibility cutoffs in this dossier.", "forbidden_selection": "Do not select susceptibility using future ulceration, later treatment benefit or successful post-randomization eradication.", "falsifier": "In prospectively defined infection-positive populations, repeated, adequately powered, well-controlled comparisons show that durable removal does not reduce adjudicated ulcer outcomes over a prespecified interval, with confidence intervals excluding a prespecified clinically meaningful reduction. Such a result contradicts that population-and-time prediction; repeated failures across the principal settings would challenge the broad major-cause account. Affected participants must not be excluded afterward as not susceptible. A single context-specific null does not erase positive evidence elsewhere.", "registration_status": "Operational clarification made during this revision; not falsely attributed to an earlier preregistration.", "ulcer_status_at_entry": "Infection-positive gastric or duodenal ulcer documented before treatment, with healing before recurrence surveillance.", "endpoint": "Subsequent gastric or duodenal ulcer recurrence after healing, using randomized treatment contrasts where available.", "follow_up": "Approximately one to two years in the cited recurrence trials; continuing ulcerogenic medication analyzed separately." }, "subclaim_type_label": "reversibility (edition B local label; not in the v5.4 type vocabulary)" }, { "id": "SC3", "statement": "The causal contribution extends to both gastric and duodenal ulcers, while the magnitude and durability of benefit vary across clinical contexts.", "subclaim_type": "generalization", "claimed_scope": "Both anatomical forms across the studied human populations; medication exposure, initial ulcer status and follow-up time are explicit strata. No validated host/strain rule or universal duration of benefit is asserted.", "key_evidence_anchor": "Gastric and duodenal clinical outcomes, medication-stratified trials and strain/age animal controls.", "rationale": "Effects replicate across ulcer sites and clinical settings. Some boundaries are observed rather than explained: HEAT late protection is unresolved, and stress associations point to additional risk heterogeneity without proving an alternative dominant cause. Pass-01: the medication boundary is partly mapped by a baseline-determinable variable — benefit in NSAID-naive but not previously treated users [20], residual aspirin-associated recurrence after eradication [22], equivalence to omeprazole in the aspirin stratum of [5] — but duration, which this subclaim explicitly asserts, is not predicted: HEAT's later loss is unexplained [14]. Held at Η.", "governing_rubric": "04-microbiome-systemic.md", "hsef_level": "Η", "confidence": "High", "governing_cap_or_threshold": "Η met; Θ not met because the subclaim asserts generalization of magnitude and duration across contexts, and the duration prediction failed unexplained in HEAT's later period [6, 14].", "scope": "Both anatomical forms across the studied human populations; medication exposure, initial ulcer status and follow-up time are explicit strata. No validated host/strain rule or universal duration of benefit is asserted.", "operational_scope": { "eligibility_is_outcome_independent": true, "baseline_infection": "Objective infection assessment before intervention or outcome ascertainment; retain the trial-specific diagnostic method.", "baseline_covariates": [ "Existing ulcer and ulcer site", "NSAID/aspirin exposure", "Age and clinical setting" ], "candidate_effect_modifiers": "CagA status, acid-output phenotype and host genotype are candidates for prospective stratification, not validated eligibility cutoffs in this dossier.", "forbidden_selection": "Do not select susceptibility using future ulceration, later treatment benefit or successful post-randomization eradication.", "falsifier": "In prospectively defined infection-positive populations, repeated, adequately powered, well-controlled comparisons show that durable removal does not reduce adjudicated ulcer outcomes over a prespecified interval, with confidence intervals excluding a prespecified clinically meaningful reduction. Such a result contradicts that population-and-time prediction; repeated failures across the principal settings would challenge the broad major-cause account. Affected participants must not be excluded afterward as not susceptible. A single context-specific null does not erase positive evidence elsewhere.", "registration_status": "Operational clarification made during this revision; not falsely attributed to an earlier preregistration.", "ulcer_status_at_entry": "Report ulcer-history and prevention populations separately; no outcome-defined responder subgroup.", "endpoint": "Clinical ulcer or ulcer-bleeding outcomes, reported by prespecified site, medication and time strata.", "follow_up": "HEAT early and later periods are both in scope; duration limits cannot be discarded after inspecting results." } } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "SC1 is primary because the user asks whether infection is a primary cause; SC2 and SC3 test trajectory and generalization. This rule was written before the scores were fixed. The original aggregation rule is retained in this revision; the new scope clarifications were not preregistered. Pass-01: the rule was pre-registered in edition A before any subclaim was scored, retained by B, and retained here; the index prescribes no rule for this entry.", "primary_subclaim_id": "SC1", "aggregation_derivation": "SC1 = Θ; the pre-registered primary-subclaim rule returns Θ. SC2 = Θ (recurrence scope); SC3 = Η.", "aggregation_alternatives": { "weakest_link_would_return": "Η", "primary_subclaim_would_return": "Θ", "scope_matched_would_return": "Θ", "note": "The letter is rule-dependent by one rung: weakest-link returns Η because SC3 (generalization of magnitude and duration) holds at Η. Weakest-link is not the appropriate rule — the claim does not assert joint necessity of durable benefit in every context — and it was not the pre-registered rule. Under edition B's scores all three rules returned Η." }, "index_rule_deviation": "", "decomposition_note": "SC1 is coextensive with the graded claim, so primary-subclaim aggregation amounts to scoring the claim directly with SC2 and SC3 as audits of its recurrence and generalization legs. Recorded by pass-01; not a defect requiring change." }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M1", "is_nominal": true, "name": "H. pylori as a primary cause", "core_claim": "Helicobacter pylori infection is a major upstream cause of human peptic ulcer disease.", "explains_what_nominal_does_not": "Nominal model.", "strongest_supporting_evidence": [ "[1-3, 15, 16] recurrence and rebleeding after removal", "[4, 18] prevention in NSAID-naive patients", "[17] infection precedes ulcer, with gradient", "[19] population mass eradication", "[7] defined-strain ulcer induction" ], "strongest_contradictory_evidence": [ "[6, 14] HEAT later-period loss, unexplained", "[21] a quarter of strictly tested US non-NSAID duodenal ulcers uninfected — defeats near-universal association, not major causation", "[5, 20, 22] medication co-cause limits eradication-alone benefit in exposed users" ], "hsef_level_for_this_model": "Θ", "rationale": "Removal, prevention, temporal-order, population and organism-addition designs confirm the claim's predictions; the one unresolved exception is HEAT's later period. Θ. (Edition B assigned Η; see SC1 dissent.)" }, { "rank_in_tournament": 2, "model_id": "M5", "is_nominal": false, "name": "Heterogeneous multiple-cause model", "core_claim": "Infection, medication injury and additional causes produce ulcers through host-dependent mucosal injury and acid-peptic exposure.", "explains_what_nominal_does_not": "Accommodates independently established medication injury; recognizes idiopathic and other residual disease without claiming their mechanisms are solved.", "strongest_supporting_evidence": [ "[1–7] infection interventions", "[12] randomized NSAID exposure", "[9] idiopathic ulcers" ], "strongest_contradictory_evidence": [ "Unresolved explanatory gaps include idiopathic disease and the time-dependent HEAT effect [9,14]; these are not reversals of the established causal routes." ], "hsef_level_for_this_model": "Η", "rationale": "Infection-removal and medication-addition experiments converge on multiple causal routes. Merely allowing other causes does not explain idiopathic disease or HEAT durability. Wider coverage therefore does not itself earn Θ. Pass-01: M5 keeps the widest coverage; on strength of causal evidence it ranks below M1 because its medication and idiopathic routes are scored at Η or below and idiopathic mechanisms are unexplained [9, 21]." }, { "rank_in_tournament": 3, "model_id": "M2", "is_nominal": false, "name": "NSAID/aspirin-associated injury", "core_claim": "Ulcerogenic medication is a causal driver in exposed patients, including patients whose H. pylori infection has been treated.", "explains_what_nominal_does_not": "Ulcers during continuing medication exposure and benefit from maintenance mucosal/acid protection.", "strongest_supporting_evidence": [ "[12] randomized ulcer induction with ibuprofen", "[5] persistent drug-context risk and protection by omeprazole" ], "strongest_contradictory_evidence": [ "[1–3] non-NSAID/infection-associated ulcers are not explained by a medication-only model." ], "hsef_level_for_this_model": "Η", "rationale": "Exposure addition with endoscopic disease and a distinct protective intervention support causal injury in the exposed context. This compressed dossier assigns Η and does not claim a full audit of medication-specific risk prediction. It coexists with infection causality; its lower coverage rank is not a population-frequency estimate." }, { "rank_in_tournament": 4, "model_id": "M3", "is_nominal": false, "name": "Autonomous acid-peptic model with infection as passenger", "core_claim": "Acid-peptic injury explains the disease while infection has no upstream causal role.", "explains_what_nominal_does_not": "Healing under acid suppression.", "strongest_supporting_evidence": [ "Acid-suppression arms in [1–3,5] and physiological effects in [8]." ], "strongest_contradictory_evidence": [ "Eradication adds durable prevention with common acid suppression [1,2]; removal also changes gastrin-mediated acid output [8]." ], "hsef_level_for_this_model": "Γ", "rationale": "Acid contributes to injury, but that is not the passenger proposition. Physiological plausibility supports Γ at most for the exclusive explanation, and clinical infection perturbations contradict its central exclusion. The letter is an evidence ceiling, not an endorsement of the contradicted passenger clause." }, { "rank_in_tournament": 5, "model_id": "M4", "is_nominal": false, "name": "Psychological stress as the dominant ulcer cause", "core_claim": "Psychological stress is the main cause of peptic ulcer disease, with infection largely secondary.", "explains_what_nominal_does_not": "Variation with life stress and health behaviors.", "strongest_supporting_evidence": [ "[10] prospective stress-ulcer association." ], "strongest_contradictory_evidence": [ "[1–4,6] infection interventions change disease outcomes without targeting stress." ], "hsef_level_for_this_model": "Β", "rationale": "The primary evidence examined is observational; universal association cap Β applies. It does not exclude a real stress contribution or behavioral mediation, but does not establish dominance. Psychological stress is not conflated with critical-illness stress-related mucosal disease." } ], "tournament_summary": "M1, the nominal, has the strongest causal evidence (Θ); M5, the multiple-cause model that contains it, has the widest coverage (Η). M2 is well supported within medication-exposed populations. M3's passenger clause is contradicted by removal trials; M4 rests on association. M5 has broadest explanatory coverage; M1 is the best-supported infection-specific account and is contained within M5. The models are not mutually exclusive. Ranks among high-scoring models describe coverage, not causal probabilities, population attribution, or a reason to demote M1.", "study_separating_rank1_from_rank2": "No study can separate compatible propositions. The studies that show where M1 alone under-covers are the medication-context trials: Chan 2001 [5], Lai 2002 [22] and the Vergara meta-analysis [20].", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true, "ranking_basis": "Pass-01 ranks by strength of causal evidence, as the review template requires; edition B ranked by explanatory coverage (M5 first). The models are compatible propositions; the level is unchanged by the tournament in either ordering." }, "evidence_inventory": [ { "evidence_id": "E1", "citation": "Hentschel E, Brandstätter G, Dragosics B, et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med. 1993;328(5):308-312.", "source_pointer": "PMID:8419816; DOI:10.1056/nejm199302043280503; reference [1]", "source_n": 1, "claim_ids": [ "C2" ], "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Antibiotics plus common acid suppression produced a large reduction in recurrent duodenal ulcer.", "what_it_does_not_show": "Does not isolate one molecular virulence pathway, guarantee cure, or estimate the population fraction of ulcers caused by infection.", "confounders_present": [ "Antibiotic pleiotropy", "Selected recurrent-ulcer patients", "Losses to follow-up; eradication-status subgroup is post-randomization" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E2", "citation": "Graham DY, Lew GM, Klein PD, et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. 1992;116(9):705-708.", "source_pointer": "PMID:1558340; DOI:10.7326/0003-4819-116-9-705; reference [2]", "source_n": 2, "claim_ids": [ "C4" ], "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Eradication changed recurrence in both gastric and duodenal ulcers after healing treatment ended.", "what_it_does_not_show": "Not universal cure; the gastric subgroup is small and bismuth has mucosal effects.", "confounders_present": [ "Bismuth cointervention", "Single Veterans Affairs setting", "Ulcer-site subgroup precision" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E3", "citation": "Sung JJ, Chung SC, Ling TK, et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995;332(3):139-142.", "source_pointer": "PMID:7800005; DOI:10.1056/nejm199501193320302; reference [3]", "source_n": 3, "claim_ids": [ "C5" ], "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Gastric ulcers healed under antibacterial therapy without acid-suppressing medication, with fewer recurrences.", "what_it_does_not_show": "The small one-year subset is not the whole randomized cohort; bismuth prevents a clean antibiotics-only interpretation.", "confounders_present": [ "Incomplete long-term follow-up", "Patients and clinicians unblinded; endoscopists blinded", "Bismuth mucosal activity" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E4", "citation": "Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet. 1997;350(9083):975-979.", "source_pointer": "PMID:9329511; DOI:10.1016/s0140-6736(97)04523-6; reference [4]", "source_n": 4, "claim_ids": [ "C6" ], "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M2", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Pretreatment reduced new ulcers after NSAID initiation in patients without ulcers at baseline.", "what_it_does_not_show": "Not proof that every ulcer requires infection or that prevention is identical in established NSAID users.", "confounders_present": [ "Antibiotic pleiotropy and bismuth", "Completer analysis", "Specific naproxen exposure" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E5", "citation": "Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344(13):967-973.", "source_pointer": "PMID:11274623; DOI:10.1056/nejm200103293441304; reference [5]", "source_n": 5, "claim_ids": [ "C7" ], "relates_to_subclaims": [ "SC2", "SC3" ], "favors_models": [ "M2", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Ongoing naproxen defines a context in which maintenance acid suppression outperformed eradication alone. In the aspirin stratum, eradication alone was equivalent to omeprazole over six months (C31).", "what_it_does_not_show": "Does not refute infection as a cause and does not itself compare eradication with untreated infection.", "confounders_present": [ "Active-comparator design", "Separate aspirin and naproxen populations", "Continuing drug injury" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A", "decisive_note": "Pass-01: not a decisive test of the nominal mechanism (no untreated arm); B had flagged it decisive.", "direction_note": "Pass-01: relative to the nominal claim this is a boundary result (active comparator, no untreated arm): the naproxen stratum limits eradication-alone benefit; the aspirin stratum (C31) found eradication equivalent to omeprazole. Favors M2/M5 for the naproxen stratum." }, { "evidence_id": "E6", "citation": "Hawkey C, Avery A, Coupland CAC, et al. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet. 2022;400(10363):1597-1606.", "source_pointer": "PMID:36335970; DOI:10.1016/s0140-6736(22)01843-8; reference [6]", "source_n": 6, "claim_ids": [ "C8" ], "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Eradication reduced early hospitalisation/death from ulcer bleeding in infected older aspirin users.", "what_it_does_not_show": "No sustained benefit established after the early period. The imprecise later estimate proves neither harm nor exact absence of benefit; the duration pattern remains unexplained [14].", "confounders_present": [ "Low event rate", "Time-varying effect", "Older aspirin-user selection", "Short PPI cointervention" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A", "study_id": "HEAT-NCT01506986" }, { "evidence_id": "E7", "citation": "Ohkusa T, Okayasu I, Miwa H, et al. Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils. Gut. 2003;52(6):797-803.", "source_pointer": "PMID:12740333; DOI:10.1136/gut.52.6.797; reference [7]", "source_n": 7, "claim_ids": [ "C9" ], "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "animal model", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Defined bacterial inoculation produced ulcer pathology with age and strain controls.", "what_it_does_not_show": "Not endogenous acquisition in humans; superficial duodenal lesions in few animals do not prove human universal sufficiency.", "confounders_present": [ "Artificial inoculum", "Species and strain selection", "Small duodenal-ulcer count", "Housing-related variables not fully assessed from abstract" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E8", "citation": "el-Omar E, Penman I, Dorrian CA, et al. Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer. Gut. 1993;34(8):1060-1065.", "source_pointer": "PMID:8174954; DOI:10.1136/gut.34.8.1060; reference [8]", "source_n": 8, "claim_ids": [ "C10" ], "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Eradication altered gastrin-mediated acid secretion in a small physiological study.", "what_it_does_not_show": "No ulcer endpoint or complete mediation test; not independently counted as decisive for ulcer causation.", "confounders_present": [ "Small nonrandomized before-after comparison", "Surrogate physiological outcome" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E9", "citation": "Wong GL, Wong VW, Chan Y, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137(2):525-531.", "source_pointer": "PMID:19445937; DOI:10.1053/j.gastro.2009.05.006; reference [9]", "source_n": 9, "claim_ids": [ "C11" ], "relates_to_subclaims": [ "SC3" ], "favors_models": [ "M5" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Ulcers and recurrent bleeding occur in patients classified as negative for infection and NSAID exposure.", "what_it_does_not_show": "The cohort comparison does not identify the cause of idiopathic ulcers or a causal mortality effect of eradication.", "confounders_present": [ "False-negative infection tests", "Unrecorded medication exposure", "Comorbidity and selection" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A", "direction_note": "Pass-01: bears on exclusivity (favors M5), not on the direction of the nominal claim." }, { "evidence_id": "E10", "citation": "Levenstein S, Rosenstock S, Jacobsen RK, et al. Psychological stress increases risk for peptic ulcer, regardless of Helicobacter pylori infection or use of nonsteroidal anti-inflammatory drugs. Clin Gastroenterol Hepatol. 2015;13(3):498-506.e1.", "source_pointer": "PMID:25111233; DOI:10.1016/j.cgh.2014.07.052; reference [10]", "source_n": 10, "claim_ids": [ "C12" ], "relates_to_subclaims": [ "SC3" ], "favors_models": [ "M4", "M5" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Stress predicted subsequent confirmed ulcer diagnoses.", "what_it_does_not_show": "Not a controlled stress perturbation and not proof of causal primacy.", "confounders_present": [ "Residual socioeconomic and behavioral confounding", "Stress and infection measurement error" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A", "direction_note": "Pass-01: supports M4/M5 as an independent risk factor; null for the nominal claim." }, { "evidence_id": "E11", "citation": "Medel-Jara PA, Latorre G, Fuentes-Lopez E, et al. Comparison between optimized bismuth quadruple therapy and standard clarithromycin-based triple therapy for first-line Helicobacter pylori eradication: a double-blind randomized controlled trial. Lancet Reg Health Am. 2026;53:101312.", "source_pointer": "PMID:41362749; DOI:10.1016/j.lana.2025.101312; reference [11]", "source_n": 11, "claim_ids": [ "C13" ], "relates_to_subclaims": [], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Current comparative treatment research tests eradication success.", "what_it_does_not_show": "A microbiological endpoint alone does not raise the ulcer-causation score.", "confounders_present": [ "Endpoint mismatch to ulcer phenotype", "Regional resistance and regimen specificity" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E12", "citation": "Laine L, Harper S, Simon T, et al. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group. Gastroenterology. 1999;117(4):776-783.", "source_pointer": "PMID:10500058; DOI:10.1016/s0016-5085(99)70334-3; reference [12]", "source_n": 12, "claim_ids": [ "C14" ], "relates_to_subclaims": [ "SC3" ], "favors_models": [ "M2", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Randomized ibuprofen exposure increased incident endoscopic ulcers relative to placebo.", "what_it_does_not_show": "Does not establish a universal medication cause or prove medication injury is absent in infected people.", "confounders_present": [ "Endoscopic lesions versus symptomatic complications", "Specific dose and arthritis population" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A", "direction_note": "Pass-01: a decisive perturbation of the rival medication route (M2); null for the nominal claim.", "decisive_note": "Pass-01: decisive for the rival medication route (M2), not for the nominal mechanism; B had flagged it decisive." }, { "evidence_id": "E13", "citation": "Marshall BJ, Armstrong JA, McGechie DB, et al. Attempt to fulfil Koch's postulates for pyloric Campylobacter. Med J Aust. 1985;142(8):436-439.", "source_pointer": "PMID:3982345; DOI:10.5694/j.1326-5377.1985.tb113443.x; reference [13]", "source_n": 13, "claim_ids": [ "C15" ], "relates_to_subclaims": [ "SC1" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A healthy volunteer with initially normal gastric histology developed biopsy-proven gastritis by day 10 after deliberate ingestion.", "what_it_does_not_show": "No ulcer was demonstrated. A short, uncontrolled single-volunteer experiment cannot establish ulcer penetrance, lifetime sufficiency or the clinical effect size.", "confounders_present": [ "Single uncontrolled volunteer", "Forced inoculation", "Gastritis rather than ulcer endpoint" ], "verification": "verified", "verification_note": "Checked primary abstract and indexed metadata, not a complete full-text risk-of-bias audit.", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A" }, { "evidence_id": "E14", "citation": "Hawkey CJ, Avery AJ, Coupland CA, et al. Eradication of Helicobacter pylori for prevention of aspirin-associated peptic ulcer bleeding in adults over 65 years: the HEAT RCT. Health Technol Assess. 2025;29(42):1-62.", "source_pointer": "PMID:40844182; DOI:10.3310/llkf7871; reference [14]", "source_n": 14, "claim_ids": [ "C8", "C20", "C21" ], "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "The extended HEAT report confirms the time-varying effect and explicitly leaves its cause unresolved; it reports the overall estimate and pre-unblinding choice of the time split. Full report: events 6 v 17 (first 2.5 years) and 12 v 9 (later); repeat breath test negative in 146 of 161 of the eradication group a median 3.95 years after randomisation (C32).", "what_it_does_not_show": "This is a second report of HEAT, not a second trial or additional independent causal line. It does not prove no benefit or harm in the later period.", "confounders_present": [ "Low event rate", "Time-varying effect", "Older aspirin-user selection", "Short PPI cointervention" ], "verification": "verified", "verification_note": "Pass-01: abstract (PubMed) plus targeted full-report passages from the NIHR Journals Library PDF (split-time analysis, clearance, discussion).", "citation_context": { "retrieved": false, "supporting_count": null, "mentioning_count": null, "contrasting_count": null, "notable_contrasting_statements": [] }, "source_tier": "A", "study_id": "HEAT-NCT01506986", "additional_independent_experiment": false, "same_study_as_evidence": "E6", "direction_note": "Pass-01: template has no \"qualifies\" value; the report confirms the early effect and the unexplained later loss; same study as [6]." }, { "citation": "Ford AC et al. 2016, Cochrane Database Syst Rev", "source_pointer": "PMID:27092708; DOI:10.1002/14651858.CD003840.pub5; reference [15]", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Pooled randomized trials: eradication superior to no treatment for preventing both duodenal and gastric ulcer recurrence (C22).", "what_it_does_not_show": "Does not add an independent line (it pools line 1); rates the evidence very low quality; no superiority over maintenance ulcer-healing drugs for duodenal recurrence.", "confounders_present": [ "old, often unblinded trials", "heterogeneous regimens" ], "verification": "verified", "verification_note": "Abstract; Tier B pooled synthesis, no number carried. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "B", "added_by": "red-team pass-01" }, { "citation": "Gisbert JP et al. 2004, Cochrane Database Syst Rev", "source_pointer": "PMID:15106235; DOI:10.1002/14651858.CD004062.pub2; reference [16]", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Eradication prevents recurrent ulcer bleeding better than non-eradicating antisecretory therapy, with or without maintenance; some rebleeding followed reinfection (C23).", "what_it_does_not_show": "Pooled controlled trials, not a new study; rebleeding in NSAID users is a separate route.", "confounders_present": [ "heterogeneous comparators", "NSAID co-exposure" ], "verification": "verified", "verification_note": "Abstract; Tier B pooled synthesis, no number carried. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "B", "added_by": "red-team pass-01" }, { "citation": "Nomura A et al. 1994, Ann Intern Med", "source_pointer": "PMID:7741826; DOI:10.7326/0003-4819-120-12-199406150-00001; reference [17]", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Infection documented in sera stored decades earlier predicted later gastric and duodenal ulcer, with a rising risk across antibody levels and persistence at 10 or more years (C24).", "what_it_does_not_show": "Association with temporal order; cannot exclude confounding by early-life circumstances; most controls were also infected.", "confounders_present": [ "socioeconomic confounding", "single ethnic cohort of men" ], "verification": "verified", "verification_note": "Abstract. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "A", "added_by": "red-team pass-01" }, { "citation": "Chan FK et al. 2002, Lancet", "source_pointer": "PMID:11809180; DOI:10.1016/s0140-6736(02)07272-0; reference [18]", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "Double-blind, omeprazole-matched randomized trial in NSAID-naive infected patients starting diclofenac: eradication lowered 6-month ulcer and complicated-ulcer probability by intention to treat (C25).", "what_it_does_not_show": "An NSAID-exposed context; does not test primary prevention without NSAIDs.", "confounders_present": [ "NSAID co-exposure" ], "verification": "verified", "verification_note": "Abstract. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "A", "added_by": "red-team pass-01" }, { "citation": "Lee YC et al. 2013, Gut", "source_pointer": "PMID:22698649; DOI:10.1136/gutjnl-2012-302240; reference [19]", "relates_to_subclaims": [ "SC1" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Moderate", "system": "natural experiment", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Community mass eradication was followed by a large fall in peptic ulcer disease, with low re-infection (C26).", "what_it_does_not_show": "Before-after comparison without a concurrent control; secular trends and endoscopic surveillance may contribute.", "confounders_present": [ "secular trend", "no concurrent control", "screening effects" ], "verification": "verified", "verification_note": "Abstract. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "A", "added_by": "red-team pass-01" }, { "citation": "Vergara M et al. 2005, Aliment Pharmacol Ther", "source_pointer": "PMID:15948807; DOI:10.1111/j.1365-2036.2005.02444.x; reference [20]", "relates_to_subclaims": [ "SC3" ], "favors_models": [ "M1", "M2", "M5" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Eradication reduces ulcers in NSAID-naive but not in previously treated NSAID users, and is less effective than maintenance PPI (C27).", "what_it_does_not_show": "Pooled trials; does not explain HEAT's time pattern.", "confounders_present": [ "heterogeneous trials" ], "verification": "verified", "verification_note": "Abstract; Tier B, no number carried. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "B", "added_by": "red-team pass-01" }, { "citation": "Ciociola AA et al. 1999, Am J Gastroenterol", "source_pointer": "PMID:10406244; DOI:10.1111/j.1572-0241.1999.01214.x; reference [21]", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [ "M5" ], "evidence_class": "Moderate", "system": "human observational", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "Under a strict two-test definition, about a quarter of US non-NSAID duodenal-ulcer trial patients were uninfected (C28).", "what_it_does_not_show": "Does not test causation; covert NSAID use and false-negative tests are possible.", "confounders_present": [ "test sensitivity", "unrecorded NSAID use" ], "verification": "verified", "verification_note": "Abstract. Evidence against near-universal association, not against major causation. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "A", "added_by": "red-team pass-01" }, { "citation": "Lai KC et al. 2002, N Engl J Med", "source_pointer": "PMID:12087138; DOI:10.1056/NEJMoa012877; reference [22]", "relates_to_subclaims": [ "SC3" ], "favors_models": [ "M2", "M5" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "After eradication, aspirin users with prior complications still had recurrent complications on placebo that lansoprazole prevented; some recurrences followed reinfection (C29).", "what_it_does_not_show": "Not an eradication-versus-no-eradication comparison; tests the aspirin co-cause after eradication.", "confounders_present": [ "reinfection", "NSAID co-exposure" ], "verification": "verified", "verification_note": "Abstract. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "A", "added_by": "red-team pass-01" }, { "citation": "Morris A, Nicholson G 1987, Am J Gastroenterol", "source_pointer": "PMID:3826027; reference [23]", "relates_to_subclaims": [ "SC1" ], "favors_models": [ "M1", "M5" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "A second deliberate ingestion produced culture-positive gastritis with raised fasting pH that persisted until bismuth (C30).", "what_it_does_not_show": "n=1; gastritis, not ulcer.", "confounders_present": [ "single subject", "no control" ], "verification": "verified", "verification_note": "Abstract. Checked by red-team pass-01, 2026-09-27.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [], "note": "Scite quota exhausted; counts not retrieved, not zero." }, "source_tier": "A", "added_by": "red-team pass-01" } ], "verification_summary": { "load_bearing_claims_checked": 34, "verified": 34, "unverified": 0, "contradicted": 0, "synthesis_claims": 5, "note": "Pass-01 re-checked every claim (redteam/claim-audit.md): 0 contradicted, 0 unverified. Synthesis claims are verified at the level of their factual premises." }, "factual_issues_found": [ { "quoted_text": "Stress-associated residual risk [10] and the absence of a prospectively validated susceptibility rule leave incomplete predictive boundaries", "problem": "Used as an SC1/SC3 Θ blocker, while B's own steelman states that \"No calibrated individual risk model ... is newly required\". 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Medel-Jara regimen optimization [11]", "problem": "A regimen trial with an eradication endpoint is neither mechanistic nor causal work on ulcers.", "source_says": "Primary outcome: successful eradication.", "source_pointer": "PMID 41362749", "affects_score": false, "action": "logged" }, { "quoted_text": "41 of 161 (24.0%) in the control group", "problem": "Source-level arithmetic inconsistency in the HEAT full report: 41/161 = 25.5%.", "source_says": "Counts carried (C32); printed percentage not carried.", "source_pointer": "DOI 10.3310/LLKF7871", "affects_score": false, "action": "logged" } ], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": false, "trigger_text_quoted": "In vitro evidence alone cannot exceed Γ.", "specific_trigger": "The scored sets contain human ulcer trials, not only cell assays.", "resulting_ceiling": null }, { "subclaim_id": "SC1", "cap": "Β", "cap_source": "universal", "triggered": false, "trigger_text_quoted": "Pure association evidence — however large, however replicated — cannot exceed Β.", "specific_trigger": "The observational pieces are corroborating; they are not the entire evidence set.", "resulting_ceiling": null }, { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": false, "trigger_text_quoted": "Overexpression in model systems caps at Γ", "specific_trigger": "No overexpression result carries a human causal level.", "resulting_ceiling": null }, { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": false, "trigger_text_quoted": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "The decisive studies measure ulcers or ulcer bleeding. 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Physiology and eradication-only items are not promoted into clinical causal endpoints.", "resulting_ceiling": null }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "universal", "triggered": false, "trigger_text_quoted": "Seeding or forced-transfer paradigms cap at Γ", "specific_trigger": "Experimental inoculation is scored within its model; human inference additionally rests on naturally acquired infection treated in clinical trials.", "resulting_ceiling": null }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "universal", "triggered": false, "trigger_text_quoted": "Genetic evidence in familial / syndromic cases generalized to sporadic disease is scope-restricted.", "specific_trigger": "No familial genetic extrapolation is used; the Γ field is a bookkeeping marker and no ceiling is triggered.", "resulting_ceiling": null }, { "subclaim_id": "SC3", "cap": "Α", "cap_source": "rubric", "triggered": false, "trigger_text_quoted": "Use for ideas sustained mainly by contaminated signal, weak association, or conceptual enthusiasm.", "specific_trigger": "Culture/clinical infection and interventional disease endpoints do not rest on a contamination signal.", "resulting_ceiling": null }, { "subclaim_id": "SC3", "cap": "Β", "cap_source": "rubric", "triggered": false, "trigger_text_quoted": "Association-only microbiome work caps at Β.", "specific_trigger": "Human intervention and animal phenotype results exceed an association-only set.", "resulting_ceiling": null }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "rubric", "triggered": false, "trigger_text_quoted": "Association plus mechanistic in vitro support, or host-pathway plausibility, caps at Γ.", "specific_trigger": "The dossier includes in vivo ulcer endpoints and positive human eradication perturbations.", "resulting_ceiling": null } ], "cap_precedence_resolutions": [ { "collision": "Legacy transfer/rescue-only wording in rubric 04 versus its explicit v5 recognition of clinical eradication trials.", "subclaim_scope_cap_binds_on": "Forced-inoculation evidence alone cannot establish endogenous human acquisition or universal human sufficiency.", "subclaim_scope_threshold_binds_on": "Naturally infected humans in ulcer/bleeding outcome trials for SC1–SC3; inoculated animals only within the animal model.", "resolution": "Apply the explicit eradication provision to the human trials. Defined-strain inoculation supplies a complementary line, not a substitute for clinical evidence. Removal/phenotype rescue is the relevant clinical rescue; deliberate human ulcer rechallenge is not required.", "note": "This is an explicit domain adaptation; the closest rubric is imperfect for a named local pathogen." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "Field-valid equivalents in this domain: strain-resolved colonization with rescue logic, antibiotic or eradication natural experiments, dose-response across independent cohorts, and eradication trials with a hard clinical endpoint.", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "[1], [4], [6], [18]; [7] supports initiation in its animal scope.", "gamma_hard_rules_triggered": [ "Association plus cell-culture metabolite assays — not triggered for the convergent clinical set.", "Association plus in vitro immune readouts — not triggered for the convergent clinical set.", "Any framework that has not crossed the transfer/rescue threshold in vivo — not triggered for the convergent clinical set." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Endoscopic ulcer/recurrence or ulcer bleeding changes positively in the qualifying trials. A later null period, a physiological surrogate, and the gastritis challenge are not counted as positive clinical-ulcer tests.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "Field-valid equivalents in this domain: strain-resolved colonization with rescue logic, antibiotic or eradication natural experiments, dose-response across independent cohorts, and eradication trials with a hard clinical endpoint.", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "[1], [2], [3].", "gamma_hard_rules_triggered": [ "Association plus cell-culture metabolite assays — not triggered for the convergent clinical set.", "Association plus in vitro immune readouts — not triggered for the convergent clinical set.", "Any framework that has not crossed the transfer/rescue threshold in vivo — not triggered for the convergent clinical set." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Endoscopic ulcer/recurrence or ulcer bleeding changes positively in the qualifying trials. A later null period, a physiological surrogate, and the gastritis challenge are not counted as positive clinical-ulcer tests.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "Field-valid equivalents in this domain: strain-resolved colonization with rescue logic, antibiotic or eradication natural experiments, dose-response across independent cohorts, and eradication trials with a hard clinical endpoint.", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "[2], [3], [4], [6]; [5] maps a boundary.", "gamma_hard_rules_triggered": [ "Association plus cell-culture metabolite assays — not triggered for the convergent clinical set.", "Association plus in vitro immune readouts — not triggered for the convergent clinical set.", "Any framework that has not crossed the transfer/rescue threshold in vivo — not triggered for the convergent clinical set." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Endoscopic ulcer/recurrence or ulcer bleeding changes positively in the qualifying trials. A later null period, a physiological surrogate, and the gastritis challenge are not counted as positive clinical-ulcer tests.", "ceiling_from_boundary_check": "Δ or higher" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "yes", "supporting_evidence": [ "Positive human eradication trials [1,4,6]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ε", "requirement_quoted": "Requires context-specific causal effect with defined limits. A transferable phenotype exists, but microbial identity or generalizability remains incomplete.", "satisfied": "yes", "supporting_evidence": [ "Ulcer-free naproxen starters and older aspirin users define prevention contexts [4,6]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Defined consortium or strain-level causal evidence\n- Rescue logic\n- Replication across at least two relevant models or cohorts", "satisfied": "yes", "supporting_evidence": [ "Clinical removal [1–6] converges with defined-strain addition [7]; their key failure modes differ." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Η", "requirement_quoted": "Requires:\n- Defined consortium or factor rescue in multiple contexts\n- Narrowed mechanism\n- Strong exclusion of diet, housing, batch, and handling confounds", "satisfied": "yes", "supporting_evidence": [ "Trajectory-changing human interventions plus induced pathology and physiology [1–8]; no major reversed-direction contradiction within the bounded claim." ], "what_would_cross_it": "" }, { "subclaim_id": "SC1", "threshold": "Θ", "requirement_quoted": "Requires high reproducibility, narrow causal attribution, and robust mechanistic pathway.", "satisfied": "yes", "supporting_evidence": [ "High reproducibility: recurrence prevention across randomized trials for both ulcer sites [1-3, 15]; rebleeding, a hard endpoint [16]; incident and complicated-ulcer prevention in two NSAID-naive RCTs [4, 18].", "Narrow causal attribution: a regimen without mucosal action with matched acid suppression [1]; omeprazole-matched placebo antibiotics [18]; recurrences confined to persistent infection [1, 3].", "Robust pathway (duodenal ulcer): removal reverses hypergastrinaemia and gastrin-driven acid output [8]; gastric-ulcer pathway less resolved — recorded as a limitation, not a blocker.", "Predictions that could have failed and did not: infection precedes ulcer with a gradient [17]; population mass eradication followed by a large fall in ulcer disease [19].", "Minimal unresolved exceptions: HEAT's later period [6, 14] is the single unexplained failed prediction within scope — one window, 21 events, in established aspirin users, with persistent clearance (C32) making reinfection unlikely. Ulcers from other causes [9, 12, 21] and infected people without ulcers [8, 17] are not exceptions to a nonexclusive cause.", "The pathway requirement is satisfied for duodenal ulcer and only partly for gastric ulcer; SC1's Θ does not rest on the pathway limb alone but on reproducibility, narrow attribution and predictions that could have failed and did not." ], "what_would_cross_it": "", "universal_requirement_quoted": "High predictive accuracy with minimal unresolved exceptions. The mechanism accounts for most major observations in its claimed scope.", "pass01_prior_value": "no (edition B)", "pathway_limb_note": "The pathway requirement is satisfied for duodenal ulcer and only partly for gastric ulcer; SC1's Θ does not rest on the pathway limb alone but on reproducibility, narrow attribution and predictions that could have failed and did not." }, { "subclaim_id": "SC1", "threshold": "Ω", "requirement_quoted": "Requires necessity and sufficiency of the claimed microbial mechanism with reproducibility across relevant systems and no disqualifying contradictory evidence.", "satisfied": "no", "supporting_evidence": [ "Not necessary: ulcers occur in uninfected, NSAID-unexposed people [9, 21] and from NSAIDs [12]. Not sufficient: many infected people do not ulcerate [8, 17]." ], "what_would_cross_it": "Nothing within the claim as graded: a nonexclusive major-cause claim cannot demonstrate universal necessity and sufficiency. Ω would require a different, narrower claim." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "yes", "supporting_evidence": [ "Randomized groups differ in recurrent ulcer outcomes [1]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ε", "requirement_quoted": "Requires context-specific causal effect with defined limits. A transferable phenotype exists, but microbial identity or generalizability remains incomplete.", "satisfied": "yes", "supporting_evidence": [ "Recurrence reduction mapped in healed infected ulcers; continuing naproxen defines a limitation [1,5]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Defined consortium or strain-level causal evidence\n- Rescue logic\n- Replication across at least two relevant models or cohorts", "satisfied": "yes", "supporting_evidence": [ "Clinical eradication plus the complementary organism-addition pathology support organism attribution; different antibiotic regimens are replication, not separate causal lines [1–3,7]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Η", "requirement_quoted": "Requires:\n- Defined consortium or factor rescue in multiple contexts\n- Narrowed mechanism\n- Strong exclusion of diet, housing, batch, and handling confounds", "satisfied": "yes", "supporting_evidence": [ "Benefit after treatment withdrawal changes trajectory rather than merely a transient physiological marker [1–3]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Θ", "requirement_quoted": "Requires high reproducibility, narrow causal attribution, and robust mechanistic pathway.", "satisfied": "yes", "supporting_evidence": [ "Large, replicated reductions in recurrence over approximately one to two years in baseline-defined ulcer cohorts [1–3]; ongoing NSAID exposure is an explicit separate limitation [5]. No extrapolation to lifelong or aspirin primary prevention.", "Replication: Cochrane synthesis of randomized trials for duodenal and gastric recurrence [15]; rebleeding [16]." ], "what_would_cross_it": "", "universal_requirement_quoted": "High predictive accuracy with minimal unresolved exceptions. The mechanism accounts for most major observations in its claimed scope." }, { "subclaim_id": "SC2", "threshold": "Ω", "requirement_quoted": "Requires necessity and sufficiency of the claimed microbial mechanism with reproducibility across relevant systems and no disqualifying contradictory evidence.", "satisfied": "no", "supporting_evidence": [ "Material risk reduction is not complete, universally necessary and sufficient control of recurrence; medication and other injury pathways remain [2,5,9]." ], "what_would_cross_it": "A prospectively specified host/strain/exposure-defined claim with both necessity and sufficiency demonstrated; this would be a narrower claim, not simply more replications of the present one." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "yes", "supporting_evidence": [ "Positive gastric and duodenal clinical ulcer results [2,3]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ε", "requirement_quoted": "Requires context-specific causal effect with defined limits. A transferable phenotype exists, but microbial identity or generalizability remains incomplete.", "satisfied": "yes", "supporting_evidence": [ "Medication type, exposure history, age, strain and time boundaries are observed [4–7]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Defined consortium or strain-level causal evidence\n- Rescue logic\n- Replication across at least two relevant models or cohorts", "satisfied": "yes", "supporting_evidence": [ "Clinical sites/cohorts and defined-strain pathology converge; the animal line is not recast as a human trial [2–7]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Η", "requirement_quoted": "Requires:\n- Defined consortium or factor rescue in multiple contexts\n- Narrowed mechanism\n- Strong exclusion of diet, housing, batch, and handling confounds", "satisfied": "yes", "supporting_evidence": [ "Clinical outcome effects replicate across ulcer sites and contexts [2–7]. Incomplete prediction of duration is not a reversal of upstream causal direction [14]." ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Θ", "requirement_quoted": "Requires high reproducibility, narrow causal attribution, and robust mechanistic pathway.", "satisfied": "no", "supporting_evidence": [ "Reproducible effects across ulcer sites and settings [2, 3, 15, 18].", "Not met: the subclaim asserts generalization of duration; HEAT's later loss is unexplained [6, 14]. The medication boundary is observed and partly mapped by baseline exposure [5, 20, 22] but duration is not predicted." ], "what_would_cross_it": "A replicated long-term trial in which eradication's effect in a baseline-defined medication context (for example aspirin or NSAID starters) is sustained, or an externally validated explanation of HEAT's time pattern.", "universal_requirement_quoted": "High predictive accuracy with minimal unresolved exceptions. The mechanism accounts for most major observations in its claimed scope." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "partly", "internal_negative_controls": [ "Uninfected and strain/age animal groups [7].", "Drug-specific human treatment comparisons [5]; not factorial randomization of drug identity.", "NSAID-naive versus previously NSAID-treated users, a baseline-determinable boundary [20]." ], "note": "Pass-01: the medication boundary is partly mapped by baseline exposure [20, 22]; HEAT's time pattern is not. This blocks Θ for SC3 (which asserts duration); for SC1 it is the single named exception. Edition B's note: An observed boundary is not necessarily mechanistically explained or prospectively predictable. These gaps block Θ for SC1/SC3, while replicated human clinical effects support Η.", "observed_unresolved_boundaries": [ "HEAT later follow-up [6,14] is a time-period comparison, not an independent baseline negative-control group.", "Stress-associated residual risk [10] is observational." ] }, "falsification_patterns_met": [], "pitfalls_flagged": [ { "subclaim_id": "SC1", "pitfall": "6. Downstream effect treated as upstream driver", "where": "Recurrence trials alone do not establish initiation; prevention [4,6] and controlled infection [7] supply that evidence." }, { "subclaim_id": "SC1", "pitfall": "11. Intervention specificity assumed rather than demonstrated", "where": "Antibiotics have off-target effects and bismuth protects mucosa; [1] removes bismuth and equalizes acid suppression, while [7] adds independent organism evidence." }, { "subclaim_id": "SC1", "pitfall": "13. Therapeutic effect misread as mechanistic proof", "where": "Eradication supports infection causality, not necessity of every proposed CagA, VacA or immune pathway." }, { "subclaim_id": "SC2", "pitfall": "8. Confirmation by biomarker", "where": "Exclude acid output [8], infection clearance alone [11] and gastritis [13] from the decisive ulcer tally." }, { "subclaim_id": "SC2", "pitfall": "18. Causal-evidence tallies that do not survive an audit", "where": "The eradication-status subgroup [1] is not a new randomized study; replication is not an independent class." }, { "subclaim_id": "SC3", "pitfall": "7. Selective generalization", "where": "Infected ulcers, NSAID-associated ulcers and idiopathic ulcers are distinct scopes." }, { "subclaim_id": "SC3", "pitfall": "21. A universal cap re-applied to a convergent evidence set", "where": "Do not cap the clinical-plus-experimental synthesis at Β because some components are observational." }, { "subclaim_id": "SC3", "pitfall": "19. Unlinked claims", "where": "Every substantive evidence item links to the claim register and source ledger." }, { "subclaim_id": "SC1/SC3", "pitfall": "Outcome-defined susceptibility (related to pitfall 20, not its verbatim original definition)", "where": "Removed the unspecified susceptible-host qualifier. Future ulcers and response must not define eligibility; biomarker candidates need independent prospective validation." }, { "subclaim_id": "SC1", "pitfall": "18. Causal-evidence tallies that do not survive an audit", "where": "Pass-01: B's cards marked [5], [9], [10], [12] \"supports\"; they support rival or boundary models. Directions reset; audited nominal tally is seven decisive perturbations." }, { "subclaim_id": "SC1/SC3", "pitfall": "22. Scope fitted to the result", "where": "Pass-01: \"in susceptible hosts\" stays deleted and is recorded in scope_qualifiers; HEAT's late window stays in scope; demanding a susceptibility rule as a Θ condition would re-import the qualifier as a requirement." }, { "subclaim_id": "SC1", "pitfall": "21. A universal cap re-applied to a convergent evidence set", "where": "Pass-01: cap 2 binds the association-only rows [17], [21] individually; it is not re-applied to the convergent set." } ], "causal_tally_audit": { "tally_claimed_by_document": 8, "tally_after_audit": 7, "items_rejected": [ "[5] active-comparator boundary result; not a positive test of the nominal claim.", "[12] decisive perturbation of the rival medication route (M2), not of the nominal claim.", "[22] tests the aspirin co-cause after eradication; not a nominal test.", "[14] second report of [6]; one study.", "[8] physiological endpoint; [13], [23] gastritis endpoints.", "[9], [10], [17], [21] observational; [19] uncontrolled before-after.", "[11] eradication endpoint only; [15], [16], [20] pooled syntheses of trials already in line 1." ], "breakdown": "Seven decisive perturbations support the nominal claim: six human randomized trials with ulcer or ulcer-bleeding endpoints [1, 2, 3, 4, 6, 18] and one animal induction experiment [7]. Edition B counted eight, including [5] and [12]; its prose labelled them correctly but its cards marked them \"supports\". 23 ledger rows describe 22 studies (HEAT twice); three rows are Tier B syntheses." }, "steelman": { "case_one_rung_higher": "Ω: within the recurrence scope, persistent infection is close to necessary (recurrence after successful eradication is rare [1, 3]) and close to sufficient in duodenal ulcer (most persistently infected patients recurred [1, 2]); the effect replicates across dozens of trials [15] and a hard endpoint [16]; organism addition reproduces gastritis in people and ulcers in animals [7, 13, 23].", "case_one_rung_lower": "Η (edition B's reading): the largest blinded hard-endpoint prevention trial, HEAT, was not significant overall (HR 0.69, 0.38–1.25) and its early benefit vanished for reasons its investigators call unclear [14]; primary prevention otherwise rests on two small NSAID-context trials [4, 18] and an uncontrolled community study [19]; Cochrane rates the recurrence evidence very low quality [15]; about a quarter of strictly tested US non-NSAID duodenal ulcers were uninfected [21].", "which_rejected": "Ω rejected. Η rejected for SC1 and the overall letter; held for SC3. Θ assigned to SC1 and SC2; overall Θ by the pre-registered primary-subclaim rule.", "blocking_cap_threshold_or_missing_experiment": "Against Ω: the Ω threshold — \"necessity and sufficiency of the claimed microbial mechanism\" — fails for a nonexclusive claim: ulcers without infection [9, 12, 21] and infection without ulcers [8, 17]; within the recurrence scope, gastric-ulcer recurrence in only about half to three-quarters of persistently infected patients [2, 3] and no second system. Against Η for SC1: the Θ threshold asks for minimal, not zero, unresolved exceptions, and HEAT's later window is the only failed prediction within scope — imprecise (21 events), in established aspirin users where a medication co-cause is already mapped [20, 22], with persistent clearance making reinfection an unlikely explanation (C32). The overall non-significance of HEAT is not a failed prediction of causation: the early effect is significant and the split was fixed before unblinding [14]. Cochrane's quality rating concerns precision, not direction. The US association share limits near-universality, which the claim does not assert. The experiment that would move SC1 back to Η: a replicated long-term eradication trial in aspirin or NSAID starters showing loss of benefit without reinfection." }, "final_score": { "hsef_level": "Θ", "hsef_descriptor": "High predictive accuracy, minimal unresolved exceptions", "confidence": "High", "confidence_rationale": "Independent investigators, countries, ulcer sites, endpoints and designs replicate the central intervention-sensitive pattern; pooled syntheses confirm direction [15, 16]. HSEF confidence, not GRADE certainty: Cochrane rates the recurrence evidence very low quality on trial conduct.", "rests_on_non_peer_reviewed_work": false, "rationale": "Removal, prevention, temporal-order, population and organism-addition designs confirm the claim's predictions with one unresolved within-scope exception, HEAT's later period. SC1 = Θ and the pre-registered primary-subclaim rule returns Θ; SC3 holds at Η because it asserts durable generalization, so weakest-link would return Η.", "pass01_prior": "Η (edition B, High confidence)" }, "role_of_mechanism": { "classification": "primary driver", "derivation_step_matched": "3", "derivation": "Removing infection markedly reduces recurrence in baseline-defined ulcer cohorts; pretreatment prevents some incident ulcers, and defined-strain infection initiates animal ulceration. These support an upstream primary driver in the infection-mediated route. Rate-limiting language is an inference from outcome changes, not a measured kinetic constant or an outcome-based patient definition. Pass-01: held. Human initiation rests on prevention in NSAID-naive patients [4, 18], infection preceding ulcer [17] and challenge-to-gastritis [13, 23]; animal initiation on [7].", "tournament_used_as_tiebreaker": false, "note": "The existence of ulcers via other pathways does not make infection a downstream consequence. Direction, not tournament rank, determines the role." }, "extended_scoring_MSD": { "momentum": { "value": "Little new work", "artifact": "The last completed causal trial with an ulcer endpoint is HEAT (reports 2022 and 2025) [6, 14]; current trials such as [11] test regimen efficacy against an eradication endpoint, not ulcer causation.", "justification": "The causal question is treated as settled; active H. pylori research concerns regimens, resistance and gastric cancer. Edition B's \"Mechanistic only\" rested on [11], a regimen trial (pass-01 F9)." }, "stability": { "value": "Stable", "trigger": "No named pending result. The foreseeable trigger, downward, would be a replicated long-term eradication trial in aspirin or NSAID starters showing HEAT's late loss without reinfection; no such trial was identified.", "justification": "Resistance and regimen changes alter treatment success, not the causal inference." }, "divergence": { "implied_level": "Θ", "implied_level_basis": "How the field presents the claim: its Cochrane reviews describe H. pylori as \"the main etiologic factor for peptic ulcer disease\" and as associated with the great majority of duodenal and most gastric ulcers [15, 16] (C34) — high predictive accuracy with exceptions (NSAIDs, idiopathic ulcers) acknowledged. Tier B framing, as the authoring standard permits for this field.", "assessed_level": "Θ", "gap_in_rungs": 0, "value": "Aligned", "justification": "Θ − Θ = 0. The field's association share is overstated for low-prevalence settings [21], a coverage point rather than a level point. Edition B derived an implied Η from trial conclusion sentences rather than field framing (pass-01 F6)." }, "calibration_note": "M/S/D assigned after the level and modify nothing (Rule 10)." }, "change_record": { "applies": true, "prior_level": "Η", "prior_confidence": "High", "prior_source": "Posted edition B (OpenAI Codex, 2026-09-27; schema 5.2 + local extensions; validator 2.2), itself a revision of edition A (Θ, pre-critique).", "derived_before_consulting_prior": false, "derived_before_consulting_prior_note": "The coordinator's brief stated B's letters before the pass began, so the derivation was not blind to the prior letter. Subclaim levels were derived from the evidence and written to a lock file before B's threshold reasoning was compared and before the sealed band was opened.", "new_level": "Θ", "direction": "raised", "what_moved_it": "SC1 Η → Θ. Two of B's three SC1 Θ blockers do not bind a nonexclusive major-cause claim (a stress association; the absence of a validated susceptibility rule, which B's own steelman disclaims). The third, HEAT's later period, is a single imprecise unexplained window and is carried as the named exception. Evidence B lacked: Cochrane recurrence [15] and rebleeding [16] syntheses; a double-blind ITT NSAID-naive prevention trial with a complicated-ulcer endpoint [18]; infection preceding ulcer with a gradient [17]; population mass eradication [19]; persistent clearance in HEAT (C32). Counter-evidence added and weighed: [20], [21], [22]. SC2 held at Θ; SC3 held at Η. Aggregation rule unchanged.", "divergence_from_other_reviewers": "Edition B (Η) and edition A (Θ) are both on record. A reached Θ with an outcome-defined qualifier and did not defend it against HEAT; B deleted the qualifier and lowered to Η; this pass reaches Θ on the unqualified claim, with HEAT named. B's case for Η is carried in the steelman and in SC1's dissent field.", "prior_additional_corrections_edition_B": [ "SC2 type is reversibility under a declared local extension.", "Existing claimed_scope fields were populated; a checked scope alias is now supplied.", "SC2 retains Θ only for the explicitly specified recurrence interval/population.", "The earlier implied-Θ field mapping is withdrawn because the source framing does not assert that level." ] }, "proposed_decisive_experiments": [ { "name": "Prospective validation of duration and baseline effect modifiers", "experiment": "Use adequately powered prospective studies or independent cohorts with verified infection, clearance, medication exposure and ulcer status, and a prespecified prediction for clinical benefit over early and longer follow-up. Candidate strain/host modifiers must be measured before outcomes. This is a proposed design, not a named ongoing trial.", "readout": "Adjudicated ulcer incidence, recurrence and ulcer bleeding in separately defined populations and time intervals.", "critical_control": "Do not pool different endpoints or select responders after observing outcomes. Account for acid suppression, continued NSAIDs/aspirin, reinfection, clearance failure and competing death. Do not withhold established treatment to recreate historical evidence.", "falsifying_result": "In prospectively defined infection-positive populations, repeated, adequately powered, well-controlled comparisons show that durable removal does not reduce adjudicated ulcer outcomes over a prespecified interval, with confidence intervals excluding a prespecified clinically meaningful reduction. Such a result contradicts that population-and-time prediction; repeated failures across the principal settings would challenge the broad major-cause account. Affected participants must not be excluded afterward as not susceptible. A single context-specific null does not erase positive evidence elsewhere.", "supporting_result": "Replicated, prospectively specified benefit patterns and a reproducible explanation or externally validated boundary for the HEAT duration pattern." }, { "name": "Long-term eradication trial in aspirin or NSAID starters", "experiment": "Randomize infected people at the start of long-term low-dose aspirin or NSAID therapy to eradication or placebo, with repeat testing for clearance and reinfection and adjudicated ulcer bleeding over at least five years, analysed in prespecified intervals. The HEAT investigators propose starters as the next population [14].", "readout": "Adjudicated ulcer bleeding and complicated ulcer, by prespecified interval.", "critical_control": "Clearance and reinfection measured in both arms; co-prescribed acid suppression recorded; competing death.", "falsifying_result": "Replicated loss of benefit after the early period in durably cleared participants, with precise intervals.", "supporting_result": "Benefit sustained across intervals in durably cleared participants." } ], "knowledge_gaps": [ { "name": "Individual progression", "statement": "Why some infected hosts develop gastric or duodenal ulcers while others do not.", "relevance": "Improves individual prediction without making infection cease to be a major cause." }, { "name": "Present-day attributable burden", "statement": "The fraction of ulcers attributable to infection depends on region, cohort and medication exposure; this review does not estimate it.", "relevance": "Needed to defend a stronger claim that infection is numerically the leading cause in a specified population." }, { "name": "Durability during aspirin exposure", "statement": "The reason early HEAT protection was not established later remains unclear in the 2025 report.", "relevance": "The single named unresolved exception to SC1's Θ and the reason SC3 holds at Η; not proof of later harm. Persistent clearance in the eradication arm (C32) makes reinfection an unlikely explanation." } ], "review_metadata": { "review_date": "2026-09-27", "reviewer": "Graders: edition A and edition B — OpenAI Codex. Red-team synthesis: Claude (Anthropic), independent model, 2026-09-27.", "evidence_base_note": "Targeted primary-record review: 23 ledger rows describing 22 studies (HEAT reported twice); 20 Tier A, 3 Tier B. Abstract depth except the HEAT full report (targeted passages). Not an exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Pass-01: PubMed E-utilities (metadata, search, publication-type filters) succeeded; PubMed, PMC and NCBI Bookshelf HTML returned a bot-check; Europe PMC REST returned HTTP 429 after two records; Scite returned a quota error; Crossref succeeded; the NIHR Journals Library report PDF was read in targeted passages. Edition B's tool log is retained in checked_sources.", "skill_version": "5.4 (validator 2.4, authoring standard 1.5)", "validator_run": "pass", "validator_warnings_addressed": "Validator 2.4: 0 FAIL. Two WARNs disclosed in Reviewer notes: the calibration entry was not graded blind (reason recorded), and the expected band was written by an author who had seen the review. Both are true and are not fixable by editing this card.", "edition_B_metadata": { "review_date": "2026-09-27", "reviewer": "Codex", "evidence_base_note": "Targeted primary-record review with a criticism-driven revision; 14 reports of 13 studies. Most checks used abstracts and indexed metadata; the HEAT 2025 scientific summary was also read. Not an exhaustive systematic review or full-text risk-of-bias assessment.", "literature_tools_available": true, "literature_tools_note": "Used Life Sciences Literature ncbi-entrez-skill and ncbi-pmc-skill. Entrez search first returned HTTP 500; later efetch succeeded. PMC metadata lookup returned no current dataset files for the queried PMCID. Europe PMC primary indexed abstracts supplied complete abstract text where compact plugin previews or public pages were incomplete. Scite citation-context call was unavailable due to account quota; no counts inferred.", "skill_version": "Supplied v5 package, active schema 5.2; local-reference-edition-1 extensions are separately declared.", "validator_run": "pass", "validator_warnings_addressed": "Supplied validator 2.2: 27 passes, 0 failures, 1 acknowledged warning because this is an unblinded reference case. Supplementary scope/type/endpoint/study-identity/aggregation/provenance checks passed; 12 defective fixtures rejected. Structural validation is not independent scientific validation or proof of blindness.", "archive_sha256": "30B23AD4C21209AFE1E683896439675995DAA85BAC10BACE71566777787E01BC", "source_status_note": "none_found is limited to status metadata inspected in indexed primary records, not a claim that all citation discussions were reviewed.", "revision_timestamp_utc": "2026-09-27T06:06:46+00:00", "supplementary_validation": { "checker": "hsef-reference-edition-checks.py", "passed": true, "negative_fixtures_rejected": 12, "rubric_quotations_verified": true, "original_archive_hash_unchanged": true, "target_commitment_verified": true, "grader_packet_target_exclusion_verified": true, "calibration_utility_test": "Synthetic freeze/compare and changed-review/changed-target refusal checks passed. No actual calibration result generated." } }, "red_team": { "pass": "pass-01", "date": "2026-09-27", "record": "redteam/pass-01-2026-09-27.md", "process_record": "PROCESS.md", "change_log": "redteam/change-log.md" }, "consensus_consistency_audit": "2026-10-09; supplementary provenance/source reconciliation; original grading retained; prior grades visible." }, "is_calibration_entry": { "value": true, "entry_role": "unblinded reference case", "blind_graded": false, "completed_blinded_calibration": false, "expected_band_sealed_at": "sources/B_posted_reference_edition/hsef-calibration/coordinator/expected-band.json (originally C:\\Users\\mjhen\\Documents\\Codex\\2026-09-26\\new-chat\\outputs\\hsef-calibration\\coordinator\\expected-band.json)", "target_sha256": "089fa7c1e1369b4e2cc67216a85aff28ff14ed9d42f788680ccef52b04e4863d", "target_authorship": "Edition B's unblinded author; not independent expert consensus.", "target_author_saw_review": true, "future_run_status": "prepared, not executed", "unblinded_reason": "A retrospectively designated reference case. Edition B's author saw edition A's Θ and the critique and wrote the band after them. The red-team reviewer was told B's letters in the brief and opened the sealed band only after locking the level; its SHA-256 matches the commitment. The band is Η–Θ; this edition's Θ falls inside it, which is not evidence of calibration.", "grader_packet_note": "The prepared grader packet ships framework v5.0 / schema 5.2, not v5.4; a v5.4 packet would carry framework text (the scope rule and pitfall 22) that names this case. Owner decision (pass-01 F14)." }, "upper_ladder_check": { "final_level_below_zeta": false, "equivalents_considered": [ { "kind": "therapeutic_perturbation_hard_endpoint", "available": true, "why_not_sufficient": "Sufficient for Θ with replication [1-4, 6, 15, 16, 18]; not for Ω." }, { "kind": "natural_experiment", "available": true, "why_not_sufficient": "Community mass eradication [19]; uncontrolled before-after, supportive only." }, { "kind": "dose_response_across_populations", "available": true, "why_not_sufficient": "Antibody-level gradient within one cohort [17]; not across independent populations." }, { "kind": "withdrawal_rechallenge", "available": true, "why_not_sufficient": "Withdrawal replicated [15]; rechallenge only as observed reinfection preceding rebleeding or recurrence [16, 22]." }, { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "No plausible genetic instrument for acquiring an infection." }, { "kind": "defined_strain_phenotype_induction", "available": true, "why_not_sufficient": "Animal scope [7]; human challenge reaches gastritis only [13, 23]." } ], "convergence_present": true, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 23, "claims_total": 34, "claims_verified": 34, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 20, "distinct_studies": 22, "generated_by": "Edition B (OpenAI Codex, schema 5.2) revised by red-team pass-01 (Claude, Anthropic); schema 5.4; validator 2.4", "gate_passed": true }, "claims": [ { "id": "C1", "text": "Helicobacter pylori infection is a major upstream cause of human peptic ulcer disease.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 1, 2, 3, 4, 6, 7 ], "verification": "verified", "verified_against": "Synthesis; factual premises verified against the primary abstracts of its sources (re-checked by pass-01).", "verified_on": "2026-09-27", "note": "Reviewer causal synthesis. The undefined susceptibility qualifier has been removed; the population cannot be selected using its future outcome.", "verification_kind": "synthesis", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C2", "text": "In Hentschel et al., recurrence among participants followed for 12 months was 4/50 (8%) with antibiotics and 42/49 (86%) with placebo; both randomized groups received ranitidine.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Follow-up denominators, not a complete all-randomized intention-to-treat analysis.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C3", "text": "The same trial reported recurrence of 1/46 (2%) after successful eradication versus 45/53 (85%) with persistent infection.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Post-randomization eradication-status comparison; not a second randomized experiment.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C4", "text": "Graham et al. reported recurrence probabilities of 12% versus 95% for duodenal ulcers and 13% versus 74% for gastric ulcers with eradication plus ranitidine versus ranitidine alone.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Reported recurrence probabilities during follow-up of up to two years, not simple event fractions.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C5", "text": "Sung et al. reported one-year gastric-ulcer recurrence of 1/22 (4.5%) versus 12/23 (52.2%) after antibacterial treatment versus omeprazole.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Small one-year follow-up subsets from a trial that randomized 100; antibacterial regimen contained mucosa-active bismuth.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C6", "text": "Chan et al. randomized ulcer-free, H. pylori-positive NSAID-naive patients before naproxen; among completers, ulcers developed in 3/45 (7%) after eradication treatment versus 12/47 (26%) with naproxen alone.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Prevention of incident ulcers in an NSAID-exposed context; completer analysis, not unqualified general-population prevention.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C7", "text": "In Chan et al. 2001, six-month recurrent bleeding among naproxen users was 18.8% after eradication therapy versus 4.4% with maintenance omeprazole.", "carries_number": true, "load_bearing_for": [ "SC2", "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Shows eradication alone can be insufficient during ongoing NSAID exposure; not a comparison of eradication against no treatment. Pass-01: the aspirin stratum of the same trial is registered as C31.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C8", "text": "HEAT randomized 5352 infected older aspirin users; the ulcer-bleeding hazard ratio was 0.35 (95% CI 0.14–0.89) in the first 2.5 years and 1.31 (0.55–3.11) thereafter.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 6, 14 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-27", "note": "Time-varying effect; the later interval includes benefit and harm. These are two reports of one study, not replication.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C9", "text": "Ohkusa et al. induced gastric ulceration in infected gerbils and found superficial duodenal ulcers in two mature animals infected with the TN2GF4 strain, demonstrating host-age and strain dependence.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Animal conditional sufficiency, not universal sufficiency in humans.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C10", "text": "El-Omar et al. found that eradication lowered gastrin-mediated acid output in duodenal-ulcer patients and included infected healthy volunteers without ulcer disease.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Supports a physiological pathway and nondeterministic infection; acid output alone is not an ulcer endpoint or complete mediation proof.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C11", "text": "Wong et al. documented recurrent bleeding in a cohort classified as H. pylori-negative, NSAID-negative idiopathic ulcer disease.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Observational scope counterexample; testing and exposure misclassification remain possible. No treatment effect is inferred by comparing their nonrandomized cohorts.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C12", "text": "Levenstein et al. found a prospective stress-ulcer association that persisted after adjustment and was similar in infected and uninfected people and those unexposed to NSAIDs.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-27", "note": "Observational evidence of risk heterogeneity; residual confounding and behavioral mediation remain. It does not establish stress as the dominant cause or negate the eradication trials.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C13", "text": "The recent Medel-Jara et al. randomized regimen comparison used successful H. pylori eradication as its primary outcome, rather than ulcer incidence or bleeding.", "carries_number": false, "load_bearing_for": [], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Research-activity and field-framing evidence only; not counted as a decisive ulcer-causation experiment.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C14", "text": "Laine et al. randomized ulcer-free osteoarthritis patients and reported twelve-week endoscopic ulcer incidence of 27.7% with ibuprofen versus 9.9% with placebo.", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-26", "note": "Direct evidence for a medication pathway; not a current treatment recommendation about rofecoxib.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C15", "text": "Marshall et al. reported normal gastric histology before experimental ingestion and biopsy-proven gastritis on day 10; no peptic ulcer was demonstrated.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-27", "note": "Third listed supporting modality: deliberate human challenge. Direct evidence concerns gastritis, not ulceration; n=1 and no concurrent control.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C16", "text": "The evidence does not establish infection as necessary for every peptic ulcer or as sufficient for ulceration in every infected person.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 7, 8, 9, 12 ], "verification": "verified", "verified_against": "Synthesis; factual premises verified against the primary abstracts of its sources (re-checked by pass-01).", "verified_on": "2026-09-27", "note": "Noninfectious ulcers undermine universal necessity. Healthy infected people and conditional animal outcomes do not establish universal sufficiency; the short gastritis challenge is not a lifetime penetrance test.", "verification_kind": "synthesis", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C17", "text": "The primary trial conclusions support intervention-sensitive causation; the extended HEAT report explicitly qualifies the durability of prevention.", "carries_number": false, "load_bearing_for": [], "source_ns": [ 1, 2, 11, 14 ], "verification": "verified", "verified_against": "Primary article abstract retrieved from the indexed record; linked identifiers and bibliographic metadata checked.", "verified_on": "2026-09-27", "note": "Premises verified. Pass-01: no longer the Divergence basis — the implied level is taken from how the field presents the claim (C34), not from trial conclusion sentences.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C18", "text": "Eradication changes the natural history of associated ulcer recurrence, beyond temporary acid suppression.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3 ], "verification": "verified", "verified_against": "Synthesis; factual premises verified against the primary abstracts of its sources (re-checked by pass-01).", "verified_on": "2026-09-27", "note": "Reviewer causal synthesis of the endoscopic outcomes.", "verification_kind": "synthesis", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C19", "text": "Causal evidence extends to gastric and duodenal ulcers, but observing medication and time dependence does not fully explain or prospectively predict those boundaries.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 2, 3, 4, 5, 6, 7, 14 ], "verification": "verified", "verified_against": "Synthesis; factual premises verified against the primary abstracts of its sources (re-checked by pass-01).", "verified_on": "2026-09-27", "note": "Clinical scope synthesis. HEAT duration remains unresolved, and no outcome-independent validated susceptibility rule is supplied.", "verification_kind": "synthesis", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C20", "text": "The extended HEAT report gives an overall hazard ratio of 0.69 (95% CI 0.38–1.25), with violation of proportional hazards; the single overall estimate is not a constant effect across follow-up.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Primary report abstract and authors' scientific summary at NCBI Bookshelf.", "verified_on": "2026-09-27", "note": "Same trial as [6]; qualifies durability rather than adding another experiment.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C21", "text": "HEAT investigators report that the 2.5-year split was chosen before unblinding and that the reason for the loss of early apparent protection is unclear.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Full report (NIHR Journals Library PDF), split-time analysis and discussion; quoted in redteam/claim-audit.md.", "verified_on": "2026-09-27", "note": "Same trial as [6]; qualifies durability rather than adding another experiment.", "rechecked_by": "red-team pass-01, 2026-09-27" }, { "id": "C22", "text": "A Cochrane review of randomized trials found eradication therapy superior to no treatment in preventing both duodenal and gastric ulcer recurrence, rated that evidence very low quality, and found no evidence that eradication outperforms maintenance ulcer-healing drugs for duodenal-ulcer recurrence.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "Tier B pooled synthesis; no figure carried. Replication within line 1, not a new line.", "added_by": "red-team pass-01" }, { "id": "C23", "text": "A Cochrane meta-analysis found eradication more effective than non-eradicating antisecretory therapy, with or without long-term maintenance, in preventing recurrent ulcer bleeding, and attributed some rebleeding to recurrence of infection.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "Tier B; hard endpoint; no figure carried.", "added_by": "red-team pass-01" }, { "id": "C24", "text": "In a nested case-control study within 5443 Japanese-American men with sera stored in 1967–1970, pre-existing infection predicted later gastric ulcer (OR 3.2, 95% CI 1.6–6.5; 150 cases) and duodenal ulcer (OR 4.0, 1.1–14.2; 65 cases); risk rose with antibody level and held for diagnoses 10 or more years after sampling.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "78% of matched controls were also seropositive.", "added_by": "red-team pass-01" }, { "id": "C25", "text": "Chan et al. 2002 randomized 100 infected, NSAID-naive patients starting diclofenac to omeprazole triple therapy or omeprazole with placebo antibiotics; by intention to treat, 6-month ulcer probability was 12.1% (95% CI 3.1–21.1) versus 34.4% (21.1–47.7), and complicated-ulcer probability 4.2% versus 27.1%.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "", "added_by": "red-team pass-01" }, { "id": "C26", "text": "After community mass eradication in a Taiwanese population, the reported reduction in peptic ulcer disease was 67.4% (95% CI 52.2–77.8%), with estimated re-infection or recrudescence of 1% per person-year; periods are compared without a concurrent control.", "carries_number": true, "load_bearing_for": [ "SC1" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "", "added_by": "red-team pass-01" }, { "id": "C27", "text": "A meta-analysis of randomized trials in NSAID users found that eradication reduced ulcer incidence in NSAID-naive patients but not in patients previously treated with NSAIDs, and was less effective than maintenance proton-pump inhibitor therapy.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "Tier B; no figure carried. Maps a baseline-determinable boundary.", "added_by": "red-team pass-01" }, { "id": "C28", "text": "In six US placebo-controlled trials of endoscopically diagnosed non-NSAID duodenal ulcer, 73% (1737 of 2394 evaluable patients) were confirmed infected under a two-test definition.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "Evidence against near-universal association in a low-prevalence setting; not against major causation.", "added_by": "red-team pass-01" }, { "id": "C29", "text": "In 123 infected patients with ulcer complications on long-term low-dose aspirin, after healing and eradication, recurrent complications over a median 12 months occurred in 9 of 61 (14.8%) on placebo versus 1 of 62 (1.6%) on lansoprazole while aspirin continued; 4 of the 10 had recurrent infection.", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "", "added_by": "red-team pass-01" }, { "id": "C30", "text": "A second volunteer with normal baseline gastric histology ingested the organism and developed culture-positive gastritis with raised fasting gastric pH that persisted through doxycycline until bismuth treatment; no ulcer is reported.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "", "added_by": "red-team pass-01" }, { "id": "C31", "text": "In the aspirin stratum of Chan et al. 2001, six-month recurrent bleeding probability was 1.9% after eradication therapy versus 0.9% with omeprazole (absolute difference 1.0%, 95% CI −1.9 to 3.9).", "carries_number": true, "load_bearing_for": [ "SC3" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Abstract (PubMed).", "verified_on": "2026-09-27", "note": "", "added_by": "red-team pass-01" }, { "id": "C32", "text": "HEAT's full report records primary-outcome events of 6 versus 17 in the first 2.5 years and 12 versus 9 thereafter (eradication versus placebo); in a 10% repeat-breath-test sample a median 3.95 years after randomisation, the test was negative in 146 of 161 eradication-group and 41 of 161 control-group participants.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Full report (NIHR Journals Library PDF), primary outcome and H. pylori clearance passages; 6 v 17 also in the Lancet abstract [6].", "verified_on": "2026-09-27", "note": "The report prints the control proportion as 24.0%; 41/161 = 25.5%. Counts carried, printed percentage not.", "added_by": "red-team pass-01" }, { "id": "C33", "text": "Across removal, prevention, population and temporal-order designs the major-cause claim's predictions were confirmed; the one unresolved within-scope failed prediction is HEAT's later period.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 6, 14, 15, 16, 17, 18, 19 ], "verification": "verified", "verified_against": "Synthesis; premises verified in C2–C8, C20–C26 and C32.", "verified_on": "2026-09-27", "note": "Load-bearing for SC1 Θ.", "added_by": "red-team pass-01", "verification_kind": "synthesis" }, { "id": "C34", "text": "Field reviews present H. pylori as the main etiologic factor of peptic ulcer disease and as associated with the great majority of duodenal and most gastric ulcers.", "carries_number": false, "load_bearing_for": [], "source_ns": [ 15, 16 ], "verification": "verified", "verified_against": "Abstract background sections (PubMed).", "verified_on": "2026-09-27", "note": "Divergence basis only; the reviews' percentages are not carried (Tier B).", "added_by": "red-team pass-01" } ], "citation_ledger": [ { "n": 1, "citation": "Hentschel E, Brandstätter G, Dragosics B, et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med. 1993;328(5):308-312.", "tier": "A", "kind": "rct", "pmid": "8419816", "doi": "10.1056/nejm199302043280503", "url": "https://pubmed.ncbi.nlm.nih.gov/8419816/", "status_flags": [ "none_found" ], "carries_claims": [ "C1", "C2", "C3", "C17", "C18", "C33" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "HENTSCHEL-1993-NEJM", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 2, "citation": "Graham DY, Lew GM, Klein PD, et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. 1992;116(9):705-708.", "tier": "A", "kind": "rct", "pmid": "1558340", "doi": "10.7326/0003-4819-116-9-705", "url": "https://pubmed.ncbi.nlm.nih.gov/1558340/", "status_flags": [ "none_found" ], "carries_claims": [ "C1", "C4", "C17", "C18", "C19", "C33" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "GRAHAM-1992-AIM", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 3, "citation": "Sung JJ, Chung SC, Ling TK, et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995;332(3):139-142.", "tier": "A", "kind": "rct", "pmid": "7800005", "doi": "10.1056/nejm199501193320302", "url": "https://pubmed.ncbi.nlm.nih.gov/7800005/", "status_flags": [ "none_found" ], "carries_claims": [ "C1", "C5", "C18", "C19", "C33" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "SUNG-1995-NEJM", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 4, "citation": "Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet. 1997;350(9083):975-979.", "tier": "A", "kind": "rct", "pmid": "9329511", "doi": "10.1016/s0140-6736(97)04523-6", "url": "https://pubmed.ncbi.nlm.nih.gov/9329511/", "status_flags": [ "none_found" ], "carries_claims": [ "C1", "C6", "C19", "C33" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "CHAN-1997-LANCET", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 5, "citation": "Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344(13):967-973.", "tier": "A", "kind": "rct", "pmid": "11274623", "doi": "10.1056/nejm200103293441304", "url": "https://pubmed.ncbi.nlm.nih.gov/11274623/", "status_flags": [ "none_found" ], "carries_claims": [ "C7", "C19", "C31" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "CHAN-2001-NEJM", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 6, "citation": "Hawkey C, Avery A, Coupland CAC, et al. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet. 2022;400(10363):1597-1606.", "tier": "A", "kind": "rct", "pmid": "36335970", "doi": "10.1016/s0140-6736(22)01843-8", "url": "https://pubmed.ncbi.nlm.nih.gov/36335970/", "status_flags": [ "none_found" ], "carries_claims": [ "C1", "C8", "C19", "C33" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "HEAT-NCT01506986", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 7, "citation": "Ohkusa T, Okayasu I, Miwa H, et al. Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils. Gut. 2003;52(6):797-803.", "tier": "A", "kind": "primary", "pmid": "12740333", "doi": "10.1136/gut.52.6.797", "url": "https://pubmed.ncbi.nlm.nih.gov/12740333/", "status_flags": [ "none_found" ], "carries_claims": [ "C1", "C9", "C16", "C19" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "OHKUSA-2003-GUT", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 8, "citation": "el-Omar E, Penman I, Dorrian CA, et al. Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer. Gut. 1993;34(8):1060-1065.", "tier": "A", "kind": "primary", "pmid": "8174954", "doi": "10.1136/gut.34.8.1060", "url": "https://pubmed.ncbi.nlm.nih.gov/8174954/", "status_flags": [ "none_found" ], "carries_claims": [ "C10", "C16" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "ELOMAR-1993-GUT", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 9, "citation": "Wong GL, Wong VW, Chan Y, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137(2):525-531.", "tier": "A", "kind": "primary", "pmid": "19445937", "doi": "10.1053/j.gastro.2009.05.006", "url": "https://pubmed.ncbi.nlm.nih.gov/19445937/", "status_flags": [ "none_found" ], "carries_claims": [ "C11", "C16" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "WONG-2009-GASTRO", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 10, "citation": "Levenstein S, Rosenstock S, Jacobsen RK, et al. Psychological stress increases risk for peptic ulcer, regardless of Helicobacter pylori infection or use of nonsteroidal anti-inflammatory drugs. Clin Gastroenterol Hepatol. 2015;13(3):498-506.e1.", "tier": "A", "kind": "primary", "pmid": "25111233", "doi": "10.1016/j.cgh.2014.07.052", "url": "https://pubmed.ncbi.nlm.nih.gov/25111233/", "status_flags": [ "none_found" ], "carries_claims": [ "C12" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "LEVENSTEIN-MONICA-DK", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 11, "citation": "Medel-Jara PA, Latorre G, Fuentes-Lopez E, et al. Comparison between optimized bismuth quadruple therapy and standard clarithromycin-based triple therapy for first-line Helicobacter pylori eradication: a double-blind randomized controlled trial. Lancet Reg Health Am. 2026;53:101312.", "tier": "A", "kind": "rct", "pmid": "41362749", "doi": "10.1016/j.lana.2025.101312", "url": "https://pubmed.ncbi.nlm.nih.gov/41362749/", "status_flags": [ "none_found" ], "carries_claims": [ "C13", "C17" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "NCT05664685", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 12, "citation": "Laine L, Harper S, Simon T, et al. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group. Gastroenterology. 1999;117(4):776-783.", "tier": "A", "kind": "rct", "pmid": "10500058", "doi": "10.1016/s0016-5085(99)70334-3", "url": "https://pubmed.ncbi.nlm.nih.gov/10500058/", "status_flags": [ "none_found" ], "carries_claims": [ "C14", "C16" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "LAINE-1999-GASTRO", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 13, "citation": "Marshall BJ, Armstrong JA, McGechie DB, et al. Attempt to fulfil Koch's postulates for pyloric Campylobacter. Med J Aust. 1985;142(8):436-439.", "tier": "A", "kind": "primary", "pmid": "3982345", "doi": "10.5694/j.1326-5377.1985.tb113443.x", "url": "https://pubmed.ncbi.nlm.nih.gov/3982345/", "status_flags": [ "none_found" ], "carries_claims": [ "C15" ], "opened": true, "opened_on": "2026-09-26", "status_checked_on": "2026-09-27", "record_access": "PubMed-indexed primary abstract and metadata, including linked status fields, retrieved through Life Sciences Literature Entrez where available and Europe PMC core records. No full-text-complete claim.", "status_scope": "No correction, retraction or expression-of-concern flag in the retrieved indexed record; linked commentaries are not corrections.", "study_id": "MARSHALL-1985-MJA", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata (edition B and pass-01)." }, { "n": 14, "citation": "Hawkey CJ, Avery AJ, Coupland CA, et al. Eradication of Helicobacter pylori for prevention of aspirin-associated peptic ulcer bleeding in adults over 65 years: the HEAT RCT. Health Technol Assess. 2025;29(42):1-62.", "tier": "A", "kind": "rct", "pmid": "40844182", "doi": "10.3310/llkf7871", "url": "https://pubmed.ncbi.nlm.nih.gov/40844182/", "additional_opened_url": "https://www.ncbi.nlm.nih.gov/books/NBK617371/", "status_flags": [ "none_found" ], "carries_claims": [ "C8", "C17", "C19", "C20", "C21", "C32", "C33" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "record_access": "Primary indexed abstract and metadata plus the authors' full scientific-summary chapter were read. The complete 62-page report was not audited.", "status_scope": "No correction, retraction or expression-of-concern flag found in the inspected indexed record.", "study_id": "HEAT-NCT01506986", "same_study_as_source": 6, "title_method_age_note": "The published title says over 65 years; the reported eligibility was age 60 years or older. Eligibility is taken from the methods, not inferred from the title.", "status_rechecked_by": "red-team pass-01: PubMed retraction filter and erratum author search; Europe PMC comment list for rows 1 and 4.", "access_depth": "full_text_partial", "access_note": "Pass-01: PubMed abstract plus targeted passages of the full report PDF from the NIHR Journals Library (split-time analysis, primary outcome, H. pylori clearance, discussion). Edition B read the scientific summary at NCBI Bookshelf; that page could not be resolved by pass-01 (bot-check).", "full_text_url": "https://doi.org/10.3310/LLKF7871" }, { "n": 15, "citation": "Ford AC, Gurusamy KS, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people. Cochrane Database Syst Rev. 2016;4(4):CD003840.", "tier": "B", "kind": "meta_analysis", "pmid": "27092708", "doi": "10.1002/14651858.CD003840.pub5", "url": "https://pubmed.ncbi.nlm.nih.gov/27092708/", "status_flags": [ "none_found" ], "carries_claims": [ "C22", "C33", "C34" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "COCHRANE-CD003840", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. Pooled synthesis; carries no number.", "added_by": "red-team pass-01" }, { "n": 16, "citation": "Gisbert JP, Khorrami S, Carballo F, Calvet X, Gené E, Dominguez-Muñoz JE. H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Cochrane Database Syst Rev. 2004;(2):CD004062.", "tier": "B", "kind": "meta_analysis", "pmid": "15106235", "doi": "10.1002/14651858.CD004062.pub2", "url": "https://pubmed.ncbi.nlm.nih.gov/15106235/", "status_flags": [ "none_found" ], "carries_claims": [ "C23", "C33", "C34" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "COCHRANE-CD004062", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. Pooled synthesis; carries no number.", "added_by": "red-team pass-01" }, { "n": 17, "citation": "Nomura A, Stemmermann GN, Chyou PH, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and the risk for duodenal and gastric ulceration. Ann Intern Med. 1994;120(12):977-981.", "tier": "A", "kind": "primary", "pmid": "7741826", "doi": "10.7326/0003-4819-120-12-199406150-00001", "url": "https://pubmed.ncbi.nlm.nih.gov/7741826/", "status_flags": [ "none_found" ], "carries_claims": [ "C24", "C33" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "HONOLULU-HEART-PROGRAM-NESTED-CC", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. ", "added_by": "red-team pass-01" }, { "n": 18, "citation": "Chan FK, To KF, Wu JC, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial. Lancet. 2002;359(9300):9-13.", "tier": "A", "kind": "rct", "pmid": "11809180", "doi": "10.1016/s0140-6736(02)07272-0", "url": "https://pubmed.ncbi.nlm.nih.gov/11809180/", "status_flags": [ "none_found" ], "carries_claims": [ "C25", "C33" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "CHAN-2002-LANCET", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. ", "added_by": "red-team pass-01" }, { "n": 19, "citation": "Lee YC, Chen TH, Chiu HM, et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013;62(5):676-682.", "tier": "A", "kind": "primary", "pmid": "22698649", "doi": "10.1136/gutjnl-2012-302240", "url": "https://pubmed.ncbi.nlm.nih.gov/22698649/", "status_flags": [ "none_found" ], "carries_claims": [ "C26", "C33" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "LEE-2013-GUT-MASS-ERADICATION", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. PubMed date is the 2012 e-publication; print 2013.", "added_by": "red-team pass-01" }, { "n": 20, "citation": "Vergara M, Catalán M, Gisbert JP, Calvet X. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther. 2005;21(12):1411-1418.", "tier": "B", "kind": "meta_analysis", "pmid": "15948807", "doi": "10.1111/j.1365-2036.2005.02444.x", "url": "https://pubmed.ncbi.nlm.nih.gov/15948807/", "status_flags": [ "none_found" ], "carries_claims": [ "C27" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "VERGARA-2005-APT", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. Pooled synthesis; carries no number.", "added_by": "red-team pass-01" }, { "n": 21, "citation": "Ciociola AA, McSorley DJ, Turner K, Sykes D, Palmer JB. Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated. Am J Gastroenterol. 1999;94(7):1834-1840.", "tier": "A", "kind": "primary", "pmid": "10406244", "doi": "10.1111/j.1572-0241.1999.01214.x", "url": "https://pubmed.ncbi.nlm.nih.gov/10406244/", "status_flags": [ "none_found" ], "carries_claims": [ "C28" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "CIOCIOLA-1999-AJG-POOLED-BASELINE", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. Pooled baseline data from six trials.", "added_by": "red-team pass-01" }, { "n": 22, "citation": "Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002;346(26):2033-2038.", "tier": "A", "kind": "rct", "pmid": "12087138", "doi": "10.1056/NEJMoa012877", "url": "https://pubmed.ncbi.nlm.nih.gov/12087138/", "status_flags": [ "none_found" ], "carries_claims": [ "C29" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "LAI-2002-NEJM", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. ", "added_by": "red-team pass-01" }, { "n": 23, "citation": "Morris A, Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol. 1987;82(3):192-199.", "tier": "A", "kind": "primary", "pmid": "3826027", "doi": "", "url": "https://pubmed.ncbi.nlm.nih.gov/3826027/", "status_flags": [ "none_found" ], "carries_claims": [ "C30" ], "opened": true, "opened_on": "2026-09-27", "status_checked_on": "2026-09-27", "study_id": "MORRIS-1987-AJG", "access_depth": "abstract_metadata", "access_note": "PubMed abstract and metadata. No DOI in PubMed.", "added_by": "red-team pass-01" } ], "independence_basis": { "required": true, "lines": [ { "label": "Removal of naturally acquired infection in human clinical-outcome trials", "sources": [ 1, 2, 3, 4, 6, 14, 15, 16, 18, 19 ], "excludes_error": "Randomization and clinical ulcer endpoints reduce reverse causation, treatment-selection bias and biomarker substitution. This entire therapeutic modality is counted as one line despite multiple regimens.", "endpoint_scope": "Human clinical ulcer recurrence, incidence and ulcer bleeding.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "evidence_role": "Direct ulcer causal line", "counts_as_direct_ulcer_causal_line": true, "limits": "Antimicrobial off-target effects and cointerventions remain; regimens and sites provide replication within one modality. Sources [6] and [14] are the same trial. Pass-01: [15], [16] pool this line; [18] replicates it with omeprazole-matched placebo; [19] is the same modality at population scale. None is a new line." }, { "label": "Addition of defined bacterial strains with ulcer pathology and host/strain controls", "sources": [ 7 ], "excludes_error": "Ulcer induction without antibiotic treatment is not explained by an antimicrobial off-target protective effect. Species/inoculation artifacts that could mislead here do not explain randomized treatment effects in naturally infected humans.", "endpoint_scope": "Experimentally induced gastric/duodenal ulcer pathology in gerbils.", "relates_to_subclaims": [ "SC1", "SC3" ], "evidence_role": "Direct ulcer causal line in an animal model", "counts_as_direct_ulcer_causal_line": true, "limits": "Species, forced inoculation, strain and age limit human extrapolation; does not demonstrate universal human sufficiency." }, { "label": "Deliberate human challenge with biopsy-proven gastritis", "sources": [ 13, 23 ], "excludes_error": "The observed upstream gastritis response occurs in a human, so it cannot be attributed to gerbil-to-human species disanalogy for that endpoint. Its induction does not depend on an antimicrobial protective effect.", "endpoint_scope": "Gastritis on day 10; no demonstrated peptic ulcer.", "relates_to_subclaims": [ "SC1" ], "evidence_role": "Supporting upstream-pathway line; not direct ulcer causation", "counts_as_direct_ulcer_causal_line": false, "limits": "Single uncontrolled volunteer, short follow-up and an intermediate endpoint. Species relevance for gastritis cannot be transferred to ulceration without additional evidence. Pass-01: [23] replicates the challenge with persistent infection; replication, not a new line." }, { "label": "Pre-existing infection in stored sera predicting later ulcer, with a gradient", "sources": [ 17 ], "excludes_error": "Reverse causation — infection colonizing already-damaged mucosa — and the antimicrobial pleiotropy and co-intervention errors that could mislead line 1: sera were drawn a decade or more before diagnosis and nothing was treated. Its own failure mode, confounding by early-life circumstances, cannot produce the randomized removal results of line 1.", "endpoint_scope": "Hospital-diagnosed gastric and duodenal ulcer in a cohort of Japanese-American men.", "relates_to_subclaims": [ "SC1", "SC3" ], "evidence_role": "Supporting temporal-order line; exposure accumulation versus line 1's withdrawal", "counts_as_direct_ulcer_causal_line": false, "limits": "Observational; one cohort; association-only on its own (cap 2 binds it individually).", "added_by": "red-team pass-01" } ], "shared_failure_mode_checked": true, "note": "Four lines listed; two directly test ulcer outcomes (human removal; animal addition); two support the upstream path (human challenge to gastritis; temporal order in stored sera). Both HEAT reports sit in line 1; pooled syntheses and the community study are replication within line 1. Edition B listed three lines; pass-01 added line 4.", "listed_line_count": 4, "direct_ulcer_line_count": 2 }, "falsification_audit": [ { "subclaim_id": "SC1", "pattern": "Phenotype fails to transfer", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC1", "pattern": "Defined consortium does not recapitulate crude-community effect", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC1", "pattern": "Rescue fails despite reinstating the proposed taxa", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC1", "pattern": "Contamination controls erase the signal", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC1", "pattern": "Independent facilities cannot reproduce the finding", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC1", "pattern": "Host phenotype persists after removing the claimed microbial driver", "triggered": false, "interpretation": "Residual ulcers do not falsify a nonexclusive major cause. HEAT durability is nevertheless an unresolved exception for broad predictive coverage, counted once at the Θ threshold; neither lack of significance nor persistence under another cause is converted into proof of no causal role.", "downgrade_applied": false }, { "subclaim_id": "SC2", "pattern": "Phenotype fails to transfer", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC2", "pattern": "Defined consortium does not recapitulate crude-community effect", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC2", "pattern": "Rescue fails despite reinstating the proposed taxa", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC2", "pattern": "Contamination controls erase the signal", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC2", "pattern": "Independent facilities cannot reproduce the finding", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC2", "pattern": "Host phenotype persists after removing the claimed microbial driver", "triggered": false, "interpretation": "Residual ulcers do not falsify a nonexclusive major cause. HEAT durability is nevertheless an unresolved exception for broad predictive coverage, counted once at the Θ threshold; neither lack of significance nor persistence under another cause is converted into proof of no causal role.", "downgrade_applied": false }, { "subclaim_id": "SC3", "pattern": "Phenotype fails to transfer", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC3", "pattern": "Defined consortium does not recapitulate crude-community effect", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC3", "pattern": "Rescue fails despite reinstating the proposed taxa", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC3", "pattern": "Contamination controls erase the signal", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC3", "pattern": "Independent facilities cannot reproduce the finding", "triggered": false, "interpretation": "Not shown as a reproducible contradiction; consortium/reinstatement tests are not literal requirements for this defined-pathogen clinical claim.", "downgrade_applied": false }, { "subclaim_id": "SC3", "pattern": "Host phenotype persists after removing the claimed microbial driver", "triggered": false, "interpretation": "Residual ulcers do not falsify a nonexclusive major cause. HEAT durability is nevertheless an unresolved exception for broad predictive coverage, counted once at the Θ threshold; neither lack of significance nor persistence under another cause is converted into proof of no causal role.", "downgrade_applied": false }, { "subclaim_id": "SC1/SC3", "pattern": "Unexplained duration of a predicted prevention benefit", "triggered": true, "interpretation": "HEAT early benefit was not established in the later period, and its cause remains unclear [6,14]. This is an unmet Θ requirement, not categorical falsification of the major-cause claim.", "downgrade_applied": false, "threshold_effect": "Pass-01: SC3 stops at Η (it asserts duration). For SC1 the pattern is the single named unresolved exception compatible with Θ's \"minimal unresolved exceptions\"; no second subtraction. Edition B had stopped SC1 and SC3 at Η." } ], "headline_finding": "H. pylori infection is a major upstream cause of peptic ulcer disease: Θ, High confidence — its predictions hold across removal, prevention and temporal-order evidence, with one unresolved exception in long-term aspirin users.", "headline_gap": "HEAT's loss of early protection against ulcer bleeding after 2.5 years in older aspirin users is unexplained; it is the one exception that keeps durable generalization (SC3) at Η.", "checked_sources": [ { "tool": "Life Sciences Literature Entrez esearch", "outcome": "HTTP 500; no evidence from failed search" }, { "tool": "Life Sciences Literature PMC metadata", "identifier": "PMC1773688", "outcome": "No current dataset version; metadata lookup did not supply full text" }, { "tool": "Scite citation context", "outcome": "Quota exhausted; no citation tallies retrieved" }, { "tool": "Direct public article pages", "outcome": "Some pages returned empty/bot-check or forbidden responses; no evidence inferred from those failures" }, { "tool": "Primary record recheck and NCBI Bookshelf scientific summary", "identifier": "PMIDs 3982345, 25111233, 36335970, 40844182; NBK617371", "outcome": "Marshall, stress and HEAT claims rechecked; 2025 HEAT report added as a second report of the same study." }, { "tool": "PubMed E-utilities (pass-01)", "outcome": "All 23 ledger PMIDs resolved and compared; retraction filter and erratum author searches run; no flags." }, { "tool": "Europe PMC REST (pass-01)", "outcome": "commentCorrectionList read for PMIDs 8419816 and 9329511 (comments only); then HTTP 429, not retried." }, { "tool": "Crossref (pass-01)", "identifier": "10.1016/j.lana.2025.101312", "outcome": "Volume 53, article 101312, issued 2026-01." }, { "tool": "NIHR Journals Library full-report PDF (pass-01)", "identifier": "DOI 10.3310/LLKF7871", "outcome": "Targeted passages read: split-time analysis, primary outcome, clearance, discussion." }, { "tool": "PubMed/PMC/Bookshelf HTML, Lancet site, Scite (pass-01)", "outcome": "Bot-check, 403 or quota error; nothing inferred from failures." } ], "schema_extensions": { "id": "local-reference-edition-1 (migrated)", "base_schema_version": "5.4", "base_validator_version": "2.4", "status": "Edition B declared local extensions on schema 5.2. study_id, access_depth, subclaim scope, scope_qualifiers and the calibration realism fields are now standard in 5.4. Retained as local: subclaim_type_label (\"reversibility\" on SC2, whose 5.4 type is necessity), the operational_scope blocks, and endpoint accounting in independence lines.", "edition_B_declaration": { "id": "local-reference-edition-1", "base_schema_version": "5.2", "base_validator_version": "2.2", "status": "Explicit local extensions; not an upstream schema release.", "added_subclaim_types": [ "reversibility" ], "scope_alias": "subclaims[].scope duplicates canonical claimed_scope; both must be nonempty and equal.", "operational_scope": "Baseline-defined eligibility, endpoint, follow-up and a possible failed prediction.", "independence_endpoint_accounting": "List supportive lines separately from direct-ulcer lines.", "study_identity": "Multiple reports of one trial share a study_id and are not new experiments.", "calibration_reference_role": "Distinguishes an unblinded reference edition from a completed blinded run." } }, "lay_summary": { "paragraphs": [ "The claim is that a stomach bacterium, Helicobacter pylori, is one of the main causes of peptic ulcers — open sores in the lining of the stomach or the first part of the small intestine. It is not a claim that the bacterium causes every ulcer: some ulcers come from painkillers of the aspirin and ibuprofen family, and some have no known cause. Many people who carry the bacterium never develop an ulcer.", "The evidence is very strong. In many clinical trials, clearing the infection with antibiotics made ulcers far less likely to come back than a course of acid-reducing treatment alone, and this has been repeated across countries and ulcer types. Clearing it before people started anti-inflammatory painkillers prevented new ulcers, infection was found years before ulcers appeared, and deliberately swallowing the bacterium inflamed the stomach lining of healthy volunteers. This review therefore places the claim on the second-highest step of its nine-step scale: its predictions have held up with very few unexplained exceptions. The main exception is a large trial in older people taking daily aspirin, where protection against ulcer bleeding was clear in the first years but was not seen later, for reasons its investigators could not explain.", "The top step is not given because the bacterium is neither needed for every ulcer nor enough to cause one on its own. The grade describes the strength of the evidence behind the causal claim; it is not a judgement on any person or group, and this review makes no treatment recommendation." ], "grade_restated_faithfully": true, "claims_referenced": [ "C1", "C16", "C8", "C21", "C22", "C24", "C25", "C6", "C15", "C30", "C33" ], "jargon_glossed": [ "peptic ulcer (open sore in the stomach or first part of the small intestine)", "NSAID (named as painkillers of the aspirin and ibuprofen family)", "eradication (clearing the infection with antibiotics)", "the HSEF ladder (described as a nine-step scale; Θ as its second-highest step)" ], "no_practical_advice": true, "written_for": "general reader, no field background" }, "consensus_validation": { "completed": true, "status": "documented_historical_discovery_and_reconciliation", "provider": "Consensus", "provider_mode": "Historical browser/connector use as recorded in the source artifacts", "local_audit_date": "2026-10-09", "primary_comparison_count": null, "reported_usage": [], "grade_changed": false, "score_before": { "hsef_level": "Θ", "hsef_descriptor": "High predictive accuracy, minimal unresolved exceptions", "confidence": "High", "confidence_rationale": "Independent investigators, countries, ulcer sites, endpoints and designs replicate the central intervention-sensitive pattern; pooled syntheses confirm direction [15, 16]. HSEF confidence, not GRADE certainty: Cochrane rates the recurrence evidence very low quality on trial conduct.", "rests_on_non_peer_reviewed_work": false, "rationale": "Removal, prevention, temporal-order, population and organism-addition designs confirm the claim's predictions with one unresolved within-scope exception, HEAT's later period. SC1 = Θ and the pre-registered primary-subclaim rule returns Θ; SC3 holds at Η because it asserts durable generalization, so weakest-link would return Η.", "pass01_prior": "Η (edition B, High confidence)" }, "score_after": { "hsef_level": "Θ", "hsef_descriptor": "High predictive accuracy, minimal unresolved exceptions", "confidence": "High", "confidence_rationale": "Independent investigators, countries, ulcer sites, endpoints and designs replicate the central intervention-sensitive pattern; pooled syntheses confirm direction [15, 16]. HSEF confidence, not GRADE certainty: Cochrane rates the recurrence evidence very low quality on trial conduct.", "rests_on_non_peer_reviewed_work": false, "rationale": "Removal, prevention, temporal-order, population and organism-addition designs confirm the claim's predictions with one unresolved within-scope exception, HEAT's later period. SC1 = Θ and the pre-registered primary-subclaim rule returns Θ; SC3 holds at Η because it asserts durable generalization, so weakest-link would return Η.", "pass01_prior": "Η (edition B, High confidence)" }, "independent_blinded_audit": false, "raw_receipts": [ { "path": "deliverables\\prepublication-enrichment-2026-10-05\\website-series\\h-pylori-peptic-ulcer\\consensus-browser-links.json", "sha256": "27a615e3904089e77daaac9016ee3c3b6be2601b4ef8199126577cf4cd708864" }, { "path": "deliverables\\prepublication-enrichment-2026-10-05\\website-series\\h-pylori-peptic-ulcer\\consensus-browser.txt", "sha256": "c4a9ea3e6123ef0d43efb3b357365ff189fd170d2a406d63a374b15b4d97432f" }, { "path": "deliverables\\prepublication-enrichment-2026-10-05\\website-series\\h-pylori-peptic-ulcer\\consensus-targeted-check.txt", "sha256": "0754e6108794cb1328039b64a8c2bbc2f4b3b4f289223575f3953f82284861c4" } ], "limitations": "This verifies documented historical use and links the record to the final edition. It adds no primary-source, full-text, independence or verification credit. Original access remains limited to the source-specific record.", "existing_primary_reconciliation": { "slug": "h-pylori-peptic-ulcer", "consensus_used": true, "rawproof": [ "deliverables/prepublication-enrichment-2026-10-05/website-series/h-pylori-peptic-ulcer/consensus-browser.txt", "deliverables/prepublication-enrichment-2026-10-05/website-series/h-pylori-peptic-ulcer/consensus-targeted-check.txt", "deliverables/prepublication-enrichment-2026-10-05/website-series/h-pylori-peptic-ulcer/consensus-browser-links.json" ], "reconciliation_existing": "Yes; 8 primary identifiers in timeline; update says primary abstract/metadata checked and distinguishes service-reported full-text details.", "primary_sources_matched": [ "3982345", "1558340", "8174954", "8419816", "9329511", "11274623", "19445937", "36335970" ], "limitations": "No independently readable original full text for additional service-reported details." } } }