Trimethoprim sulfamethoxazole prophylaxis and serious infections in granulomatosis with polyangiitis treated with rituximab
Bibliographic record
Abstract
OBJECTIVE: To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA). METHODS: This retrospective cohort study included adults with GPA (2011-2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months' enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, Pneumocystis jirovecii pneumonia (PJP) and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment or 31 Decamber 2020. RESULTS: Among 919 rituximab-treated individuals (53% female), mean (s.d.) age was 52.1 (16) years and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (interquartile range 138-979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 [95% CI: 5.0, 7.4] per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted hazard ratio [aHR] 0.5; 95% CI: 0.3, 0.9). The aHR for outpatient infections was 0.8 (95% CI: 0.6, 1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI: 0.03-1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI: 0.9, 1.9). CONCLUSIONS: TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".